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Synthesis of Vicinal anti-Amino Alcohols from N-tert-Butanesulfinyl

Aldimines and Cyclopropanols
Sandra Hernández-Ibáñez, Juan F. Ortuño, Ana Sirvent, Carmen Nájera, José Miguel Sansano,
Miguel Yus, and Francisco Foubelo*
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ABSTRACT: The stereoselective synthesis of vicinal amino

alcohols derivatives from 1-substituted cyclopropanols and chiral
N-tert-butanesulfinyl imines is described. Cyclopropanols are easily
prepared from carboxylic esters upon reaction with ethyl-
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magnesium bromide in the presence of titanium tetraisopropoxide

and undergo carbon−carbon bond cleavage by means of
diethylzinc to produce, upon base deprotonation, enolized zinc
homoenolates, which react with chiral sulfinyl imines in a highly
regio- and stereoselective manner.

1. INTRODUCTION hydroxy allylation of imines involves the use of hydroxy allyl

The allylation of imines is a matter of significant synthetic organometallic compounds.4 Among these, 3-acyloxyallyl
interest. When allylation is executed in a stereoselective bromides have proven to be easily manageable and highly
fashion, it provides access to enantioenriched homoallyl efficient precursors of these oxidofunctionalized allyl organo-
amines, which serve as invaluable building blocks.1 These metallic compounds.5 In this context, Norrby and Madsen
compounds frequently feature as intermediates in numerous established a protocol for the synthesis of vicinal amino
synthetic methodologies. The catalytic enantioselective alcohols. This method utilized a Barbier-type reaction between
allylation has been accomplished by employing substoichio- an imine and 3-benzoyloxyallyl bromide in the presence of zinc
metric quantities of chiral Lewis acids and/or bases.2 However, metal. The resulting addition products underwent debenzyla-
stereoselective allylations are more commonly conducted using tion to yield amino alcohols in good yields, with diastereomeric
stoichiometric amounts of chiral reagents, particularly when ratios favoring the anti-isomer at greater than 85:15 (Scheme
operating on a larger scale. Stereoselectivity in these processes 1a).6 Similarly, Xu and Lin successfully developed a
can be attributed to either the chiral imine (substrate diastereoselective α-hydroxyallylation approach for the asym-
diastereocontrol) or chiral allylating reagents (reagent metric synthesis of various β-amino-α-vinyl alcohols. They
diastereocontrol).3 Diastereoselective allylations of imines achieved this by employing highly diastereoselective Zn-
necessitate consideration of two critical factors: the face promoted benzoyloxyallylation of chiral N-tert-butanesulfinyl
selectivity, influenced by the chiral substrate or reagent, and imines with 3-bromopropenyl benzoate at room temperature,
regioselectivity, which comes into play when substituted allylic resulting in a wide range of vinylic amino alcohol derivatives in
reagents are involved. In the latter case, the formation of a excellent yields. The diastereomeric ratios reached up to 99:1
contiguous stereocenter with a relative anti- or syn-config- in favor of the anti-isomers (Scheme 1b).7 This methodology
uration, facilitated through an ordered acyclic or cyclic was applied in a key step of the synthesis of the marine alkaloid
transition state, is also feasible, with the metal playing a ecteinascidin 743, a compound known for its potent cytostatic
pivotal role in the governing transition state. Hydroxyallylation properties and antitumor activity. Ecteinascidin 743 is
of imines holds special significance as it leads to the formation
of vicinal allylic amino alcohols. This chemical motif is highly
versatile and intriguing, garnering significant attention in the Received: January 23, 2024
realms of natural product chemistry and drug discovery. Its Revised: April 8, 2024
unique structural features bestow compounds bearing this Accepted: April 9, 2024
motif with a wide array of biological activities, rendering them Published: April 13, 2024
promising candidates for pharmaceutical and medicinal
applications. The most straightforward method for achieving
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6193 J. Org. Chem. 2024, 89, 6193−6204
The Journal of Organic Chemistry pubs.acs.org/joc Article

Scheme 1. Hydroxyallylation of Imines and Carbonyl Compounds

Table 1. Optimization of the Reaction Conditionsa

Entry Reaction conditions 1a/3ab/4ab ratiob

1 Bpy (1 equiv), Et2Zn (2 equiv), 23 °C 100/0/0
2 Bpy (1 equiv), Et2Zn (2 equiv), 60 °C 0/82/18
3 Et3N (1 equiv), Et2Zn (2 equiv), 60 °C 0/83/17
4 Et3N (1 equiv), Et2Zn (2 equiv), 40 °C 100/0/0c
5 EtONa (2M, EtOH, 1 equiv), Et2Zn (2 equiv), 60 °C --d
6 DBU (1 equiv), Et2Zn (2 equiv), 60 °C --c
7 Cs2CO3 (1 equiv), Et2Zn (2 equiv), 60 °C --c
8 Pyridine (1 equiv), Et2Zn (2 equiv), 60 °C 0/74/26
9 DIPEA (1 equiv), Et2Zn (2 equiv), 60 °C 0/60/40
10 Et3N (1 equiv), CuCN·2LiCl (0.5M, 3 equiv), Et2Zn (2 equiv), 60 °C 0/26/74
11 CuCN·2LiCl (0.5M, 3 equiv), Et2Zn (2 equiv), 60 °C --c
a
Reactions were carried out with 0.2 mmol of 1a and 2b. bRatio determined by analysis of the 1H NMR spectrum of the crude reaction mixture.
c
Total decomposition of the starting material 1a took place, and the expected products 3/4 were not observed. dAutocondensation product of
imine 1a seems to be the reaction product.

currently utilized in the treatment of soft-tissue sarcoma and conditions used to promote ring opening, intermediates such
ovarian cancer.8 as organometallic homoenolates, β-keto radicals, and O-
Concurrently, cyclopropanols have gained significant protonated ketones are formed. Homoenolates are of particular
attention in organic synthesis as precursors of three-carbon interest due to the presence of two closely located carbon
building blocks.9 These easily accessible compounds10 contain atoms with nucleophilic (carbon−metal bond) and electro-
strained three-membered rings that readily undergo carbon− philic (carbonyl group) character. Transition metal derivatives
carbon bond cleavage to release energy. Depending on the of homoenolates have been employed in cross-coupling
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Scheme 2. Hydroxyallylation of Imine 1a with Different 1-Substituted Cyclopropanols 2a,b,c

a
Reactions were carried out with 0.3 mmol of 1a and 2. bRatio determined by analysis of the 1H NMR spectrum of the crude reaction mixture.
c
Reaction was carried out with 1.0 mmol of 1a and 2.

reactions.11 On the other hand, the direct diastereoselective derived from 3-phenylpropanal and 1-phenylcyclopropanol
synthesis of anti-1,2-diols, with oxygen atoms bonded to (2b) as the model substrates. Initially, we tested the conditions
secondary and allylic tertiary carbon atoms, as reported by described by Sekiguchi and Yoshikai for selectively obtaining
Sekiguchi and Yoshikai, is of significant importance. The zinc anti-1,2-diols (Scheme 1c).12 The reaction was conducted with
homoenolate, formed upon the opening of the cyclopropanol, 2 equiv of Et2Zn and 1 equiv of bipyridine as a base in THF at
is in equilibrium under relatively strong basic conditions with 23 °C for 1 h. Unfortunately, the reaction did not proceed
an enolized homoenolate. The enolized homoenolate acts as an under these conditions, and our analysis using 1H NMR
oxyallyl nucleophile, reacting with the aldehyde to serve as an indicated the presence of only the starting imine 1a (Table 1,
oxygen-substituted allylating reagent. The resulting vicinal entry 1). Conversely, we repeated the same conditions but
diols exhibit high diastereoselectivity, favoring the anti-isomers raised the temperature to 60 °C. Fortunately, we obtained
(Scheme 1c).12 Importantly, enolized homoenolates can also allylation products 3ab and 4ab in a 4:1 ratio, with complete
function as enolates, depending on the reaction conditions and consumption of the starting imine 1a (Table 1, entry 2).
the electrophilic partner.13 Similar results were obtained when Et3N was used as the base
Given our research group’s expertise in the diastereoselective (Table 1, entry 3). However, when the reaction was carried out
allylation of N-tert-butanesulfinyl imines,14 and considering the at 40 °C, we did not obtain the desired reaction products 3ab
bibliographic antecedents previously commented, we deemed and 4ab. Instead, we observed the starting imine 1a and what
it worthwhile to investigate the allylation of these chiral imines appeared to be decomposition products of the starting
using zinc enolized homoenolates formed by the cleavage of 1- materials (Table 1, entry 4). We noted that, apparently, the
substituted cyclopropanols. We aimed to determine the autocondensation product of imine 1a was the sole reaction
influence of the tert-butanesulfinyl group on the stereo- product when EtONa in EtOH was used as the base (Table 1,
selectivity of the process. Starting cyclopropanols can be entry 5). Complete decomposition of the starting materials
synthesized from carboxylic esters and ethylmagnesium occurred when DBU and Cs2CO3 were used as bases (Table 1,
bromide using the Kulinkovich protocol.15 Since sulfinyl entries 6 and 7). When the reaction was conducted using
imines are typically prepared from a carbonyl compound and pyridine or DIPEA as bases, we obtained the allylation
tert-butanesulfinamide, the expected outcome is the formation products 3ab and 4ab with excellent conversions but poorer
of vicinal amino alcohol derivatives resulting from the coupling diastereoselectivity (Table 1, entries 8 and 9). Subsequently,
of two carbon atoms, ostensibly with the same polarity if we performed the reaction similarly to entry 3 but with the
considering their precursors. This transformation can be addition of 3 equiv of CuCN·2LiCl. Surprisingly, under these
viewed as an umpolung reaction with respect to the enolized conditions, we obtained a diastereomeric mixture of 3ab and
homoenolate (Scheme 1d). 4ab, with a reversed diastereoselectivity, where diastereoisomer

■ RESULTS AND DISCUSSION

The study of the allylation of N-tert-butanesulfinyl imines
4ab became the major component in an almost 1:3 ratio
(Table 1, entry 10). Lastly, we conducted the reaction under
the same conditions as in entry 10 but in the absence of a base.
began with the optimization of the reaction conditions. For Unfortunately, we observed only decomposition products
this purpose, we selected the (Rs)-tert-butanesulfinamide 1a (Table 1, entry 11).
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Scheme 3. Hydroxyallylation of Imines 1 with Cyclopropanol 2aa,b

a
Reactions were carried out with 0.3 mmol of 1 and 2a. bRatio determined by analysis of the 1H NMR spectrum of the crude reaction mixture.

