Spurring Radical Reactions of Organic Halides with Tin Hydride and TTMSS Using Microreactors

Abstract

Tributyltin hydride-mediated radical reactions of organic halides were successfully carried out in a continuous flow system using a microreactor. The reactions proceeded within a very short period of time, coupled with quickly decomposing radical initiators such as V-65 and V-70. The continuous flow reaction system was applied to gram scale synthesis of a key intermediate for furofuran lignans.

Modern Developments in Aryl Radical Chemistry

“…Within a larger study on tin hydride and tris(trimethylsilyl)silane-mediated reactions, the continuous flow system has also been applied to conduct an intramolecular Meerwein reaction. The cyclization of bromide 6 to indane 7 was completed in less than 1 min (Scheme 3) [39]. Concerning the substrates suitable for intramolecular Meerwein reactions, several studies on ring strain [40], regioselectivity [41], undesired hydrogen transfer [42], and unusual cyclization modes [43,44] have been reported.…”

“…This cyclization type has been successfully applied in the synthesis of protoberberines and the pavine alkaloids. Argemonine (39) was obtained from a 6-exo cyclization of 40 passing through a well-stabilized benzylic radical (Scheme 15). Scheme 11 Synthesis of the cephalotaxine core structure 29 [81] Modern Developments in Aryl Radical Chemistry…”

Continuous‐flow syntheses of heterocycles

“…Radical reactions of organic halides with either tin hydride or tris(trimethylsilyl)silane and radical initiators such as V-40, V-65, V-70, or AIBN were carried out in a chip microreactor by Ryu and coworkers [19]. On a gram scale, a tetrahydrofuran derivative-a key intermediate for the synthesis of the naturally occurring furfuran lignans paulowin and samin-was prepared in a 185-min run, providing 7.6 g (74%) of the desired product (Scheme 7).…”

Microreactor Technology in Lithium Chemistry

“…Short residence time in a microchannel is beneficial for controlling highly reactive and unstable intermediates. By taking advantage of such features of flow microreactors, various reactions for organic synthesis and polymer synthesis have been developed [25][26][27][28][29][30][31][32][33].…”