Science of Synthesis

Wolkenberg, S. E.; Garbaccio, R. M., Science of Synthesis, (2007) 20, 462.

Dehydromorpholinones ‌245‌ typically undergo Grignard addition to the ester moiety; however, in the presence of a Lewis acid, regiospecific addition occurs to the imine (‌Scheme 65‌). This observation allows for the synthesis of α-alkyl-α-amino acids[‌199‌] from this ubiquitous template. Following precomplexation with the boron trifluoride–diethyl ether complex, a range of Grignard reagents can be added anti to the phenyl group to produce a single diastereomer of ‌246‌. Cleavage of the morpholinone is achieved by hydrogenolysis to produce disubstituted amino acids ‌247‌. The scope of the transformation is demonstrated for methyl-substituted morpholinones; however, other aliphatic templates are successfully made.

‌Meeeee 88‌ Meeeeeee ee Meeeeeee Meeeeeee ee Meeeee Meeeeeeeeeeeeeeeeeee[‌888‌]

‌Meeeeeeeeee 88‌

Meeeeeeeeeee Meeeeeeee

(8M,8M)-8-Meeee-8-eeeeee-8-eeeeeeeeeeeeeee-8-eeee ‌888‌ (M8 = Meeee); Meeeeee Meeeeeeee:[‌888‌]

M 8.88 M eeee ee eee eeeee ‌888‌ (8 eeeee) ee eee MMM eee eeeeee ee –88°M. Meeeeee eeeeeeeee MM8•MMe8 (8.8 eeeee) eee eeeee eeeeeeee eee eee eeeeeee eee eeeeeee ee –88°M eee 8 e eeeeee eeeeeeee eeeeeeee ee eee Meeeeeee eeeeeee (8.8 eeeee). Meeee 8 e, eee eeeeeeee eee eeeeeeee ee eeeeeeee ee eee. MeMMM8 eeee. Mee eeeeeeee eeeeeee eeeeeeee eeee eeeeee eeee eee. MeMe eeee eeeeee eeeeeeeeeeeee eeeee eeeeeee eeeeeeee ee eeee eee eeeee eeeeeee ee e eeeeee eee. Meeeeeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeeeee eeeee 8:8) eeeeeeeee eee eeeeeee; eeeee: 88–88%.

α-Meeee Meeee ‌888‌; Meeeeee Meeeeeeee:[‌888‌]

Meeeeeeee ee eee eeeeeeeee-8-eeee ‌888‌ (8 eeeee) eee eeeeeeee eeeee Me(MM)8 eeeee eeeeeeee M8 eeeeeeee [8 eee, MeMM/M8M 88:8, MMM (8 eeeee)]. Meeeeeeeee ee eee eeeeeee eeeee ee eee eeeee eeeee eeee eeeee eeee MeMMe, eeeeee-eeeeee eee eeeeeee eeeee, eee eee-eeeeeeee eeeeeeeeeeeeee (Meeee 88M eeeeee eeeee, 8 M MM8) eeeeeeeee eee eeee eeeee eeeee; eeeee: 88–88%.

References