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Lithium Carbenoids−Ultra-Reactive Yet Selective Reagents for Methylenation and Halomethylenation of Sulfones1

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journal contribution
posted on 21.07.2006, 00:00 authored by Bruce A. Pearlman, Sterling R. Putt, Jeffrey A. Fleming
The first efficient, one-pot method for methylenation of p-toluyl sulfones (i.e., the transformation of p-MePhSO2CHR2 into R2CCH2) is described. Methods for effecting that transformation involving alkylation of sulfones with reagents of the general formula MCH2X, where M = SiMe3, SnR3, and MgCl (the Julia method) have been previously described. However, the silicon reagent is completely unreactive toward many sulfones, the tin reagent typically affords only moderate yields, and the magnesium reagent typically gives incomplete reaction (9−40% starting material). This article reports that excellent yields are obtained by alkylating the sulfone with the more ionic lithium methylene carbenoids (LiCH2X, where X = Cl, Br, and I). For example, treatment of sulfone 1 with 3 equiv of n-BuLi (THF, −100 °C) followed by 2 equiv of CH2Br2 affords olefin 2 in 96% yield. Although the carbenoid is generated in the presence of a 1:2 mixture of α-lithio-sulfone and n-BuLi, it reacts selectively with the α-lithio-sulfone (Krel = 9.6 ± 0.8 with LiCH2Br). The chlorocarbenoid LiCH2Cl reacts somewhat less selectively (Krel = 3.5). The alkyl-substituted carbenoid n-BuCHBrLi reacts ≥ 40 times more slowly than LiCH2Br, suggesting that olefination occurs by the SN2 mechanism rather than by metal-assisted ionization (MAI), the mechanism by which cyclopropyl and vinylidene carbenoids react with nucleophiles. Finally, sulfones can be transformed into vinyl halides by treatment with 3 equiv of n-BuLi (THF, −78 °C), followed by >2 equiv of diisopropylamine, followed by 3 equiv of dihalomethane (CH2X2, where X2 = Cl2, BrCl, Br2, or I2). All products are formed in high yield and purity.

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