Enantioselective Synthesis of N,S-Acetals by an Oxidative Pummerer-Type Transformation using Phase-Transfer Catalysis

Article abstract of DOI:10.1002/anie.201711277

Reported is the first enantioselective oxidative Pummerer-type transformation using phase-transfer catalysis to deliver enantioenriched sulfur-bearing heterocycles. This reaction includes the direct oxidation of sulfides to a thionium intermediate, followed by an asymmetric intramolecular nucleophilic addition to form chiral cyclic N,S-acetals with moderate to high enantioselectivites. Deuterium-labelling experiments were performed to identify the stereodiscrimination step of this process. Further analysis of the reaction transition states, by means of multidimensional correlations and DFT calculations, highlight the existence of a set of weak noncovalent interactions between the catalyst and substrate that govern the enantioselectivity of the reaction.

Full text of DOI:10.1002/anie.201711277

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Accepted Article
Title: Enantioselective Synthesis of N,S-Acetals by an Oxidative
Pummerer Type Transformation Using Anionic Phase-Transfer
Catalysis
Authors: F. Dean Toste, Souvagya Biswas, Koji Kubota, Matthew S
Sigman, Manuel Orlandi, Mathias Turberg, and Dillon Miles
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10.1002/anie.201711277
Angewandte Chemie International Edition
COMMUNICATION
Enantioselective Synthesis of N,S-Acetals by an Oxidative
Pummerer Type Transformation Using Anionic Phase-Transfer
Catalysis
Souvagya Biswas,[a], [b] Koji Kubota,[a], [b] Manuel Orlandi,[c] Mathias Turberg,[a] Dillon H. Miles,[a] Matthew
S. Sigman,* [c] and F. Dean Toste* [a]
Abstract: We report the first enantioselective oxidative Pummerer-
type transformation using anionic phase-transfer catalysis, resulting
in the formation of enantioenriched sulfur bearing heterocycles. This
reaction includes the direct oxidation of sulfides to the thionium
intermediate, followed by an asymmetric intramolecular nucleophilic
addition to form the chiral cyclic N,S-acetals with moderate to high
enantioselectivites. Deuterium labelling experiments were performed
to identify the stereodiscrimination step of this process. Further
analysis of the reaction transition states by means of
multidimensional correlations and DFT computations highlight the
existence of a set of weak noncovalent interactions between the
catalyst and substrate that governed the enantioselectivity of the
reaction.
chiral phosphate. This strategy would enable the first
enantioselective construction of cyclic N,S-acetal skeletons.[9]
a Pummerer-type transformation
R2
R2
thionium ion
classic
R1
Nu
S
nucleophile
Nu–H
R2
R2
O
R1
S
R1
racemic
oxidative
S
R1
S
b General chiral anion phase-transfer (CAPT) process
– MX
*
*
enantioenriched
product
–
+
+
–
M
+
X
chiral anion
insoluble
cationic
reagent
soluble chiral
ion pair
with reagent
C–X, C–N
C–C
c This work : Enantioselective Pummerer-type reaction under CAPT catalysis
Since its discovery in 1909, the Pummerer reaction and
related thionium chemistry have been successfully applied to the
synthesis of a variety of synthetically and biologically useful
3 cationic oxidant
CAPT catalysis
S
the first catalytic asymmetric
Pummerer-type transformation
R
S
R3
N
R4
the first asymmetric synthesis
of cyclic chiral N,S-acetals
NH
R4
base
compounds
and
natural
products.[1,2]
Mechanistically,
6
4
Pummerer-type reactions are proposed to proceed via
nucleophilic addition to an in situ generated thionium species to
form sulfur containing motifs (Scheme 1a). Despite significant
investigation of this transformation, there have been no reports
to date describing catalytic enantioselective variants.[3]
Development of this transformation would provide an
Proposed
mechanism
Base
[O]
X
H
O
O
*
P
insoluble
oxidant
O
O
Base
2
X
O
O
*
P
1
O
soluble
oxidant
O
*
O
OH
P
enantioselective
entry
into
sulfur
containing
carbon
O
O
[O]
stereocenters previously deemed challenging or inaccessible.[4,5]
Given our recent success in applying chiral anion phase-
transfer (CAPT) catalysis to various challenges in asymmetric
synthesis (Scheme 1b),[6,7] we envisioned that this strategy may
be applied to the enantioselective construction of stereogenic C–
S bonds through a Pummerer-type reaction (Scheme 1c). In this
scenario, under basic conditions chiral phosphoric acid 1
generates chiral phosphate anion 2, which participates in a salt
metathesis with an appropriately identified insoluble cationic
oxidant to form soluble ion pair 3 in a non-polar solvent. Species
3 presumably reacts with sulfide 4 to generate chiral thionium
ion pair 5[8] that undergoes a nucleophilic attack to provide the
enantioenriched product, cyclic N,S-acetal (6), and release the
3
R3
O
S
O
R3
*
S
H
S
N
R4
P
O
N
R4
R3
O
5
NH
R4
6
chiral thionium
ion pair
4
Scheme 1. Application of CAPT catalysis to the oxidative
Pummerer-type C–N bond forming reaction for the synthesis of
enantioenriched N,S-acetals.
