Details

Autor(en) / Beteiligte

• Fässler, Jürg
• McCubbin, J. Adam
• Roglans, Anna
• Kimachi, Tetsutaro
• Hollett, Joshua W
• Kunz, Roland W
• Tinkl, Michael
• Zhang, Yousheng
• Wang, Ruiyao
• Campbell, Michael
• Snieckus, Victor

Titel

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

Ist Teil von

• Journal of organic chemistry, 2015-04, Vol.80 (7), p.3368-3386

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• We report the enantioselective, lateral deprotonation of ortho-protected or functionalized tertiary N,N-dialkyl aryl O-carbamates 5–7 (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 11–13 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 ).