A convergent fragment coupling strategy to access quaternary stereogenic centers. Issue 16 (4th April 2023)

• Record Type: Journal Article
• Authors: Kerkovius, Jeff K.; Wong, Alice R.; Mak, Victor W.; Reisman, Sarah E.
• Is Part Of: Chemical science. Volume 14:Issue 16(2023)
• Page Start: 4397
• Page End: 4400
• Publication Date: 2023-04-04
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2sc07023e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A fragment coupling strategy for the formation of quaternary stereogenic centers in polycyclic systems based upon the semi-pinacol reaction is reported. Abstract : The formation of quaternary stereogenic centers via convergent fragment coupling is a longstanding challenge in organic synthesis. Here, we report a strategy for the formation of quaternary stereogenic centers in polycyclic systems based upon the semi-pinacol reaction. In the key transformation, two fragments of a similar size and complexity are joined by a 1, 2-addition of an alkenyl lithium to an epoxy ketone, and the resulting epoxy silyl ether undergoes a semi-pinacol rearrangement catalyzed by N -(trimethylsilyl)bis(trifluoromethanesulfonyl)imide (TMSNTf2 ) or trimethylsilyl trifluoromethanesulfonate (TMSOTf). Polycyclic scaffolds were generated in high yields and the reaction conditions tolerated a variety of functional groups including esters, silyl ethers, enol ethers, and aryl triflates. This method provides a useful strategy for the synthesis of complex polycyclic natural product-like scaffolds with quaternary stereogenic centers from simplified fragments.