Review Article

https://doi.org/10.1038/s41557-021-00671-9

Aromatic hydrocarbon belts

Qing-Hui Guo1,2, Yunyan Qiu , Mei-Xiang Wang
1 3 ✉ and J. Fraser Stoddart 1,2,4 ✉

Aromatic hydrocarbon belts (AHCBs) have fascinated scientists for over half a century because of their aesthetically appeal-
ing structures and potential applications in the field of carbon nanotechnology. One of the enduring challenges in synthesizing
AHCBs is how do we cope with the build-up of energy in the highly strained structures during their synthesis? Successful prepa-
rations of AHCBs offer the prospect of providing well-defined templates for the growth of uniform single-walled carbon nano-
tubes—a long-standing interest in nanocarbon science. In this Review, we revisit the protracted historical background involving
the rational design and synthesis of AHCBs and highlight some of the more recent breakthroughs, with emphasis being placed
on the different strategies that have been used for building up curved and fused benzenoid rings into molecular belts. We also
discuss the scientific challenges in this fledgling field and provide some pointers as to what could transpire in years to come.

T
he quest to unlock allotropes of carbon and create new car- belts, [n]cyclophenacnenes, [n]cyclacenes and highlight significant
bon forms in a precise manner has become1–5 stronger with advances20–22,29,36,37 reflecting the resurgence during the past few
the passage of time. Even before the discovery of fuller- years in the synthesis of armchair and chiral CNBs as well as zigzag
enes6–9 and carbon nanotubes10 (CNTs), the structures (Fig. 1a) belt[n]arenes. In winding up our discussion, we proffer suggestions
of aromatic hydrocarbon belts (AHCBs), which are defined here in the wake of current achievements and provide pointers to what
as double-stranded and belt-shaped molecules consisting of fully lies ahead for this field. Our mission is not to discuss every exam-
unsaturated and fused benzenoid rings, had been discussed already ple from the past in detail but, rather, to offer readers an in-depth
in the chemical literature11,12. Heilbronner11 first proposed cycla- and rigorous overview of the ongoing cutting-edge research into
cenes as molecules for theoretical investigation in 1954. Later, in AHCBs. Scholarly analyses and comprehensive examples can be
1983, Vögtle12 proposed both a cyclacene and an armchair belt, found in books38,39 as well as in other informative perspectives40–49.
which became known as the Vögtle belt, as synthetic targets. Four In this Review, we focus on the exclusive design principles and syn-
years later, one of us pioneered13 both regio- and diastereoselective thetic approaches towards AHCBs, with emphasis being placed on
approaches to precursors of [12]cyclacene and, in 1988, reported14 recent breakthroughs20–22,29,36,37 and the ingenious strategies that are
the synthesis of [12]collarene, on the eve of the isolation10 of CNTs. being pursued for building up strain energies in belts with fused
Although Cory15,16 and Schlüter17,18 pursued similar approaches to benzenoid rings, as well as the characteristic properties that arise in
making these belts, research activity had become, by the turn of the compounds with curved and fused π systems.
millennium, close to dormant because of the lack of good and effi- The characteristics41,50,51 (Fig. 1d) of the aromatic hydrocarbon
cient strategies for the syntheses of AHCBs. rings (AHCRs) and AHCBs are distinctive. The cyclic structures of
After a long period of stagnation, the synthesis of cycloparaphen- AHCRs can be opened to generate linear analogues upon cleavage
ylene (CPP) by Jasti and Bertozzi19 in 2008 gave a much needed fillip of one bond, while those of AHCBs can only be opened by cleav-
to synthetic approaches to curved and conjugated benzenoid rings. age of at least two bonds. The distinguishing structural features
Three years ago, Itami20 announced a breakthrough by synthesizing of AHCBs are that their lower and upper edges are conjugated,
a fully unsaturated armchair carbon nanobelt (CNB), while Miao21 yet they never coincide—in other words, no common atoms are
announced, in 2019, the first synthesis of a chiral CNB, which rep- shared by the edges. The aromatic hydrocarbons discussed in this
resents a sidewall segment of a chiral CNT. There was, however, no Review are limited to double-stranded AHCBs, which are classified
answer to the question as to whether the cyclacenes can be synthe- (Fig. 1d(ii–iv)) into armchair, chiral and zigzag belts, while
sized until earlier this year when one of us addressed this challenge the closely related single-stranded rings, such as the CPPs42,52
and observed22 the formation of a substituted [8]cyclacene—which (Fig. 1d(i)) and their π-extended analogues53–56, as well as the [n]
we called a belt[8]arene—from carefully chosen and well-defined cycloparaphenyleneacetylenes57,58, are recognized as AHCRs.
synthetic precursors. These state-of-the-art contributions to the
syntheses of armchair, chiral and zigzag AHCBs have heralded23,24 Challenges in the syntheses of AHCBs
an upsurge of research into the bottom-up precision synthesis The first challenge faced in preparing AHCBs is the out-of-plane
(Fig. 1b,c) of SWCNTs with uniform diameters and single chirali- conformations of the benzenoid rings, which not only have to
ties25–28. Given the most recent breakthroughs22,29,30, we expect this embrace the pent-up high energies associated with the disruption
field to evolve even more rapidly in the future. of the alignment of their molecular orbitals, but also have to reduce
In this Review, we begin by reflecting on the historical back- the driving force for aromatization. Theoretical calculations have
ground and identify some of the obstacles preventing the success- allowed us to quantify51,59 the strain energies (Fig. 1d) that need to be
ful syntheses of AHCBs. In the discussion that follows, we critically overcome during the synthesis of AHCBs. The energies are highly
examine some representative attempts13,14,31–35 to make Vögtle [n] dependent on the sizes and constitutions of the cyclic structures. For

Department of Chemistry, Northwestern University, Evanston, IL, USA. 2Stoddart Institute of Molecular Science, Department of Chemistry, Zhejiang
1

University, Hangzhou, China. 3MOE Key Laboratory of Bioorganic Phosphorous and Chemical Biology, Department of Chemistry, Tsinghua University,
Beijing, China. 4School of Chemistry, University of New South Wales, Sydney, New South Wales, Australia. ✉e-mail: [email protected];
[email protected]

402 Nature Chemistry | VOL 13 | May 2021 | 402–419 | www.nature.com/naturechemistry

NAtuRe CHemIStRy Review Article
a

Cyclacenes Vögtle belts Collarenes Nanotubes CPPs Carbon nanobelts Beltarenes

Proposed Proposed Synthesized Isolated Synthesized Synthesized Observed

1954 1983 1988 1991 2008 2017 2019 2020

Heilbronner Vögtle Stoddart Iijima Jasti Itami Miao Wang

b c
Valence Valence
bond bond

Angular fused Flank fused

Clar Clar
sextet sextet

Cyclophenacenes Armchair CNTs Cyclacenes/beltarenes Zigzag CNTs

(metallic) (semiconducting or metallic)

d
(i) Armchair rings (ii) Armchair belts (iii) Zigzag belts (iv) Chiral belts

n–5 n–7
n–5 n–5 n–3
n–2
[n]CPPs [2n,2n]CNBs [2n]cyclophenacenes Vögtle [2n]belts Belt[n]arenes Chiral CNBs
580.3 × n–1 358.4 × n–1 690.6 × n–1 872.3 × n–1 1324.3 × n–1 460.5 × n–1
kcal mol–1 kcal mol–1 kcal mol–1 kcal mol–1 kcal mol–1 kcal mol–1

Fig. 1 | History and structural formulae of aromatic hydrocarbon belts. a, Timeline from the early 1950s up to the present day, highlighting some of
the historically acquired descriptors for the constitutions of AHCBs11,12,14,20–22 and hydrocarbon rings, such as the CPPs19. Names are shown of some
of the leading researchers who proposed, synthesized, isolated or observed AHCBs and CPPs for the first time. b,c, Structure–property relationships
between CNTs with armchair (metallic) and zigzag (semiconducting or metallic) structures and their angular-fused benzenoid rings in the case of the
cyclophenacenes and the flank-fused benzene rings in the case of the cyclacenes/beltarenes represented by valence bond and Clar sextet notations. Note
that in 2019, Miao21 described the first synthesis of a chiral carbon nanobelt which is a sidewall segment in a chiral carbon nanotube. d, Structural formulae
for (i) armchair rings, (ii) armchair belts, (iii) zigzag belts and (iv) chiral belts with their common names and their total strain energies51,59 in kcal mol–1
where n–1 is the reciprocal of the number of repeating units. Benzenoid rings are highlighted in red in order to draw attention to the different constitutions
associated with armchair rings in CPPs and armchair, zigzag and chiral belts.

