Chiral auxiliaries, diastereoface

Various chiral auxiliaries and catalysts have been developed that allow diastereoface-and enantioface-selective Michael additions. 

One possible explanation for the diastereoface selection (AAGt -78°C 3 kcal/mol) observed for these chiral enolates is illustrated in Scheme 23. In the respective aldol transition states derived from conformers A and B leading to erythro diastereomers A and B, it may be assumed that developing imide resonance (118) will lock the chiral auxiliary in one of the in-plane conformations illustrated in products A or B. Based on an examination of models, it is projected that developing CHj R, allyhc strain steric interaction (37) disfavors that transition state leading to A. These steric considerations are largely attenuated in the transition state leading to the observed erythro adduct B. ... 

A second way (method ) uses a chiral auxiliary by converting the propenoic acid into an amide. Catalytic hydrogenation with the achiral catalyst 5 shows a modest diastereoface selection, 6/7 1.9 1. Both methods lead to the (5) configuration at C-2 and combining the effects, i.e., chiral auxiliary with ( + )-3 ( matched combination ), increases the (5) selectivity from 11 1 to 16 1 (calculated value 11 x 1.9 = 21 1). In contrast, the use of the chiral auxiliary with (—)-3 counteracts the inherent (S) induction in the starting amide ( mismatched combination ) and favors (R) induction, 6/7 1 4.5 (calculated value 1.9 11 = 1 6). 

Since its introduction in 1975 by E. J. Corey and H. E. Ensley3 8-phenylmenthol has found widespread use as a chiral auxiliary in organic syntheses. It has proved to be dramatically superior in diastereoface discriminating ability to the commonly used chiral auxiliaries such as menthol, borneol, etc. 

The iT-face differentiation in favor of adducts (443) was more pronounced with increasing amounts of the Lewis acid and at lower reaction temperatures (cf. entries 3/4 and 8/9). The cooperative effect of chiral auxiliaries at the diene and at the dienophile units is exemplified by the double diastereoface selective addition presented in entry 2. Particularly noteworthy is the outstanding ir-face selectivity, observed in the [4 + 2) cycloaddition of juglone (445). Removal of the prosthetic group fiom adducts (443) was accomplished via hydrogenolysis or allylic displacement, as illustrated by the key step (447) (448) of a synAesis of enantiomerically emiched (+)-ibogamine (Scheme 105). ... 

TiCl4 acts as a stereochemical template and consequently the silyl ketene acetal additions to C=X occur with high diastereoface selectivity. The chiral auxiliary can then be removed (and recycled) by reduction, saponification or displacement with other nucleophiles to give useful synthetic intermediates. 

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