Iridium-Catalyzed Enantioselective Synthesis of α-Chiral Bicyclo[1.1.1]pentanes by 1,3-Difunctionalization of [1.1.1]Propellane

Songjie Yu, Changcheng Jing, Adam Noble, Varinder K. Aggarwal*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Bicyclo[1.1.1]pentanes (BCPs) have found application as bioisosteres of aromatic rings in drug development. However, catalytic construction of this motif with adjacent stereocenters with high enantioselectivity from readily available starting materials still constitutes a significant synthetic challenge. Herein we report a direct stereoselective synthesis of α-chiral allylic BCPs by 1,3-difunctionalization of [1.1.1]propellane with Grignard reagents and allyl carbonates using iridium catalysis. This mild protocol proceeds via initial organometallic addition to [1.1.1]propellane followed by asymmetric allylic substitution, providing the products with high enantioselectivities over a broad range of substrates. Further derivatization of the products demonstrates the applicability of this method to the preparation of structurally diverse libraries of chiral BCP derivatives.
Original languageEnglish
Pages (from-to)5650-5655
Number of pages6
JournalOrganic Letters
Volume22
Issue number14
Early online date8 Jul 2020
DOIs
Publication statusPublished - 17 Jul 2020

Fingerprint Dive into the research topics of 'Iridium-Catalyzed Enantioselective Synthesis of α-Chiral Bicyclo[1.1.1]pentanes by 1,3-Difunctionalization of [1.1.1]Propellane'. Together they form a unique fingerprint.

Cite this