Scheme 4. Hydroxyallylation of Imine 1a with Different 1-Substituted Cyclopropanols 2 in the Presence of CuCN·2LiCla,b

a
Reactions were carried out with 0.3 mmol of 1a and 2. bRatio determined by analysis of the 1H NMR spectrum of the crude reaction mixture.

With the optimized conditions in hand (Table 1, entry 3), in through the same stereochemical pathway. The allylation
order to obtain diastereoisomer 3 as the major reaction occurred via nucleophilic attack on the Si face of imines with
product, we initially explored the reaction of various RS configuration, resulting in vicinal amino alcohols with a
cyclopropanols 2 with sulfinyl imine 1a (Scheme 2). Alkyl relative anti-configuration.
and aryl cyclopropanol derivatives 2 participated in the It is worth noting that hydroxyallylations can also be carried
hydroxyallylation with imine 1a, yielding the corresponding out under the same reaction conditions outlined in Scheme 2,
products 3ab−ai in moderately isolated yields. The scope of using cyclopropanol (2a) as the hydroxyallylation agent.
the reaction was explored at a 0.3 mmol scale, with the Interestingly, in the work of Sekiguchi and Yoshikai, all the
exception of 1-phenylcyclopropanol (2b), for which the examples presented involve substituted cyclopropanols.12 The
reaction was also conducted on a 1.0 mmol-scale. This reaction products obtained in these cases are secondary allylic
resulted in the production of the amino alcohol derivative 3ab alcohols with a sulfonamide group in the neighboring position.
with an 56% isolated yield, a little bit lower to that achieved at The isolated yields, indicated in parentheses in Scheme 3 for
the 0.3 mmol scale. In Scheme 2, diastereomeric ratios of the major reaction product 3, were moderate, as were the
diastereoisomers 3 (always the major isomer) and 4 are diastereomeric ratios in the case of imines derived from
provided in parentheses. Unfortunately, the reactions with 1- benzaldehyde (1b), isobutyraldehyde (1c), and O-TBS-
benzhydrylcyclopropan-1-ol (2h) did not yield the expected protected hydroxyacetaldehyde (1d). In contrast, better
1,2-aminoalcohol 3ah. Instead, only decomposition products diastereoselectivity, albeit with lower yield, was observed in
were observed. Regarding the configuration of compounds 3, it the case of the imine derived from 3-phenylpropanal (1a)
was determined through crystal X-ray analysis (see the (Scheme 3).
Supporting Information) of solid compounds 3ab and 3ai.16 We proceeded to investigate the reaction’s scope using the
The configurations of the remaining compounds 3 were same cyclopropanols 2 and sulfinyl imine 1a. However, we
assigned by analogy, assuming that they all were formed applied the reaction conditions outlined in entry 10 of Table 1,
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Scheme 5. Hydroxyallylation of Imines 1a, 1b, and 1e with Cyclopropanol 2b in the Presence and Absence of CuCN·2LiCla,b

a
Reactions were carried out with 0.3 mmol of 1 and 2b. bRatio determined by analysis of the 1H NMR spectrum of the crude reaction mixture.

Figure 1. Speculative working models for explaining the stereochemical outcomes of the hydroxyallylations.

aiming to favor the formation of diastereoisomers 4 as the The formation of syn-isomers resulting from an attack on the Si
major reaction products. The only deviation from the face of the imine could be an alternative possibility.
conditions previously employed in Scheme 2 was the addition To expand the range of the reaction, we also investigated the
of 3 equiv of CuCN·2LiCl (0.5 M in THF) (Scheme 4). reaction of 1-phenylcyclopropanol (2b) with various sulfinyl
Consequently, we consistently obtained the corresponding imines 1 under the reaction conditions outlined in Schemes 2
products 4ab−ai in moderately isolated yields as the primary (Method A) and 4 (Method B). We observed slightly higher
components of the reaction products, with aminoalcohol diastereoselectivities and yields when employing the reaction
derivatives 3 appearing as minor isomers (diastereomeric ratios conditions of Method A. This consistently led to the formation
are indicated in parentheses). Moreover, as observed with the of the anti-diastereoisomer 3 as the major component of the
prior conditions, the reaction failed to occur with 1- reaction mixture, resulting from the nucleophilic attack on the
benzhydrylcyclopropan-1-ol (2h). Additionally, in the case of Si face of imines with RS configuration (Scheme 5). In contrast,
cyclopropanol 2f (3-bromopropyl derivative), the reaction did anti-diastereoisomers resulting from the nucleophilic attack on
not yield the expected product 4af. An unexpected outcome the Re face of imines with RS configuration predominated when
arose in the hydroxyallylation involving 1-(2-bromophenyl)- using the reaction conditions of Method B, producing
cyclopropanol (2i), as the predominant reaction product was compounds 4. Surprisingly, there was an exception to this
the anti-isomer 3ai, the same one produced when working general rule. When 1-phenylcyclopropanol (2b) reacted with
without copper cyanide. The configuration of compounds 4 the imine derived from benzaldehyde 1b under the conditions
was established after a simple sulfur atom epimerization of the of Method B, it yielded the anti-isomer 3bb in fairly good yield
sulfinyl unit in compound 3ae (vide infra). In this scenario, the with an 8:1 diastereomeric ratio. This anomalous result may be
nucleophilic attack of the allylic reagent occurred preferentially elucidated by considering steric or π−π stacking interactions
on the Re face of imines with RS configuration, resulting in 1,2- between the two adjacent phenyl groups, potentially directing
aminoalcohol derivatives 4 with relative anti-configurations. the process predominantly through the primary operating
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Scheme 6. Epimerization of the Sulfur Atom of Amino Alcohol Derivative 3ae