To initiate this study, we first tested Bobbitt’s salt 7a,[10,11]
as this reagent was successfully applied to produce an iminium
ion pair using CAPT catalysis in an enantioselective cross-
dehydrogenative coupling.[7] It should be noted that direct
oxidation of sulfides to thionium species using this class of
oxidant has not been reported to date.[12] Encouragingly, the
reaction of 4a in the presence of 10 mol % (R)-TRIP (1a)
catalyst, the oxidant 7a (3.0 equiv) and Na3PO4 (3.0 equiv) in
toluene under air at room temperature gave the desired cyclic
N,S-acetal 6a in good yield (62%) and promising
enantioselectivity (62% ee, entry 1, Table 1).[13] Introducing alkyl
chains onto the binaphthyl backbone of the phosphoric acid (1b)
to enhance catalyst solubility marginally improved the
enantioselectivity of the reaction (64% ee, entry 2).
Unfortunately, the use of another conventional phosphoric acid
[a]
Dr. Souvagya Biswas, Dr. Koji Kubota, Mathias Turberg, Dr. Dillon
H. Miles, Prof. Dr. F. Dean Toste
Department of Chemistry, University of California, Berkeley,
California 94720, United States
E-mail: fdtoste@berkeley.edu
[b]
These authors contributed equally
[c]
Dr. Manuel Orlandi, Prof. Dr. Matthew S. Sigman
Department of Chemistry, University of Utah, Salt Lake City, Utah
84112, United States
Email: sigman@chem.utah.edu
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201711277
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COMMUNICATION
Enantioselective Oxidative Pummerer-Type Cyclization.[a]
Table 1. Optimization of Reaction Conditions for the
Table 2. Scope and Limitations of the Enantioselective Oxidative
Pummerer-Type Cyclization.[a,b]
BF4
1h (10 mol %)
Na3PO4 (3.0 equiv)
oxidant 7a (3.0 equiv)
R2
S
S
S
S
O
N
NHAc
n
R2
n
7a
N
N
NH
R1
(3.0 equiv)
toluene/EC (1:1, 0.1 M)
0 °C, 48 h
EC = ethylcyclohexane
NH
S
R1
O
O
S
O
Na3PO4 (3.0 equiv)
catalyst (10 mol %)
solvent (0.1 M), rt, 48 h
4 (n=1,2)
(R)-6, 8-10
O
a Sulfonamide scope
Me
Me
Ar = 4-Me-C6H4, (R)-6a, 55%, 76% ee
Ar = 4-OMe-C6H4, (R)-6b, 61%, 76% ee
Ar = 4-NO2-C6H4, (R)-6c, 50%, 56% ee
Ar = 4-Cl-C6H4, (R)-6d, 49%, 74% ee
Ar = 3,5-(CH3)2-C6H3, (R)-6e, 44%, 76% ee
Ar = 2,4,6-(CH3)2-C6H2, (R)-6f, 38%, 62% ee
Ar = 1-naph, (R)-6g, 51%, 84% ee
4a
(R)-6a
S
R3
1a: R1 = H, R2 = R3 = iPr
1b: R1 = C8H11, R2 = R3 = iPr
1c: R1 = C8H11, R2 = R3 = Cy
1d: R1 = H, R2 = R3 = Me
1e: R1 = R2 = H, R3 = iPr
1f: R1 = R3 = H, R2 = iPr
1g: R1 = H, R2 = iPr, R3 = Ph
1h: R1 = H, R2 = iPr, R3 = 1-Ada
1i: R1 = H, R2 = iPr, R3 = tBu
1j: R1 = H, R2 = iPr, R3 = 2,4,6-(iPr)3C6H2
R2
NO+BF4- (7b)
N
S
R1
O
R2
O
O
BF4
O
Ar
P
O
N
OH
