Diethylzinc-Mediated Metalloamination–Alkylation of N,N-Dimethylhydrazinoalkenes. Catalysis of C–Zn Alkylation Using Simple Cu(I) Salts

This manuscript is dedicated to Professor Albert Padwa on the occasion of his 80^th birthday

Abstract

Metalloamination–alkylation of representative N,N-dimethylhydrazinoalkenes has been shown to be effectively catalyzed by ­CuBr·SMe₂, CuCN, and CuI. The current method obviates the use of ­stoichiometric CuCN(LiCl)₂ as a promoter for the electrophilic functionalization event.

Key words

metalloamination–cyclization - Cu(I) catalysis - allylation

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• 9 General Procedure for CuBr·SMe₂-Catalyzed Metalloamination–Allylation An oven-dried J. Young tube under an argon atmosphere was charged with Et_2Zn (50 μL, 2.0 M in BTF, 0.1 mmol, 1.0 equiv), BTF (0.4 mL), and the requisite N,N-dimethylhydrazinoalkene (0.1 mmol, 1.0 equiv). The tube was then placed into an oil bath (of indicated temperature) and metalloamination–cyclization was monitored using BTF as an internal standard (as evidenced by the disappearance of the alkene signals with concurrent emergence of new C–Zn methylene peaks). The temperature of the reactant mixture was subsequently returned to 23 °C for the addition of THT (0.1 mL) followed by the addition of the Cu(I) catalyst (5 mol%). Allyl bromide (4.0 equiv) was then added and its consumption, with simultaneous recession of the intermediate C–Zn methylene resonance, was monitored by No-D proton NMR. Upon completion of allylation, the reactant mixture was dispersed in Et₂O (2 mL) and washed with 1:1 sat. NH₄Cl (aq)/sat. aq NH₄OH (3 × 3mL). The aqueous layers were then extracted with Et₂O (3 mL), and the combined organic layers were dried successively with brine (5 mL) and MgSO₄, and then filtered through a plug of silica. To the ethereal solution was added TFA (8.5 μL, 0.11 mmol, 1.1 equiv), and the mixture was concentrated in vacuo. The resulting salt was triturated with pentane (3 × 1 mL), and the volatiles were removed to provide the cyclization–allylation product (>95%) as a clear viscous oil (which could also be isolated as the mono-TFA salt).