Stereoselective cyclopropanations via gold(i)-catalyzed retro-buchner reactions

Resumen

The formation of gold(I) carbenes via the retro-Buchner reaction of 7-substituted-1,3,5-cycloheptatriene derivatives has recently emerged as a versatile and safe alternative to, for example, the decomposition of diazocompounds with transition metals. The formation of benzylic gold(I) carbenes and the subsequent cyclopropanation of stilbenes in moderate to good yields with varying diastereoselectivity, and several application of this chemistry in intramolecular Friedel-Crafts-type reactions, and [4+1] cycloadditions with methylenecyclopropanes and cyclobutenes have been reported. A considerable drawback is the elevated temperatures at which the retro-Buchner reaction takes place, putting limitations on the scope and applicability of this transformation. In order to lower the activation energy for the formation gold(I) carbenes, 1-substituted-1a,9b-dihydro-1H-cyclopropa[l]phenanthrene instead of cycloheptatriene derivatives were considered as carbene precursors because of their structural resemblance to norcaradiene, and their know predisposition to release carbenes upon light irradiation. Several derivatives were synthesized bearing distinct electronic functional groups, or configurations. However, the electronic factors had little effect on the reaction temperature, while yields were poor (10 to 25%) throughout the series. The feeble reactivity can be ascribed to the increased C9-C10 double bond character of phenanthrene as opposed to the aromatic character in benzene. Control experiments demonstrated the cyclopropanation of phenanthrene with gold(I) carbenes formed by the retro-Buchner reaction of cycloheptatriene reagents. The difficulty of obtaining the desired cyclopropa[l]phenanthrene derivatives, the poor atom economy and the reduced reactivity led us to discard this method as a viable option. Vinylcyclopropanes constitute an important motif in biologic and synthetic compounds, besides their use as synthetic intermediate -because of their ability to undergo a plethora of rearrangement and cycloaddition reactions- is noteworthy. Allylic gold(I) carbenes (II), formed via the retro-Buchner reaction of alkenyl-cycloheptatriene derivatives, could benefit from enhanced stabilization through the π-system, making their formation easier Indeed, after optimization, a large scope of vinylcyclopropanes was prepared at 75 °C in EtOAc with good yield and excellent cis-selectivity. With a novel Julia-Kocienski reagent, the desired 7-alkenyl-1,3,5-cycloheptatriene derivatives can be prepared from aldehydes and ketones in one step. The versatility applicability of the retro-Buchner reaction was greatly enhanced by the improved reaction conditions and the easy access to the cycloheptatriene derivatives. Similarly good yields were obtained when using N-vinylphthalimide as the olefin partner in the cyclopropanation, although the stereoselectivity was generally lower. The vinyl-aminocyclopropanes constitute their own important class of reagents. The diminished cis-selectivity for the vinyl-aminocyclopropanes and the arylcyclopropanes, prompted us to investigate the reaction pathway with greater detail. Combined experimental and computational studies demonstrated the excellent intrinsic cis-selectivity for the cyclopropanation. Based on DFT calculations, we were able to propose a refined stereochemical model for selectivity in gold-catalyzed cyclopropanation reactions. By combining the knowledge obtained during the investigations on both the scope and mechanism with the olefination approach to form the cycloheptatriene reagents, a novel class of cycloheptatriene derivatives was developed. The substituted cycloheptatriene, the energy barrier for the retro-Buchner reaction was overcome at room temperature, opening the door to enantioselective gold(I)-catalyzed cyclopropanation reactions.