Synthesis and Structure Determination of an Intramolecularly Alkylated Bridged Cobaloxime

Abstract

the tetraketone (10) in 70 % yield. The crystalline tetraoxime (1 1) obtained therefrom was then treated with a stoichiometric amount of cobalt(r1) chloride, twice the amount of pyridine, three equivalents of potassium hydroxide, and an excess of NaBH4. C kH3 CHs(61 In continuation of our attempts['% ' 1 to imitate coenzyme B12-dependent enzymatic rearrangements with model catalysts we have synthesized the bridged alkylcobaloxime ( 1 ). The starting material employed was 5-heptyn-1-01 (2) which is obtainable either by condensation of lithium 1 -propyn-1 -ide with tetrahydropyranyl 4-bromobutyl ether or by fragmentation of 2,3-epo_xy-2-methylcyclohexane to~ylhydrazone[~] and subsequent reduction of the resulting aldehyde with LiAIH4.Compound (2) was extended by two C atoms uia the mesylate (3) in a malonic ester synthesis to form 7-nonyn-1-01 (4), the mesylate of which (5) could be used for double alkylation of dimethyl malonate. Upon hydrolysis, decarboxylation, and reduction, the bisalkylated malonic ester (6) afforded 2-(7-nonynyl)-9-undecyn-I -01 (7), which was converted via the mesylate (8) into the bromomethyl derivative (9). Ozonization of (9) at -18°C in and subsequent treatment of the peroxide with dimethylsulfide gave The product mixture contained six alkylated cobalt complexes (overall yield ca. 20 %) which were separated by thinlayer chromatography. The major product ( 1 ) [& =0.39 Using a Picker diffractometer (Mo,, radiation, graphite monochromator) 4625 symmetrically independent reflections were measured of which 2307 were classified as observed

Artificial Enzymes

“…It is obvious that an apoprotein plays an important role in such radical reactions as mediated by vitamin B 12 -dependent enzymes. , The model reactions, which were designed in consideration of the role of apoenzymes, are as follows. The first example of the active site around adenosylcobalamin was demonstrated by Rétey et al. − They synthesized a number of intramolecularly bridged cobaloximes, simulating the stereochemical conditions at the active site of methylmalonyl-CoA mutase (Scheme ). The substrate is anchored covalently with two methylene bridges to a planar part of the complex.…”

A new model compound for vitamin B12 coenzyme: synthesis and crystal structure of a tetraazamacrocyclic alkylcobalt(III) compound with a pendant coordinating alkyl arm

“…In order to obtain a closer resemblance to the corrin ring of coenzyme BIZ, we have chosen to use the tetraaza macrocycle 5,14-dihydro-6,8,15,17-tetramethyldibenzo[h, i] [ 1,4,8,11]tetraazacyclotetradecine (HZL) as a precursor for forming alkylcobalt(r1r) compounds with an intramolecular cobalt(ii1)carbon bond. The coordination chemistry of this ligand has recently been reviewed,6 and Goedken and coworker^^^^ have reported a cycloaddition of ethyne to [Co(L)]+, giving a pentadentate macrocyclic ligand with a vinyl group coordinated to the metal ion.…”