Science of Synthesis

Wolkenberg, S. E.; Garbaccio, R. M., Science of Synthesis, (2007) 20, 413.

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 (63–75%) to give imino esters ‌85‌ (‌Scheme 25‌). Acidic hydrolysis of this system yields four distinct α-amino acids ‌86‌ in excellent yield (85–95%) 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.

‌Meeeee 88‌ Meeeeeeeee Meeeeeeeeeeee Meeee Meeeee-Meeee Meeeee Meeee Meeeee ee Meeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

Meeeeeeeeeee Meeeeeeee

α-Meeee Meeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

M 8.8 M eeee ee ‌88‌ (8 eeee) ee MeMM eee eeeeeeeeeeee eeee 8% Me/M (888 ee) eee eee eeeeeeee eee eeeeeeee ee MMM. Meee eee eeeeeeee eee eeeeeeee, eee eeeeeeee eee eeeeeee ee eeeeeeeeee eee eee eeeeeeee eee eeeeeeeeee ee eeeeeee ee eeeeee eee eeeeeeeeeeeee eeeeeee ‌88‌ ee e eeeeee eeeeeeeeeeee. Meeeeeeeeeee eee eeeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, Me8M/eeeeee 8:8); eeeee: 88–88% (>88% ee).

Meeeeeeeee ee ‌88‌ (8 eeee) eee eeeeeeeee ee MMM eee 8 M MMe (88 eM) ee 88°M eee 8 e. Mee eeee eee eeeeeeeee eeee Me8M eee eee eeeeeee eeeee eee eeeeeeeeee ee eeee e eeeeeeeeeee eeeeeee. MeMM (8 eM) eee eeeee, eeeeeeee eeee e eeeee eeeeee ee eeeeeee eeeee. Mee eeeeeee eee eeeeeeee eee 88 eee eee eee eeee eeeee eeee eeeeeeeee eeeeeeeeeeee. Meeee eeeeeee ee eee MeMM, eee eeeee eeeeeee eee eeeeeeeee ee eeeeeeeee M8M (8 eM) eee eeeeee eeeeeee e M88 eeeeeee-eeeee Mee-eee eeeeeeeee. Meeeeee ee M8M eeee eee eeeeeeeeeeeee eeeee eeee ‌88‌; eeeee: 88–88%.

References