Twofold Radical-Based Synthesis of N,C-Difunctionalized Bicyclo[1.1.1]pentanes

Abstract

Bicyclo[1.1.1]pentylamines (BCPAs) are of growing importance to the pharmaceutical industry as sp 3 -rich bioisosteres of anilines and N-tert-butyl groups. Here we report a facile synthesis of 1,3-disubstituted BCPAs using a twofold radical functionalization strategy. Sulfonamidyl radicals, generated through fragmentation of α-iodoaziridines, undergo initial addition to [1.1.1]propellane to afford iodo-BCPAs; the newly formed C−I bond in these products is then functionalized via a silyl-mediated Giese reaction. This chemistry also translates smoothly to 1,3-disubstituted iodo-BCPs. A wide variety of radical acceptors and iodo-BCPAs are accommodated, providing straightforward access to an array of valuable aniline-like isosteres.

Multicomponent Direct Assembly of N-Heterospirocycles Facilitated by Visible-Light-Driven Photocatalysis

“…The residue was then subjected to flash chromatography to yield the desired sulfonamide. The literature data for compounds 1h , 1i , and 1ai matched the data obtained using this procedure.…”

Synthesis and Biological Evaluation of Bicyclo[1.1.1]pentane-Containing Aromatic Lipoxin A4 Analogues

“…Inspired by recent work reported by Anderson, − we believed the key BCP moiety could be readily installed via a triethylborane-initiated atom transfer radical addition (ATRA) reaction between α-iodoketone 12 or 15 and [1.1.1]­propellane ( 13 ).…”

Radical Multicomponent Alkyl Alkynylation of Propellane via Synergistic Photoredox and Copper Catalysis

“…Given its practicality and importance, many examples regarding the synthesis of monosubstituted- and 1,3-disubstituted-BCP-containing compounds have been reported . Generally, these molecules are synthesized through the processes of [1.1.1]­propellane attacked by radical additions, one-pot organometallic addition/electrophilic trappings, and one-pot organometallic addition/metal-catalyzed cross-coupling reactions. , While these methods have significantly extended the synthetic accessibility of BCP motifs, developing new convenient procedures that allow for the rapid construction of structurally complex and diverse drug-like BCPs is still highly desirable.…”