Scheme 7. Synthetic Transformations of Amino Alcohol Derivatives 3

mechanism under the reaction conditions of Method A (see experiment revealed identical Rf values for 4ae and the
Figure 1a). epimerized product of 3ae (ent-4ae).
We determined the configuration of vicinal amino alcohol It is important to emphasize that amino alcohol derivatives 3
derivatives 4 by conducting a straightforward epimerization of and 4, featuring various functionalities within their structures,
the sulfur atom within the sulfinyl group under acidic hold significant potential for applications in synthesis as
conditions, employing a nonprotic solvent such as dichloro- precursors to both carbo- and heterocyclic compounds, as well
methane.17 We selected the anti-isomer 3ae as our model as others with potential biological activity. In this context, we
substrate. Under these conditions, the sulfinyl group was present three examples of direct transformations of these
removed from the sulfinamide, resulting in the formation of the
amino alcohols in Scheme 7. To illustrate, the ring-closing
hydrochloride derivative 5ae and racemic tert-butanesulfinyl
metathesis of diene amino alcohol 3eb yielded the amino-
chloride. Subsequent addition of triethylamine led to the
generation of sulfonamide derivatives as a mixture of cycloheptenol derivative 6 in 55% yield (Scheme 7a).
diastereoisomers, 3ae and ent-4ae (Scheme 6). We analyzed Conversely, the bromo-substituted compound 3af was
the 1H NMR spectrum of the crude reaction mixture and converted into hydroxy vinyl piperidine 7, nearly quantita-
identified two distinct sets of signals: one corresponding to the tively, through the removal of the sulfinyl group under acidic
starting anti-isomer 3ae and another set perfectly matching the conditions, followed by a basic workup (Scheme 7b). Lastly,
signals of compound 4ae. This unequivocally confirmed the cross-metathesis involving the selectively protected amino diol
anti-relative configuration of amino alcohol derivatives 4, as the derivative 3da and pentadec-1-ene resulted in N-tert-
1
H NMR spectra of ent-4ae and 4ae were entirely identical butanesulfinyl 1-O-TBS protected L-sphingosine 8 in 60%
(see Supporting Information). Furthermore, a simple TLC yield (Scheme 7c).
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The stereochemical outcomes of these reactions were direct conversion into various valuable carbo- and heterocyclic
elucidated by considering the formation of an enolized zinc compounds. This work offers new avenues for the efficient
homoenolate with a Z configuration, featuring a stabilizing synthesis of complex molecules with potential biological
interaction between the oxygen of the enolate and the zinc- activities. As such, it holds great potential in the realms of
bound homoenolate, which interacts with the chiral sulfinyl medicinal chemistry and natural product synthesis.
imine 1. The formation of the enolized zinc homoenolate is
supported by DFT calculations.12 These calculations, con-
ducted for the reaction of this organometallic intermediate
with aldehydes, anticipate that the allylation proceeds through
■ EXPERIMENTAL SECTION
General Remarks. Reagents and solvents were purchased from
commercial suppliers and used as received. (R)-tert-Butanesulfina-
a chairlike Zimmerman−Traxler transition state. In this mide was a gift of Medalchemy (>99% ee by chiral HPLC on a
transition state, the larger alkyl or aryl group of the aldehyde Chiracel AS column, 90:10 n-hexane/i-PrOH, 1.2 mL/min, λ = 222
occupies an axial position, while the R1 group of the enolate is nm). Optical rotations were measured using a Jasco P-1030
positioned equatorially. In the case of N-tert-butanesulfinyl polarimeter with a thermally jacketed 5 cm cell at approximately 23
imines 1, under the reaction conditions of Method A, we °C, and concentrations (c) are given in g/100 mL. Low-resolution
propose a working model A in which the zinc homoenolate mass spectra (EI) were obtained with an Agilent GC/MS5973N
coordinates with both the nitrogen of the imine and the spectrometer at 70 eV, and fragment ions in m/z with relative
intensities (%) in parentheses. High-resolution mass spectra (HRMS)
oxygen of the sulfinyl group, forming a bicyclic environment
were also carried out in the electron impact mode (EI) at 70 eV and
composed of a 4-membered ring (N−S−O−Zn), and a on a Finnigan MAT95S spectrometer equipped with a time-of-flight
chairlike 6-membered ring. In this configuration, the R1 (TOF) analyzer and the samples were ionized by ESI techniques and
group of the enolate assumes a pseudoequatorial position, introduced through an ultrahigh pressure liquid chromatography
while the R2 and sulfinyl groups of the imine are diaxially (UPLC) model. NMR spectra were recorded at 300 or 400 MHz for
1
disposed. In this scenario, hydroxyallylation occurs at the Si H NMR and at 75 or 100 MHz for 13C NMR with a Bruker AV300
face of the imine with RS configuration, yielding the anti- Oxford or a Bruker AV400 spectrometers, respectively, using CDCl3
diastereoisomer 3, consistent with experimental observations as solvent, and TMS as internal standard (0.00 ppm). The data are
(Figure 1a). The formation of other anti-diastereoisomers 4 reported as s = singlet, d = doublet, t = triplet, q = quartet, m =
under the reaction conditions of Method B could be explained multiplet or unresolved, br s = broad signal, coupling constant(s) in
Hz, integration. 13C NMR spectra were recorded with 1H-decoupling
by considering an acyclic model. When hydroxyallylation is at 100 MHz and referenced to CDCl3 at 77.16 ppm. DEPT-135
conducted in the presence of a large excess of copper cyanide, experiments were performed to assign CH, CH2, and CH3. TLCs
the formation of cyclic intermediates could be avoided due to were performed on prefabricated Merck aluminum plates with silica
the formation of zinc−copper couple intermediates with gel 60 coated with fluorescent indicator F254 and were visualized with
saturated coordination spheres, avoiding the formation of phosphomolybdic acid (PMA) stain. The Rf values were calculated
cyclic intermediates. Consequently, the addition to the imine under these conditions. Flash chromatography was carried out on
may occur through an open transition state. The most stable handpacked columns of silica gel 60 (230−400 mesh). Compounds
configuration of the imine assumes an s-cis conformation, with 1a [R = Ph(CH2)2],18 1b (R = Ph),19 1c (R = i-Pr),19 1d (R =
the Re face of N-tert-butanesulfinyl imines 1 (with RS TBSOCH2),20 and 1e [R = CH2�CH(CH2)3]21 were prepared from
the corresponding aldehyde and (R)-tert-butanesulfinamide according
configuration) being the less hindered face. In this manner, to previously published procedures. Compound 2a was commercially
the configuration of the stereogenic center bonded to the available. Compounds 2b (R = Ph),22 2c [R = CH3(CH2)9],23 2d [R
nitrogen in the hydroxyallylated product is the opposite of that = Br(CH2)6], 2e [R = Br(CH2)5],24 2f [R = Br(CH2)3],25 2g [R =
obtained when using Method A. Regarding the relative anti- CH2�CH(CH2)3], 2h (R = Ph2CH), and 2i (R = 2-BrC6H4)26 were
configuration, it can be explained by considering an open prepared from the corresponding ethyl ester and ethylmagnesium
transition state (Transition State B) that minimizes destabiliz- bromide in the presence of titanium tetraisopropoxide.15
ing dipole interactions with the nitrogen of the imine and the General Procedure for the Reaction of Sulfinyl Imines 1 and
oxygen of the enolate in an antiperiplanar disposition, thereby Cyclopropanols 2 and Synthesis of Compounds 3 (Method A). To a
solution of corresponding cyclopropanol 2 (0.3 mmol) in dry THF
accounting for the preferential formation of anti-diaster-
(1.8 mL) was sequentially added Et3N (42 μL, 0.3 mmol), a 1 M
eoisomer 4 (Figure 1b). As a result, both reaction pathways solution of Et2Zn in toluene (0.6 mL, 0.6 mmol), and the
illustrated in Figure 1 could be operating to varying extents corresponding sulfinyl imine imine 1 (0.3 mmol). The reaction
under the reaction conditions for Methods A and B, which mixture was stirred at 60 °C (oil bath) for 15 h. Then, the reaction
explains why mixtures of diastereoisomers 3 and 4 were was cooled to room temperature and hydrolyzed with a saturated
consistently obtained. aqueous solution of NH4Cl (5.0 mL), extracted with AcOEt (3 × 10
mL), the combined organic phases dried over anhydrous MgSO4, and
■ CONCLUSIONS
In conclusion, our investigation into the hydroxyallylation of
the solvents evaporated (15 Torr). The residue was purified by
column chromatography (silica gel, hexane/EtOAc) to yield pure
compounds 3.
N-tert-butanesulfinyl imines with cyclopropanols has provided (RS,3S,4R)-4-Amino-N-(tert-butanesulfinyl)-6-phenylhex-1-en-3-
valuable insights into the diastereoselective formation of vicinal ol (3aa). Following the general procedure, compound 3aa (24.8 mg,
amino alcohols. Notably, our research not only fine-tuned the 0.085 mmol, 28%) was obtained as a yellow solid; mp 66−68 °C
reaction conditions for this transformation but also showcased (hexane/CH2Cl2); [α]23 D = +33.3 (c = 0.99, CH2Cl2); Rf = 0.30
the method’s versatility across a wide range of substrates. (hexane/EtOAc, 1:1); 1H NMR (300 MHz, CDCl3) δ 7.40−7.19 (m,
Furthermore, by unraveling the stereochemical outcomes of 5H), 5.89 (ddt, J = 15.8, 10.6, 4.6 Hz, 1H), 5.43−5.36 (m, 1H), 5.29
(dt, J = 10.6, 1.6 Hz, 1H), 4.34−4.20 (m, 1H), 3.47−3.34 (m, 1H),
these reactions, we gained significant understanding of the 2.90 (dddt, J = 18.9, 14.1, 9.3, 4.4 Hz, 2H), 2.79−2.62 (m, 2H), 1.32
mechanistic intricacies governing the preferential formation of (s, 9H); 13C{1H} NMR (75 MHz, CDCl3) δ 141.4 (C), 136.5 (CH),
anti-diastereoisomers as the predominant reaction products. 128.5 (CH), 128.3 (CH), 126.0 (CH), 117.0 (CH2), 75.0 (CH), 60.8
These densely functionalized amino alcohol derivatives hold (CH), 56.3 (C), 32.1 (CH2), 31.2 (CH2), 22.9 (CH3); LRMS (EI)
promise for diverse synthetic applications, exemplified by their m/z 295 (M+, < 1%), 150 (14), 134 (20), 117 (19), 104 (24), 91

