title: Regio- and Diastereoselective and Enantiospecific Metal-Free C(sp(3) )-H Arylation: Facile Access to Optically Active 5-Aryl 2,5-Disubstituted Pyrrolidines.
abstract: Optically active 5-aryl 2,5-disubstituted pyrrolidines are the principal structural moiety of many bioactive compounds including natural products and catalysts for asymmetric synthesis. A highly regio- and diastereoselective and enantiospecific method for direct C-H arylation of aliphatic amine has been developed. Structurally diverse enantiopure arylated pyrrolidines were synthesized from commercially available starting materials, through a single-step three-component reaction under metal- and oxidant-free conditions. Furthermore, the complex analogous structure of CCK antagonist RP 66803 and angiotensin-converting enzyme inhibitors was easily constructed using the synthesized arylated pyrrolidine derivative. Detailed theoretical calculations (M06-2X/TZVPP/SMD//M06-2X/6-31+G(d,p) level) were also carried to investigate the mechanism and high level of stereocontrol involved in this direct sp(3) C-H arylation reaction. Preference for a given regio- and stereoselectivity in the arylated product can be explained through elucidation of the mechanism for dehydration, generating azomethine ylide, and for the final re-aromatization step. The calculated energies reveals that the re-aromatization step is essentially rate determining, accompanying an activation barrier of Δ(≠) G=25.6 kcal mol(-1) .
authors.affiliation: Department Of Chemistry, Indian Institute of Technology Guwahati, Guwahati-781039, Assam (India).
authors.forename: Surajit
authors.initials: S
authors.lastname: Haldar
authors.affiliation: Department Of Chemistry, Indian Institute of Technology Guwahati, Guwahati-781039, Assam (India).
authors.forename: Subhra Kanti
authors.initials: SK
authors.lastname: Roy
authors.affiliation: Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur-741246 (India).
authors.forename: Bholanath
authors.initials: B
authors.lastname: Maity
authors.affiliation: Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur-741246 (India). koley@iiserkol.ac.in.
authors.forename: Debasis
authors.initials: D
authors.lastname: Koley
authors.affiliation: Department Of Chemistry, Indian Institute of Technology Guwahati, Guwahati-781039, Assam (India). ckjana@iitg.ernet.in.
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Jana
keywords: CH activation; amines; arylation; density functional calculations; stereoselectivity