1,2-Disubstituted Alkenes as Migratory Insertion Participants in Zn(II)-Promoted Metalloamination/Cyclization of N,N-Dimethylhydrazinoalkenes

Abstract

Diethylzinc-mediated metalloamination/cyclization of unsaturated N,N-dimethylhydrazines has been extended to the use of 1,2-disubstituted alkenes as N-Zn migratory insertion acceptors. Representative 2-arylethenes and vinylcyclopropanes readily serve as reaction participants in metalloamination/cyclization-allylation cascades.

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

“…We have previously reported that stoichiometric CuCN(LiCl) 2 5 is an effective reagent for promoting allylations of the C-Zn bond present in nitrogenous heterocycles of the type 2 . 2a,b In this communication we show that CuBr-SMe 2 , CuCN, and CuI are effective catalysts for allylation at carbon.…”

“…Specific cases include the metalloamination-allylation of 1a to provide pyrrolidines 3a (cis/trans ≥20:1) and 1c to give pyrrolidine 3c (cis/trans = 1:15). 2a As revealed by Table 2, entry 4, facile metalloamination-allyla- tion is also extendible to the formation of piperidines from a Ν , Ν -dimethylhydrazinoalkene that lacks conformational biasing favoring ring closure ( 1d → 3d ).…”

“…1c We have previously advanced a powerful new method for achieving N- C/C-C bond construction by way of simultaneous N-C/C-Zn metalloamination. 2a,b Several laboratories have documented synthetically viable methods for achieving sequential N-C → C-M → C-C bond formation, with the seminal discoveries of the Bower, 3a,b Chemler, 3c,d Knowles 3e-g and Wolfe 3h-k laboratories being major advancements. 4 From a synthetic standpoint, it is significant that virtually all current procedures are limited in the final C-C bond-forming step due to the fleeting nature of their requisite organometallic or free-radical intermediates.…”

“…Upon workup (vide infra) the pyrrolidine 3a (95%, dr ≥ 20:1) was furnished as a clear liquid (which could also be conveniently isolated as the trifluoroacetate salt). Although methallyl chloride had previously been found highly satisfactory as a trapping agent when stoichiometric CuCN(LiCl) 2 2a was used as a promoter, this complex proved much less effective when used as a catalyst (5 mol%) with the less reactive methallyl chloride. In sharp contrast, the use of CuCN(LiBr) 2 admixed with LiBr (1 equiv) led to rapid and highly efficient methallylation (possibly due to an internal Finkelstein activation process).…”

Copper(I)-Catalyzed Cross-Coupling of 1-Bromoalkynes with N-Heterocyclic Organozinc Reagents

“…We have previously reported one such method involving the use of Et 2 Zn in a Zn(II)-mediated metalloamination/cyclization cascade with subsequent electrophilic functionalization ( Scheme 1 ) [ 9 , 10 , 11 ].…”