Reduction Reactions Involving Hydrogen Atom Donors

Reduction Reactions Involving Hydrogen Atom Donors 

Reduction by hydrogen atom donors involves free radical intermediates and usually proceeds by chain mechanisms. Tri-n-butylstannane is the most prominent example of this type of reducing agent. Other synthetically useful hydrogen atom donors include hypophosphorous acid, dialkyl phosphites, and tris-(trimethylsilyl)silane. The processes that have found most synthetic application are reductive replacement of halogen and various types of thiono esters. 

Tri-rc-butylstannane is able to reductively replace halogen by hydrogen. Mechanistic studies indicate a free radical chain mechanism.199 The order of reactivity for the halides is RI RBr RC1 RF, which reflects the relative ease of the halogen atom abstraction.200 

A procedure that is catalytic in Bu3SnH and uses NaBH4 as the stoichiometric reagent has been developed.201 This method has advantages in the isolation and purification of product. Entry 5 is an example of this procedure. The reaction was carried 

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Reduction Reactions Involving Hydrogen Atom Donors... 

An alternative method for reductive dediazonation involves in situ diazotization by an alkyl nitrite in dimethylformamide.96 This reduction is a chain reaction with the solvent acting as the hydrogen atom donor. 

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. 

In the absence of the activating second carbonyl functionality, it is necessary to use more ingenious methods to produce the same net effect. These procedures more often than not involve radical reactions. Among them is the thermolysis of tert-butyl esters of peroxyacids 437, which are readily synthesized in a standard esterification of tert-butyl hydroperoxide with an acid chloride. Decarboxylation proceeds via an initial homolytic cleavage of the 0-0 bond, elimination of CO2, and reduction of the incipient alkyl radical by an added hydrogen atom donor such as 438 (Scheme 2.143). Examples showing the exceptional synthetic importance of this decarboxylation procedure will be presented later. 

For reductions DMF has a usable potential range comparable to that of acetonitrile, but it is inferior for oxidations. In the presence of inorganic ions their discharge is the cathodic limiting reaction, whereas it is more uncertain whether it is the solvent or the cation that is reduced in solutions of tetraalkylammonium ions. The anodic limiting reaction at a Pt electrode is an oxidation of DMF, which involves the removal of an electron from the amide nitrogen. Its autoprotolysis constant is 29.4. DMF is a better hydrogen atom donor than MeCN and DMSO. 

Hydrogen atom donors such as non-nucleophilic tertiary thiols or tri-n-butyltin hydride are extremely efficient traps for the capture of the alkyl radical R derived from O-acyl thiohydroxamates, thus providing a very efficient method for reductive decarboxylation (Scheme 3). In practical terms, the use of the mercaptan is preferred since the tertiary alkyl pyridyl disulfide can be easily removed during work up by a simple acid extraction. The reaction has been successfully applied to a very wide range of complex substrates [8] possessing primary, secondary, or tertiary aliphatic carboxylic acids, and reactions at room temperature or below require only photolysis from a simple tungsten lamp and often involve in situ O-acyl thiohy-droxamate derivatization. 

Oxidative reactions in catabolic sequences involve the removal of electrons from an intermediate. This process is controlled by dehydrogenases and often involves the participation of the cofactor nicotinamide adenine dinucleotide (NAD or NAD+). Electrons from the donor are transferred to NAD in the form of the hydride ion [ H-] to produce reduced NAD (NADH). In many reactions two hydrogen atoms are removed from the substrate, one in the form of the hydride ion, the other liberated as a proton accordingly, the reduction of NAD+ is often written as... 

The oxidative deamination mediated by 3,5-di-t-butyl-o-quinone [257] could very well involve aC- 0 1,5-sigmatropic hydrogen shift within the Schiff base network. This process in essence accomplishes oxidation of the amine and reduction of the quinone. The interesting point is the strong donor oxygen forces the nitrogen atom into an acceptor role during the reaction. 

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