TOTAL SYNTHESIS OF (+)-LAURENCIN - USE OF ACETAL-VINYL SULFIDE CYCLIZATIONS FOR FORMING HIGHLY FUNCTIONALIZED EIGHT-MEMBERED CYCLIC ETHERS

摘要

The enantioselective total synthesis of (+)-laurencin (1) is accomplished in 24 steps from allyl alcohol. The synthesis features an acetal-vinyl sulfide cyclization that forms the oxocene ring and introduces, with complete control, the Delta(4) unsaturation and requisite functionality at carbons 3, 4, and 9. Starting with allyl alcohol, mixed acetal 17 is constructed in seven steps and 38% overall yield (Scheme 2). Exposure of 17 to excess BF3 . OEt(2) in t-BuOMe at -70 --> -40 degrees C affords Delta(4)-oxocene 27 in 55-65% yield (Scheme 4). Removal of the phenylthio group, followed by elaboration of the C(9) side chain and introduction of bromine at C(4), completes the construction of (+)-laurencin (Schemes 4 and 5). [References: 40]