Total Synthesis of (±)-Galanthamine via a C3-Selective Stille Coupling and IMDA Cycloaddition Cascade of 3,5-Dibromo-2-pyrone

Abstract

A new efficient synthetic route to (+/-)-galanthamine was devised by using a tandem C3-selective Stille coupling-IMDA cascade of 3,5-dibromo-2-pyrone as a key strategy.

Cyclopropanation of Some Alkaloids

“…14,15-Dihydrovindoline (11) is known from the literature [48], and was obtained by catalytic hydrogenation of vindoline (8). Analogously with the previous reaction, bromination of the saturated derivative 11 resulted in 10-bromo-14,15-dihydrovindoline (12). The cyclopropane ring was built into position 14,15 by a typical Simmons-Smith reaction from 10-bromovindoline (10) using diethylzinc and diiodomethane, yielding compound 13.…”

Inverse‐Electron‐Demand Diels–Alder Reactions of 2‐Pyrones: Bridged Lactones and Beyond

“…The intramolecular IEDDA reaction of 5‐bromo‐3‐aryl‐2‐pyrone bearing a vinyl group on the aryl ring was investigated by Cho and co‐workers, and used for the synthesis of (±)‐narwedine, (±)‐lycoraminone and (±)‐galanthamine [39] . Under thermal conditions, the regioselective Stille coupling of 3,5‐dibromo‐2‐pyrone 140 with aryltin 232 allowed to furnish tetracyclic lactones endo ‐ 233 and exo ‐ 233 directly rather than the expected Stille coupling product.…”

Recent Advances in the Synthesis of 2-Pyrones

“…Based on the cumulative information on the reactivity of 3,5-dibromo-2-pyrone ( 143 ), several excellent total syntheses of complex natural products including (±)- trans -dihydronarciclasine [ 76 , 77 ], (±)-crinine [ 78 , 79 ], (±)-crinamine [ 78 ], (±)-pancratistatin [ 80 , 81 ], (±)-galanthamine [ 82 ], (±)-aspidospermidine [ 83 ], (±)-joubertinamine [ 84 ], (±)-lycorane [ 85 , 86 ], etc. , have been accomplished.…”