Alkylzinc reagents, Negishi coupling

A salient feature of the Negishi coupling is that the reaction also works for alkylzinc reagents. This could be exploited in the design of alkylpyridine syntheses. 

Total synthesis of (+)-pumiliotoxin A (39) has been achieved based on the Negishi coupling of the alkylzinc chloride 37, derived from the alkyl iodide, with the alkenyl iodide 38 at room temperature, and subsequent deprotection [58], The alkylzinc reagent 41 was prepared conveniently by the reaction of the alkyl iodide 40 with Zn/Cu couple, and treated with 2-iodoimidazole 42 to afford the adduct 43 [47],... 

Scheme 3.62 Use of PEPPSI-IPr precatalyst in the Negishi alkyl-alkyl coupling with alkylzinc reagents [235].

Fu et al. reported Ni-catalyzed alkyl-alkyl cross-couphng reactions of diverse alkylzinc reagents with unactivated secondary alkyl halides under very mild conditions. Ni(cyclooctadiene)2 and sBu-pyridine-bis(oxazohne) (Pybox) catalyzed the Negishi coupling of various functional alkyl bromides and iodides at room... 

The total synthesis of fluvirucinine A1 127 provides a powerful illustration of the utility of Fu s methodology in natural product synthesis (Scheme 13.34). The asymmetric Negishi reaction of racemic allylic chloride 122 with alkylzinc bromide 123 in the presence of Ni/Pybox catalyst system provided ester 124 in 93% yield and 96% ee. After few steps, the organozinc reagent of bromide 125 was subjected to a second Negishi reaction with chloride 122 under identical coupling conditions to furnish derivative 126 in 80% yield and excellent enantioselectivity. 

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