Stereochemistry of hydrogen transfer

Beedle, A. S., Munday, K. A., Wilton, D. C. The stereochemistry of hydrogen transfer from NADPH catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A reductase from rat liver. European J. Biochem. 28, 151—155 (1972). 

Biellmann, J.-F., Rosenheimer, N. Dogfish lactate dehydrogenase The stereochemistry of hydrogen transfer. FEBS Letters 34, 143—144 (1973). 

The stereochemistry of hydrogen transfer has been studied with the liver enzyme by using the labeled NAD derivative354 (91). The reduced pyridine nucleotide was shown to have the structure 92, thus indicating that both hydride ions that are transferred from 89a... 

Hydrogen transfer to C2 of acetaldehyde by EAL is nonstereospecific, implying the formation of a torsionally symmetrized intermediate. (i )- and (6 )-2-aminopropanol are also substrates of EAL and are deaminated to propionaldehyde. These transformations might appear similar to the action of DDH on the enantiomers of propane-1,2-diol however, the stereochemistry of hydrogen transfer by EAL is unlike that by DDH. In the reaction of (d )-2-aminopropanol, hydrogen at the l-pro-S position is transferred to the 2-pro-S position in propionaldehyde, with retention of configuration at C2, as in Equation (11). 

However, this approach could not be used to establish the absolute stereochemistry of hydrogen transfer because the reduced and oxidized forms of S-deazaflavin, once released from the enzyme, undergo a rapid scrambling reaction that results in racemization at C-5 of the reduced species (83). Nevertheless, subsequent X-ray crystallographic measurements on the stable ternary enzyme-FAD-NADP complex demonstrated that the re and si faces of the isoalloxazine and nicotinamide rings (respectively) are next to one another (74) ... 

Corey EJ, Pasto DJ, Mock WL. Chemistry of diimide. n. Stereochemistry of hydrogen transfer to carbon-carbon multiple bonds. J. Am. Chem. Soc. 1961 83 2957-2958. 

Wawzonek et al. first investigated the mechanism of the cyclization of A-haloamines and correctly proposed the free radical chain reaction pathway that was substantiated by experimental data. "" Subsequently, Corey and Hertler examined the stereochemistry, hydrogen isotope effect, initiation, catalysis, intermediates, and selectivity of hydrogen transfer. Their results pointed conclusively to a free radical chain mechanism involving intramolecular hydrogen transfer as one of the propagation steps. Accordingly, the... 

Porter, D. J. 1993 J. Biol. Chem. 268, 66-73 S-adenosylhomocysteine hydrolase. Stereochemistry and kinetics of hydrogen transfer. 

Analogs with an acetyl, thioacetamide, or cyano group in the 3 position of the pyridine ring have all been shown 219) to exhibit the same stereochemistry for hydrogen transfer as NAD+. It was concluded 219) that interactions between enzyme and coenzyme were solely responsible for the A-side stereo specificity of NAD in LADH which agrees with the X-ray results (Section II,C,3,a). 

Surprisingly, the stereochemistry of hydrogen atom abstraction has not been investigated in a systematic way. However, the analogy of the transition states of cyclization reactions and those of hydrogen atom abstractions lead us to speculate that stereoselective hydrogen transfers could be achieved. Malacria has reported an example of a totally diastereoselective 1,5-hydrogen atom abstraction (Scheme 45)... 

The Invertlve nature of the initial displacement reaction may be utilized In a 1,3 transfer of stereochemistry from the hydroxylic center to the S olefinlc carbon (eq 6). Precedence also exists for the use of more distant stereocenters to control the stereoselectiv Ity of hydrogen transfer to the -olefinic carbon (eq 7). ... 

Another important family of elimination reactions has as its common mechanistic feature cyclic TSs in which an intramolecular hydrogen transfer accompanies elimination to form a new carbon-carbon double bond. Scheme 6.20 depicts examples of these reaction types. These are thermally activated unimolecular reactions that normally do not involve acidic or basic catalysts. There is, however, a wide variation in the temperature at which elimination proceeds at a convenient rate. The cyclic TS dictates that elimination occurs with syn stereochemistry. At least in a formal sense, all the reactions can proceed by a concerted mechanism. The reactions, as a group, are often referred to as thermal syn eliminations. 

On the other hand a direct hydrogen transfer through a Meerwein-Ponndorf mechanism, involving coordination of both the donor alcohol and the ketone to the copper site may also be considered. In this case, by using alcohols other than 2-propanol, we could expect some difference in stereochemistry. This would also imply the possibility of carrying out the enantioselective reduction of a prochiral ketone with a chiral alcohol as donor. 

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

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