Stereoselective synthesis of cyclic ethers using vinylogous sulfonates as radical accepters: Effect of E/Z geometry and temperature on diastereoselectivity

Treatment of the E-vinylogous sulfonates 1a-g with tris(trimethylsilyl)sila ne and triethylborane, in the presence of air, furnished the cyclic ethers 2/3a-g with good to excellent diastereoselectivity favoring the cis-isomer 2. This study demonstrated the level of stereocontrol in a 6-exo radical cy clization and may be attributed to the type of radical intermediate. Hence, the modest selectivity obtained for the cyclization of le may be a functio n of the acyl radical geometry (sp(2)) and high inversion barrier (29 kcal/ mol) as compared to the alkyl (1 kcal/mol) and vinyl (2.9 kcal/mol) radical s. This is consistent with the acyl radical cyclization having an earlier t ransition state than the corresponding alkyl and vinyl radicals. The modest diastereoselectivity can be improved dramatically using the Z-vinylogous s ulfonate (greater than or equal to 34:1; R = Ph) to promote kinetic trappin g of the s-trans rotamer I and III, respectively (Figure 1). The 5-exo alky l radical cyclization reaction under nonreductive Keck-allylation condition s was also examined, in which 8 was formed in 91% overall yield. This trans formation provides a convenient method for in situ homologation and should be applicable to target directed synthesis.