Novel Carbanion-Type Reagents for Organic Synthesis Richard A. Kjonaas, Department of Chemistry and Physics, Indiana State University
The chemo-, regio-, and stereoselective formation of carbon-carbon bonds is perhaps the most challenging aspect of synthetic organic chemistry. Since the early 1980’s I’ve had the privilege of working with a very talented group of graduate and undergraduate students in an effort to make some meaningful progress towards that extremely elusive goal. This talk will focus mainly on two aspects of our work—carboxylate-stabilized enolates and triorganozincate reagents. Carboxylate-stabilized enolates. Our studies aimed at an easily-to-remove enolate stabilizing group led to a new compound, dilithioacetoacetate. The use of this carboxylate- stabilized acetone enolate to convert an alkyl halide to a methyl ketone (eq 1) offers a huge advantage over the classical acetoacetic acid ketone synthesis—it eliminates the need to carry the alkyl moiety through a saponification reaction prior to decarboxylation, thus leading to higher yields and opening up the possibility of having a base-sensitive functional group on R.1
Triorganozincate reagents. It had been reported by Isobe et. al.2 that trialkyl zincate reagents transfer an alkyl group efficiently in a 1,4-fashion to α,β-unsaturated ketones much like the more well-known lithium dialkyl curprate reagents. These zincates offered a distinct advantage over cuprates in that they could be made and used at 0° rather than -78°. However, they also carried a huge disadvantage—only one out of three R groups was transferred and the other two were protonated (destroyed) in the workup. We became very interested in these thermally stable reagents because of the challenge of finding a way to overcome this disadvantage. Thus began our search for non-transferring ligands whose loss would be tolerable (eq 2 and 3).3
1. Kjonaas, R.A.; Patel, D. D. Tetrahedron Lett., 1984, 25, 5467-5468. 2. Isobe, M.; Kondo, S.; Nagasawa, N.; Goto, T. Chem. Lett., 1977, 679-682. 3. Watson, R. W.; Kjonaas, R. A. Tetrahedron Lett., 1986, 27, 1437-1440.