Asymmetric lithiation trapping of N-Boc heterocycles at temperatures above -78 °C
Giacomo Gelardi1, Graeme Barker, Peter O'Brien
1Department of Chemistry, University of York , Heslington, York YO10 5DD, U. K., and Neusentis Chemistry, Pfizer Worldwide Research and Development , The Portway Building, Granta Park, Cambridge CB21 6GS, U. K.
Abstract:
The asymmetric lithiation trapping of N-Boc heterocycles using s-BuLi/chiral diamines at temperatures up to -20 °C is reported. Depending on the N-Boc heterocycle, lithiation is accomplished using s-BuLi and (-)-sparteine or the (+)-sparteine surrogate in the temperature range -50 to -20 °C for short reaction times (2-20 min). Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered functionalized N-Boc heterocycles in 47-95% yield and 77:23-93:7 er. With N-Boc pyrrolidine, trapped products can be generated in ∼90:10 er even at -20 °C.
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