Biomimetic Hydride Transfer Studies

Abstract

Hydride transfer is an elementary biochemical step performed by coenzymes like 5,10-methylenetetrahydrofolate (MTHF) and 5,10-methylenetetrahydromethanopterin (H4MPT). This thesis describes new reactivities of imidazolidines and formaldehyde aminals acting as model compounds for MTHF and H4MPT. The hydride/halide exchange between imidazolidines and halocarbons discovered by our group has been generalized and now offers a tool for chemical synthesis and an approach for in-situ remediation of halogenated pollutants. These accomplishments take the form of a high yield, large-scale procedure for the purification of commercially expensive imidazolidine precursors, the discovery of a catalytic approach for the dehalogenation of unreactive aryl halides, and the synthesis of an immobilized hydridic polymer based on the imidazolidine motif that has been incorporated into a flow-through dehalogenation reactor. Model compounds of the hydrogenase coenzyme system H4MPT/H4MPT+ found in methanogenic archaea have been obtained that mimic the in vivo reactivity of the biomolecules. The simple models based on a protonated imidazolidine/imidazolidinium cation reversibly activate molecular hydrogen analogously to the natural biochemical process. This reactivity appears to represent the first in vitro observation of hydrogenase activity with a series of simple organic molecules and suggests application of the compounds as components of a hydrogen storage solution. The reactivity of formaldehyde aminals with water and hydrogen in the presence of the identified palladium and platinum dehalogenation catalysts was mapped to gain a generalized understanding of the reductive reactivity. The by-products formed depend critically on the aminal ring size and nitrogen substituents and can be accounted for by assuming the formation of metal-surface carbene complexes as reaction intermediates. A hydrogen-deuterium exchange reaction with one of the aminals was optimized to allow a high yield synthesis of 1,3-dimethylhexahydropyrimidine-d2, a compound which holds promise as a substitute for deuterated tin hydrides. The hydride transfer reactivity of formaldehyde aminals has been extended to the sulfur heterocumulenes carbon disulfide and carbonyl sulfide. Several new organosulfur compounds, including the scarcely studied dithioformate anion, were obtained and structurally characterized by single crystal X-ray crystallography. The straightforward synthesis of this previously inaccessible species promises to facilitate its use as a synthetic building block and ligand. Like the reactivity of halocarbons with formaldehyde aminals as models for MTHF, the reactivity of sulfur heterocumulenes suggests they are capable of deactivating MTHF-dependent biochemical pathways in vivo.