Synlett 2018; 29(02): 181-184
DOI: 10.1055/s-0036-1588578
letter
© Georg Thieme Verlag Stuttgart · New York

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

Ky Mickelsen
Department of Chemistry and Biochemistry, 103 CBB, Montana State University, Bozeman, MT 59717, USA   Email: [email protected]
,
Sean Zabawa
Department of Chemistry and Biochemistry, 103 CBB, Montana State University, Bozeman, MT 59717, USA   Email: [email protected]
,
Tom Livinghouse*
Department of Chemistry and Biochemistry, 103 CBB, Montana State University, Bozeman, MT 59717, USA   Email: [email protected]
› Author Affiliations
Generous financial support from the NIGMS (GM116949) is gratefully acknowledged.
Further Information

Publication History

Received: 29 June 2017

Accepted after revision: 01 September 2017

Publication Date:
12 October 2017 (online)


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

Supporting Information

 
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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 Et2Zn (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).