Ar = C6H5, (R)-6h, 50%, 69% ee
O
R2
(7c)
b Benzyl sulfide scope (R = 1-Naphthyl)
R1
S
N
S
S
R2
R3
SMe
Me
tBu
N
N
Entry
Catalyst
Solvent
Yield(%)[b]
ee (%)[c]
SO2R
SO2R
SO2R
(R)-6j, 59%, 88% ee
(R)-6k, 44%, 72% ee
(R)-6i, 52%, 82% ee
1
2
3
4
5
1a
1b
1c
1d
1e
toluene
toluene
toluene
toluene
toluene
62
60
64
61
62
62
64
52
49
26
S
S
S
Cl
Br
F
N
SO2R
N
N
SO2R
SO2R
(R)-6l, 42%, 88% ee
(R)-6m, 50%, 84% ee
(R)-6n, 44%, 86% ee
OMe
Me
6
7
1f
1g
1h
1i
toluene
toluene
59
58
56
50
44
<5
22
60
55
56
60
68
62
62
–
S
S
S
CF3
N
SO2R
N
SO2R
8
toluene
N
SO2R
9
toluene
(R)-6o, 51%, 84% ee
(R)-6p, 51%, 90% ee
(R)-6q, 60%, 74% ee
10
11[d]
12[e]
13
14[g]
1j
toluene
CF3
Br
F
1h
1h
1h
1h
toluene
S
S
S
toluene
77
68
76
N
SO2R
N
N
toluene/EC[f]
toluene/EC[f]
SO2R
(R)-6r, 49%, 82% ee
SO2R
(R)-6s, 45%, 90% ee
(R)-6t, 50%, 90% ee
c Six membered ring (R = Tol)[c]
[a] See the Supporting Information for complete optimization data. [b] Isolated
yield after silica gel column chromatography. [c] Determined by HPLC analysis
using a chiral stationary phase. [d] Reaction was carried out with nitrosyl
tetrafluoroborate salt (7b) as oxidant, gave complex mixture of products. [e]
Reaction was carried out with 2,2,6,6-tetramethylpiperidine-1-oxoammonium
tetrafluroborate salt (7c) as oxidant. [f] EC = ethylcyclohexane. [g] Reaction
was carried out at 0 °C.
Me
S
S
N
S
Me
N
N
SO2R
SO2R
SO2R
(R)-6u,35%, 80% ee
(R)-8a, 51%, 88% ee
(R)-8b, 44%, 83% ee
CF3
(TCYP) (1c, entry 3) resulted in lower enantioselectivity. In
order to probe steric effects, various other phosphates
displaying unique substitution patterns were examined. This
systematic investigation (entries 4–10, Table 1) revealed that the
substituent at the R2 position on the 3,3’-phenyl ring is crucial
(entry 6) and that a bulky substituent at R3 further improved the
enantioselectivity (entry 8-10). To further explore improvements
S
S
S
OMe
F
N
N
N
SO2R
SO2R
SO2R
(R)-8c, 42%, 74% ee
(R)-8d, 56%, 92% ee
(R)-8e, 58%, 74% ee
e Limitation
d Different N-nucleophiles
S
S
S
N
n
N
NO2
to the reaction,
a
stronger cationic oxidant, nitrosyl
N
SO2R
O
O
HN
tetrafluoroborate salt (7b), was evaluated but unfortunately gave
a complex mixture of products (entry 11). Interestingly, the
structurally analogous oxidant, 2,2,6,6-tetramethylpiperidine-1-
oxoammonium tetrafluoroborate salt (7c), improved the
enantioselectivity significantly (77% ee), although a poor yield
was observed (22%, entry 12).[14] Finally, we found that the use
of toluene/ethylcyclohexane (EC) as a co-solvent system at 0 °C
resulted in formation of the product in improved
enantioselectivity (76% ee, entry 14).