example, the total strain energies calculated for those AHCBs with approaches towards molecular belts need to encompass these
a diameter of around 8 Å, including (6,6)CNB, [12]cyclophenacene, impediments by building up strain energies, while investing sta-
the Vögtle [12]belt, the chiral CNB and belt[11]arene, are 119.5, bility in the final structures. Well-orchestrated strategies can be
115.1, 145.4, 115.1, and 120.4 kcal mol−1, respectively. Furthermore, classified into at least five categories: (1) starting from a highly
belt[n]arenes are predicted60,61 to be highly reactive because of their strained and well-defined precursor such as a fullerene, (2) creat-
open shell radicaloid ground states—reflected by the Clar sextet62,63 ing a single-stranded macrocycle, followed by stitching up all the
resonance form in Fig. 1c—which constitute the second challenge appropriate sites in the precursors, (3) expanding the π-conjugated
synthetic chemists have to face in making them. structures of AHCRs by the so called ‘ring-to-belt’ methodol-
The obstacles chemists have to face in the synthesis of AHCBs ogy, (4) making double-stranded, partially saturated macrocycles
are not only their highly strained structures but also the rampant and aromatizing the precursors subsequently, and (5) sequentially
reactivities of several target molecular belts. Successful synthetic combining pathways (2) and (4). The ingenuity that has gone into

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Review Article NAtuRe CHemIStRy

devising these synthetic strategies is discussed in relation to the tar- 3, 4 and 5. Deprotonation of the cyclopentadiene unit in [10]
geted compounds which will include Vögtle belts, cyclophenacenes, cyclophenacene derivatives with base, followed by complexation
carbon nanobelts (CNBs) and cyclacenes/beltarenes. with [PdCl(π-allyl)]2, gave the palladium complex 3. Treatment
of [10]cyclophenacene derivative with [FeCp(CO)2]2 in PhCN
Armchair and chiral aromatic hydrocarbon belts under 185 °C afforded the double-decker iron complexes 4 and 5.
As short sidewall segments of armchair CNTs, cyclophenacenes, Compounds with the generic descriptor 2a are chemically stable
Vögtle belts and CNBs are classified4,12,20 as armchair AHCBs and EPR-silent. Nucleus-independent chemical shift (NICS) calcu-
because the adjacent benzenoid rings in both their upper and lower lations on model compounds 2c and [10]cyclophenacene indicate
edges are fused in angular fashions. They can be regarded as con- that both the belt-shaped 40 π-electron systems are aromatic. X-Ray
jugated analogues of π-extended CPPs with various layers. Since crystallographic analyses of 3 and 4 reveal that (1) the double bonds
Vögtle belts were suggested12 as synthetic targets in 1983, extensive on the edges are shorter than those located on the equator, (2) the
endeavours by many research groups from all around the world bond alternations in the regions of the equator are very small and
have been devoted to the synthesis of AHCBs. Herges64,65 proposed (3) the electrons in the benzenoid structures are delocalized. Their
the stepwise build-up of a Vögtle belt from a tetraanthracenyli- closed-shell state, conjugative stabilization, aromatic character and
dene (picotube) precursor through ring enlargement metathesis unique geometries are all in agreement with theoretical predictions.
(REM) and subsequent cyclodehydrogenation. Vögtle66, Iyoda39 Photophysical spectra of 2a and 2b with radially oriented p orbitals
and Bodwell43 all chose valence isomerization and dehydrogenation reveal that these [10]cyclophenacene derivatives are strongly lumi-
(VID) in order to construct AHCBs. Since the successful synthesis, nescent, emitting bright yellow light with the maximum emissions
in 2008, of CPPs, Müllen67 and Jasti23 have explored straightforward occurring at around 560 and 620 nm.
‘ring-to-belt’ routes68 to various AHCBs, starting from π-extended Following in the footsteps of Nakamura’s stepwise strategy, Gan35
AHCR precursors. Meanwhile, Ito69 and Hughes70 have suggested reported the synthesis of the Vögtle [10]belt derivatives 7a and 7b with
and deployed an alternative ‘ring-to-belt’ strategy, which could be 50 π-electron systems (Fig. 2b) by regioselective multi-amination
tailored easily to synthesize armchair, chiral, and zigzag AHCBs, of [70]fullerene. The reagent N-fluorobenzene-sulfonimide (NFSI)
involving the Diels–Alder reaction of arylene–ethynylene conju- directed the successive penta-additions of secondary amines such
gated macrocycles and subsequent cyclodehydrogenation. Some as 4-methylpiperidine and p-toluidine, to the two poles through an
of these explorations have enjoyed limited success. For example, isolable intermediate 6, without touching the conjugated π systems
Bodwell71 achieved the synthesis of a precursor with a giant curva- of the Vögtle [10]belt fragment on the equator of the elliptical [70]
ture, which can be identified as half the structure of a Vögtle belt, fullerene.
while Iyoda39 claimed to have detected a [10]cyclophenacene by In the strictest sense, the [10]cyclophenacene and Vögtle [10]
subjecting a phenanthrene-containing all-(Z)-benzannulene ana- belt derivatives, synthesized by Nakamura31,32 and Gan35, do not
logue to laser desorption ionization time-of-flight mass spectros- qualify to be accorded the status of molecular belts, because nei-
copy. None of the above approaches, however, led to the isolation ther are their structures, taken as a whole, belt-shaped, nor are their
of the fully unsaturated hydrocarbons. In the event, it was Itami20,37 cavities accessible. Nevertheless, these multi-substituted and dou-
who developed a strategy that combines sequential (Z)-selective bly capped derivatives, however, are undoubtedly appealing and, in
Wittig reactions and Ni-mediated homocouplings to prepare arm- themselves, constitute remarkable achievements in unnatural prod-
chair CNBs. Subsequently, Miao succeeded21 in producing both uct synthesis72. The research provides us with the knowledge, for the
armchair and chiral CNBs from well-chosen precursors and finely first time, of the properties of fully conjugated and fused benzenoid
tuned Scholl reactions. rings in cyclic structures. What this research into cyclophenacene
Prior to discussing successful approaches to CNBs, it is timely and Vögtle belt derivatives has done is to facilitate the retrosynthetic
to introduce the top-down procedures (Fig. 2) of extracting [10] analyses and realistic synthesis of the closely related AHCBs. Most
cyclophenacene and Vögtle [10]belt derivatives from fullerenes. importantly of all, this research gave chemists hope in their quest to
Rather than pursuing the de novo design and synthesis, these pursue the synthesis of armchair AHCBs.
approaches31–35 circumvent the obstacle of building up strain by
beginning with highly strained and well-defined precursors with Carbon nanobelts
curved surfaces composed of sp2 carbons. From a structural point In more recent times, Itami20 broke new ground by reporting the
of view, [10]cyclophenacene and Vögtle [10]belt derivatives are first synthesis (Fig. 3a) and isolation of (6,6)CNB. Inspired by
embedded around the equators of [60]- and [70]fullerene, respec- Iyoda’s extensive attempts39 to synthesize [10]cyclophenacene from
tively. In principle, these derivatives can be extracted selectively all-(Z)-benzannulene analogues and Stępień’s approach73 to syn-
from their conjugated arrays in the middle of both the north and thesizing highly strained aromatic compounds with bowl shapes,
south poles of the fullerenes. Itami applied intramolecular Ni-mediated couplings to construct
CNBs. Starting from the highly brominated aromatic aldehyde 8,
Cyclophenacenes and Vögtle belt derivatives the following iterative deprotections and (Z)-selective Wittig reac-
Almost 20 years ago, Nakamura31,32 reported the first synthesis of [10] tions, afford the bifunctional trimer 9a, which undergoes sequen-
cyclophenacene derivatives (Fig. 2a). Regioselective penta-addition tial cyclodimerization in the presence of base. A single-stranded
of methyl groups, followed by protection with a cyano group at macrocycle in which carefully predetermined reaction sites are
one pole of [60]fullerene, generated a partially unsaturated moi- substituted with bromine atoms in precursor 10 sets the stage for
ety 1. The regioselective penta-addition of phenyl groups at the intramolecular couplings. Subsequent Ni-mediated intermolecular
other pole and reductive deprotection of the cyano group resulted homocouplings stitch up all the adjacent reactive sites in 10, fur-
in the formation of a [10]cyclophenacene derivative 2a. The total nishing the conjugated and double-stranded (6,6)CNB macrocycle.
yield of this stepwise procedure was less than 10%. Subsequently, A year later, the researchers37 modified functional groups on the
Nakamura34 developed a more efficient one-step regioselective bipyridine ligand in the Ni catalyst, increasing the final yield of the
addition of ten 4-butylphenyl groups in the presence of pyridine, belt-forming step from 1 to 5%. Meanwhile, the larger (8,8)CNB
leading to an increase in the yield of 2b to 35%. The resulting [10] and (12,12)CNB analogues were also reported in the same paper37.
cyclophenacene derivatives can be manipulated during oxidation31,32 Both the NICS analysis and the X-ray single-crystal structure
and coordination32–34, with the end result leading to other ana- of (6,6)CNB suggest that the molecular geometry (Fig. 3b) comes
logues, such as single-decker and double-decker metal complexes close to following Clar’s rule62. In the major resonance form, all the

