Cyclizations via Palladium‐Catalyzed Allylic Alkylations [New Synthetic Methods (79)]

Abstract

The history of ring systems in organic chemistry parallels their synthetic accessibility. Transition-metal-catalyzed cyclizations offer a new opportunity to create carbo-and heterocyclic compounds with great facility. Among these methods, allylic alkylations catalyzed by palladium have proven unusually productive because of the extraordinary chemo-, regio-, and diastereoselectivity and the continuing possibility for the development of enantioselectivity. The rules for ring closure differ from those for non-transition-metal-catalyzed reactions. A major benefit is the ability to generate medium (eight-, nine-, ten-, and eleven-membered) and large rings in preference to normal (five-, six-and seven-membered) rings. With the appropriate substrate, efficient macrocyclizations are possible under conditions of normal concentrations. A second major benefit derives from the complementary stereochemistry of the metalcatalyzed substitution (net retention of configuration) compared to non-metal-catalyzed reactions (inversion of configuration). Further, the requirement for the substrate to conform to the transition-metal template may impose a stereochemical preference in the intermediate that ultimately translates into the thermodynamically less stable organic product regardless of the stereochemistry of the starting material. While more work has focused on carbocyclic synthesis, the possibilities for heterocyclic synthesis are just beginning to be tapped. In addition to forming heterocycles by C-C bond formation, use of a heteroatom as a nucleophile has already proven effective for oxygen and nitrogen, with other nucleophiles awaiting investigation. New dimensions for cyclization via allylic alkylation arise by generating the requisite 7r-allylpalladium intermediates by methods other than palladium(0)-initiated allylic ionizations. In addition, metals other than palladium will clearly expand the possibilities, but as yet remain untapped.

A versatile synthetic approach to grandisol monoterpene pheromone

“…Unfortunately, upon cyclization of 3 in the presence of Pd(0) and PPh 3 in CH 2 Cl 2 , we obtained cyclohexene 10 as a sole product (entry 1). This result was likely due to the preferred 6-endotrig cyclization rather than the desired 4-exo-trig cyclization (Trost, 1989) leading to the purposed cyclobutane 9. Our effort for the improved results including regioselctivity is summarized in Table I.…”

“…The Pd(0)-catalyzed intramolecular alkylations of allylic carbonate have been considered as one of the effective synthetic methods to prepare carbocycles with high chemo-, regio-and stereo-selectivity (Trost, 1989). Recently, we have been working on regio-and stereoselective synthesis of cyclohexanes and cyclopentanes via Pd(0)-catalyzed intramolecular alkylation of the corresponding allylic carbonates (Suh et al, 2000).…”

Vinylepoxides in Organic Synthesis

“…Palladium-catalyzed allylic alkylation of these substrates with soft carbon nucleophiles (pK a 10-20) proceeds under neutral conditions and with excellent regioselectivities [103,104]. The sulfone 51, for example, was cyclized through the use of catalytic amounts of Pd(PPh 3 ) 4 and bis(diphenylphosphino)ethane (dppe) under high-dilution conditions to give macrocycle 52, an intermediate in a total synthesis of the antitumor agent roseophilin, in excellent yield (Scheme 9.26) [115,116].…”

Palladium-catalyzed approach to the synthesis of five-membered O-heterocycles

“…The intra-and intermolecular carbon-heteroatom bond forming reactions using alkenyl epoxides and aziridines have been utilized for the synthesis of heterocyclic compounds [249,250]. There are two major processes for the preparation of heterocycles using these substrates, as illustrated in Scheme 120: (a) intramolecular allylation of alkenyl epoxides and aziridines with Y-H and (b) intermolecular cycloaddition of vinyl epoxides and aziridines with the heterocumulenes, such as isocyanates, carbodiimides, and isothiocyanates [251][252][253][254][255]13].…”