Using this set of conditions, the scope of this process was
explored as depicted in Table 2. Aryl sulfonamides bearing both
electron-rich and electron-poor groups at the para position were
tolerated, resulting in moderate to good enantioselectivities (6e–
6f, 62-72% ee). While methyl substituents on the sulfonamide
backbone (6a–6d, 56–76% ee, Table 2a). did not improve the
enantioselectivities, the 1-naphthyl substrate 4g afforded the
10[e]
32%
56% ee
9[d]
51%
70% ee
n = 1,2 (R = Tol)
no conversion
no product
CF3
F3C
[a] Isolated yields are shown. Remainder of the mass balance is starting
material and products derived from oxidative debenzylation of the sulfide. [b]
The ee values were determined by HPLC analysis using a chiral stationary
phase, the absolute configuration of the product 6a was established by the
comparison of the retention time of the HPLC analysis of the optically active
authentic sample. The structures of other products were assigned by analogy.
[c] 1c was used as a catalyst. [d] H8-TCYP was used as a catalyst at -30 °C.
[e] 1b was used as a catalyst.
product (R)-6g in high enantiomeric excess (84% ee). We next
turned our attention to the scope of the benzyl sulfide moiety
using the 1-naphthyl sulfonamide backbone (Table 2b). Benzylic
groups bearing both electron-rich (6i–6k, 6u) and electron-poor
groups (6l–6o, 6r–6t) were tolerated to furnish the
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10.1002/anie.201711277
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COMMUNICATION
corresponding N,S-acetal products with good to high
enantioselectivities (72-90% ee). Notably, substrates having a
sterically hindered-substituent (6j) and meta substituents (6p,
6r–6t) were prone to give higher ee (82–90% ee). Moreover, the
developed reaction conditions were readily applicable to the
enantioselective synthesis of six-membered N,S-acetals (8a–8e,
74-92% ee, Table 2c) and substrates bearing different N-
nucleophiles (9, 10, Table 2d). Unfortunately, substrates bearing
an electron-deficient 4-nitrobenzyl group were not oxidized
under the reaction conditions.
maximum width of the entire catalysts’ aryl substituent; B12 and
B14, minimum width of the substituents in the 2,6-positions and
of the substituent in the 4-position of the aryl group respectively.
B12 presented the largest coefficient and accounted for the
necessity of large groups in the 2,6-positions. However, despite
enhancements provided by bulky 2,6-groups, increasing their
length negatively impact the ee as highlighted by the presence
of parameter B5 with a negative coefficient. Finally, the smallest
coefficient was associated to B14, which accounted for fine
tuning resulting from the presence of substituents with
increasing size at the 4-position of the phosphate aryl group
(compare catalysts 1a with 1g-1j).[19]
Further information about the interaction mode between
the catalyst and the substrate was gained by transition state
(TS) analysis of the reaction between (R)-TRIP 1a and substrate
4h. As the D-labelling experiments suggested that the thionium
ring closure is stereodetermining, computations were focused on
this reaction step. The low-lying TSs leading to the (R)- and (S)-
products (TS-R and TS-S) are depicted in Figure 1c (see SI for
computational details). TS-R is favored consistent with the
experimentally observed product configuration, and the relative
energy of TS-S (1.03 kcal/mol) matched with the selectivity
measured experimentally (56% ee, 0.75 kcal/mol). The two TSs
showed several NCIs between the phosphate and the
substrate.[20] However, TS-R displayed a better accommodation
of the benzenesulfonamide group via a plethora of CH-π
interactions that involved the iPr substituents and the binaphthyl
backbone of the catalyst.[17b, 21] This provides an interpretation
for the statistical model in Figure 1a (vide infra). Additionally, a
stronger CH-π interaction between the catalysts aryl substituent
(iPr3Ph) and the substrate’s electron-deficient alkyl chain was
present in TS-R (three CH-π contacts, while TS- S presents only
one CH-π contact).
A series of experiments were conducted in order to gain
insight into the reaction mechanism. Reaction of the sulfoxide 11
under both the optimized phase-transfer and non-
enantioselective conditions resulted in no observed product,
discounting a sulfoxide-mediated mechanism (Scheme 2a).
