Practical synthetic approach to chiral sulfonimides (CSIs) - Chiral bronsted acids for organocatalysis

Article abstract of DOI:10.1002/ejoc.201000477

A general approach to the synthesis of optically pure 3,3'diaryl chiral sulfonimides (CSIs) from racemic BINOL has been developed. ortho-Lithiation is directed by the sulfonyl groups, and the resulting dihalides serve as the common precursors for the aryl-substituted CSIs.

Full text of DOI:10.1002/ejoc.201000477

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201000477
Practical Synthetic Approach to Chiral Sulfonimides (CSIs) – Chiral Brønsted
Acids for Organocatalysis
Hao He,[a] Ling-Yan Chen,[a] Wai-Yeung Wong,[a] Wing-Hong Chan,[a] and
Albert W. M. Lee*[a]
Keywords: Sulfonimides / Brønsted acids / Chirality / Organocatalysis
A general approach to the synthesis of optically pure 3,3Ј-
diaryl chiral sulfonimides (CSIs) from racemic BINOL has
been developed. ortho-Lithiation is directed by the sulfonyl
groups, and the resulting dihalides serve as the common pre-
cursors for the aryl-substituted CSIs.
mild conditions. In most cases, the organocatalytic reac-
tions can be carried out under ambient conditions without
the exclusion of air or moisture. Among the four types of
organocatalysts,[3b] many believe that Brønsted acid cata-
lysts have the potential to provide the reactivities and selec-
tivities that could match up with metal-based asymmetric
catalysis.[4] For example, BINOL-derived chiral phosphoric
acids 2a discovered independently by Akiyama[5a] and Tera-
da,[5b] and the more acidic corresponding N-triflyl phos-
phoramides 2b developed by Yamamoto,[5c,5d] are the most
widely used Brønsted acid organocatalysts of today.
Introduction
Two recent publications from the groups of List and
Giernoth prompted us to report our efforts on developing
binaphthyl-derived chiral sulfonimides (CSIs) as Brønsted
acids in organocatalysis. Giernoth reported the synthesis of
parent compound 1a (X, Y = H),[1] whereas List demon-
strated elegantly that in situ generated silylated sulfonimine
1c (Y = SiMe3, via 1b) is a highly efficient Lewis acid organo-
catalyst for Mukaiyama aldol reactions.[2]
Recently, Barbero reported that o-benzenedisulfonimide
3 is a strong Brønsted acid for various acid-catalyzed trans-
formations such as etherification, esterification, acetaliza-
tion, and acylation, as well as for the acid-catalyzed Ritter,
Nazarov, and Hosomi–Sakurai reactions.[6] It has been re-
ported that the pKa value of 3 in water is –4.1.[6b,7] For
the corresponding aliphatic sulfonimides 4 and 5, their pKa
values in water are –3.1 and –1.7, respectively.[7] We envision
that a chiral version of 3 could be an effective Brønsted
acid for asymmetric organocatalysis, and we selected bi-
naphthyl as the chiral backbone in the design of the CSI.
Results and Discussion
Our approach to the synthesis of chiral sulfonimides 1 is
different from those of List and Giernoth. They both
started with optically pure BINOL, and Giernoth only pre-
pared parent compound 1a (X, Y = H). In the case of List’s
synthesis of 1b, the 3,3Ј-substituent is already in place at the
beginning of the synthesis. Instead, we started with racemic
BINOL and deferred the resolution to a later stage by using
readily available (S)-α-methylbenzylamine [(–)-11] as the re-
solving agent. In addition, we would like to explore the pos-
sibility of using the sulfonyl groups at the 2,2Ј-positions as
the directing groups for the functionalization of the 3,3Ј-
positions by ortho-lithiation.[8] Resulting dihalide 1e could
In recent years, the rapid development of organocatalysis
has complemented the traditional organometallic and enzy-
matic approaches to asymmetric catalysis in the construc-
tion of chiral molecules and scaffolds.[3] With organocata-
lysis, synthetic chemists can construct chiral molecules in a
highly efficient and stereoselective manner under rather
[a] Department of Chemistry, Hong Kong Baptist University,
Kowloon Tong, Hong Kong SAR, China
E-mail: alee@hkbu.edu.hk
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000477.
Eur. J. Org. Chem. 2010, 4181–4184