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(86), 70 (19), 57 (37), 43 (100); HRMS (EI-TOF) Calcd for 2.63−2.48 (m, 1H), 2.02−1.93 (m, 2H), 1.87−1.73 (m, 2H), 1.63−
C16H25NO2S [M+] 295.1606, found 295.1613. 1.45 (m, 4H), 1.40−1.33 (m, 2H), 1.33 (s, 9H); 13C{1H} NMR (100
(RS,3R,4R)-4-Amino-N-(tert-butanesulfinyl)-3,6-diphenylhex-1- MHz, CDCl3) δ 141.3 (C), 139.8 (CH), 128.7 (CH), 128.7 (CH),
en-3-ol (3ab). Following the general procedure, compound 3ab (68.5 126.3 (CH), 118.2 (CH2), 76.6 (C), 65.3 (CH), 56.8 (C), 38.05
mg, 0.19 mmol, 65%) was obtained as a white solid. The reaction was (CH2), 34.8 (CH2), 34.1 (CH2), 32.8 (CH2), 32.8 (CH2), 28.6
also performed with 1.0 mmol of cyclopropanol 2b (134.2 mg, 1.0 (CH2), 23.1 (CH3), 22.0 (CH2); LRMS (EI) m/z 308 [M+(81Br)−
mmol), 1.0 mmol of sulfinyl imine 1a (237.4 mg), 1.0 mmol of Et3N C4H10NO2S, 13%], 306 [M+(79Br)−C4H10NO2S, 13%], 238 (61),
(101.2 mg, 139 μL), and 2.0 mmol of a 1 M solution of Et2Zn in 207 (14), 205 (14), 182 (14), 164 (34), 157 (19), 134 (29), 117
toluene (2.0 mL), in 6.0 mL of dry THF. After stirring the reaction at (74), 91 (100), 67 (12), 57 (53), 55 (35), 41 (19); HRMS (EI-
60 °C (oil bath) for 15 h, it was cooled to room temperature and TOF): Calcd for C17H26NO2S [M+−C4H8Br] 308.1684, found
hydrolyzed with a saturated aqueous solution of NH4Cl (15.0 mL), 308.1695.
extracted with AcOEt (3 × 15 mL), the combined organic phases (RS,3R,4S)-3-Amino-7-bromo-N-(tert-butanesulfinyl)-1-phenyl-4-
dried over anhydrous MgSO4, and the solvents evaporated (15 Torr). vinylheptan-4-ol (3af). Following the general procedure, compound
The residue was purified by column chromatography (silica gel, 3af (51.2 mg, 0.12 mmol, 41%) was obtained as a yellow oil; [α]23 D =
hexane/EtOAc, 4:1) to yield pure compound 3ab (208.1 mg, 0.56 +6.1 (c = 1.20, CH2Cl2); Rf = 0.20 (hexane/EtOAc, 3:1); 1H NMR
mmol, 56%) as a white solid; mp 130−133 °C (hexane/CH2Cl2); (400 MHz, CDCl3) δ 7.34−7.08 (m, 6H), 5.71 (dd, J = 17.1, 10.6 Hz,
[α]23D = −7.9 (c = 1.24, CH2Cl2); Rf = 0.25 (hexane/EtOAc, 3:1); H
1
1H), 5.35−5.00 (m, 2H), 3.99−3.76 (m, 3H), 3.28 (ddd, J = 9.6, 7.0,
NMR (400 MHz, CDCl3) δ 7.43−7.09 (m, 8H), 7.03−6.79 (m, 2H), 2.7 Hz, 1H), 2.97−2.81 (m, 1H), 2.55 (ddd, J = 13.7, 10.2, 6.7 Hz,
6.45 (dd, J = 17.1, 10.7 Hz, 1H), 5.83−5.54 (m, 2H), 5.21 (s, 1H), 1H), 2.30−2.13 (m, 1H), 1.96−1.79 (m, 3H), 1.79−1.61 (m, 2H),
3.66 (d, J = 10.3 Hz, 1H), 3.44 (td, J = 10.7, 2.0 Hz, 1H), 2.73 (ddd, J 1.29 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 142.2 (C), 140.0
= 13.5, 8.8, 4.4 Hz, 1H), 2.51−2.33 (m, 1H), 1.71−1.54 (m, 2H), (CH), 128.6 (CH), 128.5 (CH), 126.0 (CH), 114.35 (CH2), 87.8
1.34 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.3 (C), 140.9 (C), 68.9 (CH), 61.1 (CH2), 56.5 (C) 35.45 (CH2), 33.9 (CH2),
(C), 137.3 (CH), 128.5 (CH), 128.5 (CH), 127.7 (CH), 126.9 32.95 (CH2), 25.2 (CH2), 23.2 (CH3); LRMS (EI) m/z 279 (M+−
(CH), 126.2 (CH), 119.8 (CH2), 78.8 (C), 67.4 (CH), 56.8 (C), C4H9Br, 24%), 239 (12), 238 (73), 216 (12), 187 (19), 182 (26), 164
34.4 (CH2), 32.7 (CH2), 23.1 (CH3); LRMS (EI) m/z 297 (M+− (67), 134 (46), 118 (11), 117 (100), 104 (17), 99 (18), 97 (92), 91
C4H9O, 2%), 239 (12), 238 (78), 234 (34), 164 (52), 143 (55), 133 (92), 79 (13), 57 (46), 55 (65), 41 (21); HRMS (EI-TOF): Calcd for
(53), 117 (100), 91 (98), 57 (40), 55 (36); HRMS (EI-TOF) Calcd C15H21NOS [M+−C4H9BrO] 263.1344, found 263.1337.
for C18H20NO2S [M+−C4H9] 314.1215, found 314.1212. (RS,3R,4S)-3-Amino-N-(tert-butanesulfinyl)-1-phenyl-4-vinyldec-
(RS,3R,4S)-3-Amino-N-(tert-butanesulfinyl)-1-phenyl-4-vinylte- 9-en-4-ol (3ag). Following the general procedure, compound 3ag
tradecan-4-ol (3ac). Following the general procedure, compound 3ac (36.2 mg, 0.09 mmol, 32%) was obtained as a yellow oil; [α]23 D = −4.6
(60.7 mg, 0.14 mmol, 48%) was obtained as a yellow wax; [α]23 D = (c = 1.13, CH2Cl2); Rf = 0.41 (hexane/EtOAc, 3:1); 1H NMR (400
−2.1 (c = 1.80, CH2Cl2); Rf = 0.54 (hexane/EtOAc, 3:1); 1H NMR MHz, CDCl3) δ 7.43−6.97 (m, 5H), 5.89−5.62 (m, 2H), 5.51−5.22
(400 MHz, CDCl3) δ 7.39−7.04 (m, 5H), 5.77 (dd, J = 17.2, 10.6 Hz, (m, 2H), 5.05−4.85 (m, 2H), 4.67 (s, 1H), 3.56 (d, J = 10.2 Hz, 1H),
1H), 5.46−5.33 (m, 2H), 4.67 (s, 1H), 3.56 (d, J = 10.2 Hz, 1H), 3.13 (m, 1H), 2.85 (m, 1H), 2.55 (m, 1H), 1.98 (m, 4H), 1.57−1.39
3.22−3.04 (m, 1H), 2.85 (ddd, J = 13.7, 9.1, 4.6 Hz, 1H), 2.62−2.47 (m, 4H), 1.31 (s, 9H), 1.33−1.25 (m, 2H); 13C{1H} NMR (100
(m, 1H), 1.55−1.41 (m, 4H), 1.31 (s, 9H), 1.29−1.16 (m, 16H), 0.88 MHz, CDCl3) δ 141.4 (C), 140.0 (CH), 139.15 (CH), 128.7 (CH),
(t, J = 6.9 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 141.45 (C), 128.65 (CH), 128.7 (CH), 128.6 (CH), 128.5 (CH), 128.4 (CH),
140.1 (CH), 128.7 (CH), 128.65 (CH), 126.3 (CH), 118.0 (CH2), 126.3 (CH), 118.1 (CH2), 114.4 (CH2), 76.7 (C), 65.4 (CH), 56.8
76.7 (C), 65.4 (CH), 56.7 (C), 38.3 (CH2), 34.8 (CH2), 33.0 (CH2), (C), 38.1 (CH2), 34.8 (CH2), 33.8 (CH2), 33.0 (CH2), 29.5 (CH2),
32.1 (CH2), 30.2 (CH2), 29.8 (CH2), 29.7 (CH2), 29.7 (CH2), 29.5 23.1 (CH3), 22.4 (CH2); LRMS (EI) m/z 321 (M++1−C4H8, 1%),
(CH2), 23.1 (CH3), 22.8 (CH2), 14.3 (CH3); LRMS (EI) m/z 379 320 (2), 238 (54), 182 (13), 164 (32), 139 (17), 134 (31), 117 (75),
(M+−C4H8, 1%), 361 (3), 298 (15), 238 (70), 197 (27), 182 (15), 91 (100), 83 (14), 57 (53), 55 (41), 41 (28); HRMS (EI-TOF)
164 (31), 157 (11), 134 (44), 117 (79), 91 (100), 57 (77), 55 (27), Calcd for C18H27NO2S [M+−C4H8] 321.1762, found 321.1759.
43 (27), 41 (25); HRMS (EI-TOF) Calcd for C26H45NO2S [M+] (RS,3R,4R)-4-Amino-3-(2-bromophenyl)-N-(tert-butanesulfinyl)-
435.3171, found 435.3168. 6-phenylhex-1-en-3-ol (3ai). Following the general procedure,
(RS,3R,4S)-3-Amino-10-bromo-N-(tert-butanesulfinyl)-1-phenyl- compound 3ai (66.2 mg, 0.15 mmol, 49%) was obtained as a white
4-vinyldecan-4-ol (3ad). Following the general procedure, com- solid; mp 38−40 °C (hexane/CH2Cl2); [α]23 D = −5.0 (c = 1.10,
pound 3ad (60.5 mg, 0.13 mmol, 44%) was obtained as a yellow oil; CH2Cl2); Rf = 0.19 (hexane/EtOAc, 3:1); 1H NMR (400 MHz,
[α]23D = +9.5 (c = 0.80, CH2Cl2); Rf = 0.29 (hexane/EtOAc, 3:1); H
1
CDCl3) δ 7.58 (dd, J = 7.9, 1.4 Hz, 1H), 7.38−7.04 (m, 7H), 6.96
NMR (400 MHz, CDCl3) δ 7.38−7.07 (m, 5H), 5.77 (dd, J = 17.2, (dd, J = 7.9, 1.6 Hz, 1H), 6.52 (dd, J = 16.9, 10.6 Hz, 1H), 5.90−5.54
10.6 Hz, 1H), 5.49−5.24 (m, 2H), 4.68 (s, 1H), 3.56 (d, J = 10.2 Hz, (m, 2H), 5.18 (s, 1H), 4.60 (td, J = 9.9, 3.2 Hz, 1H), 3.75 (d, J = 9.9
1H), 3.38 (t, J = 6.9 Hz, 2H), 3.20−3.05 (m, 1H), 2.93−2.72 (m, Hz, 1H), 2.83−2.69 (m, 1H), 2.54−2.40 (m, 1H), 1.63−1.45 (m,
1H), 2.63−2.45 (m, 1H), 1.81 (dt, J = 14.5, 6.9 Hz, 2H), 1.60 (s, 2H), 1.32 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 141.1 (C),
4H), 1.55−1.44 (m, 3H), 1.31 (s, 9H), 1.37−1.26 (m, 3H); 13C{1H} 137.65 (CH), 136.25 (CH), 130.8 (CH), 129.2 (CH), 128.6 (CH),
NMR (100 MHz, CDCl3) δ 141.4 (C), 139.9 (CH), 128.7 (CH), 128.5 (CH), 127.0 (CH), 126.2 (CH), 121.9 (C), 120.1 (CH2), 79.7
128.7 (CH), 128.6 (CH), 126.35 (CH), 118.1 (CH2), 76.7 (C), 65.4 (C), 62.3 (CH), 56.6 (C), 35.1 (CH2), 32.9 (CH2), 23.1 (CH3);
(CH), 56.8 (C), 38.2 (CH2), 34.8 (CH2), 34.1 (CH2), 32.9 (CH2), LRMS (EI) m/z 314 [M+(81Br)−C4H9NO2S, 16%], 312 [M+(79Br)−
32.8 (CH2), 29.3 (CH2), 28.2 (CH2), 23.15 (CH3), 22.7 (CH2); C4H9NO2S, 16%], 239 (12), 238 (74), 182 (22), 164 (55), 134 (18),
LRMS (EI) m/z 322 [M+(81Br)−C4H10NO2S, 12%], 320 [M+(79Br)− 132 (49), 117 (100), 91 (99), 77 (13), 57 (40), 55 (13), 41 (11);
C4H10NO2S, 12%], 239 (10), 238 (63), 221 (14), 219 (14), 182 (15), HRMS (EI-TOF) Calcd for C18H20NO2S [M+−C4H8Br] 314.1215,
164 (33), 157 (16), 134 (33), 117 (75), 91 (100), 67 (13), 57 (60), found 314.1212.
55 (29), 41 (24); HRMS (EI-TOF) Calcd for C18H27NO2S [M+− (RS,1R,2S)-1-Amino-N-(tert-butanesulfinyl)-1-phenylbut-3-en-2-
C4H9Br] 321.1762, found 321.176. ol (3ba). Following the general procedure, compound 3ba (40.8 mg,
(RS,3R,4S)-3-Amino-9-bromo-N-(tert-butanesulfinyl)-1-phenyl-4- 0.153 mmol, 51%) was obtained as a yellow solid; mp 52−54 °C
vinylnonan-4-ol (3ae). Following the general procedure, compound (hexane/CH2Cl2); [α]23 D = +27.8 (c = 0.98, CH2Cl2); Rf = 0.31
3ae (52.0 mg, 0.12 mmol, 39%) was obtained as a yellow oil; [α]23 D = (hexane/EtOAc, 1:1); 1H NMR (300 MHz, CDCl3) δ 7.34−7.18 (m,
+6.7 (c = 2.30, CH2Cl2); Rf = 0.35 (hexane/EtOAc, 3:1); 1H NMR 6H), 5.55 (ddd, J = 17.2, 10.5, 4.8 Hz, 1H), 5.32 (dq, J = 17.3, 1.6 Hz,
(400 MHz, CDCl3) δ 7.39−7.08 (m, 5H), 5.78 (dd, J = 17.2, 10.6 Hz, 1H), 5.23−5.14 (m, 1H), 4.57 (dd, J = 7.4, 4.2 Hz, 1H), 4.50−4.41
1H), 5.50−5.30 (m, 2H), 4.73 (s, 1H), 3.58 (d, J = 10.2 Hz, 1H), (m, 1H), 4.11 (d, J = 7.4 Hz, 1H), 1.12 (s, 9H); 13C{1H} NMR (75
3.38 (t, J = 6.8 Hz, 2H), 3.20−3.07 (m, 1H), 2.93−2.80 (m, 1H), MHz, CDCl3) δ 138.3 (C), 135.6 (CH), 128.5 (CH), 127.8 (CH)

