Chemical Science
Edge Article
initial acidic cleavage of the tert-butyl ester and subsequent
methyl ester formation under acidic conditions afforded 4a in
78% yield without compromising stereochemical integrity.
Oxidation of 4e afforded sulfone 5a without any observable
racemization in near quantitative yield. Finally, b-mercap-
toester 4m was reduced to the alcohol in excellent yield, without
appreciable loss of enantiopurity.20
5 The electrophile-specic reactivity parameters E of trans-b-
nitrostyrenes have been determined to be ꢁ15 < E < ꢁ12:
I. Zenz and H. Mayr, J. Org. Chem., 2011, 76, 9370.
6 Preliminary studies indicate the electrophile-specic
reactivity parameters E of ethyl cinnamate and ethyl
crotonate are in the range of ꢁ25 < E < ꢁ23: H. Mayr,
personal communication.
¨
7 For a review on iminium catalysis, see: A. Erkkila,
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8 For reviews on organocatalytic conjugate addition reactions,
In summary, we have developed the rst organocatalytic
enantioselective SMA of alkyl thiols to unactivated
b-substituted-a,b-unsaturated esters. Impressive reactivity and
excellent levels of enantioselectivities were achieved across
a range of linear, branched, cyclic alkyl and benzylic thiols, in
SMA reactions to various b-substituted-a,b-unsaturated esters
using a novel bifunctional iminophosphorane catalyst. This
work demonstrates that the high reactivity of the BIMP catalysts
enables low reactivity electrophiles such as b-substituted-a,b-
unsaturated esters to undergo highly enantioselective conjugate
addition reactions for the rst time and thus represents
´
see: (a) J. L. Vicario, D. Badıa, L. Carrillo and E. Reyes,
Organocatalytic Enantioselective Conjugate Addition
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9 The organocatalytic enantioselective conjugate addition of
benzyl mercaptan to activated aryl crotonate esters was
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S. Meng, J. Chen and Y. Huang, Synlett, 2016, 27, 1068.
a signicant advance in the eld. Work to uncover further 10 To the best of our knowledge, only a single isolated example
capabilities of the BIMP catalyst family is ongoing in our labo-
ratories and the results will be disclosed in due course.
of a moderately enantioselective organocatalytic Michael
addition to ethyl crotonate has been reported, see:
X. Dong, X. Fang and C.-J. Wang, Org. Lett., 2011, 13, 4426.
11 For reviews on Brønsted base H-bond donor bifunctional
organocatalysts, see: (a) Y. Takemoto, Org. Biomol. Chem.,
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Acknowledgements
We thank the EPSRC (Studentship and Doctoral Training Grant
[EP/M50659X/1] to A. J. M. F.), AstraZeneca (Studentship to A. J.
M. F.), the SCI (Postgraduate Scholarship to A. J. M. F.) and the 12 For the use of chiral organosuperbase catalysts to enhance
China Scholarship Council-University of Oxford Scholarship
(Studentship to J. Y.) for funding.
reactivity, see: (a) J. S. Bandar and T. H. Lambert, J. Am.
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Notes and references
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Chem. Sci.
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