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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H. He, L.-Y. Chen, W.-Y. Wong, W.-H. Chan, A. W. M. Lee
SHORT COMMUNICATION
then serve as a common precursor for a series of 3,3Ј-substi- formed in 88% yield with optically (S)-α-methylbenzyl-
tuted CSIs. Our approach should provide a more general amine [(–)-11]. The formation of the cyclic sulfonimide has
and convergent synthesis to a wide variety of CSIs with to be conduct under high-dilution conditions. Otherwise,
different substituents at the 3,3Ј-positions by using dihalide bis(sulfonamide) will be formed as the major product. The
1e as the common starting material.
absolute configuration of 1d was confirmed by X-ray analy-
Our synthesis of the CSIs is outlined in Scheme 1. Race- sis (Figure 1). Hydrogenolysis in MeOH/EtOAc afforded
mic 1,1Ј-binaphthalene-2,2Ј-dithiol [(Ϯ)-9] was prepared the optically pure (R) and (S) enantiomers of parent CSI
from racemic BINOL [(Ϯ)-6] by Newman–Kwart thermal (R)-1a and (S)-ent-1a in almost quantitative yield. The X-
rearrangement[9] of 1,1Ј-binaphthalene-2,2Ј-diyl O,O- ray structure of (R)-1a is also shown in Figure 2.
bis(N,N-dimethylthiocarbamate) [(Ϯ)-7] into 1,1Ј-binaphth-
In general, bulky aryl substituents at the 3,3Ј-positions
alene-2,2Ј-diyl S,S-bis(N,N-dimethylthiocarbamate) [(Ϯ)-8]. are needed for an effective binaphthyl-type catalyst. There-
Under carefully controlled conditions, the Newman–Kwart fore, functionalization of the 3,3Ј-positions of the bi-
rearrangement at 270–280 °C (sand bath) can be carried out naphthyl backbone was explored. It has been reported that
in a gram scale with good overall yields. Lithium aluminum the sulfonamide group could serve as a director for ortho-
hydride reduction of (Ϯ)-8 afforded dithiol (Ϯ)-9 in good lithiation in an aromatic system.[8] However, direct lithi-
yield.[9a,9c,9e] Oxidative chlorination to sulfonyl chloride ation of N-substituted 1d with various organolithium rea-
(Ϯ)-10 was achieved by using potassium nitrate and TMSCl gents was not successful. The major products were the ring-
as the oxidizing and chlorinating agents, respectively.[10a] opened products of the sulfonimide, even when a bulky rea-
Alternatively, (Ϯ)-10 could be obtained directly from (Ϯ)-8 gent such as tert-butyllithium was used. Finally, lithiation
by using N-chlorosuccinimide (NCS), as reported by Gier- of parent CSI 1a with an excess amount of nBuLi followed
noth.[1,10b]
by bromination with either Br2 or 1,2-dibromotetrachloro-
Diastereomeric sulfonimides 1d and 1dЈ, which can be ethane[11] at –40 °C afforded 3,3Ј-dibromo CSI 1e in 56%
separated by silica gel column chromatography, were then yield. Iodination with I2 also afforded the corresponding
Scheme 1. Synthetic route to CSIs.
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Eur. J. Org. Chem. 2010, 4181–4184

Chiral Sulfonimides (CSIs) – Chiral Brønsted Acids for Organocatalysis
BINOL. ortho-Lithiation is directed by the sulfonyl groups,
and the resulting dihalides serve as the common precursors
for the aryl-substituted CSIs. The application of these CSIs
and the corresponding conjugated bases[13] in organocata-
lysis is under investigation.
CCDC-771830 (for 1a) and -771831 (for 1d) contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, compound characterization data, copies
of the NMR spectra.
Acknowledgments
Figure 1. X-ray structures of 1d.
Financial support from the Faculty Research Grant of Hong Kong
Baptist University (FRG/08–09/II-45) and a Visiting Professorship
from the Research Center of Materials Science of the Nagoya Uni-
versity are gratefully acknowledged.
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size of the sulfonyl group, restricted rotation appears be-
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In summary, we have developed a general approach to
the synthesis of binaphthyl-based chiral sulfonimides with
aryl substituents at the 3,3Ј-positions starting from racemic
Eur. J. Org. Chem. 2010, 4181–4184
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Received: April 8, 2010
Published Online: June 16, 2010
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Eur. J. Org. Chem. 2010, 4181–4184