Synthesis of 12-, 14-, and 16-Membered Propargylic Alcohols through Lewis Acid-Promoted Ene Cyclization

Article abstract of DOI:10.1021/jo00067a024

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 equiv of EtAlCl2 in CH2Cl2 at -78 deg 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 cyclizations were 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 alcohol was produced in 84percent yield.