American Chemical Society
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Highly Enantioselective (−)-Sparteine-Mediated Lateral Metalation-Functionalization of Remote Silyl Protected ortho-Ethyl N,N‑Dialkyl Aryl O‑Carbamates

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journal contribution
posted on 2015-04-03, 00:00 authored by Jürg Fässler, J. Adam McCubbin, Anna Roglans, Tetsutaro Kimachi, Joshua W. Hollett, Roland W. Kunz, Michael Tinkl, Yousheng Zhang, Ruiyao Wang, Michael Campbell, Victor Snieckus
We report the enantioselective, lateral deprotonation of ortho-protected or functionalized tertiary N,N-dialkyl aryl O-carbamates 57 (Scheme ) and meta-protected carbamates 14, 15, and 20 (Schemes and ) by s-BuLi/(−)-sparteine and subsequent quench with a variety of electrophiles to give products 1113 and 16, 17, and 21 in yields up to 96% and enantiomeric ratios up to 99:1. The influence of organolithium reagents, ratio of organolithium/(−)-sparteine pair versus N,N-dialkyl aryl O-carbamate starting materials, temperature, solvents, electrophiles, substituents located ortho or meta to the O-carbamate moiety, and O-carbamate N-substituents was investigated. The identical absolute configuration of the stereogenic center of the major enantiomers of the products, as established by single-crystal X-ray analysis for substrates (S)-11c, (S)-19, and (S)-21a, provides evidence for a consistent stereochemical course in the enantioselective deprotonation. Mechanistic investigations, including an estimate of the configurational stability of the benzyllithium species 9 (starting from 12e; Scheme ) and 23 (starting from 17e; Scheme ), both derived by tin–lithium exchange, and 24 (starting from 20; Scheme ) are reported. The experimental results, together with semiempirical molecular orbital calculations (PM3/SMD), are consistent with a process in which enantioinduction occurs in the deprotonation step (Scheme ).