Reductive hydrogen atom transfer

Yang H, Deng Y, Shi F et al (2015) Carbon-catalysed reductive hydrogen atom transfer reactions. Nat Conumm 6 6478. doi 10.1038/ncomms7478... 

It is important to emphasize that the hydroxy dithioketal cyclization can be conducted under mild reaction conditions and can be successfully applied to a variety of substrates.15 However, the utility of this method for the synthesis of didehydrooxocane-contain-ing natural products requires the diastereoselective, reductive removal of the ethylthio group. Gratifyingly, treatment of 13 with triphenyltin hydride and a catalytic amount of the radical initiator, azobisisobutyronitrile (AIBN), accomplishes a homolytic cleavage of the C-S bond and furnishes didehydrooxocane 14 in diastereo-merically pure form (95 % yield), after hydrogen atom transfer. 

Hydrogen-Atom Transfer. Many oxidation and reduction reactions are free-radical substitutions and involve the transfer of a hydrogen atom. For example, one of the two main propagation steps of 14-1 involves abstraction of... 

Classification exclusively in terms of a few basic mechanisms is the ideal approach, but in a comprehensive review of this kind, one is presented with all reactions, and not merely the well-documented (and well-behaved) ones which are readily denoted as inner- or outer-sphere electron transfer, hydrogen atom transfer from coordinated solvent, ligand transfer, concerted electron transfer, etc. Such an approach has been made on a more limited scale. Turney has considered reactions in terms of the charges and complexing of oxidant and reductant but this approach leaves a large number to be coped with under further categories. 

Hydrogen atom transfer implies the transfer of hydrogen atoms from the chain carrier, which is the stereo-determining step in enantioselective hydrogen atom transfer reactions. These reactions are often employed as a functional group interconversion step in the synthesis of many natural products wherein an alkyl iodide or alkyl bromide is converted into an alkane, which, in simple terms, is defined as reduction [ 19,20 ]. Most of these reactions can be classified as diastereoselective in that the selectivity arises from the substrate. Enantioselective H-atom transfer reactions can be performed in two distinct ways (1) by H-atom transfer from an achiral reductant to a radical complexed to a chiral source or alternatively (2) by H-atom transfer from a chiral reductant to a radical. 

The use of free-radical reactions in organic synthesis started with the reduction of functional groups. The purpose of this chapter is to give an overview of the relevance of silanes as efficient and effective sources for facile hydrogen atom transfer by radical chain processes. A number of reviews [1-7] have described some specific areas in detail. Reaction (4.1) represents the reduction of a functional group by silicon hydride which, in order to be a radical chain process, has to be associated with initiation, propagation and termination steps of the radical species. Scheme 4.1 illustrates the insertion of Reaction (4.1) in a radical chain process. 

It was found that most synthetic processes that are employed to prepare the diimide reagent generate trans-diimide, but ds-diimide undergoes faster hydrogen atom transfer to a double bond than does the trans isomer. It follows that a fast trans-cis isomerization precedes reduction. The transfer of hydrogen atoms takes place in a synchronous process188 via the transition state 19 ... 

The D KIE ( hAd) in reaction 269 has been found to be 3.2 at 28 °C. Small primary DKIEs are usually associated with unsymmetrical TS in hydrogen transfer and non-linear atomic arrays. The above value of k /ko observed in this study suggests that C—H bond polarization is occurring. No radical species have been found in reaction of 456 with CS2 by ESR study514. Therefore it was suggested that the reduction does not proceed by initial SET from manganese species followed by hydrogen atom transfer but directly by a concerted one-step hydride ion transfer. The course of reaction 269 between 456-H... 

An important aspect of enzymatic oxidation-reduction reactions involves the transfer of hydrogen atoms. This transfer is mediated by coenzymes (substances that act together with enzymes) nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). These two species pick up H atoms to produce NADH and NADPH, respectively, both of which can function as hydrogen atom donors. Another pair of species involved in oxidation-reduction processes by hydrogen atom transfer consists of flavin adenine triphosphate (FAD) and its hydrogenated form FADH2. The structural formulas of NAD and its cationic form, NAD+, are shown in Figure 4.7. 

The fragmentation leads to the simultaneous generation of two neutral radicals in close proximity, separated only by the carbonyl product. Depending on the nature of the substrate, these fragments may react by hydrogen atom transfer, either to the aminoalkyl (benzyl) radical or to the sensitizer derived radical. Accordingly, the acceptor can act either as a sensitizer or undergo two-electron reduction. 

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