Synergistic organocatalysis in the kinetic resolution of secondary thiols with concomitant desymmetrisation of an anhydride.
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2010Citation:
A. Peschiulli, B. Procuranti, C. J. O' Connor and S. J. Connon, Synergistic organocatalysis in the kinetic resolution of secondary thiols with concomitant desymmetrisation of an anhydride., Nature Chemistry, 2, 2010, 380 384Download Item:
Abstract:
An organocatalytic process mediated by a single small-molecule catalyst involving the highly enantioselective
desymmetrisation of an achiral electrophile while it simultaneously kinetically resolves a racemic nucleophile has been
developed which allows the efficient direct acylative kinetic resolution of sec-thiol substrates for the first time. The
levels of enantioselectivity associated with both processes (which exhibit verifiable synergy) are excellent using a
readily accessible cinchona alkaloid-derived organocatalyst at low loadings. The inexpensive achiral glutaric
anhydride electrophiles are desymmetrised as the resolution progresses with excellent levels of stereocontrol and can
be later cleaved to afford highly enantioenriched products (up to 97% ee). The potential synthetic utility of the
methodology was demonstrated by the synthesis of a drug precursor antipode in excellent yield and enantioselectivity
as a by-product of a process which also resolved a sec-thiol substrate with a selectivity of S=226 (i.e. both thiol
antipodes produced in >95% ee at 51% conversion).
Sponsor
Grant Number
Science Foundation Ireland (SFI)
Irish Research Council for Science and Engineering Technology (IRCSET)
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http://people.tcd.ie/connonsDescription:
PUBLISHEDHighlighted in Synfacts (2010, 925).
Sponsor:
Science Foundation Ireland (SFI)Irish Research Council for Science and Engineering Technology (IRCSET)
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Nature Chemistry2
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Full text availableKeywords:
Biochemistry, sec-thiol substrateSubject (TCD):
Nanoscience & MaterialsMetadata
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