Pd-Mediated Coupling in Organic Synthesis Recent Milestones

Pd-Mediated Coupling in Organic Synthesis Recent Milestones 

Alkynes are usually alkylated under strongly basic conditions. Gregory Fu of MIT recently reported (J. Am. Chem. Soc. 125 13642, 2003) a much milder Pd and Cu mediated coupling, illustrated by the reaction of the terminal alkyne 7 with the alkyl iodide 8 to give 9. Alkyl bromides work equally well. It is exciting that ketones, esters, alkyl chlorides, alkenes, nitriles and acetals are compatible with the procedure. The key to the reaetion is the use of the supporting carbene ligand 10. 

The enantioselective addition of allyl organometallics to carbonyls has become one of the workhorses of organic synthesis. Dennis Hall of the University of Alberta reports (J. Am. Chem. Soc. 125 10160, 200.3) the scandium triflate catalysis chiral allylboronic acids become more effective tools. The best of these, the Hoffmann camphor derivative 2, adds to aldehydes under ScfOTOj catalysis with excellent enantiomeric excess. The reaction works equally well for methallyl, and for the E and Z crotyl boronic acids. The crotyl derivatives react with the expected high diastereocontrol. A limitation to the boronate additions is that branched chain aldehydes give low yields. 

A complementary method for allylation reported (J. Org. Chem. 68 5593, 2003) by Hishashi Yamamoto, now of the University of Chicago, works particularly well with branched aldehydes. The allyl source is the inexpensive allyltrimethoxysilane, with BINAP-complexed Ag ion as the catalyst. Activation of the allylsilane with KF and 18-crown-6 is critical to the success of this reaction, 

Thomas Lectka of Johns Hopkins University has reported (J. Org. Chem. 68 5819, 2003) that benzoylquinine (BQ) catalyzes the two-carbon homologation of a ketene, derived from the acid chloride, with chloroamide such 7, to give the P-amino acid derivative 8 with control of both relative and absolute configuration. The authors suggest that the BQ is involved five times in the course of the transformation of 6 into 8. The two esters of the product are differentiated, so one can imagine, inter alia, reduction of 

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