SYNTHESIS OF 12-MEMBERED, 14-MEMBERED, AND 16-MEMBERED PROPARGYLIC ALCOHOLS THROUGH LEWIS ACID-PROMOTED ENE CYCLIZATION

The scope of the Lewis acid-promoted ene cyclization has been expanded to include 12-, 14-, and 16-membered rings. Thus, the ynals 1.8, 2.5, and 3.5 undergo efficient type-I cyclization upon addition to 1.0 equ iv of EtAlCl2 in CH2Cl2 at -78-degrees-C. The epoxy ynal 4.3 undergoes pinacol rearrangement under these conditions. However, treatment with a 1:1 mixture of Et2AlCl and EtAlCl2 effects conversion to the cyclic products 4.4/4.5 (92:8) in satisfactory yield. Facile type-II cycliza tions readily achieved with ynals 5.7, 6.4, 7.6, and 8.3 with EtAlCl2 as the Lewis acid. In the latter case, a 16-membered propargylic alcoh ol was produced in 84% yield.