404 Nature Chemistry | VOL 13 | May 2021 | 402–419 | www.nature.com/naturechemistry

NAtuRe CHemIStRy Review Article
a
Me CN R1 R1 H R1
Me Me Me Me R1 R1

Methylation Arylation

Protection Deprotection
[10]Cyclophenacene
R2
R2 R2
R2 R2
[60]Fullerene 1 H

2a: R1 = Me, R2 = Ph
2b: R1 = R2 = nBuC6H4
2c: R1 = R2 = H

Me Me CN Me
Me Me Me Me Fe Me
Me
Me

Ph
Ph R
Ph R
Ph Pd Ph R
4: R = Me Fe R R
3
5: R = Ph

NHSO2Ph NHSO2Ph
N N
N N N
N N N
N N

NFSI NFSI

Amination Amination

Vögtle [10]belt
R
R
R R
R NHSO2Ph
[70]Fullerene 6

7a: R = N Me

H
7b: R = N Me

Fig. 2 | Top-down syntheses of cyclophenacenes and Vögtle belts from fullerenes. a, Syntheses of [10]cyclophenacene derivatives by regioselective
methylations and arylations starting from [60]fullerene. Regioselective addition of five methyl groups, followed by locating a cyano protecting group
at one of the two poles on [60]fullerene, produced the unsaturated compound 1. Regioselective addition of five phenyl groups at the other pole of 1,
followed by reductive deprotection of the cyano group, gave31 the [10]cyclophenacene derivative 2a in an overall yield of 10%. Regioselective addition
of ten 4-butylphenyl groups in one step produced34 2b in 35% yield. Calculations indicate that both [12]cyclophenacene and the model compound 2c,
which each have 40 π-electrons, are aromatic. The [10]cyclophenacene derivatives coordinate with palladium and iron reagents, leading to single-decker32
(3) and double-decker33 (4 and 5) metal complexes. b, Treatment of [70]fullerene with N-fluorobenzene sulfonamide (NFSI) directed35 the addition of
five secondary amines such as 4-methylpiperidine and p-toluidine to the two poles, affording 6 as an isolatable intermediate on the way to 7a and 7b.
Belt-shaped substructures embedded in the fullerenes are highlighted in solid red. Molecular belts with curved and conjugated systems, which have been
extracted from fullerenes, are shaded with red surfaces. Panels adapted with permission from: refs. 31–33, American Chemical Society (a); ref. 34, Wiley (a);
ref. 35, Wiley (b).

equatorial six-membered rings are aromatic with the associated edges in the range (1.34–1.35 Å) for a typical double bond. Hence,
C–C bonds around their circumferences displaying slight bond (6,6)CNB can actually be viewed, on the basis of its major reso-
alternations. The remaining six-membered rings exhibit weak aro- nance form, as a [6]CPP in which its equatorial benzenoid rings are
matic character with the C–C bond lengths on the upper and lower connected alternately by bridging C=C bonds. The values (–2.00

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Review Article NAtuRe CHemIStRy

a b
Br Br Br
Br Br Deprotection Br Br Br CHO Br –7.44
Br
PF6 Wittig
Br Br
Wittig
reactions reactions Br Br
OHC Br Ph3P Br Br Br
n Br Br –2.00
n
8 9a: n = 1 Br Br Major
9b: n = 2

Br
Br
n
Br
Intramolecular Br
(6,6)CNB 1 couplings Br
Br
Br n Minor
(8,8)CNB 2 Br
Br Br
(12,12)CNB 4 R
R
n d R
R = OPrn R
Br R
Br R
10
R
R
c

R RR
R R
R R R

R R
R 11 R
R
R

(6,6)CNB (8,8)CNB (12,12)CNB Scholl reactions

R
R
R R
R
R
R
R

R R R
8.3 Å 10.8 Å 15.4 Å R R R
R R

R
R
R 12 R
R
8.3 Å 11.2 Å 17.5 Å R

Fig. 3 | Syntheses of carbon nanobelts. a, In his synthesis of (6,6)CNB, Itami20 started from the highly brominated aromatic aldehyde 8 and, following
iterative deprotections and (Z)-selective Wittig reactions, obtained the trimeric precursor 9a, which, in the presence of base, undergoes sequential
cyclodimerization to afford 10. Sequential Ni-mediated intramolecular homocouplings gave (6,6)CNB in low yield. The synthesis of (8,8)CNB and
(12,12)CNB have also been reported by Itami37. b, The calculated NICS values (–2.00 and –7.44) show20 how the major and minor resonance forms of
CNBs have aromatic equatorial benzenoid rings connected alternatively by bridging C=C double bonds. c, Side-on and plan views in the form of tubular
representations of the solid-state crystal structures of (6,6)CNB (circular), (8,8)CNB (elliptical) and (12,12)CNB (elliptical). d, Miao’s synthesis21 of (12,12)
CNB[42] (12) from a [12]CPP derivative (11) using a ring-to-belt strategy which relies on 18 Scholl reactions taking place at low temperature (–20 °C) in
CH2Cl2. Note that, by applying the same strategy, the first synthesis of a chiral carbon nanobelt has also been achieved by Miao21. The benzenoid rings
in (6,6)CNB, (8,8)CNB, (12,12)CNB and 12 are highlighted in red. Panels adapted with permission from: ref. 20, AAAS (a,b,c); ref. 37, American Chemical
Society (a,b); ref. 21, Elsevier (d).

and –7.44) of nucleus-independent chemical shift (NICS) also indi- nearly perfect circular shape with a diameter of around 8.3 Å. Both
cate the characteristic structure and aromaticity. (8,8)CNB and (12,12)CNB adopt elliptical shapes with significant
In their crystal structures, all the (n,n)CNBs adopt (Fig. 3c) rigid differences in their lengths between the short and long axes. Their
and belt-shaped conformations in which every benzenoid ring is photophysical properties in solution are highly size-dependent.
fully conjugated and fused to its neighbours. (6,6)CNB exhibits a (6,6)CNB shows a broad red emission band (λmax = 635 nm), while

