| There are two major methods of performing radical-anion induced reductive lithiations that result in the cleavage of carbon-heteroatom bonds to produce organolithium compounds. The conventional (PAR) method uses a stoichiometric amount of preformed aromatic radical-anion. The newer catalytic aromatic (CA) method is growing rapidly in popularity and has been claimed to be far more powerful than the PAR method. The CA method uses a large excess of lithium in the presence of a catalytic quantity of the aromatic compound, usually naphthalene or 4,4'-di-tert-butylbiphenyl. It is revealed here that a major disadvantage of the CA method is that at any given temperature, the method is far slower than the PAR method. One other disadvantage of the CA method is that it is very wastesful of lithium metal, the most expensive ingredient used in reductive lithiations since the aromatic can easily be recovered and recycled.;A far more surprising and significant result is that N-phenylaziridine not only does not require naphthalene as a catalyst during its reductive cleavage but the naphthalene is actually an inhibitor of the reductive lithiation.;In collaboration with others, a Pd-catalyzed Zn-ene cyclization, using allyl phenyl sulfones instead of allyl acetates as precursors of allylzincs, was developed for the preparation of five-membered rings bearing adjacent cis vinyl and CH2ZnEt or CHZnEt groups. Also in collaboration with others, this methodology has been used for the total syntheses of the highly physiologically active prostaglandin (±)-15-deoxy-Δ 12,14-PGJ2 in 13 linear steps in 7.7% overall yield and it analog 15-deoxy-9,10-2H-Δ12,14-PGJ 2, and (-)-kainic acid, an extremely neuroexcitatory amino acid that is in great demand for medical research, in sulfone approach by 10 linear steps from commercially available D-serine methyl ester with an overall yield of 11% and in chloride approach by11 linear steps from the same starting material, but with a much higher overall yield of 48%, which is by far the highest of any kainic acid synthesis to date and it can be carried out on the largest scale to date. |
