TOTAL SYNTHESIS OF (-LAURENCIN - USE OF ACETAL-VINYL SULFIDE CYCLIZATIONS FOR FORMING HIGHLY FUNCTIONALIZED 8-MEMBERED CYCLIC ETHERS())

The enantioselective total synthesis of (+)-laurencin (1) is accomplis hed in 24 steps from allyl alcohol. The synthesis features an acetal-v inyl sulfide cyclization that forms the oxocene ring and introduces, w ith complete control, the Delta(4) unsaturation and requisite function ality at carbons 3, 4, and 9. Starting with allyl alcohol, mixed aceta l 17 is constructed in seven steps and 38% overall yield (Scheme 2). E xposure 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 a nd introduction of bromine at C(4), completes the construction of (+)- laurencin (Schemes 4 and 5).