Regio‐ and Diastereoselective and Enantiospecific Metal‐Free C(sp3)H Arylation: Facile Access to Optically Active 5‐Aryl 2, 5‐Disubstituted Pyrrolidines. Issue 43 (7th September 2015)

• Record Type: Journal Article
• Authors: Haldar, Surajit; Roy, Subhra Kanti; Maity, Bholanath; Koley, Debasis; Jana, Chandan K.
• Is Part Of: Chemistry. Volume 21:Issue 43(2015)
• Page Start: 15290
• Page End: 15298
• Publication Date: 2015-09-07
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201502297
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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<sup>3</sup> 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<sup>≠</sup><inline-formula><alternatives><tex-math notation="tex"><![CDATA[${G{{{\rm S}\hfill \atop {\rm L}\hfill}}}$]]></tex-math><inline-graphic xlink:href="ark:/27927/pgkhm3cdwb" mimetype="image" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></alternatives></inline-formula>=25.6 kcal mol<sup>−1</sup>.</p> </abstract>