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NAtuRe CHemIStRy Review Article
(12,12)CNB exhibits a sharp blue fluorescence band at a λmax of to be overcome during the macrocyclization, however, result in
466 nm. By contrast, (8,8)CNB emits green light with both a sharp thermodynamically unfavoured reactions. The design could rely
(λmax = 478 nm) and broad (λmax = 524 nm) band. on masked benzenoid ring equivalents—cyclohexane or cyclo-
Recently, Miao21 described a ‘ring-to-belt’ methodology (Fig. hexene—integrated into partially saturated and doubly stranded
3d) for synthesizing armchair (12,12)CNB[42] 12 from a [12] precursors of [n]cyclacenes, followed by complete aromatiza-
CPP derivative 11 carrying 12 aryl substituents. The well-chosen tion at the end of a sequence of reactions. Back in 1987, one of
single-stranded macrocyclic precursor 11 not only reduces the us pioneered13 a substrate-directed approach to the synthesis of
strain energies during the belt-forming step, but also minimizes the [12]cyclacenes, employing curved precursors as a result of suc-
number of Scholl reactions in order to facilitate the efficient for- cessive diastereoselective Diels–Alder reactions93. Subsequently,
mation of CNBs. The installation of propyloxy (OnPr) groups on Cory15,16,38 and Schlüter17,18,94 modified the substrates for Diels–
the precursor is an important design feature, since they facilitate Alder reactions in attempts to make [n]cyclacenes. All efforts at
the cyclization by serving as directing groups as well as lowering74 full aromatization of the doubly stranded precursors, however, were
the oxidation potential on account of them being electron-donating unsuccessful. In more recent times, Itami95 has attempted to synthe-
substituents. The OnPr groups also ensure the necessary solubility size benzannulated [12]cyclacenes by intramolecular cyclizations
of the product. The fine-tuned conditions of the Scholl reactions of single-stranded precursors. Instead of forming the targeted [12]
at low temperature (–20 °C) in CH2Cl2, circumvent undesired rear- cyclacene analogue, an unexpected rearranged product was charac-
rangements and lead to the formation of the targeted 12 in 21% terized. Notably, despite the fact that Cory put on record in 1998 the
yield. The CH2Cl2 solution of (12,12)CNB[42] is yellow and exhib- optimistic prognosis, “it is now all but certain that we are closing in
its strong green luminescence (λmax = 498 and 532 nm). Notably, the on the synthesis of the first cyclacene”38, we had to wait until 2020
first synthesis of a chiral CNB, which represents a sidewall segment for the formation of a substituted [8]cyclacene to be detected by one
of chiral (18,12)CNT, was also realized by this ‘ring-to-belt’ strategy of us22, and the synthesis of zigzag CNBs by Itami96 and Chi97. In the
in the same paper21. following subsection, we will discuss the pioneering work13,14 and
These triumphs in unnatural product synthesis72 achieved by distinct examples22,29,36,96,97 taken from research carried out in recent
Itami20,37 and Miao21 have done much to refresh the long-standing years.
interest of synthetic chemists in aromatic molecular belts. The
creative chemistry and knowledge gained during the successful Substrate-directed syntheses of cyclacenes
synthesis of armchair AHCBs can ultimately be applied24 to the In the late 1980s/early 1990s, one of us pioneered13,14,98–104 a
predictable synthesis of single-chirality and uniform-diameter substrate-directed approach (Fig. 4a,b) towards the syntheses of
single-walled carbon nanotubes (SWCNTs), an advance, which, if [12]- and [14]cyclacenes. Our stepwise protocol relied on trebly
it were to be made, would represent a revolution in the field. The diastereoselective Diels–Alder reactions, starting from the bisdiene
ground-breaking achievements of Itami20,37 and Miao21 will hope- 13 and bisdienophile 14. The remarkably precise stereoelectronic
fully motivate more investigators to tackle the next challenge, that control of the substrate-directed cycloadditions proved to be key to
is, the synthesis of cyclacene/beltarene. our making good progress in the early stages of the attempted syn-
theses of the cyclacenes. Only one of the 10 possible105–107 diastereo-
Zigzag aromatic hydrocarbon belts isomeric 2:1 adducts, 15, was formed exclusively in 80% yield after
[n]Cyclacenes or belt[n]arenes are the shortest sidewall seg- a mixture of 2.5 molar equivalents of 13 and 1.0 molar equivalent
ments of zigzag CNTs. [n]Cyclacene is the traditional name for a of 14 were heated in PhMe. The Diels–Alder reactions between the
double-stranded and lateral-fused poly[n]acene. When one of us bisdiene 13 and the bisdienophile 14 to give the 2:1 adduct 15 pro-
described the formation22 of a substituted [8]cyclacene derivative ceed108,109 approximately 100–300 times faster than the subsequent
in 2020, we recommended using the name belt[n]arenes to refer to Diels–Alder reactions between 15 and 14. Hence, cycloadditions
this class of belt-shaped molecules. This nomenclature system fol- between 13 and 14 are arrested completely at the 2:1 adduct 15 at
lows the tradition in macrocyclic chemistry of naming cyclic com- atmospheric pressure. The advantage of these differences in rates
pounds after everyday objects according to the shapes of their most means that further reaction by 15 does not occur. Two subsequent
stable conformations. Well-known examples include the crown Diels–Alder reactions with the same treble diastereoselectivity pro-
ethers75,76, calixarenes77,78, cucurbiturils79,80, pillararenes81 and coro- ceeded between equimolar amounts of 14 and 15 under ultra-high
narenes82,83. The name belt[n]arene can also be extended easily to pressure, promoted the cyclization and produced Kohnkene 16 in
heteroaromatic ring-containing analogues. In this Review, we use 36% yield.
[n]cyclacene and belt[n]arene interchangeably in order to keep the The treble diastereoselectivity exercised during the Diels–Alder
nomenclature of the compounds coinciding with those used in the reactions is worthy of some comment. Let us consider the forma-
original literature. tion of a 1:1 adduct of 13 and 14 as an example when discussing the
Since the structural formula of [12]cyclacene was suggested by mechanism of the reaction. The electron density in the π orbital on
Heilbronner11, [n]cyclacenes have attracted much attention in terms the exo-face of 14 is much greater than that on the endo-face of 14
of both theoretical treatments44 and their potential syntheses40,41. and so exo attack on 14 is favoured110,111. The torsional effect112–114
Their molecular geometries60,84–86, electronic configurations61,85,87–91, also accentuates exo attack on 14. There are, in principle, two geom-
strain energies51,84 and aromatic properties60,90,92 have been predicted etries, namely syn/exo-14/endo-13 and syn/exo-14/exo-13 when it
extensively by a large number of theoretical investigations. There comes to considering possible Diels–Alder transition states. The lat-
is, however, some debate in relation to their anticipated character- ter can be ruled out on account of a highly disfavoured steric effect.
istics for the simple reason that the computed results are, to some The former, namely endo attack on 13 is also favoured by second-
extent, dependent on the levels of theory and methods of calcula- ary interactions115–117 arising from exo attack on 14. The preferred
tion employed. syn/exo-14/endo-13 geometry in the transition state of the Diels–
Synthetic chemists need to rise to the challenge of devising Alder reaction affords exclusively the syn/endo-H diastereoisomer.
high-yielding syntheses of [n]cyclacenes to bring a conclusion to Starting from the double-stranded, yet partially unsaturated
these debates based on theory alone. Obviously, the most straight- precursor, Kohnkene 16, further synthetic elaboration might be
forward strategy to employ in the synthesis of [n]cyclacenes is to expected to give [12]collarene 19, [12]beltene 20, and ultimately
build curvature into a linear poly[n]acene so that they can ulti- [12]cyclacene 21. Deoxygenation of 16 with a low-valent titanium
mately undergo cyclization. The large strain energies that have reagent removed two of the six oxygen atoms smoothly and afforded

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Review Article NAtuRe CHemIStRy

a
H H H H H H
O O O O O O O O

H 15 H H H Deoxygenation H H Dehydration
Diels–Alder Diels–Alder
O 13 O O O O O
reactions reactions
H H H H
O O O O O O O O
H H H H

14 Kohnkene (16) 17 18

Torsional effect Hydrogenation

Exo-14 Exo-13
O
Syn/ O O
Exo-14/
Endo-13
Endo-14 Endo-13 Dehydrogenation Hydrogenation
Stereoelectronically favoured
Hydrogenation
Steric effect
Syn/ O
O
Exo-14/ O
Exo-13 [12]Beltene (20)
[12]Cyclacene (21) [12]Collarene (19)
Sterically disfavoured

b R R R
c
H H
O O O H
O O O
O R O H R O H R
Diels–Alder Diels–Alder H
22 O O
reactions reactions
O R O O H
H R H R
O O O
O O O H
H H
R R R Kohnkene (16) 17
14 R = H; 14' R = Me 23a R = H; 23b R = Me 24a R = H; 24b R = Me

Fig. 4 | Substrate-directed syntheses of cyclacenes. a, Synthesis of Kohnkene 16 was achieved13 by a sequence of trebly diastereoselective Diels–Alder
reactions starting from the bisdiene 13 and the bisdienophile 14. It is the relative importance of steric, electronic and torsional effects which dictate that
the Diels–Alder Syn/Exo-14/Endo-13 transition state is favoured105,107,123 over the Syn/Exo-14/Exo-13 one. Cycloadditions between 13 and 14 yielded the 2:1
adduct 15 as an intermediate in 80% yield when heated in toluene. Diels–Alder reactions that are also trebly diatstereoselective between the bisdienophile
14 and the extended bisdiene 15 proceeded under ultra-high pressure in toluene to give13,101 Kohnkene 16 in 36% yield. Deoxygenation of 16 with a
low-valent titanium reagent afforded the cyclophane 17 in 43% yield14,101,which was dehydrated in acetic acid to give 18. Birch reduction of 18 resulted in
its partial hydrogenation to give [12]collarene 19. All attempts to make [12]beltene 20 and [12]cyclacene 21 were unsuccessful at the time. b, Syntheses
of the [14]cyclacene precursors 24a and 24b were achieved99,101 by carrying out trebly diastereoselective Diels–Alder reactions between the bisdiene 22
and bisdienophile 14 (R = H) or a methylated derivative 14′ (R = Me) to give the intermediate extended bisdienophiles 23a and 23b, which reacted under
high pressure with the bisdiene 13 to give 24a and 24b, respectively. c, Plan views in the form of tubular representations of the solid-state structures13,14,101
of Kohnkene 16 and its deoxygenated derivative 17, which plays host in its cavity to a disorder water molecule. The bisdienes and components in structural
formulae derived therefrom are highlighted in pink. The bisdienophiles and components in structural formulae derived therefrom are highlighted in blue.
The cyclohexene rings in compounds 15, 16, 17, 23 and 24 are highlighted in pale yellow. In hydrocarbon belts 18, 19 and 20, the 1,4-cyclohexadiene rings
are highlighted in green. In compounds 17, 18, 19 and 21, the benzenoid rings are highlighted in red. Panels adapted with permission from: refs. 13,14, Wiley
(a,c); ref. 107, Wiley (a); ref. 99, Wiley (b); ref. 101, American Chemical Society (b).

