Catalytic Enantioselective C-H Insertions

The development of catalytic, enantioselective C-H insertion reactions has been relatively slow in comparison with the diastereoselective variants described in Section 15.7. It was only in 1990 that McKervey reported the first such example in the context of an intramolecular ring closure (Equation 28) [51]. Exposure of 169 to chiral rhodium catalyst 170 thus afforded 171 in 12% ee. 

The area of intermolecular C-H activation has undergone explosive growth in recent years this can largely be attributed to the use of substituted carbenes in these processes [20]. A pivotal contribution by Davies in 1997 disclosed the first examples of intermolecular enantioselective C-H insertion processes onto simple hydrocarbons such as hexane and cyclopentane (Equation 31) [96], The stabilized carbene generated upon the interaction of Rh catalyst 78 with diazoester 179 underwent effective insertion into the C-H bond of cyclopentane to furnish the adduct 180 in 72 % yield and 96 % ee. 

Davies demonstrated that functionalized substrates including N-Boc-pyrrolidine (181) participated in enantioselective C-H insertion reactions to give products such as 182 in 94% ee and 96 4 dr (Equation 32) [97]. 

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