These results are consistent with the proposed phase-transfer
mechanism that includes direct oxidation of a sulfide to a
thionium cation using an oxoammoium-phosphate chiral ion-pair
(Scheme 1c). We sought to establish whether the
enantioselectivity was determined during substrate oxidation or
the cyclization of the oxidized intermediate. Although the
stereogenic center of the product (Scheme 1c, 6) is formally set
in the cyclization of the oxidized intermediate (Scheme 1c, 5),
substrate-catalyst interactions during the oxidation event may
preorganize the system for the enantioselective cyclization. In
order to examine these possibilities, enantiopure substrate (S)-
12 (92% ee, 97% D incorporation) was subjected to the
oxidative Pummerer-type cyclization (Scheme 2b). The
observation that the isolated products (Scheme 2b, 13a and
13b) exhibited equal but opposite levels of enantioselectivity,
with different levels of H-incorporation, is consistent with a
mechanism in which the chiral phosphate is involved in
substrate oxidation, but the redox event is decoupled from the
enantiodetermining cyclization.
The importance of this interaction in the stereochemical
recognition was also highlighted by multidimensional analysis of
the substrate’s arylsulfonylamide group. Descriptors for
compounds 4a-4h (for a full set of substrates, see Supporting
Information) were calculated from the uncatalyzed cyclization TS
of the corresponding thionium cation.[22] Comparison of the
enantioselectivity and the corresponding parameters resulted in
the statistical model in Figure 1b (R2=0.86, intercept=0.13,
L1O=0.81), which contains two parameters condensed in only
one term. The simple equation obtained can be readily
interpreted. as B5Ar accounts for the steric hindrance or the
shape of the aryl substituent, and while NBOAlkH describes the
average charge of the thionium alkyl chain. The presence of this
latter descriptor in the model supports the importance of the
interaction highlighted in TS-R. Moreover, calculation of the
electron density map of the uncatalyzed TS for the benchmark
substrate 6d, showed that the acidic N‒H proton and the alkyl
chain close to the thionium cation were the most electron-poor
regions of the cyclizing substrate (Figure 1d). Thus, the TS
computational analysis and the multidimensional correlation
analyses agree as a mutual validation of the presented results.
In summary, we have developed an oxidative Pummerer-
type cyclization for the synthesis of cyclic N,S acetals from
readily available starting materials. This operationally simple and
mild protocol provides a powerful means to access a broad
range of enantioenriched cyclic N,S-acetals using an anionic
phase transfer catalyst. Deuterium labelling experiments were
performed to identify the stereodiscrimination step of this
process. Additionally, the origin of the enantioselectivity was
investigated by means of DFT TS analysis and of
a Possibility of sulfoxide mechanism
O
1h (10 mol %)
7a (3.0 equiv)
S
Ph
no reaction
>95% SM
recovery
7a (2.0 equiv)
no reaction
>95% SM
recovery
MeCN, rt, 24 h
Na3PO4 (3.0 equiv)
toluene/EC (1:1)
0 °C, 48 h
NH
Ts 11
b Origin of enantioselectivity
~ 11% H
~ 41% H
(S)-1a (10 mol %)
7a (3.0 equiv)
(R)-1a (10 mol %)
7a (3.0 equiv)
S
Ph
S
S
D/H
Ph
D/H
D
Ph
N
NH
Ts
N
Na3PO4 (3.0 equiv)
toluene, rt, 24 h
Na3PO4 (3.0 equiv)
toluene, rt, 24 h
Ts
Ts
(S)-12
13a, 43%,
13b, 39%,
59% ee
92% ee, 97% D
-59% ee
Scheme 2. Mechanistic Investigations.
Multidimensional correlation analysis was performed to
gain additional information about the features of the catalyst that
contribute to the stereoselectivity.[15] A set of parameters for
several phosphates 1a-1h (see SI for full set of catalysts) was
computed using the molecular model in Figure 1a.[16] This
parameter set included IR vibrational frequencies (ν) and
intensities (i),[17] NBO charges, and Sterimol steric descriptors
(B1, B5 and L).[18] When the parameters acquired were
correlated with the measured ee expressed as ΔΔG‡, the
multidimensional model in Figure 1a was obtained. This model
presented a good correlation (R2=0.96, intercept=0.03) and was
statistically validated leave-one-out cross validation (L1O=0.89).
