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DOI: 10.1055/sos-SD-020-00343

Wolkenberg, S. E.; Garbaccio, R. M.Science of Synthesis, (200720413.

Chiral cyclic imino esters 83 based on 2-hydroxypinan-3-one can be condensed with aldehydes to provide chiral didehydroamino acids 84.[‌97‌] Chemoselective and diastereospecific reduction of the alkene occurs from the convex face of the bicyclic compound with excellent (>95%) stereocontrol and moderate yield (6375%) to give imino esters 85 (Scheme 25). Acidic hydrolysis of this system yields four distinct α-amino acids 86 in excellent yield (8595%) and allows for recovery of the chiral source. Interestingly, asymmetric protonation was also attempted with this system in the hope of reversing the topicity and accessing both amino acid enantiomers from the same intermediate. However, following 1,4-reduction with L-selectride (lithium tri-sec-butylborohydride), protonation still occurred from the same face as the gem-dimethyl group. This method, as described, is therefore limited to S-amino acids based on the use of commercial pinan-3-one.

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