Angewandte
Chemie
Organocatalysis
Design, Synthesis, and Application of a Chiral Sulfinamide Phosphine
Catalyst for the Enantioselective Intramolecular Rauhut–Currier
Reaction**
Xiao Su, Wei Zhou, Yangyan Li, and Junliang Zhang*
Abstract: A novel class of chiral sulfinamide phosphine
catalysts (Xiao-Phos) are reported, which can be easily
prepared from inexpensive commercially available starting
materials. The Xiao-Phos catalysts showed good performance
in enantioselective intramolecular Rauhut–Currier reactions,
generating a-methylene-g-butyrolactones in high yields with
up to 99% ee under mild conditions. Moreover, kinetic
resolution and parallel kinetic resolution were also observed
with the use of two different substituted racemic precursors.
asymmetric transition-metal catalysis and the sulfinamide
plays a second role in stereoselectivity control.[5] With a series
of chiral Ming-Phos ligands in hand and as a part of our
program for developing chiral-phosphine-catalyzed enantio-
selctive transformations,[6] we wished to expand the applica-
tions of Ming-Phos variants from transition-metal catalysis to
nucleophilic phosphine catalysis. In this context, recent
elegant work by Sasai and co-workers[7] attracted our
attention. They successfully accomplished a chiral-phos-
phine-catalyzed enantioselective intramolecular Rauhut–
Currier (RC) reaction,[8] efficiently furnishing synthetically
valuable a-methylene-g-butyrolactones.[9] However, the per-
formance of the Ming-Phos variants was disappointing; in
most cases, the reaction did not give high conversions because
of the low nucleophilic catalyst activity. We then envisaged
that a new type of chiral sulfinamide phosphines, called Xiao-
Phos, should have better nucleophilic activity than the Ming-
Phos variants. With two stereocenters, an H-bonding site, and
tunable side chains, the Xiao-Phos series may be applicable to
asymmetric nucleophilic catalysis for organic transformations
such as RC reactions (Figure 1). Herein, we report our efforts
toward the stereodivergent synthesis of these new chiral
phosphines and their application in enantioselective intra-
molecular RC reaction.
After many attempts, we were pleased to find that Xiao-
Phos variants could be easily prepared from commercially
available Ph2PCH3, tert-butylsulfinamide, and aldehyde
(Scheme 1).[10] Treatment of Ph2PCH3 with BuLi in the
presence of TMEDA at room temperature produced a solu-
tion of Ph2PCH2Li in THF according to the reported
procedure,[11] which then undergoes nucleophilic addition to
chiral (Rs)-sulfinimines, thereby furnishing the corresponding
phosphines X1–X7 in good yield with moderate to high
diastereoselectivity. Notably, X8 was obtained from the
corresponding o-hydroxyl-substituted sulfinimines. X9–X12
were made through the silylation of X8 under mild conditions.
(see the Supporting Information). The absolute configura-
Over the past decade, asymmetric nucleophilic catalysis
with chiral phosphines has emerged as a powerful approach to
structurally diverse and synthetically valuable optically active
organic building blocks.[1] Among the many types of chiral
phosphines, chiral b-aminephosphines represent one of the
most attractive and have been utilized as nucleophilic
catalysts[2] or chiral ligands[3] in a broad spectrum of useful
organic transformations. Compared to the intensive attention
focused on the utility of chiral b-aminephosphines in organic
synthesis, only a handful of methods have been reported so far
for their synthesis. Among these, the approach from readily
available natural or unnatural chiral amino acids is the most
attractive.[4] Despite the fact that much progress has been
made in the construction of chiral phosphine catalysts, the
development/design of highly efficient new types of chiral
phosphines, especially from inexpensive, commercially avail-
able chiral resources, remains a considerable challenge.
Recently, our group developed a new type of chiral
sulfinamide phosphine (Ming-Phos ligands), which could be
easily prepared in good yields from inexpensive commercially
available chiral tert-butylsulfinamide in two steps. Gratify-
ingly, Ming-Phos ligands have shown good performance in
[*] X. Su,[+] W. Zhou,[+] Y. Li, Prof. Dr. J. Zhang
Shanghai Key Laboratory of Green Chemistry and Chemical
Processes, School of Chemistry and Molecular Engineering
East China Normal University, Shanghai, 200062 (P.R. China)
E-mail: jlzhang@chem.ecnu.edu.cn
Prof. Dr. J. Zhang
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry, CAS
345 Lingling Road, Shanghai, 200032 (P.R. China)
[+] These authors contributed equally to this work.
[**] We are grateful to 973 Programs (2011CB808600), the National
Natural Science Foundation of China (21372084, 21425205), and
Changjiang Scholars and Innovative Research Team in University
(PCSIRT) for financial supports.
Supporting information for this article is available on the WWW
Figure 1. The design of novel chiral sufinamide phosphines.
Angew. Chem. Int. Ed. 2015, 54, 1 – 5
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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