title: Highly enantioselective (-)-sparteine-mediated lateral metalation-functionalization of remote silyl protected ortho-ethyl N,N-dialkyl aryl O-carbamates.
abstract: We report the enantioselective, lateral deprotonation of ortho-protected or functionalized tertiary N,N-dialkyl aryl O-carbamates 5-7 (Scheme 2 ) and meta-protected carbamates 14, 15, and 20 (Schemes 5 and 7 ) 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 8 ) and 23 (starting from 17e; Scheme 9 ), both derived by tin-lithium exchange, and 24 (starting from 20; Scheme 9 ) 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 11 ).
authors.affiliation: †Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Jürg
authors.initials: J
authors.lastname: Fässler
authors.affiliation: †Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: J Adam
authors.initials: JA
authors.lastname: McCubbin
authors.affiliation: †Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Roglans
authors.affiliation: †Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Kimachi
authors.affiliation: ‡Department of Chemistry, University of Winnipeg, Winnipeg, Manitoba R3B 2E9, Canada.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Hollett
authors.affiliation: #Institute of Organic Chemistry, University of Zurich, Winterthurerstr. 190, CH-8057 Zurich, Switzerland.
authors.forename: Roland W
authors.initials: RW
authors.lastname: Kunz
authors.affiliation: †Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Tinkl
authors.affiliation: †Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: †Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Ruiyao
authors.initials: R
authors.lastname: Wang
authors.affiliation: ⊥Thunder Bay Regional Research Institute, 980 Oliver Road, Thunder Bay, Ontario P7B 6V4, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Campbell
authors.affiliation: ∥Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Victor
authors.initials: V
authors.lastname: Snieckus
mesh_terms: D002219:Carbamates / Q000737:chemistry*; D018360:Crystallography, X-Ray; D018020:Lithium Compounds / Q000737:chemistry*; D015394:Molecular Structure; D012821:Silanes / Q000737:chemistry*; D013034:Sparteine / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D002219:Carbamates; D018020:Lithium Compounds; D012821:Silanes; D013034:Sparteine