6200 https://doi.org/10.1021/acs.joc.4c00198
J. Org. Chem. 2024, 89, 6193−6204
The Journal of Organic Chemistry pubs.acs.org/joc Article

127.1 (CH), 117.8 (CH2), 74.7 (CH), 60.7 (CH), 56.9 (C), 22.9 After that, the corresponding sulfinyl imine 1 (0.3 mmol) was added
(CH3); LRMS (EI) m/z 267 (M+, < 1%), 210 (12), 154 (37), 130 to the reaction mixture and continued stirring at 60 °C (oil bath) for
(25), 104 (15), 77 (11), 57 (32), 43 (100); HRMS (EI-TOF) Calcd 15 h. Then, the reaction was cooled to room temperature and
for C14H21NO2S (M+) 267.1293; found 267.1279. hydrolyzed with a saturated aqueous solution of NH4Cl (5.0 mL),
(RS,1R,2R)-1-Amino-N-(tert-butanesulfinyl)-1,2-diphenylbut-3- extracted with AcOEt (3 × 10 mL), the combined organic phases
en-2-ol (3bb). Following the general procedure, compound 3bb (87.6 dried over anhydrous MgSO4, and the solvents evaporated (15 Torr).
mg, 0.26 mmol, 85%) was obtained as a white solid; mp 192−195 °C The residue was purified by column chromatography (silica gel,
(hexane/CH2Cl2); [α]23 D = +25.9 (c = 2.44, CH2Cl2); Rf = 0.18 hexane/EtOAc) to yield pure compounds 4.
(hexane/EtOAc, 3:1); 1H NMR (400 MHz, CDCl3) δ 7.44−7.10 (m, (RS,3S,4S)-4-Amino-N-(tert-butanesulfinyl)-3,6-diphenylhex-1-
8H), 6.95−6.84 (m, 2H), 6.35 (dd, J = 17.1, 10.7 Hz, 1H), 5.55−5.33 en-3-ol (4ab). Following the general procedure, compound 4ab (72.1
(m, 2H), 4.66 (d, J = 5.6 Hz, 1H), 4.11 (d, J = 5.3 Hz, 1H), 3.87 (s, mg, 0.20 mmol, 68%) was obtained as a yellow oil; [α]23D = −24.2 (c =
1H), 1.20 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 142.5 (C), 1.70, CH2Cl2); Rf = 0.28 (hexane/EtOAc, 3:1); 1H NMR (400 MHz,
138.4 (CH), 137.5 (C), 129.0 (CH), 128.3 (CH), 128.0 (CH), 127.9 CDCl3) δ 7.43−7.14 (m, 10H), 6.04 (dd, J = 17.0, 10.7 Hz, 1H), 5.43
(CH), 127.8 (CH), 127.7 (CH), 126.7 (CH), 117.4 (CH2), 79.0 (C), (dd, J = 17.0, 1.6 Hz, 1H), 5.17 (dd, J = 10.7, 1.6 Hz, 1H), 4.82 (s,
68.5 (CH), 22.8 (CH3); LRMS (EI) m/z 269 (M+−C4H9OH, 1%), 1H), 3.69−3.61 (m, 1H), 3.48 (d, J = 3.2 Hz, 1H), 2.97−2.83 (m,
210 (31), 206 (40), 154 (100), 136 (30), 133 (47), 106 (41), 105 1H), 2.66−2.55 (m, 1H), 2.28−2.16 (m, 2H), 1.06 (s, 9H); 13C{1H}
(27), 77 (23), 57 (29), 55 (30); HRMS (EI-TOF) Calcd for NMR (100 MHz, CDCl3) δ 144.5 (C), 141.5 (C), 140.3 (C), 137.3
C16H16NO2S [M+−C4H9] 286.0902, found 286.0914. (CH), 128.9 (CH), 128.7 (CH), 128.6 (CH), 127.2 (CH), 126.9
(RS,3S,4R)-4-Amino-N-(tert-butanesulfinyl)-5-methylhex-1-en-3- (CH), 126.15 (CH), 125.7 (CH), 114.8 (CH2), 79.1 (C), 64.2 (CH),
ol (3ca). Following the general procedure, compound 3ca (30.0 mg, 55.8 (C), 32.45 (CH2), 29.8 (CH2), 28.3 (CH2), 22.7 (CH3); LRMS
0.13 mmol, 43%) was obtained as a yellow solid; mp 35−37 °C (EI) m/z 297 (M+−C4H9O, 1%), 239 (11), 238 (69), 234 (33), 182
(hexane/CH2Cl2); [α]23 D = +31.6 (c = 1.05, CH2Cl2); Rf = 0.35 (16), 164 (56), 143 (49), 134 (34), 133 (63), 117 (97), 105 (22), 91
(hexane/EtOAc, 1:1); 1H NMR (300 MHz, CDCl3) δ 5.93 (ddd, J = (100), 57 (44), 55 (39); HRMS (EI-TOF) Calcd for C18H20NO2S
18.1, 10.3, 3.9 Hz, 1H), 5.49 (dt, J = 17.3, 1.9 Hz, 1H), 5.41 (dd, J = [M+−C4H9] 314.1215, found 314.1203.
10.9, 4.3 Hz, 1H), 4.70 (dt, J = 15.2, 7.1 Hz, 1H), 4.52 (br s, 1H), (RS,3S,4R)-3-Amino-N-(tert-butanesulfinyl)-1-phenyl-4-vinylte-
1.28 (s, 9H), 1.05 (d, J = 6.7 Hz, 3H), 1.01 (d, J = 6.7 Hz, 3H); tradecan-4-ol (4ac). Following the general procedure, compound 4ac
13
C{1H} NMR (75 MHz, CDCl3) δ 133.4 (CH), 119.8 (CH2), 71.10 (52.28 mg, 0.12 mmol, 40%) was obtained as a yellow wax; [α]23 D =
(CH) 61.9 (CH), 29.7 (C), 27.6 (CH), 22.4 (CH3), 19.7 (CH3), 19.5 −48.3 (c = 0.38, CH2Cl2); Rf = 0.29 (hexane/EtOAc, 3:1); 1H NMR
(CH3); LRMS (EI) m/z 233 (M+, < 1%), 207 (20), 183 (27), 152 (400 MHz, CDCl3) δ 7.40−7.03 (m, 5H), 5.71 (dd, J = 17.3, 10.8 Hz,
(11), 108 (24), 77 (11), 57 (3), 43 (100); HRMS (EI-TOF) Calcd 1H), 5.36−5.12 (m, 2H), 3.37 (d, J = 7.2 Hz, 1H), 3.11 (ddd, J =
for C7H13NOS [M+−C4H10O] 159.0718, found 159.0713. 10.4, 7.2, 2.2 Hz, 1H), 2.97 (ddd, J = 13.9, 9.1, 4.6 Hz, 1H), 2.88 (s,
( R S , 3 S , 4 R ) - 4 - A m i n o - N - ( t e r t - b u t a n e s u l fi n y l ) - 5 - [ ( t e r t - 1H), 2.70 (dt, J = 13.9, 8.4 Hz, 1H), 1.58−1.41 (m, 2H), 1.30 (s,
butyldimethylsilyl)oxy]pent-1-en-3-ol (3da). Following the general 9H), 1.28−1.14 (m, 12H), 0.92−0.84 (m, 5H); 13C{1H} NMR (100
procedure, compound 3da (53.30 mg, 0.159 mmol, 53%) was MHz, CDCl3) δ 141.75 (C), 140.1 (CH), 128.8 (CH), 128.6 (CH),
obtained as a yellow oil; [α]23 D = +31.6 (c = 1.05, CH2Cl2); Rf = 0.21 128.5 (CH), 126.8 (CH), 115.3 (CH2), 77.5 (C), 64.2 (CH), 56.7
(hexane/EtOAc, 2:1); 1H NMR (300 MHz, CDCl3) δ 5.91 (ddd, J = (C), 38.3 (CH2), 32.5 (CH2), 32.4 (CH2), 32.05 (CH2), 30.2 (CH2),
17.2, 10.6, 5.0 Hz, 1H), 5.37 (dt, J = 17.2, 1.7 Hz, 1H), 5.24 (dt, J = 29.7 (CH2), 29.7 (CH2), 29.45 (CH2), 23.2 (CH2), 23.2 (CH3), 22.8
10.6, 1.6 Hz, 1H), 4.28 (br s, 1H), 3.99 (dd, J = 10.3, 3.5 Hz, 2H), (CH2), 14.3 (CH3); LRMS (EI) m/z 379 (M+−C4H8, 2%), 298 (13),
3.83 (dd, J = 10.2, 4.5 Hz, 1H), 3.33 (dt, J = 4.8, 3.9 Hz, 1H), 1.23 (s, 238 (57), 197 (18), 182 (16), 181 (22), 164 (34), 134 (38), 117
10H), 0.89 (s, 9H), 0.09 (s, 6H), 0.08 (s, 6H); 13C{1H} NMR (75 (100), 91 (99), 57 (75), 55 (28), 43 (33), 41 (27); HRMS (EI-TOF)
MHz, CDCl3) δ 137.5 (CH), 116.3 (CH2), 73.9 (CH), 63.8 (CH2), Calcd for C26H45NO2S [M+] 435.3171, found 435.3181.
59.9 (CH), 56.2 (C), 25.8 (CH3), 22.7 (CH3), 18.1 (C), −5.5 (CH3), (RS,3S,4R)-3-Amino-10-bromo-N-(tert-butanesulfinyl)-1-phenyl-
−5.6 (CH3); LRMS (EI) m/z 335 (M+, < 1%), 279 (32), 261 (7), 4-vinyldecan-4-ol (4ad). Following the general procedure, com-
204 (21), 173 (28), 156 (13), 141 (44), 116 (64), 100 (18), 83 (64), pound 4ad (52.3 mg, 0.11 mmol, 38%) was obtained as a yellow wax;
73 (99), 57 (100), 41 (34); HRMS (EI-TOF) Calcd for C7H13NOS [α]23D = −29.5 (c = 0.90, CH2Cl2); Rf = 0.14 (hexane/EtOAc, 3:1); H
1