Three Sterimol parameters appeared in the equation: B5,
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10.1002/anie.201711277
Angewandte Chemie International Edition
COMMUNICATION
1.25
1.00
0.75
Δ
0.50
0.25
0.00
0.00 0.25 0.50 0.75 1.00 1.25
Measured ΔΔG‡ (kcal/mol)
2.0
1.5
1.0
0.5
0.0
0.0
0.5
1.0
1.5
2.0
Measured ΔΔG‡ (kcal/mol)
Figure 1. [a] Multidimensional correlation analysis for the set of catalysts 1a-1h and [b] for the set of substrates 4a-4h. [c] TS-R and TS-S
computed at the wB97XD/6-31G(d) level of theory. wB97XD/6-311+G(2d,p)[PCM=Tol] energies are reported. The substrate is highlighted
in green and interatomic distances are shown as dashed lines. [d] electron density map of the uncatalyzed TS of 6d.
organocatalytic C-S bond formations, see: (d) P. Chauhan, S. Mahajan,
multidimensional correlation techniques, which revealed that a
D. Enders, Chem. Rev. 2014, 114, 8807-8864; For leading books, see:
set of subtle yet important NCIs are responsible for the observed
level of enantioselectivity (up to 92% ee).
(e) T. Toru, C. Bolm, (Eds.), Organosulfur Chemistry in Asymmetric
Synthesis Wiley-VCH: Weinheim, 2008. (f) P. Bichler, J. A. Love, Top.
Organomet. Chem. 2010, 31, 39-64.
Acknowledgements
[5]
(a) C. Chatgilialoglu, K. D. Asmus, Sulfur-Centered Reactive
Intermediates in Chemistry and Biology, Springer, New York, 1991; (b)
J. J. R. Fraústo da Silva, R. J. P. Williams, The Biological Chemistry of
the Elements, Clarendon Press, Oxford, 2001; (c) K. Yamamoto, M.
Fujita, K. Tabashi, Y. Kawashima, E. Kato, M. Oya, J. Iwao, J. Med.
Chem. 1988, 31, 919-930; (d) N. T. Burford, M. J. Clark, T. S.
Wehrman, S. W. Gerritz, M. Banks, J. O’Connell, J. R. Traynor, A. Alt,
Proc. Natl. Acad. Sci. USA 2013, 110, 10830-10835.
We gratefully acknowledge NIGMS (R35 GM118190 to F. D. T. and
R01 GM121383 to M. S. S.) for financial support of this work. K.K. is
grateful to the JSPS for their scholarship support. Computations
were performed at the Center for High Performance Computing
(CHPC) of the University of Utah.
Keywords: phase-transfer catalysis • chiral anions • Pummerer
reaction • N,S-acetal • synthetic method • theoretical study
[6]
V. Rauniyar, A. D. Lackner, G. L. Hamilton, F. D. Toste, Science 2011,
334, 1681-1684.
[7]
(a) A. J. Neel, J. P. Hehn, P. F. Tripet, F. D. Toste, J. Am. Chem. Soc.
2013, 135, 14044-14047; (b) A. J. Neel, A. Milo, F. D. Toste, M. S.
Sigman, Science 2015, 347, 737-743.
[1]
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Pummerer, Ber. Dtsch. Chem. Ges. 1910, 43, 1401-1412.
[2]
Reviews about transformations based on Pummerer reactions: (a) S. K.
Bur, A. Padwa, Chem. Rev. 2004, 104, 2401-2432; (b) K. S. Feldman,
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Layout 1:
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Text for Table of Contents
Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
((Insert TOC Graphic here))
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Souvagya Biswas, Koji Kubota, Manuel
Orlandi, Mathias Turberg, Dillon H.
Miles, Matthew S. Sigman, F. Dean
Toste
Ar2
O
Ar2
S
S
S
n
n
Ar2
n
O
N
*
CAPT
H
O
P
N
S
O
NH
O
O
S
O
oxidant
S
O
O
Ar1
Ar1
Ar1
O
Page No. – Page No.
chiral thionium
ion pair
Enantioselective Synthesis of N,S-
Acetals by an Oxidative Pummerer
Type Transformation Using Anionic
Phase-Transfer Catalysis
The first catalytic enantioselective Pummerer type transformation has been
developed employing chiral anion phase-transfer catalysis. This chemical
transformation allows the facile construction of a wide variety of enantioenriched
cyclic N,S-acetal motifs that were previously difficult to access.
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