the cyclophane 17 in 43% yield. Dehydration of 17 using acetic 1.0 molar equivalent 22 under ultra-high pressure provided the
anhydride generated an unexpected product, namely 18, which was 2:1 adduct 23 in 30% yield. The cyclization with 13 proceeded
most likely formed as a result of an acid-catalysed isomerization of smoothly without the use of ultra-high pressure under mild ther-
the anticipated more symmetrical intermediate. Birch reduction of mal conditions to generate the precursor 24a of [14]cyclacene in
18, in an attempt to make [12]beltene 20, resulted in the isolation 78% yield. The more soluble tetramethyl-substituted analogue 24b
of the dodecahydro[12]cyclacene derivative, [12]collarene 19, with was also synthesized starting from 14′ and following the cyclization
six 1,4-cyclohexadiene and six benzenoid rings fused alternately. between 23b and 13.
Full dehydrogenation of precursor 18 was expected to lead to [12] The solid-state structures (Fig. 4c) of the [12]cyclacene precursors
cyclacene 21, while partial hydrogenation of all six benzene rings in Kohnkene 16 and the cyclophane 17 were analysed by single-crystal
[12]collarene 19 was anticipated to yield [12]beltene 20. Success in X-ray diffraction. In the solid-state structure of Kohnkene, the four
carrying out these two reactions eluded us at the time. endo-methine hydrogen atoms all point into the centre of the cavity,
In order to prove the generality of the trebly diastereoselec- while the six oxygen atoms are situated on the outer rim of the mol-
tive Diels–Alder chemistry, the substrate-directed strategy was ecule. This solid-state structure verified unambiguously the treble
applied99 to the cyclization of the bisdienophile 14 and the extended diastereoselectivities of four Diels–Alder reactions. The removal of
bisdiene 22, which, if it could have been achieved, would have pro- two of the six oxygen atoms in Kohnkene resulted in the forma-
vided access to [14]cyclacene and its derivatives with even larger tion of two more benzenoid rings, endowing 17 with a cavity that
diameters. The reaction between 2.0 molar equivalents of 14 and formed an inclusion compound with water in its solid state.

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NAtuRe CHemIStRy Review Article
Although we were frustrated at the time by the fact that full aro- characterizations of cyclacene derivatives by stepwise deoxygen-
matization of the precursors eluded us, we feel in the light of recent ation (Fig. 5b) of the precursors 29 and 34. Upon low-temperature
breakthroughs22,29 in the field, that we might be able to complete the deposition, followed by thermal annealing operations on a Cu(111)
syntheses of both [12]- and [14]cyclacenes. surface, the precursors assembled into islands (Fig. 5c(i) and 5d(i)),
The most striking feature of our substrate-directed strat- driven by intermolecular [π···π] interactions between benzenoid
egy is that the sequential use of thermally promoted and high- rings. The lying adsorption geometry of each molecule allowed the
pressure-promoted cycloadditions to assemble the small building tip-induced deoxygenation to proceed smoothly. After STM-based
blocks precisely into ordered, rigid and large molecular structures atom manipulations on 29_4O and 34_4O, the selected zoomed-in
is reminiscent of construction using LEGO101,107,118. (Two papers AFM images revealed (Fig. 5c,d) that the removal of the first and
published in the Journal of the American Chemical Society, the second atoms in the precursors were successful and afforded the
first101 in 1992 and the second104 in 1993, changed from titles start- partially aromatized products 29_3O, 29_2O and 34_3O, 34_2Oa,
ing ‘Molecular LEGO’ because a letter from the LEGO Company in 34_2Ob with bent curvatures. Further manipulations to remove
early 1993 warned that the full force of the law would be unleashed the third atoms under increasingly harsher conditions led to the
if their brand name continued to be used!) The usefulness and gen- degradations of the molecules. In the final analysis, there were no
erality of this substrate-directed strategy allows synthetic chemists compounds with less than two oxygen atoms and the targeted cycla-
to create a range of carbon skeletons, including molecular belts and cenes were not identified. Density functional theory (DFT) calcula-
collars105,119, strips106,120, angular belts121–123, as well as cages121–123, by tions indicate that the energies associated with the deoxygenations
programming different molecular building blocks without having increase the more so, the fewer the atoms present in the substrates.
to use complicated multistep syntheses and external reagent control. In other words, the energies for the deoxygenations of 29_2O and
Both Cory15,16 and Schlüter17,18,94 employed similar approaches 34_2O compounds were so high that the atom manipulations could
in their attempts to synthesize [6]-, [8]-, [9]- and [18]cyclacenes not be conducted with sufficient control. The calculations, however,
in the 1990s. Last year, Gross and Peña36 also relied on modified suggested that, in the case of the larger precursors, it should be pos-
substrate-directed Diels–Alder reactions to prepare precursors for sible to produce cyclacenes.
their on-surface approach to the syntheses of [8]- and [10]cycla- This on-surface synthetic approach addresses one of the
cenes. Recently, Miao124 reported a similar synthetic approach to the long-standing hurdles—that is the potential instabilities60,89 in air
precursor of tetrabenzo[10]cyclacene, which has four more ben- associated with the cyclacenes. It would appear that all operations
zenoid rings fused selectively to [10]cyclacene, rendering it more have to be conducted under ultra-high vacuum. Considering the
stable as a result. recent on-surface synthesis and characterization of cyclo[18]car-
bon1,139, this strategy seems to be a promising one for making cycla-
On-surface synthesis of cyclacenes cenes from larger precursors, in which the energies for the complete
In recent years, scanning tunnelling microscopy125–129 (STM), atomic deoxygenations will be much lower.
force microscopy130 (AFM) with functionalized tips131, and atom
manipulation techniques132,133 have been developed134,135 in the hands Strategy of stitching up fjords to belt[n]arenes
of physicists, chemists and biologists. Concurrently, on-surface One of us has introduced a straightforward synthetic protocol22,29
synthesis136–139 has emerged as a powerful tool to prepare140–142 (Fig. 6) to the belt[n]arenes and observed the formation (Fig. 6b) of
highly reactive species and characterize them with submolecular a substituted belt[8]arene for the first time. The key design principle
resolution. Facing the failures of previous attempts to synthesize lies in the use of the pre-organized and pre-functionalized constitu-
cyclacenes conducted in solution and, bearing in mind that insta- tions of single-stranded resorcin[n]arenes143,144 (n = 4, 6), followed
bility is most likely associated with the open-shell ground states60 by stitching up their fjords by employing intramolecular Friedel–
in 2019, Gross and Peña36 reported an on-surface synthetic route Crafts alkylations. In the synthetic route to belt[8]arene, the syn-
(Fig. 5) to the [8]- and [10]cyclacenes. They employed STM-based thesis started from an asymmetric, yet easily accessible resorcin[4]
atom manipulation on an inert surface, at low temperature and arene 35, which was converted to resorcin[4]arene 36 with four
under ultra-high vacuum. Inspired by the substrate-directed strat- phenolic hydroxy groups precisely installed at predesigned sites
egy13,14,101,106,107,120,122,123, the cyclic precursors tetraepoxycyclacenes 29 for use through several transformations. Triflations of the hydroxy
and 34 were first of all prepared (Fig. 5a) from the corresponding groups and subsequent Pd-catalysed Stille couplings afforded resor-
arynes and furans by successive Diels–Alder reactions. The cyclo- cin[4]arene 37 and the tetravinylated derivative 38 in 93 and 66%
phane 29 was obtained, following a cascade four-step cycloaddition yields, respectively. Ozonolysis of 38 generated 39 in 62% yield and
of the bifunctional intermediate 28 containing both a diene and the following Grignard reactions produced the macrocyclic tetraol
dienophile, which was generated from a highly reactive isoben- 40 in 67% yield. Closing all four fjords in the resorcin[4]arene 40
zofuran 27 by an inverse electron-demand Diels−Alder (IEDDA) by intramolecular Friedel–Crafts alkylations produced the partially
reaction between diepoxyanthracene 25 and a tetrazine-containing saturated belt[8]arene derivative 41 as pairs of crystalline stereoiso-
derivative 26. The total yield of 29, following a one-pot cyclization, mers which were characterized by X-ray crystallography.
was 5%. The larger precursor 34 was prepared in multiple steps Oxidative aromatization of a mixture of stereoisomers 41 with
from the diepoxyanthracene 30. The cycloaddition between 2.0 excess of DDQ resulted in the formation of the unstable, yet isol-
molar equivalents of the bistriflate 32 and 1.0 molar equivalent of able, belt[8]arene-DDQ4 adduct 42, following cascade reactions,
the benzodifuran 31, which was generated in situ by the IEDDA including quadruple aromatizations and Diels−Alder additions in
reaction from 30 and 26, produced four isomers (anti-33a/b and one pot. In the solid state, the belt[8]arene precursor 42, with four
syn-33a/b) in 43% overall yield. In the presence of CsF as base, benzene rings and four 1,4-cyclohexadiene rings alternately fused
the mixture of two regioisomers syn-33a/b was subjected to reac- in the core structure, adopts a spectacular geometry with four DDQ
tion with the benzodifuran 31 and the cyclization step afforded the moieties wrapped around the outer rim of the belt-shaped cavity
cyclophane 34 in 15% yield. X-Ray single-crystal diffraction analy- which is crowned with 3,5-dimethylphenyl units on its upper rim.
ses36 of macrocycles 29 and 34 reveal their rigid, as well as respective The belt[8]arene derivative 43 was observed (Fig. 6b) in the MALDI
square- and rectangular-shaped conformations with all the bridging mass spectrum when precursor 42 was subjected to laser irradia-
oxygen atoms situated on the periphery of the molecules. tion (λ = 355 nm) and underwent stepwise retro-Diels−Alder reac-
STM manipulations and AFM imaging with CO-functionalized tions. By finely tuning the intensity of laser, substituted belt[8]arene
tips were employed36 to effect on-surface syntheses and 43 became the major product. By application of a similar approach

