bifunctional catalysts - density-functional-theory calculations - hydrogen bonds -
Michael addition - thiourea-based catalysts
Significance
<P>A computational mechanistic study of the enantioselective Michael addition of acetylacetone
to nitroolefin promoted by a thiourea-based chiral bifunctional organocatalyst is
presented. The optimal structural arrangement of the active sites of the catalyst
has been attained via protonation of its basic center by the nucleophilic substrate
through a reversible kinetic process. The generally accepted mechanism for the adduct
formation involves electrophile activation through hydrogen bonds with the thiourea
moiety and subsequent C-C bond formation between simultaneously activated components
(pathway 1). An alternative reaction mechanism for the C-C coupling step is the electrophile
activation by the protonated amine group of the catalyst (pathway 2), involving a
ternary H-bonded complex and a transition state more stable than those formed along
the former pathway. Both reaction pathways account for the observed enantioselectivity.</P>
Comment
<P>The enantioselective Michael addition of nucleophiles to nitroolefins represents
one of the most extensively studied thiourea-organocatalyzed reactions. Recently,
a novel bifunctional thiourea catalyst combining H-bond donors and a chiral tertiary
amine group has been developed by Takemoto. It has been assumed that the two substrates
involved in the reaction are activated simultaneously: the nitroolefin via multiple
H-bonds with the thiourea moiety and the nucleophile through interactions with the
tertiary amine group and subsequent deprotonation, followed by C-C bond creation via
the formation of a ternary H-bonded complex (Y. Takemoto et al.
J. Am. Chem. Soc. 2005,
127, 119-125). In this paper, theoretical investigations showed that the energetically
more favorable pathway to form the Michael product takes place via nitroolefin activation
by the protonated tertiary amine group. Further mechanistic studies are required to
confirm and generalize the proposed mechanism.</P>
