Allyltrimethoxysilane Addition to N-Acylhydrazones: Two Catalytic Methods Employing CuCl and Fluoride

Abstract

Two alternative reaction conditions developed for allyl­trimethoxysilane addition to N-benzoylhydrazones enable efficient and versatile access to homoallylic α-branched amines. Aldehyde hydrazones, both aromatic and aliphatic, and ketone hydrazones all give good yields. One set of conditions employs catalytic amounts of CuCl and tetrabutylammonium triphenyldifluorosilicate (TBAT); improved yields and reaction times are obtained at 80 °C in the presence of bis(diphenylphosphino)ethane (dppe) and t-BuOH as additives. The second set of conditions employs 20 mol% TBAT as a fluoride source in a metal-free catalytic system; here t-BuOH offers only modest improvement, and ambient temperatures are optimal. For example, under this second set of conditions, the N-benzoylhydrazone from ethyl pyruvate affords the homoallylic tert-alkyl amine adduct in 78% yield.

Key words

addition reactions - allylation - catalysis - hydrazones - silicon

References

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• 10a

  Some control experiments were examined in order to obtain evidence about the roles of the reagents. First, hydrazone 1 was mixed with the CuCl and t-BuBOX ligand for 2 h, followed by addition of a mixture of allyltrimethoxysilane and TBAT; no reaction occurred. Under conditions otherwise identical to the first control experiment, additional CuCl was included in the silane mixture; still there was no reaction. On the other hand, including both CuCl and dppe in the silane mixture restored the reactivity, affording 2 in 67% yield. These experiments suggest that the main role of CuCl is in generating the active nucleophilic species, not as a Lewis acid activator of the benzoylhydrazone. The phosphine may serve as a stabilizing ligand within a Cu-containing allyl nucleophile; the exact identity of this nucleophile is unclear. Shibasaki has suggested an allylcopper or an allylsilicate-Cu⁺ ion pair (ref.⁶).

• 10b

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9

In combination with t-BuOH as proton source, the yield with t-BuBOX improved to 51%, but the enantioselectivity decreased to only 1.8% ee.

14

Proton transfer would convert 8 to a more stable amide anion, which could react with allyltrimethoxysilane at the amide oxygen. This O-silylation pathway for the autocatalysis is consistent with the complete absence of reactivity when the proton transfer is blocked by N-methylation (see ref.^10b).