Enantioselective aldehyde alpha-nitroalkylation via oxidative organocatalysis.

The first enantioselective organocatalytic alpha-nitroalkylation of aldehydes has been accomplished. The aforementioned process involves the oxidative coupling of an enamine intermediate, generated transiently via condensation of an amine catalyst with an aldehyde, with a silyl nitronate to produce a beta-nitroaldehyde. Two methods, one that furnishes the syn beta-nitroaldehyde and a second that provides access to the anti isomer, have been developed. Data are presented to support a hypothesis that explains this phenomenon in terms of a silyl group-controlled change in mechanism. Finally, a three-step procedure for the synthesis of both syn- and anti-alpha,beta-disubstituted beta-amino acids is presented.

Rhodium(I)-catalyzed ene-allene carbocyclization strategy for the formation of azepines and oxepines.

[reaction: see text] A novel strategy for the preparation of seven-membered heterocyclic compounds has been realized. Treatment of ene-allene 1 with a catalytic quantity of rhodium biscarbonyl chloride dimer affords the cyclization product 2 in moderate to high yields. The scope and limitations of this new method are currently under investigation, and the results obtained to date are discussed within.

Kinetic and biochemical analysis of the mechanism of action of lysine 5,6-aminomutase.

Lysine 5,6-aminomutase (5,6-LAM) catalyzes the reversible and nearly isoenergetic transformations of D-lysine into 2,5-diaminohexanoate (2,5-DAH) and of L-beta-lysine into 3,5-diaminohexanoate (3,5-DAH). The activity of 5,6-LAM depends on pyridoxal-5(')-phosphate (PLP) and adenosylcobalamin. The currently postulated multistep mechanism involves at least 12 steps, two of which involve hydrogen transfer. The deuterium kinetic isotope effects on k(cat) and k(cat)/K(m) have been found to be 10.4+/-0.3 and 8.3+/-1.9, respectively, in the reaction of DL-lysine-3,3,4,4,5,5,6,6-d(8). The corresponding isotope effects for reaction of DL-lysine-4,4,5,5-d(4) are 8.5+/-0.7 and 7.1+/-1.2, respectively. Neither cob(II)alamin nor a free radical can be detected in the steady state by UV-Vis spectrophotometry or electron paramagnetic resonance (EPR) spectroscopy. Therefore, hydrogen abstraction from carbon-5 of the substrate side chain is rate limiting in the mechanism. DL-4-Oxalysine is an alternative substrate for 5,6-LAM. DL-4-Oxalysine reacts irreversibly because the product breaks down into ammonia, acetaldehyde, and DL-serine. The value of K(m) for the reaction of DL-4-oxalysine is lower than that for DL-lysine and that of k(cat) for DL-4-oxalysine is slightly lower than that for DL-lysine. As measured by values of k(cat)/K(m), 5,6-LAM uses DL-4-oxalysine essentially as efficiently as the best substrates, D-lysine and L-beta-lysine, and more efficiently than DL-lysine. DL-4-Oxalysine induces the same suicide inactivation by electron transfer as do the biological substrates. The putative substrate-related radical intermediate is not sufficiently stabilized by the nonbonding 4-oxa electrons to be detectable by EPR spectroscopy.