3243-01-4

A new B12 (cobalamin, Cbl) model system with the potentially quinquedentate ligand, 2,3,9,10-tetramethyl-6,2-pyridylmethyl-1,4,8,11-tetraazaundeca-1,3,8,10-tetraen- 1,11-diolo (C1py), has unique properties attributable to the coordinated pendant pyridine, which is attached covalently at the 2-position by a one-methylene link to the central C of the propylene chain of (DO)(DOH)pn (N2N2′-propanediylbis(2,3-butanedione 2-imine 3-oxime)). Treatment of C1py, constructed from the new diamine, 2-(2-pyridylmethyl)-1,3-propanediamine, with hydrated CoBr2 afforded [BrCo(C1py)]ClO4 (5). From 5, salts of [XCo(C1py)]+ (X = CN, N3, Cl) and of [RCo(C1py)]+ (R= CH3, i-C3H7, neo-C5H11 CH2CF3) were synthesized by substitution and by oxidative addition of RX to in situ generated Co-(C1py), respectively. In contrast to previous model systems, the C1py model behaves more like Cbls; for example, no dicyano complex was obtained. Coordination of the pyridyl moiety in the C1py derivatives is confirmed by X-ray structural analysis of [ClCo(C1py)]PF6 (7) and [CH3Co(C1py)](ClO4/BF4) (9a). The pendant arm forces the pyridine to adopt an orientation 90° different from that in the [pyCo((DO)(DOH)pn)Cl(or R)]PF6 derivatives. This new orientation greatly decreases butterfly bending, a structural feature relevant to triggering of Co-C bond homolysis by B12 enzymes. This result is strong evidence that a planar N-donor ligand can induce butterfly bending. In 7 the axial Co-N distance is 1.959 (4) A?, shorter than this distance (2.06 (1) and 2.07 (1) A?, for two independent molecules) in 9a and similar to that in [pyCo((DO)(DOH)pn)Cl]PF6. Although electrochemical reduction of the latter was not reversible, the reversible formation of Co(II) and Co(I) species from 7 (and 5) can be attributed to the pendant nature of the axial pyridine. The Co(III)/Co(II) redox couple was more cathodic for 7, consistent with better electron donation by the pendant pyridine. The Co(II)/Co(I) redox potential (-1.0 V vs 0.01 M Ag+/Ag) of 7 and 5 was similar to that for nonalkyl (DO)(DOH)pn derivatives, which lack a pendant base; this suggests that Co(II)/Co(I) reduction in nonalkyl C1py derivatives proceeds through a base-off form in which the Co-pyridine interaction is weak, at best. Such a mechanism was proposed previously for Cbls. For both [CNCo(C1py)]ClO4 and cyanoCbl (vitamin B12), a single two-electron wave was observed upon reduction. For alkylC1py derivatives, only one cathodic wave was observed upon reduction. Just one prominent cathodic peak has been reported for alkylCbls. For [CH2Co(C1py)]ClO4 (9), reduction formed a dealkylated Co(I) species, which was oxidized to Co(II) on the reverse anodic scan. Similarly, dealkylated Co(I) species formed after one-electron reduction of alkylCbls, including methylCbl, are oxidized to Cbl(II) in the return anodic scan. The Co(III)/Co(II) reduction potentials of C1py and Cbl derivatives were influenced nearly identically by changes in the axial ligand; for R(or X) = solvent, Cl, CN, neo-C5H11, CH3, an excellent correlation with a slope of unity was obtained. The simpler chemistry of the C1py derivatives, as illustrated here by electrochemical studies, makes them excellent models to study fundamental chemistry relevant to Cbls.

(Chemical Equation Presented) Cyclodehydration using the Burgess reagent provided a novel approach toward the synthesis of N-bridged 5,6-bicylic pyridines including pyrolo-, imidazo-, and triazolopyridines under mild and neutral conditions. The methodology tolerates acid-sensitive functional groups. A novel addition product was observed between the resulting pyrrolo- or imidazopyridine and an additional equivalent of the Burgess reagent, producing the corresponding sulfonylcarbamate adduct.

Tartronic acid acetalic ethers and esters of the general formula: STR1 are provided and are useful in treatment of bone dysmetabolism. As examples, Ra and Rb may be hydrogen, B is a C2 -C12 acyl group, R is phenyl and n is 0-12.

The oxidation of substituted diethyl 2-,3-, or 4-picolylmalonates (1a-g) by Mn(III) acetate in acetic acid, Ce(IV) ammonium nitrate in methanol, and Fe(III) perchlorate in acetonitrile in the presence of substituted alkenes (2) and alkynes (3) affords substituted tetra- or dihydroquinolines and/or isoquinolines (4-9) in good to excellent yield.The influence of reaction medium on yield and isomer distribution has been investigated.A mechanism involving oxidative deprotonation of malonic esters by high-valent metal salts to malonyl radicals, their addition to olefins, and intramolecular homolytic substitution to protonated or metal-complexed heteroaromatic bases by the resulting substituted carbon radicals is suggested.