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Review Article NAtuRe CHemIStRy

a
26 O O
N N O
N N Aryne O Diels–Alder
TMS N N TMS formation reactions 5.74 Å
O O
OTf OTf 5%
O
O
25 27 O O
28 29
32
TMS OTf

26 TfO TMS TMS R1 TMS R1

O O O O O O O O
43% TfO R2 TfO R2

30 31 anti-33a/b syn-33a/b
a: R1 = TMS / R2 = OTf
b: R1 = OTf / R2 = TMS

O O O Aryne
O O
O Diels–Alder formation
reactions
7.83 Å

15%

O O
O
O
34

b
34_2Oa

34_1O
Remove Remove
atom atom
34_2Oc
34_4O 34_3O 34_2Ob [10]Cyclacene

STM/AFM tip-mediated manipulations Unsuccessful manipulations

c d
(i) z = –1.6 Å (ii) z = –1.0 Å (iii) z = –1.0 Å (i) (ii) (iii) z = –2.6 Å (iv) z = –2.3 Å

5Å 5Å 5Å 5Å 5Å

29_4O 29_3O 29_2O 34_4O 34_3O 34_2Oa 34_2Ob

−O −O −O −O

Fig. 5 | On-surfaces syntheses of cyclacenes36. a, Cyclophane 29 was obtained following a cascade of Diels–Alder reactions performed on the bifunctional
intermediate 28 containing both a diene and a dienophile. It was generated from a highly reactive isobenzofuran 27 resulting from an IEDDA reaction
between 25 and a tetrazine-containing derivative 26. The larger cyclophane 34 was prepared by employing sequential Diels–Alder reactions in several steps
from the diepoxyanthracene 30. An IEDDA reaction between 30 and 26 afforded the benzodifuran 31, which was subjected to a Diels–Alder reaction with
the diyne generated from the bistriflate 32 to produce four isomers, namely anti-33a/b and syn-33a/b. The mixture of the two regioisomers syn-33a/b was
subjected to a reaction with the benzodifuran 31 in the presence of CsF as base: cyclization afforded the cyclophane in 15% yield. b, Graphical representations
of the STM manipulation and AFM imaging during syntheses on a Cu(111) surface leading to the characterization of 34_4O, 34_3O and three regioisomers
34_2Oa, 34_2Ob and 34_2Oc. In the event, 34_1O and [10]cyclacene were not detected. c, Zoomed-in AFM images corresponding to the precursors 29_4O
(i), 29_3O (ii) and 29_2O (iii). d, Zoomed-in images corresponding to precursors 34_4O (i), 34_3O (ii), 34_2Oa (iii) and 34_2Ob (iv). The benzenoid and
oxanorbornadiene rings in cyclic compounds 29 and 34, are highlighted in red and yellow, respectively. Adapted with permission from ref. 36, Wiley.

(Fig. 6c), the larger analogue 45 and the belt[12]arene precursor 46, Compared with all previous attempts, this synthetic approach
both of which are substituted collar[12]arene derivatives, have also tackles both major challenges involving the high strain energy
been synthesized29 from the symmetrical resorcin[6]arene 44. and potential instability of belt[n]arenes during their synthesis.

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NAtuRe CHemIStRy Review Article
a b
70
MeO OH OH OTf 43 43 DDQ3 adduct
60 DDQ1 adduct DDQ4 adduct
HO OMe HO TfO DDQ2 adduct
Et Et Et Et Triflation Et Et DDQ1 adduct 50

Percentage (%)
Et Et Et Et Et Et 40
MeO OH OH OTf
30
HO OMe HO TfO
20
35 36 37
DDQ2 adduct
10
Stille couplings
Ar 0
OH O
OH Grignard O 1,000 1,500 2,000 40 50 60 70 80 90 100
Ar reaction
Et Et Et Et Ozonolysis Et Et m/z Intensity of laser irradiation (%)

Et Et Et Et Et Et
Ar c Ph
HO O
HO O HO OH
OH OH
Ar Ph Ph
40 39 Ar = 3,5- 38
Et Et Et Et
Friedel–Crafts dimethylphenyl HO OH Et Et Et Et
O Cl Et Et or
alkylation HO OH Et Et Et
NC
Cl Et Et Et Et Et
Ar Ar NC O Ar Ar Ph Ph
Ar Cl O Ar OH OH
CN NC HO OH
Ar Ar O Ar
Cl Ar NC
Ar DDQ Et Et Cl Laser Ar Ph
Et O Et
CN O Cl 44 45 46
Cascade Retro-
reaction EtO CNEt Diels–Alder
Et Cl Et
CN reaction
Et Et
Cl O
41 42
Substituted
belt[8]arene (43) Ar
Ar
Ar

Ar
Ar Et
Ar Et
10.5 Å
Et
Et
Et

42 42 Substituted belt[12]arene
(a,e,a,e)-41

Fig. 6 | Synthesis of beltarenes from resorcinarenes by stitching-up-fjords strategy. a, Toward the synthesis22 of substituted belt[8]arene 43 from
resorcin[4]arene 35. The modified resorcin[4]arene 36 with four phenolic hydroxy groups installed at predesigned sites was obtained from 35 through
several transformations. The triflations of all hydroxy groups in 36 afforded resorcin[4]arene 37 in 93% yield and subsequent Pd-catalysed Stille couplings
gave the tetravinylated derivative 38 in 66% yield. Aldehyde-functionalized derivative 39 was generated from the ozonolysis of 38 in 62% yield and the
following Grignard reactions produced macrocyclic tetraol 40 in 67% yield. The intramolecular Friedel–Crafts alkylations closed all four fjords in 40 and
produced the partially saturated belt[8]arene derivative 41 with pairs of stereoisomers, which underwent oxidative aromatization with DDQ to produce
belt[8]arene-DDQ4 adduct 42. The substituted belt[8]arene 43 was observed under the irradiation of laser. The conformations of one (a,e,a,e)-stereoisomer
of 41 and precursor 42 were verified by their single-crystal structures. b, Mass spectrum of 43 and its DDQ adducts22. Right, dependence of the production,
expressed as percentages of 43 and its DDQ adducts on the intensity of the laser radiations. The five plots indicate that the stronger intensity of the
laser favours the more efficient formation of 43 from the stepwise retro-Diels–Alder reactions of the belt[8]arene-DDQ4 adduct 42. c, Synthesis29 of
substituted collar[12]arenes 45 and 46 as well as the transformation toward a substituted belt[12]arene starting from resorcin[6]arene 44 utilizing the
stitching-up-fjords strategy. Bottom right, tubular representations of the solid-state structures of 46 obtained by X-ray crystallography. The benzenoid and
cyclohexadiene rings in hydrocarbon belts 41, 42, 43, 45, 46 and substituted belt[12]arene are highlighted in red and green, respectively. Panels adapted with
permission from: ref. 22, American Chemical Society (a,b); ref. 29, Wiley (c).

