DIRECT FORMATION AND SUBSEQUENT SUBSTITUTION OF REMOTE KETONE-FUNCTIONALIZED ORGANOCOPPER REAGENTS

Remote ketone-functionalized aryl- and alkylcopper reagents have been synthesized by the use of a highly activated form of zero-valent copper. 5-Bromo-2-pentanone and 4-iodobenzophenone undergo oxidative addition with activated copper to form 5-cuprio-2-pentanone and 4-cupriobenzophenone, respectively. These, in turn, can be cross-coupled with alkyl halides to produce the corresponding alkylated ketones and with acid chlorides to form the corresponding diketones. By use of this methodology, a two-step, one-pot synthesis of methyl (E)-9-oxo-2-decenoate and 8-nonen-2-one have been achieved. The former compound is the methyl ester of the ''queen substance'' of the honey bee, and the latter is part of an ''attractant mixture'' for cheese mites found in cheddar cheese. These syntheses were accomplished by converting commercially available 6-bromo-2-hexanone to 6-cuprio-2-hexanone followed by cross-coupling with commercially available methyl 4-bromocrotonate and allyl bromide, respectively.