Au(I)-catalyzed enantioselective 1,3-dipolar cycloadditions of münchnones with electron-deficient alkenes.

Synthetic methods relying on gold complexes as catalysts have recently been the focus of intense development.1 Despite numerous advances, relatively few enantioselective gold-catalyzed transformations have been described. The earliest example of an enantioselective gold(I)-catalyzed transformation, the Hayashi-Ito aldol reaction, was proposed to rely on activation of the nucleophile as a chiral monophosphineAu(I) enolate.2 In contrast, the majority of recently reported methods rely on the electrophilic nature of cationic bisphosphinegold(I) complexes to activate π-bonds toward addition of nucleophiles.3 Therefore, the utility of chiral bisphosphinegold(I) complexes would be signficantly extended if they could be employed as catalysts for enantioselective transformations that are not predicated on π-bond activation. To this end, herein we describe the development of a bisphosphinegold(I)-catalyzed enantioselective 1,3-dipolar cycloaddition4 reaction of mesoionic azomethine ylides (münchnones) with alkenes. We were inspired by Tepe’s recent report of silver(I)acetatecatalyzed münchnone/alkene 1,3-dipolar cycloadditions,5,6 to consider the use of our recently developed bisphosphinegold(I) carboxylate complexes as catalysts for this transformation.3c Gratifyingly, treatment of a THF solution of azlactone 1a and 1.5 equiv of N-phenylmaleimide (3) with 2 mol % triphenylphosphinegold(I) benzoate at room temperature, followed by in situ esterification, afforded the desired ∆1-pyrroline (()-2a in 85% yield with excellent diastereoselectivity (Table 1, entry 1). Having established an achiral phosphinegold(I) benzoate as a catalyst for the formation for 2a, we next focused on the enantioselective reaction of 1a and 3 (Table 1). In general, the diphenyl-substituted biarylphosphinegold(I) benzoate complexes successfully employed in the hydroamination gave modest selectivity for the reaction of 1a and 3 (entries 2-5). While substitution on the phosphine aryl ring resulted in improved selectivity (entry 8), we were pleased to find the (S)-Cy-SEGPHOS(AuOBz)2 (4)7-catalyzed cycloaddition gave 2a with a notable increase in enantioselectivity (88% ee) (entry 9). Further optimization of reaction conditions revealed that the reaction performed similarly in various solvents;8 however, employing fluorobenzene (PhF) as the solvent produced a further improvement and provided 2a in 76% yield and 95% ee (entry 10).9 Notably, in all cases only the exo-adduct was observed.