[M+−C3H5O] 278.1581, found 278.1576. NMR (400 MHz, CDCl3) δ 7.46−7.09 (m, 5H), 5.72 (dd, J = 17.2,
(RS,3R,4R)-4-Amino-N-(tert-butanesulfinyl)-3-phenylnona-1,8- 10.8 Hz, 1H), 5.39−5.14 (m, 2H), 3.47 (d, J = 7.1 Hz, 1H), 3.40 (t, J
dien-3-ol (3eb). Following the general procedure, compound 3eb = 6.6 Hz, 2H), 3.17−3.06 (m, 1H), 3.06−2.87 (m, 3H), 2.82−2.59
(73.5 mg, 0.22 mmol, 73%) was obtained as a white solid; mp 106− (m, 3H), 1.90−1.72 (m, 5H), 1.32 (s, 9H), 1.44−1.01 (m, 4H);
13
109 °C (hexane/CH2Cl2); [α]23 D = −62.4 (c = 0.86, CH2Cl2); Rf = C{1H} NMR (100 MHz, CDCl3) δ 141.7 (C), 139.9 (CH), 128.8
0.29 (hexane/EtOAc, 3:1); 1H NMR (400 MHz, CDCl3) δ 7.54− (CH), 128.7 (CH), 128.6 (CH), 128.6 (CH), 128.4 (CH), 126.1
7.18 (m, 5H), 6.48 (dd, J = 17.0, 10.7 Hz, 1H), 5.76−5.54 (m, 3H), (CH), 115.5 (CH2), 77.4 (C), 64.4 (CH), 56.8 (C), 38.0 (CH2), 34.1
5.22 (s, 1H), 4.90−4.79 (m, 2H), 3.56 (d, J = 10.3 Hz, 1H), 3.48− (CH2), 32.8 (CH2), 32.5 (CH2), 29.85 (CH2), 29.2 (CH2), 28.2
3.37 (m, 1H), 1.99−1.84 (m, 1H), 1.85−1.71 (m, 1H), 1.54−1.35 (CH2), 23.2 (CH3), 23.0 (CH2); LRMS (EI) m/z 322 [M+(81Br)−
(m, 1H), 1.28 (s, 9H), 1.25−1.05 (m, 3H); 13C{1H} NMR (100 C4H10NO2S, 10%], 320 [M+(79Br)−C4H10NO2S, 10%], 238 (53),
MHz, CDCl3) δ 143.6 (C), 138.2 (CH), 137.3 (CH), 128.5 (CH), 221 (11), 219 (10), 182 (14), 164 (37), 157 (17), 134 (26), 117
127.65 (CH), 126.9 (CH2), 119.6 (CH), 114.85 (CH2), 78.8 (C), (77), 91 (100), 67 (13), 57 (58), 55 (28), 41 (25); HRMS (EI-TOF)
68.5 (CH), 56.7 (C), 32.9 (CH2), 32.0 (CH2), 25.9 (CH2), 23.0 Calcd for C18H28NO2S [M+−C4H8Br] 322.1841, found 322.1838.
(CH3); LRMS (EI) m/z 261 (M+−C4H9OH, 2%), 203 (12), 202 (RS,3S,4R)-3-Amino-9-bromo-N-(tert-butanesulfinyl)-1-phenyl-4-
(96), 198 (32), 169 (10), 156 (26), 146 (79), 133 (100), 130 (20), vinylnonan-4-ol (4ae). Following the general procedure, compound
128 (29), 105 (35), 98 (21), 94 (16), 81 (55), 77 (30), 57 (85), 55 4ae (50.7 mg, 0.11 mmol, 38%) was obtained as a colorless wax; [α]23 D
(83), 41 (34); HRMS (EI-TOF) Calcd for C15H21NO2S [M+−C4H8] = −40.3 (c = 2.10, CH2Cl2); Rf = 0.18 (hexane/EtOAc, 3:1); 1H
279.1293, found 279.1295. NMR (400 MHz, CDCl3) δ 7.40−7.16 (m, 5H), 5.72 (dd, J = 17.3,
General Procedure for the Reaction of Sulfinyl Imines 1 and 10.8 Hz, 1H), 5.38−5.15 (m, 2H), 3.47 (d, J = 7.1 Hz, 1H), 3.39 (t, J
Cyclopropanols 2 in the Presence of CuCN·LiCl and Synthesis of = 6.8 Hz, 2H), 3.11 (ddd, J = 10.5, 7.2, 2.1 Hz, 1H), 3.05−2.90 (m,
Compounds 4 (Method B). To a solution of corresponding 2H), 2.77−2.62 (m, 2H), 2.13−1.94 (m, 1H), 1.91−1.70 (m, 4H),
cyclopropanol 2 (0.3 mmol) in dry THF (1.8 mL) was sequentially 1.66−1.41 (m, 4H), 1.32 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3)
added Et3N (42 μL, 0.3 mmol), a 1 M solution of Et2Zn in toluene δ 141.7 (C), 139.8 (CH), 128.8 (CH), 128.7 (CH), 128.6 (CH),
(0.6 mL, 0.6 mmol), and a 0.5 M solution of CuCN·LiCl in THF (1.8 128.4 (CH), 126.1 (CH), 115.6 (CH2), 77.3 (C), 64.3 (CH), 56.8
mL, 0.9 mmol). The reaction mixture was stirred at 23 °C for 15 min. (C), 37.9 (CH2), 34.0 (CH2), 32.9 (CH2), 32.5 (CH2), 32.3 (CH2),

6201 https://doi.org/10.1021/acs.joc.4c00198
J. Org. Chem. 2024, 89, 6193−6204
The Journal of Organic Chemistry pubs.acs.org/joc Article

