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Total Synthesis of (−)-Tetrahydropalmatine via Chiral Formamidine Carbanions: Unexpected Behavior with Certain Ortho-Substituted Electrophiles

1996; American Chemical Society; Volume: 61; Issue: 2 Linguagem: Inglês

10.1021/jo951611q

1520-6904

Mark A. Matulenko, A. I. Meyers,

Synthesis and bioactivity of alkaloids

A method has been developed by alkylation of chiral lithioformamidines to construct protoberberine alkaloids with a C(9) and C(10) D-ring substitution pattern. This ring pattern was established using an ortho-substituted hydroxymethylbenzene electrophile protected as a silyl ether to ultimately provide (-)-tetrahydropalmatine in 88% ee. Additionally, we have discovered limitations with ortho-substituted electrophiles in the asymmetric formamidine alkylation. These electrophiles have the potential to disrupt the lithium formamidine chelate and cause the selectivity in the alkylation to be uncharacteristically low. The total synthesis of (+/-)-canadine and (-)-tetrahydropalmatine along with the limitations to the formamidine alkylation technology are delineated herein.