posted on 2016-08-08, 00:00authored byMichael
J. Houghton, Christopher J. Huck, Stephen W. Wright, David B. Collum
A lithium enolate derived from an
acetonide-protected pyroglutaminol
undergoes a highly selective azaaldol addition with (E)-N-phenyl-1-[2-(trifluoromethyl)phenyl]methanimine.
The selectivity is sensitive to tetrahydrofuran (THF) concentration,
temperature, and the presence of excess lithium diisopropylamide base.
Rate studies show that the observable tetrasolvated dimeric enolate
undergoes reversible deaggregation, with the reaction proceeding via
a disolvated-monomer-based transition structure. Limited stereochemical
erosion stems from the intervention of a trisolvated-monomer-based
pathway, which is suppressed at low THF concentrations and elevated
temperature. Endofacial selectivity observed with excess lithium diisopropylamide
(LDA) is traced to an intermediate dianion formed by subsequent lithiation
of the monomeric azaaldol adduct, which is characterized as both a
dilithio form and a trilithio dianion–LDA mixed aggregate.