The strategy of stitching up fjords builds up the strain energies oxanorbornadiene units as masked benzenoid ring equivalents.
successfully, while the installation of bulky aryl groups on the The benzannulated analogue of the cyclacene 53, in which six
rim of the structure is valuable when it comes to stabilizing the benzenoid rings and six di-tertbutylpyrene units are connected
final product. The observation of the saturated belt[8]arene deriv- alternately with each other in a cyclic fashion, is predicted to be
ative shows that the full aromatization of zigzag precursors is stable according to Clar’s sextet rule62.
surmountable. We believe that the general principles employed in The Diels–Alder reaction between furan and reactive aryne
this research will encourage more chemists to try to isolate stable intermediate, derived from 4,5,9,10-tetrabromo-2,7-di-ter
belt[n]arenes. tbutylpyrene 47, and a subsequent retro-Diels–Alder reaction
mediated by a tetrazine derivative afforded 48 in 57% yield. In the
The synthesis of a zigzag carbon nanobelt presence of 0.35 equiv of nBuLi, 48 was induced to undergo Diels–
During the writing of this Review, Itami96 reported the first syn- Alder dimerization to give an intermediate, which, when subjected
thesis (Fig. 7a) of a zigzag CNB by employing an iterative sequence to rhenium-catalysed deoxygenative aromatization afforded 49 in
of Diels–Alder reactions concluding with reductive aromatization. 54% yield, based on the consumed 48. Compound 49 was trans-
The synthetic route was inspired by the substrate-directed strat- formed into 50 following a Diels–Alder reaction with furan. The
egy13,14,101,106,107,120,122,123 which was pioneered by one of us, using Diels–Alder reaction of 50 with the aryne generated from 47

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Review Article NAtuRe CHemIStRy

a
Diels–Alder Diels–Alder
Diels–Alder
R reaction R Diels–Alder R R R R R R R
reaction reaction
with furan reaction 47
with furan
Br Br Br Br Br
O O O O O O
Br Br Br Br Retro- Br
Retro- Aromatization
Diels–Alder
R Diels–Alder R R R R R R R R
reaction
reaction
47 48 49 50
R = tBu
R
R R R R R R
R R O
O O O
Diels–Alder O O
R R R R R R R R
R R R reactions R R 51 R
Aromatization

R R R R R R
R R R R R Aryne
R O Br Br
O formation
O O
R R R
R R R
R
53 52

b c

A
–7.54

14 Å C B
–7.44 0.99

53'

Fig. 7 | The synthesis of a zigzag carbon nanobelt96. a, The benzannulated analogue of [18]cyclacene 53, in which benzenoid rings and di-tertbutylpyrene
units are connected alternately, was synthesized by employing a sequence of Diels–Alder reactions followed by aromatization. The Diels–Alder reaction
between 47 and furan, followed by a retro-Diels–Alder reaction mediated by 3,6-di-2-pyridyl-1,2,4,5-tetrazine gave 48 in 57% yield. The Diels–Alder
dimerization of 48 was induced by nBuLi and subsequent rhenium-catalysed deoxygenative aromatization gave 49 in 54% yield. The Diels–Alder reaction
with furan transformed 49 into 50, which underwent a Diels–Alder reaction with the aryne generated from 47 and a subsequent retro-Diels–Alder to
produce the key precursor 51 in 75% yield. Compound 51 adopts a bent and concave conformation, which favours the cyclization involving a bifunctional
intermediate with both a diene and a dienophile. The cyclic precursor 52 was subjected directly to aromatization with low-valent titanium and 53 was
obtained in a 5.4% yield, over two steps. b, Side-on and plan views in the form of tubular representations of the single-crystal structure of 53 with a
rigid belt-shaped conformation and a diameter of 14 Å. c, The calculated (NICS(0)) values (–7.54, 0.99, –7.44) and induced current density (ACID) plot
reveal that rings A and C are aromatic, whereas ring B is nonaromatic. The benzenoid rings in hydrocarbon belts 52 and 53 are highlighted in red. The
oxanorbornadiene rings in hydrocarbon belt 52 are highlighted in yellow. Adapted with permission from ref. 96, Springer Nature Ltd.

and a subsequent retro-Diels–Alder reaction aided and abetted by The synthesis of an octabenzo[12]cyclacene
tetraphenylcyclopentadienone, produced 51 in 75% yield. When Chi97 independently reported her synthesis (Fig. 8a) of an octa-
hexafluorobenzene was present to act as a template, the cyclization benzo[12]cyclacene 58, which was also achieved by employing
of 51 was favoured by its bent and concave conformation, origi- iterative Diels–Alder reactions and a subsequent reductive aro-
nating from the oxanorbornadiene unit in 51. By avoiding separa- matization. The accumulated strain energy from the build-up of a
tion of 52, the residue was subjected directly to aromatization with belt-shaped structure was overcome by the stepwise introduction of
low-valent titanium and the zigzag CNB 53 was obtained, over two oxanorbornadiene units. The stability of the final structure benefits
steps, in a 5.4% yield. from the presence of both the fused and attached phenyl substitu-
The structure of 53 was unambiguously characterized by NMR ents at the edges.
spectroscopy and single-crystal X-ray crystallography. In the In the presence of nBuLi, excess of the aryne was generated
solid-state structure, 53 adopts (Fig. 7b) a rigid belt-shaped confor- in situ from 54, followed by a Diels–Alder addition with
mation with a zigzag-type sidewall defusing both edges. The diam- bisfuran 55, affording the syn-isomer of 56 in 48% yield. A sub-
eter of the close-to-circular nanobelt is about 14 Å. sequent iterative Diels–Alder addition between syn-56 and 55
In order to probe the electronic and structural behaviour of 53, gave the tetraepoxy precursor 57 in 4% yield. Cyclization
calculations were performed on its unsubstituted analogue. The was favoured by the concave conformation of 56, originating from
(NICS(0)) values and induced current density (ACID) plot indicate two oxanorbornadiene units in its constitution. The aromatiza-
(Fig. 7c) that rings A and C are aromatic, whereas ring B is non- tion of 57 was realized by a TiCl4/LiAlH4-mediated deoxygenation
aromatic. The zigzag CNB 53 does not have electronic structure of and the final zigzag CNB 58 was obtained as an off-white solid
conjugated beltarene. The diluted dichloromethane solution of 53 in 8% yield.
is colourless and the absorption spectrum shows a strong band at The conformation of 58 in the solid-state was revealed by
around 336 nm in addition to a weak peak at 405 nm. Under UV single-crystal X-ray crystallography. The CNB 58 adopts (Fig. 8b) a
irradiation, the solution emits blue light with the maximum emis- symmetric, cylinder-like shape with the pyrene units bent outward
sion occurring at around 407 and 432 nm. from the belt-shaped backbone at the core. The diameter of the

412 Nature Chemistry | VOL 13 | May 2021 | 402–419 | www.nature.com/naturechemistry

NAtuRe CHemIStRy Review Article
a b
R1 R1 O R2 R1 O
R2
1. Aryne R2
R2 R2
Br Br formation R2
R1
O O R1 R1
Br Br 2. Diels–Alder syn -56
2 2
R R reaction R1
R1 9.2 Å
R1 R1
Br Br Br
54 55 Br

R1 = tBu; R2 = tBu 1. Aryne formation

2. Diels–Alder reaction with 55

R1 O R2 R1
R2 R1 O
R2
R2 c d
R1 R2
R2 2 R1
R
R2 Aromatization R1 R1
R1
R1 R2 A
1
R 1 R –26.9
R2 R 1
R2 C B
R2 R2 –22 –1.6
R1
R2
R2
R2 O O R2
R1 1 R2
R R1
R1
58 57 58

Fig. 8 | The synthesis of an octabenzo[12]cyclacene97. a, The synthetic route involves employing iterative Diels–Alder reactions and a subsequent
reductive aromatization. The Diels–Alder addition between eight molar equivalents of 54 and one molar equivalent of 55 was induced by nBuLi. The 2:1
adducts 56 were generated as pairs of stereoisomers from which the syn-isomer was separated in 48% yield. A subsequent iterative Diels–Alder addition
between syn-56 and 55 gave tetraepoxy precursor 57 in 4% yield. The cyclization was favoured by the concave conformation of 56 in which the two
oxanorbornadiene units have a syn configuration. The zigzag CNB 58 was obtained in 8% yield by a TiCl4/LiAlH4-mediated aromatization of 57. b, Side-on
and plan views in the form of tubular representations of the single-crystal X-ray structure of 58 with its belt-shaped conformation and a diameter of 9.2 Å.
c, The NICS(1)zz values of rings A, B and C (–26.9, –1.6, –22) as well as an ACID plot, which displays a clockwise diatropic ring current flowing in the sextet
rings A and C, confirming that these rings are aromatic, whereas ring B is nonaromatic. d, The calculated 3D chemical shielding surface (ICSS) map shows
the spherical area (in yellow) inside the belt-shaped cavity of 58 is more shielded than its outer region. The benzenoid rings in hydrocarbon belts 57 and
58 are highlighted in red. The oxanorbornadiene rings in hydrocarbon belt 57 are highlighted in yellow. Adapted with permission from ref. 97, Wiley.

