Regioselective Rhodium-Catalyzed Allylic Alkylation

By 1984, the palladium-catalyzed aUyhc alkylation reaction had been extensively studied as a method for carbon-carbon bond formation, whereas the synthetic utility of other metal catalysts was largely unexplored [1, 2]. Hence, prior to this period rhodium s abihty to catalyze this transformation was cited in only a single reference, which described it as being poor by comparison with the analogous palladium-catalyzed version [6]. Nonetheless, Yamamoto and Tsuji independently described the first rhodium-catalyzed decarboxylation of allylic phenyl carbonates and the intramolecular decarboxylative aUylation of aUyl y9-keto carboxylates respectively [7, 8]. These findings undoubtedly laid the groundwork for Tsuji s seminal work on the regiospecific rho- 

Modem Rhodium-Catalyzed Organic Reactions. Edited by P. Andrew Evans 

Copyright 2005 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30683-8 

Evans and Nelson reexamined the rhodium-catalyzed allylic substitution reaction, in which they demonstrated that a triorganophosphite-modified Wilkinson s catalyst facilitates the allylic alkylation of secondary and tertiary aUyhc carbonates with excellent regioselectivity (Eq. 2). This work provided a convenient method for the construction of ternary and quaternary allylic products [11]. Additionally, they demonstrated that the modification of Wilkinson s catalyst with triorganophosphites serves to increase the re- 

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Evans and Kennedy later combined the regioselective rhodium-catalyzed allylic alkylation, using a-substituted malonates, with ring-closing metathesis for the construction of five-, six-, and seven-membered carbocycles (Scheme 10.2) [13]. The combination of these methodologies allowed for the rapid and flexible assembly of carbocycles possessing vicinal ternary-quaternary or quaternary-quaternary stereogenic centers. 

Tab. 10.3 The scope of the regioselective rhodium-catalyzed allylic alkylation with copper(l) enolates.

Tab. 10.1 Regioselective and enantiospecific rhodium-catalyzed allylic alkylation of enantiomerically enriched allylic carbonates.

Tab. 10.8 summarizes the application of rhodium-catalyzed allylic etherification to a variety of racemic secondary allylic carbonates, using the copper(I) alkoxide derived from 2,4-dimethyl-3-pentanol vide intro). Although the allyhc etherification is tolerant of linear alkyl substituents (entries 1-4), branched derivatives proved more challenging in terms of selectivity and turnover, the y-position being the first point at which branching does not appear to interfere with the substitution (entry 5). The allylic etherification also proved feasible for hydroxymethyl, alkene, and aryl substituents, albeit with lower selectivity (entries 6-9). This transformation is remarkably tolerant, given that the classical alkylation of a hindered metal alkoxide with a secondary alkyl halide would undoubtedly lead to elimination. Hence, regioselective rhodium-catalyzed allylic etherification with a secondary copper(l) alkoxide provides an important method for the synthesis of allylic ethers. 

A combination of rhodium complexes and phosphates promotes a highly regioselective allylic alkylation of unsym-metric allylic esters, where alkylation occurs at the more substituted allylic terminus of the esters (Equation (46)). As Evans and his co-workers reported, both the regio- and stereochemistry of the starting allylic esters are maintained in the allylic alkylated products (Equation (47)). Thus, the rhodium-catalyzed allylic alkylation takes place at the carbon substituted by a leaving group with net retention of configuration. A variety of carbon-centered... 

Regio- and stereoselective rhodium-catalyzed allylic alkylations of chelated amino add ester enolates have been elaborated. Rhodium complexes in comparison with palladium complexes show a different regioselectivity and have less tendency to isomerize (Scheme 19). ... 

The regio- and diastereoselective rhodium-catalyzed sequential process, involving allylic alkylation of a stabilized carbon or heteroatom nucleophile 51, followed by a PK reaction, utilizing a single catalyst was also described (Scheme 11.14). Alkylation of an allylic carbonate 53 was accomplished in a regioselective manner at 30 °C using a j-acidic rhodium(I) catalyst under 1 atm CO. The resulting product 54 was then subjected in situ to an elevated reaction temperature to facilitate the PK transformation. 

The rhodium-catalyzed [5-1-2] cycloadditions have been used in cascade with other processes to synthesize molecules of more complexity in a single operation. The first example was reported by Martin who developed a cascade sequence involving allylic alkylation and [5-1-2] cycloaddition (see (20)) [42,43]. The catalyst [Rh(CO)2Cl]2 could be used to catalyze both the highly regioselective allylic alkylation and the following intramolecular [5-1-2] cycloaddition. As another example, Wender and co-workers combined intermolecular [5-1-2] cycloaddition with... 

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