28.6 (CH2), 23.2 (CH3), 22.4 (CH2); LRMS (EI) m/z [M+(81Br)− extracted with CH2Cl2 (5 × 5 mL), and the combined organic layers
C4H10NO2S, 12%], 306 [M+(79Br)−C4H10NO2S, 12%, 238 (53), 205 were dried over anhydrous MgSO4, and the solvents evaporated (15
(10), 182 (14), 164 (39), 157 (21), 134 (22), 117 (83), 91 (100), 67 Torr). The residue was purified by column chromatography (silica
(13), 57 (55), 55 (32), 41 (19); HRMS (EI-TOF) Calcd for gel, hexane/EtOAc) to yield pure compound 7 (6.5 mg, 0.028 mmol,
C17H25NO2S [M+−C4H9Br] 307.1606, found 307.1615. 93%) as a white solid; mp 39−41 °C (hexane/CH2Cl2); [α]23 D = +8.6
(RS,3S,4R)-3-Amino-N-(tert-butanesulfinyl)-1-phenyl-4-vinyldec- (c = 0.45 CH2Cl2); Rf = 0.67 (hexane/EtOAc, 1:1); 1H NMR (400
9-en-4-ol (4ag). Following the general procedure, compound 4ag MHz, CDCl3) δ 7.40−7.07 (m, 5H), 5.72 (dd, J = 17.1, 10.6 Hz, 1H),
(39.6 mg, 0.10 mmol, 35%) was obtained as a yellow wax; [α]23 D = 5.37−5.07 (m, 2H), 3.95−3.71 (m, 2H), 2.94 (ddd, J = 14.6, 10.3, 4.8
−45.7 (c = 1.11, CH2Cl2); Rf = 0.20 (hexane/EtOAc, 3:1); 1H NMR Hz, 1H), 2.75−2.47 (m, 2H), 1.95−1.73 (m, 4H), 1.71−1.63 (m,
(400 MHz, CDCl3) δ 7.33−7.12 (m, 5H), 5.91−5.61 (m, 2H), 5.36− 2H), 1.25 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 142.45 (C),
5.14 (m, 2H), 5.02−4.84 (m, 2H), 3.45 (d, J = 7.3 Hz, 1H), 3.16− 138.5 (CH), 128.5 (CH), 128.4 (CH), 125.8 (CH), 115.4 (CH2),
3.02 (m, 1H), 3.00−2.88 (m, 2H), 2.86 (s, 1H), 2.76−2.59 (m, 2H), 88.5 (C), 67.6 (CH2), 59.1 (CH), 35.2 (CH2), 34.0 (CH2), 33.5
2.11−1.94 (m, 4H), 1.89−1.68 (m, 2H), 1.64−1.39 (m, 2H), 1.30 (s, (CH2), 25.5 (CH2); LRMS (EI) m/z 231 (M+, < 1%), 134 (100), 117
9H); 13C{1H} NMR (100 MHz, CDCl3) δ 141.7 (C), 140.0 (CH), (35), 91 (94), 55 (25) 43 (15); HRMS (EI-TOF) Calcd for C15H19N
139.0 (CH), 128.8 (CH), 128.7 (CH), 128.6 (CH), 128.55 (CH), [M+−H2O] 214.1595, found 214.1587.
128.4 (CH), 126.1 (CH), 115.4 (CH2), 114.5 (CH2), 77.4 (C), 64.35 Synthesis of (RS,2R,3S,E)-2-Amino-N-(tert-butanesulfinyl)-1-O-
(CH), 56.8 (C), 38.1 (CH2), 33.8 (CH2), 32.6 (CH2), 32.4 (CH2), (tert-butyldimethylsilyl)-octadec-4-ene-1,3-diol (8) from Amino
29.45 (CH2), 23.2 (CH3), 22.7 (CH2); LRMS (EI) m/z 321 (M+− Diol Derivative 3da. To a solution of allylic amino alcohol derivative
C4H8, 1%), 238 (42), 182 (12), 164 (33), 139 (11), 136 (14), 134 3da (67.0 mg, 0.2 mmol), 1-pentadecene (84.0 mg, 108.4 μL, 0.4
(21), 117 (81), 108 (10), 104 (12), 91 (100), 67 (12), 57 (49), 55 mmol), and 1,7-octadiene (88.0 mg, 108.0 μL, 0.8 mmol) in
(35), 41 (25); HRMS (EI-TOF) Calcd for C18H27NO2S [M+−C4H8] anhydrous CH2Cl2 (1.0 mL) was added Hoveyda−Grubbs II catalyst
321.1766, found 321.1764. (12.5 mg, 0.02 mmol). This mixture was stirred at 45 °C (oil bath) for
(RS,3S,4S)-4-Amino-N-(tert-butanesulfinyl)-3-phenylnona-1,8- 3 h. After that, the solvents evaporated (15 Torr). The residue was
dien-3-ol (4eb). Following the general procedure, compound 4eb purified by column chromatography (silica gel, hexane/EtOAc) to
(61.1 mg, 0.18 mmol, 61%) was obtained as a yellow wax; [α]23 D =
yield pure compound 8 (62.0 mg, 1.20 mmol, 60%) as a colorless oil;
+11.4 (c = 0.92, CH2Cl2); Rf = 0.29 (hexane/EtOAc, 3:1); 1H NMR [α]23D = −42.7 (c = 0.97 CH2Cl2); Rf = 0.48 (hexane/EtOAc, 2:1); H
1

(400 MHz, CDCl3) δ 7.53−7.29 (m, 5H), 6.12 (ddd, J = 17.0, 10.7, NMR (300 MHz, CDCl3) δ 5.81 (dtd, J = 15.4, 6.8, 1.5 Hz, 1H), 5.50
1.4 Hz, 1H), 5.89−5.70 (m, 1H), 5.48 (dd, J = 17.0, 1.6 Hz, 1H), 5.19 (ddt, J = 15.5, 5.2, 1.4 Hz, 1H), 4.42 (br s, 1H), 4.02 (d, J = 9.7 Hz,
(dd, J = 10.7, 1.6 Hz, 1H), 5.09−4.89 (m, 2H), 4.78 (d, J = 1.4 Hz, 1H), 3.82−3.70 (m, 2H), 3.58 (dd, J = 10.2, 6.5 Hz, 1H), 3.52−3.42
1H), 3.74−3.58 (m, 1H), 3.40 (d, J = 3.1 Hz, 1H), 2.16−1.94 (m, (m, 1H), 2.08 (dd, J = 7.8, 6.5 Hz, 2H), 1.27 (s, 22H), 1.25 (s, 9H),
2H), 1.97−1.80 (m, 2H), 1.32−1.17 (m, 2H), 1.02 (s, 9H); 13C{1H} 0.91 (s, 9H), 0.90 (t, J = 6.6 Hz, 3H), 0.09 (s, 3H), 0.08 (s, 3H);
13
NMR (100 MHz, CDCl3) δ 144.8 (C), 140.5 (CH), 138.6 (CH), C{1H} NMR (75 MHz, CDCl3) δ 134.5 (CH), 127.7 (CH), 72.4
128.9 (CH), 127.2 (CH), 125.8 (CH), 114.9 (CH2), 114.7 (CH2), (CH), 64.3 (CH2), 62.5 (CH), 55.8 (C), 32.5 (CH2), 31.9 (CH2),
79.2 (C), 65.3 (CH), 55.7 (C), 33.6 (CH2), 26.3 (CH2), 26.0 (CH2), 29.7 (CH2), 29.6 (CH2), 29.6 (CH2), 29.5 (CH2), 29.4 (CH2), 29.3
22.7 (CH3); LRMS (EI) m/z 335 (M+, < 1%), 202 (39), 146 (44), (CH2), 29.3 (CH2), 25.8 (CH3), 22.7(CH3), 22.6 (CH2), 14.1
133 (59), 115 (10), 105 (23), 81 (28), 70 (15), 55 (44), 43 (100); (CH3), −5.5 (CH3), −5.6 (CH3); LRMS (EI) m/z 517 (M+, < 1%),
HRMS (EI-TOF) Calcd for C19H29NO2S [M+] 335.1928, found 460 (7), 345 (19), 323 (100), 278 (89), 239 (16), 203 (16), 174
335.1923. (65), 133 (11), 116 (47), 105 (10), 89 (57), 75 (78), 57 (88), 41
Synthesis of (RS,1R,7R)-7-Amino-N-(tert-butanesulfinyl)-1-phe- (32); HRMS (EI-TOF) Calcd for C24H50NO3SSi [M+−C4H9]
nylcyclohept-2-en-1-ol (6) from Amino Alcohol Derivative 3eb. A 460.3281, found 460.3286.
solution of compound 3eb (0.022 g, 0.065 mmol), Hoveyda−Grubbs
second generation catalyst (4.34 mg, 0.007 mmol, 10 mol %), and 1,7-
octadiene (44 μL, 0.3 mmol) in dry CH2Cl2 (2.0 mL) was stirred at
■ ASSOCIATED CONTENT
Data Availability Statement
40 °C (oil bath) for 17 h. Then the solvent was evaporated (15 Torr). The data underlying this study are available in the published
The residue was purified by column chromatography (silica gel,
article and its Supporting Information.
hexane/EtOAc) to give compound 6 (10.1 mg, 0.033 mmol, 55%) as
a white solid; mp 64−66 °C (hexane/CH2Cl2); [α]23 D = +38.7 (c =
*
sı Supporting Information

