Copper(I)‐Mediated Highly Stereoselective syn‐Carbometalation of Secondary or Tertiary Propargylic Alcohols with Primary Grignard Reagents in Toluene with a High Linear Regioselectivity

Abstract

Abstract:A highly regio-and stereoselective syn-carbometalation of terminal secondary or tertiary propargylic alcohols with primary alkyl Grignard reagents in toluene or phenylmagnesium bromide in Et 2 O was developed, in which the alkyl or phenyl group from the Grignard reagents is introduced into the terminal position of the alcohols. The organometallic intermediate formed may be used directly for the coupling reaction with organic halides. Upon treatment with I 2 after the carbometalation, iodides may be obtained, which may undergo Sonogashira coupling reaction and highly stereoselective Novozym-435-catalyzed kinetic resolution to afford the optically active products.

Copper mediated carbometalation reactions

“…The first example shows the effect of a chelating tertiary metal alcoholate to direct the copper into the α-position to afford the linear product 3 (eqn (1), Scheme 3). 16 When the alcohol is slightly further away and protected by a TMS group, it acts as a blocking group providing the normal branched product 4 (eqn (2)). 17 Eqn (3) shows the exceptional but highly important case of primary propargylic alcohol which undergoes unexpected trans allyl-addition to provide the branched product 5 (eqn (3)).…”