This paper is concerned with the nature of the chiral inducer in
the high pressure-induced conjugate
addition of amines to auxiliary-tethered crotonates. Almost
complete stereocontrol was obtained
in the addition of diphenylmethanamine to crotonates derived from the
“arylmenthol” auxiliaries
18a, 18c, and 4 bearing an
o-methoxyphenyl, p-phenoxyphenyl, or β-naphthyl
substituent,
respectively. This high efficiency has been attributed to the
predominance of stacked conformations
in such crotonates, a hypothesis supported by the 1H NMR
spectra, calculated energy of
conformational optima of the corresponding crotonates, and X-ray
crystal structure of 5a. The
arene and enoate appendages are roughly coplanar, separated by 3.4−4
Å. In contrast, only
moderate selectivities could be achieved using various
trans-2-arylcyclohexanols (27, 28,
2c, 29)
as auxiliaries. In these cases the efficiency appears to be
seriously compromised by the “widening
V” arrangement exhibited by the two π-systems, as shown in the
X-ray crystal structures of
crotonates 5h and 5k. The sense of
stereochemical induction of this conjugate addition has
been
determined by condensing diphenylmethanamine with enantiopure crotonate
(+)-5a. The adduct
9a was converted to amino alcohol
(S)-11, of known configuration. This
correlation is consistent
with the preferential attack of the amine to the less sterically
hindered enoate π-face of (+)-5a, in
its s-trans conformation. Finally, the stereochemistry
of the proton transfer was determined by
adding N,N-dideuteriodiphenylmethanamine to
crotonate (±)-5a. The stereochemical outcome
of
this addition is consistent with the anti-addition of the
incoming nitrogen nucleophile and the
deuterium atom.
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