close-to-circular molecular belt is about 9.2 Å, as measured from of both oxygen- and sulfur-embedded zigzag molecular belts after
the distance between two opposite pyrene moieties. successive copper-catalysed Ullmann couplings and intramolecu-
The local aromatic character of 58 is revealed (Fig. 8c) by the lar nucleophilic aromatic substitutions (SNAr). Miao149 achieved
calculated NICS(1)zz values (labelled in the rings) and an ACID the synthesis of a tetraepoxy precursor of N-doped zigzag belt in
plot, which displays clockwise diatropic ring current in the sextet 2019. Two of us150 recently reported facile syntheses of oxygen- and
rings A and C. In other words, rings A and C are aromatic and ring nitrogen-embedded zigzag hydrocarbon belts by stitching up all the
B is nonaromatic. The 3D chemical shielding surface (ICSS) map fjords of resorcin[4]arene through intramolecular SNAr and inter-
reveals (Fig. 8d) that the spherical area inside the cavity of 58 is molecular Pd-catalysed C–N bond formation reactions.
more shielded than its outer region. Computational strain analysis
suggests that the phenyl substituents at the zigzag edges are crucial Outlook
to release strain and avoid further hydrogenation reaction during With the continuous efforts being devoted to overcoming the
the final reductive aromatization step. The absorption bands of 58 numerous hurdles to make the long-awaited AHCBs, significant
in dichloromethane are in the UV-Vis region with the maximum advances have been made during the past three years. Armchair20,37
absorption wavelength being observed at 332 nm. In addition, there and chiral21 AHCBs have been isolated and fully characterized. The
is a weak shoulder peak at 405 nm with a tail extending beyond precursors of zigzag AHCBs, belt[n]arenes, have been prepared22,29
500 nm. The maximum emission wavelength of the solution is and the formation of a belt[8]arene derivative has been observed22,
442 nm and the absolute external quantum yield is 4.3%. starting from a well-known precursor143. These breakthroughs bode
well for an evolving future of success and would suggest that AHCBs
The synthesis of heteroatom-embedded hydrocarbon belts are getting their second wind. The advances in this chemistry may
With the syntheses of hydrocarbon belts now well establis­ open up new avenues in the fields of geodesic polyarenes4,154 and
hed20–22,29,36,37,96,97,101,104,145, heteroatom-embedded hydrocarbon belts carbon nanoscience27,28. A new frontier in unnatural product syn-
have begun to be explored146–150 recently. The site-selective introduc- thesis72 is being established, inviting creative thought and interdis-
tion of heteroatoms, such as oxygen, sulfur and nitrogen into hydro- ciplinary collaboration in relation to both the fundamental science
carbon belts, is generating a diverse range of molecular belts with and advanced applications. Let us now try to foresee some critical
finely tuned photophysical and electrochemical properties, which goals that need to be achieved on a short time scale before shedding
may find applications151–153 in optoelectronics. some light on a blueprint for the next decade.
In 2019, Tanaka146 reported the first synthesis of Apart from the real demand for practical, large-scale synthetic
oxygen-embedded hydrocarbon belts. The armchair146, planar chi- routes to AHCBs, the first goal to be tackled is the characteriza-
ral zigzag147 and Möbius-shaped belts146 were obtained by employing tion of belt[n]arenes with unequivocal spectroscopic data155. The
efficient rhodium-catalysed intramolecular alkyne cyclotrimeriza- observation22 of substituted belt[8]arenes in the mass spectrometer
tions. As recently as this year (2020), Zhu148 described the syntheses implies that the belt[8]arenes, modified with bulky aryl groups, are

Nature Chemistry | VOL 13 | May 2021 | 402–419 | www.nature.com/naturechemistry 413

Review Article NAtuRe CHemIStRy

a b

π electrons Seed Zigzag

Cyclophenacene Template
π
electrons
Growth
Template to CNTs Armchair

Möbius
beltarene
Seed
[12]Cyclacene Beltarene

c e
O O

O Trinacrene
Stepwise
synthesis
Coupling
O O
O

X
O O
O

d Aromatization
H H H H

O O O O O O O O O O

H H H H
Aromatic
Ladder oligomer molecular
cage
Molecular strip

X=O Stepwise
Ar1 X Ar2 X Ar1 Ar1 Ar3 Ar2 Ar3 Ar1
synthesis
Aromatization
X = CH2 / O Ladder polymer Large fullerenes

Fig. 9 | Structural traits of AHCBs and proposed bottom-up syntheses of uniform CNTs, ladder oligomers and large fullerenes. a, In-plane orientations
and alignments of p orbitals in a cyclacene (top-left). The structure of a Möbius beltarene (bottom-left). The π electrons in [12]cyclacene (right).
b, Seeded growth of constitutionally well-defined CNTs from AHCB templates on metal surfaces. While one expects a cyclophenacene to seed the growth
of armchair CNTs, a beltarene would be expected to seed the growth of zigzag CNTs. c, Graphical illustrations of a proposed total synthesis of SWCNTs
with precise diameters, lengths and chiralities. d, Structural formula of a ladder oligomer and graphical illustration of the coiled ladder oligomer. The
all-syn configurations at the four saturated ring junctions define a molecular strip-like conformation106,121,123 for the ladder oligomer. Dehydration, if it were
to be carried out, would produce a more extended conformation. The conformational change that would take place during this reaction is reminiscent
of a party blower! e, Structural formula of trinacrene100,104 and the proposed synthesis of an aromatic molecular cage that could become a precursor of
large fullerene-like compounds. The benzenoid rings in the aromatic hydrocarbon belt, ladder polymer and cage are highlighted in red. The components
in structural formulae derived from bisdienes are highlighted in pink and those derived from bisdienephiles are highlighted in blue. The cyclohexene and
cyclobutene rings are highlighted in pale yellow. The 1,3-cyclobutadiene rings are highlighted in green. Panel d adapted with permission from ref. 106, Wiley.

stable under high vacuum. The next steps will be (1) to work out polyarenes. Analyses of unusual in-plane alignments of their bent p
how they can be taken outside their comfort zone and, at the same orbitals91 and degrees of conjugation, as well as the unique topolo-
time, (2) to prevent undesired reactions occurring on their highly gies159 present in various molecular belts, will undoubtedly add yet
reactive constitutions in air. The day is coming when cutting-edge another dimension to our knowledge about molecular strain160,161,
STM-AFM systems will be so well-developed that they will be able ring currents and electron delocalization162,163 in cyclic polyarenes.
to produce non-planar molecules as reliably as they can planar The optical and electronic properties of armchair AHCBs and ana-
ones156 in terms of atom manipulation and characterization under logues20,21,37 have been probed exhaustively. The inevitable questions
high vacuum. Another tantalizing possibility is the use of supramo- (Fig. 9a) about the orbitals164, aromaticity165,166 and topologies167–169
lecular tenets to facilitate the stability of belt[n]arenes in confined of belt[n]arenes are awaiting responses from both experimental-
spaces157, a development that could fundamentally change their ists and theorists. The band gap between singlet and triplet states,
physical and chemical properties, as encapsulated molecules. the degree of delocalization170–172 of π-electrons, and the possible
The structural properties of AHCBs are especially important existence of Möbius topologies173 all have direct relevance to the
for the development of a theory of aromaticity158 as it relates to properties of belt[n]arenes. Which aromaticity rules—including

414 Nature Chemistry | VOL 13 | May 2021 | 402–419 | www.nature.com/naturechemistry

NAtuRe CHemIStRy Review Article
Hückel’s174, Baird’s175, Möbius rules176,177 and others178,179—will the and graphene nanoribbons, it may be made possible to synthe-
belt[n]arenes obey? This question is of fundamental importance in size molecular cages100,102,104, from macrobicyclic structures like
the field of polyarenes. trinacrene (Fig. 9e), by employing Diels–Alder reactions under
In terms of potential applications, the distinctive photo- and tight stereoelectronic control. The adaption of substrate-directed
electro-physical properties, in relation to luminescence21,37 and approaches of this kind towards the syntheses of three-dimensional
magnetism180, associated with unconventional π-electron delocal- molecules, such as fullerenes197, all-carbon frameworks226 and
ization and radially oriented p orbitals in ACHBs, may find181 appli- mechanically interlocked molecules227–230, could have far-reaching
cations in optoelectronic materials. New potential applications will consequences for chemistry.
no doubt be sought from the viewpoints of both physics and materi- Along with the history of discovering new aromatic hydrocarbon
als science. Furthermore, their rigid and cylindrical cavities, along belts, which have caught the imaginations of researchers across the
with the different electronic features that characterize their convex scientific landscape, an increasing number of synthetic carbon allo-
and concave surfaces, could end up making ACHBs and derivatives tropes also beckons. We would encourage talented young scientists
valuable hosts182 towards appropriately shaped and stereoelectroni- to devote their intellects and expertise to science that has never been
cally complementary guests183–185. We can also expect belt[n]arenes done before and ask themselves ‘Why not give it a try?’
and all-carbon compounds to be explored as composites in a supra-
molecular context186–188. Received: 22 March 2020; Accepted: 23 February 2021;
Fulfilling these expectations relates to how far we can manage Published online: 15 April 2021
to extend189–191 the lengths of AHCBs and, ultimately, apply them
as templates in the structurally precise synthesis24,192 of uniform References
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