Significant differences for competitive efficiencies in directed ortho lithiations for single functional groups in three series, the secondary benzamides 1-4, the tertiary benzamides 5-1 1, and the benzylic alcohols 12-17, are reported. For both amide series the efficiencies increase as the oxygen and ortho hydrogen in the substrate are more coplanar with the aromatic ring; however, for the alcohol series the opposite order is observed. Rationalizations are offered for these observations.
Investigation of the structure and reactivity of β-lithiated
β-phenylcarboxamides is reported. NMR
spectroscopic investigations of β-lithiated amides 15 and
24 establish that the benzylic lithium is complexed by
the
nitrogen of the amide. The β-lithiated N-methyl amide
15 forms a complex with (−)-sparteine (4) which
undergoes
electrophilic substitution to provide enantioenriched products.
The β-lithiated N-isopropyl amide 24 does
not form
a complex with 4, so there is no asymmetric induction.
The enantioselectivity of the reaction is shown to arise
by
the pathway of asymmetric substitution in which asymmetry is induced in
a postdeprotonation step. Asymmetric
induction in this lithiation−substitution sequence is suggested to
occur via a dynamic thermodynamic resolution.
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