| Abstract: | A study of the use of nitrogen stabilized carbanions in carbon-carbon bond forming reactions has been performed. Two aspects of asymmetric synthesis have been examined: (1) The dynamic structure of azaallylmetal reagents and implications for asymmetric electrophilic carbon-carbon bond formation and (2) The combined use of enzymatic and chemical catalysis using nitroparaffins as starting materials for the synthesis of optically pure compounds. The barrier to carbon-carbon bond rotation as determined by dynamic ¹H NMR, has been determined for a number of simple azaallylmetal reagents. Deprotonation of the acetaldehyde imine 1, followed by transmetalation with magnesium, aluminum, and zinc reagents allowed the preparation of 4, 5, and 6. The barrier to carbon-carbon bond rotation in these reagents was found to be 14.5, 14.2, and [greater than or equal to]19 kcal/mol, respectively. Electrophilic substitution of nitroalkanes and α-nitroesters using carbon electrophiles allowed the preparation of a variety of biologically significant compounds. The Michael addition of nitroalkanes to Michael acceptors was found to be efficiently catalyzed by KF adsorbed on basic alumina. α-Nitropropanaote esters were converted to a number of α-methyl amino acid precursors by treatment with carbon electrophiles. The enzymatic resolution of the 4- and 2-nitroesters was effected by the esterase catalyzed transesterification of hydrolysis of these esters. The 4-nitroesters were transesterified with octanol using porcine pancreative lipase, allowing the isolation of 22 in 28% yield with an optical purity of 57%. The chymotrypsin catalyzed hydrolysis of the α-methyl amino acid precursors 40, 43, 45, 49, 50, and 51 allowed the isolation of these esters in optical purities ranging from 85-[greater than or equal to]95% e.e. after 60% hydrolysis. It was found that chymotrypsin catalyzed the hydrolysis of the D-α-nitropropanoate ester. The α-nitroester 50 was converted to α-methyltryptophan by PtO₂ catalyzed reduction in 86.2% yield. |
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