Synthesis of Oxacycles by Tandem Radical Addition−Cyclization Reactions

Abstract

Abstractβ‐Alkoxyalkylidenemalonates undergo tandem radical addition−cyclization reactions to provide oxacycles of different ring sizes in good chemical efficiency. A variety of nucleophilic radicals participate in the addition−cyclization reactions, and the reaction requires the use of lanthanide triflates as Lewis acids. Compound 9 gave the 5‐exo cyclization product 13 in 80 % yield and greater than 50:1 diastereoselectivity favoring the trans isomer. Radical addition−cyclization reactions using substrate 26, in which the 5‐exo pathway was blocked, gave exclusively the 6‐endo products 27−32 in good yields (68−88 %) and moderate to good selectivity (1.2:1 to 14:1). Generally, 7‐endo cyclization dominated over the 6‐exo mode. Addition of various nucleophilic radicals to substrate 33 using ytterbium triflate as a Lewis acid gave the 7‐endo products 34−39 in moderate to good yield (49−75 %). Substrate 41, in which the 6‐exo pathway was blocked, gave the 7‐endo products 42−47 cleanly. The diastereoselectivities in these cyclizations were dependent on the size of the radical; bulky radicals gave lower selectivities. Radical addition−cyclization using 48 gave the 8‐endo products 49−53 in good yield (58−86 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)