Stereoselective synthesis of aporphine alkaloids using a hypervalent lodine(III) reagent-promoted oxidative nonphenolic biaryl coupling reaction.: Total synthesis of (S)-(+)-glaucine

The aporphine alkaloid (+)-glaucine (8a) and two other analogues 8b.c have been synthesized in good yield and high ee from the appropriate 1.2-diarylethylamine derivatives, which were in turn prepared using (S)-(+)-phenylglycinol as chiral support. Next. a sequence of simple transformations: N-alkylation with bromoacetaldehyde diethyl acetal. N-methylation, Pommeranz-Fritsch cyclization. and ionic hydrogenation led to the key intermediate, optically active. 1-benzyltetrahydroisoquinolines 7a-c. The final C-ring closure step was performed by C-C biaryl bond formation by an hypervalent iodine(III) reagent promoted oxidative coupling, affording the target heterocycles 8a-c in good yields and with no racemization at the formerly created stereogenic center.