| A novel, mild, and general copper-assisted cycloisomerization of alkynyl imines into 1,2- and 1,2,4-trisubstituted pyrroles has been developed. This methodology was successfully employed for the cycloisomerization of heterocyclic alkynyl imines to produce fused pyrroloheterocycles. Mechanistic studies strongly supported the involvement of a base-assisted isomerization of the alkynyl imine into an allenyl imine intermediate. Experiments with deuterated substrates showed significant scrambling during cycloisomerization, thus supporting an ionic rather than carbenoid pathway for this reaction.; Cascade [3,3]-, 1,2-, and [3,3]/1,2-migration/cycloisomerization methodologies towards multisubstituted furans have been developed. Thus, employment of propargylphosphatyloxy alkynyl ketones led to the synthesis of 3-phosphatyloxy furans through a copper-catalyzed [3,3]-migration/cycloisomerization sequence. Employment of propargylacyloxy alkynyl ketones led to the discovery of a novel 1,2-acyloxy migration in allenes, which, when incorporated into the cycloisomerization cascade, allowed for efficient synthesis of 3-acyloxyfurans. Further studies allowed for the development of a silver-catalyzed [3,3]/1,2-migration/cycloisomerization of acyloxy, tosyloxy, and phosphatyloxy propargyl ketones to afford tetrasubstituted furans. Furthermore, development of methods toward 3-halofurans via the gold-catalyzed 1,2-halogen migration/cycloisomerization cascade of haloallenyl ketones has been accomplished. The use of complementary catalytic systems allowed for regiodivergent synthesis of 2- or 3-halofurans from ambident terminal haloallenyl ketones. Mechanistic investigations supported halogen migration through a halirenium intermediate, caused by activation of the enone moiety by oxophilic Au(III) catalyst during cycloisomerization towards 3-halofurans. In contrast, deuterium experiments supported the involvement of a gold carbenoid intermediate for the synthesis of 2-halofurans employing Au(I) catalyst. The development of the different cycloisomerization methodologies allowed for the synthesis of very diversely substituted, functionalized furans, important building blocks in synthetic organic chemistry. |
