Intramolecular S Transfer Promoted by Brønsted Acids
A R T I C L E S
Chart 1. Survey of â-Mono- and â,â-Disubstituted N-Enoyl
efficiency and selectivity under catalytic conditions is rather
challenging, and methods that provide regularly high enanti-
oselectivity (ee’s above 90%) are scarce.9 Moreover, the range
of thiols well suited for both catalytic and stoichiometric
methodologies is limited, being in most cases restricted to
thiophenols.
Oxazolidine-2-thiones Used Across This Study
Quite recently, we reported on a conceptually new approach
to â-thio carbonyls, which relies on the Lewis acid promoted
intramolecular sulfur transfer in N-enoyl oxazolidine-2-thiones
(Chart 1).10,11 Our method, Scheme 1, complements most of
the existing ones in that it directly produces mercaptans instead
of sulfides, a transformation that can be conceived as a formal
conjugate addition of a “SH-” anion. An additional strength of
the method is the remarkably high stereoselectivity obtained
with â,â-disubstituted enoyl acceptors (R1, R2 * H) to give
quaternary C-S stereocenters. The overall process involves a
dual function of the oxazolidine-2-thione auxiliary: as the
controller of the reaction stereochemistry and as the sulfur
transfer reagent.12
Scheme 1. General Pictogram of the Intramolecular Sulfur
Transfer in N-Enoyl Cyclic Thiocarbamates (Oxazolidine-2-thiones)
Promoted by Lewis Acids
Herein we report full details of our work that demonstrates
for the first time the validity of Brønsted acids as promoters of
the sulfur migration process, which makes the method free from
metal. New experimental and computational results toward
getting some mechanistic insights of the reaction are also
disclosed.
Results and Discussion
Activation of the Michael Acceptor: Lewis Acid-Brøn-
sted Acid Dichotomy. Prior reports from this laboratory have
documented the efficiency of certain Lewis acids, particularly
SnCl4 and BF3‚Et2O,13 in promoting the intramolecular sulfur
transfer reaction shown in Scheme 1.10,11 In the absence of the
Lewis acid, no reaction is observed even at room temperature
for prolonged reaction times. In subsequent, closely related work
by Kataoka and co-workers, the tandem Michael-aldol reaction
of N-enoyl oxazolidine-2-thiones with aldehydes or acetals was
shown to proceed in the presence, again, of BF3‚Et2O or SnCl4
as the reaction promoters.14 In general, Lewis acid assisted
conjugate additions to enoyl systems are presumed to be
accelerated via carbonyl-metal complexation which lowers the
substrate LUMO energy. Nevertheless, for the Lewis acid
mediated hetero-Michael addition reactions, Spencer and co-
workers have recently revealed that protons, generated through
hydrolysis of metal complexes, can be the true active catalysts.15
We also found circumstantial evidence for the intervention of
protons during the sulfur transfer process. Hence, pairs of
reactions were carried out, respectively, in the presence or
absence of 2,6-di-tert-butylpyridine, a base that binds to protons
but is apparently unable to coordinate to metal ions,16 and the
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