0.83, CH2Cl2); Rf = 0.20 (hexane/EtOAc, 2:1); 1H NMR (400 MHz, The Supporting Information is available free of charge at
CDCl3) δ 7.61−7.48 (m, 2H), 7.46−7.21 (m, 3H), 6.13 (ddd, J = https://pubs.acs.org/doi/10.1021/acs.joc.4c00198.
12.1, 7.7, 4.3 Hz, 1H), 5.82−5.64 (m, 1H), 4.90 (s, 1H), 3.98−3.80
Experimental procedures and characterization data for
(m, 2H), 2.29−2.02 (m, 2H), 1.78−1.64 (m, 1H), 1.57−1.42 (m,
3H), 1.28 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 141.85 (C), compounds 1 and 2. Experimental epimerization
137.5 (CH), 132.0 (CH), 128.6 (CH), 127.9 (CH), 127.25 (CH), conditions of the sulfur atom of amino alcohol derivative
81.1 (C), 65.2 (CH), 56.0 (C), 31.4 (CH2), 28.75 (CH2), 22.9 3ae. Copies of 1H, 13C NMR, and DEPT spectra for all
(CH3), 20.7 (CH2); LRMS (EI) m/z 305 (M+, < 1%), 233 (20), 202 the reported compounds (1, 2, 3, 4, 6, 7, and 8), and X-
(13), 170 (100), 159 (25), 142 (29), 128 (11), 105 (40), 91 (20), 77 ray structures of compounds 3ab and 3ai. (PDF)
(23), 56 (38), 43 (26); HRMS (EI-TOF) Calcd for C13H17NO2S
[M+−C4H8] 250.0892, found 250.0890. Accession Codes
Synthesis of (2R,3S)-2-Phenethyl-3-vinylpiperidin-3-ol (7) from CCDC 2309871 and 2309873 contain the supplementary
Amino Alcohol Derivative 3af. To a solution of compound 3af crystallographic data for this paper. These data can be obtained
(0.012 g, 0.03 mmol) in MeOH (0.5 mL) was added a 2 M solution free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
of HCl in Et2O (115.0 μL, 0.23 mmol) at 0 °C. The reaction mixture emailing [email protected], or by contacting The
was stirred at the same temperature for 30 min. After that, a 2 M Cambridge Crystallographic Data Centre, 12 Union Road,
aqueous solution of NaOH (2.0 mL, 2.0 mmol) was added to the Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
reaction mixture at 0 °C, and after 10 min, it was extracted with
CH2Cl2 (4 × 5 mL), the combined organic phases dried over
anhydrous MgSO4, and the solvents evaporated (15 Torr). To a
solution of the resulting residue in CH2Cl2 (2.0 mL) was added a 2 M
■ AUTHOR INFORMATION
Corresponding Author
aqueous solution of NaOH (2.0 mL, 4.0 mmol), and the reaction Francisco Foubelo − Departamento de Química Orgánica,
mixture was stirred at 23 °C for 15 h. After that, the aqueous layer was Facultad de Ciencias, Universidad de Alicante, 03080
6202 https://doi.org/10.1021/acs.joc.4c00198
J. Org. Chem. 2024, 89, 6193−6204
The Journal of Organic Chemistry pubs.acs.org/joc Article

Alicante, Spain; Instituto de Síntesis Orgánica (ISO) and (2) Yus, M.; González-Gómez, J. C.; Foubelo, F. Catalytic
Centro de Innovación en Química Avanzada Enantioselective Allylation of Carbonyl Compounds and Imines.
(ORFEO−CINQA), Universidad de Alicante, 03080 Chem. Rev. 2011, 111, 7774−7854.
Alicante, Spain; orcid.org/0000-0001-7847-8440; (3) Yus, M.; González-Gómez, J. C.; Foubelo, F. Diastereoselective
Allylation of Carbonyl Compounds and Imines: Application to the
Email: [email protected]
Synthesis of Natural Products. Chem. Rev. 2013, 113, 5595−5698.
Authors (4) Lombardo, M.; Trombini, C. α-Hydroxyallylation Reaction of
Carbonyl Compounds. Chem. Rev. 2007, 107, 3843−3879.
Sandra Hernández-Ibáñez − Departamento de Química (5) (a) Lombardo, M.; Girotti, R.; Morganti, S.; Trombini, C. The
Orgánica, Facultad de Ciencias, Universidad de Alicante, First Zinc-Promoted, Environmentally Friendly, and Highly Efficient
03080 Alicante, Spain; Instituto de Síntesis Orgánica (ISO) Acetyloxyallylation of Aldehydes in Aqueous Ammonium Chloride.
and Centro de Innovación en Química Avanzada Chem. Commun. 2001, 2310−2311. (b) Lombardo, M.; Girotti, R.;
(ORFEO−CINQA), Universidad de Alicante, 03080 Morganti, S.; Trombini, C. A New Protocol for the Acetoxyallylation
Alicante, Spain of Aldehydes Mediated by Indium in THF. Org. Lett. 2001, 3, 2981−
Juan F. Ortuño − Departamento de Química Orgánica, 2983. (c) Lombardo, M.; Morganti, S.; Trombini, C. 3-Bromopro-
Facultad de Ciencias, Universidad de Alicante, 03080 penyl Esters in Organic Synthesis: Indium- and Zinc-Mediated Entries
Alicante, Spain; Instituto de Síntesis Orgánica (ISO) and to Alk-1-ene-3,4-diols. J. Org. Chem. 2003, 68, 997−1006. (d) Ahuja,
Centro de Innovación en Química Avanzada B. B.; Sudalai, A. One-Pot Highly Enantio- and Diastereoselective
(ORFEO−CINQA), Universidad de Alicante, 03080 Synthesis of anti,anti-Vinylic 3-Amino-1,2 Diols via Proline Catalyzed
Sequential α-Amination/ Benzoyloxyallylation of Aldehydes. RSC
Alicante, Spain Adv. 2015, 5, 21803−21805.
Ana Sirvent − Departamento de Química Orgánica, Facultad (6) Keinicke, L.; Fristrup, P.; Norrby, P.-O.; Madsen, R. Nonradical
de Ciencias, Universidad de Alicante, 03080 Alicante, Spain; Zinc-Barbier Reaction for Diastereoselective Synthesis of Vicinal
Instituto de Síntesis Orgánica (ISO) and Centro de Amino Alcohols. J. Am. Chem. Soc. 2005, 127, 15756−15761.
Innovación en Química Avanzada (ORFEO−CINQA), (7) Liu, M.; Sun, X.-W.; Xu, M.-H.; Lin, G.-Q. Highly Efficient
Universidad de Alicante, 03080 Alicante, Spain; Asymmetric Synthesis of Vinylic Amino Alcohols by Zn-Promoted
orcid.org/0000-0001-6127-4011 Benzoyloxyallylation of Chiral N-tert-Butanesulfinyl Imines: Facile
Carmen Nájera − Centro de Innovación en Química and Rapid Access to (−)-Cytoxazone. Chem.�Eur. J. 2009, 15,
Avanzada (ORFEO−CINQA), Universidad de Alicante, 10217−10224.
03080 Alicante, Spain; orcid.org/0000-0003-0063-5527 (8) Nakajima, N.; Yoshida, E.; Toma, T.; Nishiyama, Y.; Inoue, M.;
Fukuyama, T.; Yokoshima, S. Formal Synthesis of Ecteinascidin 743
José Miguel Sansano − Departamento de Química Orgánica,
via an Intramolecular Cascade Heck Reaction to Construct the
Facultad de Ciencias, Universidad de Alicante, 03080 Diazabicyclo[3.3.1]nonane Framework. Org. Lett. 2022, 24, 8228−
Alicante, Spain; Instituto de Síntesis Orgánica (ISO) and 8232.
Centro de Innovación en Química Avanzada (9) McDonald, T. R.; Mills, L. R.; West, M. S.; Rousseaux, S. A. L.
(ORFEO−CINQA), Universidad de Alicante, 03080 Selective Carbon−Carbon Bond Cleavage of Cyclopropanols. Chem.
Alicante, Spain; orcid.org/0000-0002-5536-2717 Rev. 2021, 121, 3−79.
Miguel Yus − Centro de Innovación en Química Avanzada (10) Liu, Q.; You, B.; Xie, G.; Wang, X. Developments in the
(ORFEO−CINQA), Universidad de Alicante, 03080 Construction of Cyclopropanols. Org. Biomol. Chem. 2020, 18, 191−
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(11) For reviews, see: (a) Nikolaev, A.; Orellana, A. Transition-
Complete contact information is available at: Metal-Catalyzed C−C and C−X Bond-Forming Reactions Using
https://pubs.acs.org/10.1021/acs.joc.4c00198 Cyclopropanols. Synthesis 2016, 48, 1741−1768. (b) Cai, X.; Liang,
W.; Dai, M. Total Synthesis via Cyclopropanols. Tetrahedron 2019,
Notes 75, 193−208. (c) Sekiguchi, Y.; Yoshikai, N. Metal-Catalyzed
The authors declare no competing financial interest. Transformations of Cyclopropanols via Homoenolates. Bull. Chem.
Soc. Jpn. 2021, 94, 265−280. For other significant examples of

■ ACKNOWLEDGMENTS
We acknowledge the continued financial support from the
synthetic applications of cyclopropanols as precursors of homoeno-
lates, see: (d) Das, P. P.; Belmore, K.; Cha, J. K. SN2′Alkylation of
Cyclopropanols via Homoenolates. Angew. Chem., Int. Ed. 2012, 51,
Spanish Ministerio de Economía y Competitividad 9517−9520. (e) Mills, L. R.; Barrera Arbelaez, L. M.; Rousseaux, S. A.
(CTQ2017-85093-P), Ministerio de Ciencia, Innovación y L. Electrophilic Zinc Homoenolates: Synthesis of Cyclopropylamines
Universidades (RED2018-102387-T, PID2019-107268GB- from Cyclopropanols and Amines. J. Am. Chem. Soc. 2017, 139,
100), Generalitat Valenciana (IDIFEDER/2021/013, GVA- 11357−11360. (f) Sekiguchi, Y.; Yoshikai, N. Enantioselective
COVID19/2021/079), MedalChemy S. L. (Medalchemy- Conjugate Addition of Catalytically Generated Zinc Homoenolate.
22T), and the University of Alicante (VIGROB-068). J. Am. Chem. Soc. 2021, 143, 4775−4781. (g) Hou, L.; Huang, W.;
Wu, X.; Qu, J.; Chen, Y. Nickel-Catalyzed Carbonylation of

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