Domino reaction of 1-3-bis(trimethylsilyloxy)-1,3-dienes with oxalyl chloride: General and stereoselective synthesis of gamma-alkylidenebutenolides

The Lewis acid catalyzed cyclization of oxalyl chloride with 1,3-bis-(trime thylsilyloxy)-1,3-dienes 3, derived from 1,3-dicarbonyl compounds 1, provid es a new and general approach for the synthesis of gamma-alkylidenebutenoli des 4, a pharmacologically and synthetically important class of substances. A variety of butenolides were efficiently prepared in good yields and with very good regio- and stereoselectivities. An up-scaling of the reaction wa s possible. The use of the Lewis acid trimethylsilyl-trifluoromethanesulfon ate (TMSOTf) proved to be superior to other activation conditions. Sterical ly undemanding gamma-alkylidenebutenolides could be prepared alternatively by reaction of the corresponding 1,3-dicarbonyl dianions with N,N'-dimethox y-N,N'-dimethylethanediamide (2d), In contrast to the dianion method, the L ewis acid catalyzed reaction also facilitated the cyclization of sterically hindered, base-labile, cyclic and functionalized substrates. From a method ology viewpoint, the dianion reaction represents the first cyclization of a bis-Weinreb amide and the first cyclization of an oxalic acid-synthon with an ambident dianion. The TMSOTf-catalyzed reactions are both the first cyc lizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes with a C-2 dielectrophil e and the first cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes With 9 carboxylic acid dichloride or a related dielectrophile.