Improved Synthesis of the Benzyne Precursor 2-(Trimethylsilyl)phenyl Trifluoromethanesulfonate

Abstract

An alternate procedure for the preparation of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate, a coveted benzyne precursor, is described. Modifications to existing methods result in a dramatic reduction in the overall reaction time and eliminate the use of organolithium reagents. This new procedure proceeds in four steps in 81% overall yield from 2-chlorophenol.

A simple method for N-arylation of secondary amides/amines through a NaH-initiated aryne generation strategy

“…Alternatively, Kobayashi's o -silylaryl triflate/fluoride salt protocol could generate arynes in a mild and controlled manner and thus was widely applied in organic synthesis (Scheme 1b, right). 12 d However, the synthetic route to obtain o -silylaryl triflate is tedious, 16 which restricts its practical application, particularly in an industrial setting.…”

Scalable Transition-Metal-Free Synthesis of Aryl Amines from Aryl Chlorides through X@RONa-Catalyzed Benzyne Formation

“…Apparently, the o -silylaryl triflate and other newly emerged benzyne precursors all require laborious prefunctionalization. − On the other hand, aryl chlorides are arguably the simplest benzyne precursors, but their applications were unfortunately limited by high cost, harsh conditions, and potential safety hazards of conventional elimination protocols. − Recent breakthroughs disclosed that NaH could be implemented as a mild and inexpensive base to produce benzyne from o- diiodobenzenes . However, in these methods, prefunctionalized precursors were still necessary.…”