Stereoretentive Pd-catalysed Stille cross-coupling reactions of secondary alkyl azastannatranes and aryl halides

Abstract

The development of transition metal-catalysed cross-coupling reactions has greatly influenced the manner in which the synthesis of complex organic molecules is approached. A wide variety of methods are now available for the formation of C(sp(2))-C(sp(2)) bonds, and more recent work has focused on the use of C(sp(3)) electrophiles and nucleophiles. The use of secondary and tertiary alkyl nucleophiles in cross-coupling reactions remains a challenge because of the propensity of these alkyl groups to isomerize under the reaction conditions. Here, we report the development of a general Pd-catalysed process for the stereoretentive cross-coupling of secondary alkyl azastannatrane nucleophiles with aryl chlorides, bromides, iodides and triflates. Coupling partners with a wide range of electronic characteristics are well tolerated. The reaction occurs with minimal isomerization of the secondary alkyltin nucleophile, and with retention of absolute configuration. This process constitutes the first general method to use secondary alkyltin reagents in cross-coupling reactions.

Single-electron transmetalation in organoboron cross-coupling by photoredox/nickel dual catalysis

“…Nearly all cross-coupling reactions of stereo-defined nucleophiles reported heretofore have demonstrated the transmetalation event to be stereospecific (32). Thus, enantioenriched products may only be accessed from nonracemic and configurationally stable organometallic reagents, which are often difficult to access.…”

Single-Electron Transmetalation: An Enabling Technology for Secondary Alkylboron Cross-Coupling

“…10 However, their lack of both atom economy and commercial availability would appear to inhibit their widespread adoption, particularly given the perceived toxicity of organostannanes.…”

Enantiospecific sp2–sp3 coupling of secondary and tertiary boronic esters

“…[20][21][22] and the stereospecific cross-coupling of chiral secondary benzylethers. 23,24 Our alternative strategy has centred on utilizing the readily accessible, stereo-defined, secondary boronic esters.…”