Alternative Hydride Sources

Multienzyme cascade synthesis combining ene-reductases with alcohol dehydrogenases, (a) Synthesis of optically pure y-butyrolactones (the building block is circled) and (b) optically pure primary or secondary tetralin orchroman derivatives, (c) Three-enzyme system for the generation of a valuable chiral building block. 

This multienzyme process includes the ER-catalyzed reduction of an a,p-unsaturated diester (22a) and subsequent hydrolysis of 22b by a hydrolase to fhe monoester (22c). 

A disadvantage of nicofinamide-dependenf enzymes is fhe high cosf of fhe coenzyme (if used in stoichiomefric amounts) making their use cost prohibitive for many synthetic industrial purposes. Therefore, alternative strategies have been adopted to supply the necessary hydride equivalents  

respectively, in comparison to 3.1 mMh in the presence of a twofold access of NADPH. Additionally, enzyme and mediator stability and reusability were maintained over 12 h. 

Benzyl —CONH2 -Butyl —CONH2 Benzyl —CO2H Benzyl —COCH3 Benzyl —CN 

---

For the use of dimethylamine-borane as an alternative hydride source, see David, H., Dupuis, L., Guillerez, M.-G., Guibe,... 

C.E. Lundin, F.E. Lynch, Modification of hydriding properties of AB5 alloy type hexagonal alloys through manganese substitution, Proceedings of the Miami International Conference Alternate Energy Sources, United States, 5-7 December 1977. University of Miami, (1978)... 

The precise mechanism of these intermolecular reactions is not known. Transient disproportionation processes, although well documented in less acidic media (see below and Section V.A.l), seem unlikely if alkyl cations alone are involved. Two possible explanations for the observed results may be considered. Small amounts of polymeric impurities may be present in the reaction mixture which could serve as a hydride source, catalyzing the intermolecular reaction as indicated in Eq. (16)4°). Alternatively, the intermolecular reactions may result from inefficient mixing during reaction initiation. In this case, unionized alcohols would serve as the hydride source. This latter alternative is consistent with the observation 4°1 that the deuterium in the 1-adamantanol obtained from the rearrangement of 38 is distributed between bridgehead and methylene positions. Unless more than one re-... 

In the phase-transfer processes discussed in Section 11.2 it is assumed that the anionic hydride source, i.e. borohydride or a hypervalent hydrosilicate, forms an ion-pair with the chiral cationic phase-transfer catalyst. As a consequence, hydride transfer becomes enantioselective. An alternative is that the nucleophilic activator needed to effect hydride transfer from a hydrosilane can act as the chiral inducer itself (Scheme 11.6). 

As an alternative strategy, lysine residues can be modified through reductive alkylation. Fig. 2e. This method is most frequently carried out by exposing the protein to aldehydes in the presence of hydride-containing agents that reduce the transiently formed imines. NaB(CN)H3 and NaB(OAc)3H are commonly used for this purpose. As an alternative, transfer hydrogenation can be carried out in the presence of an Ir(III)[Cp ]2(bipyridyl) catalyst, which allows imine reduction to occur under mild conditions using buffered formate as the hydride source (14). 

Homogeneous (or heterogeneous) catalyst systems offer the exciting perspective of high efficiency, optimal use of (chiral) ligands in enantioselective reactions, and the possibility of taking many different compounds as hydride sources. The use of isopropyl alcohol has been illustrated in this regard, but di-oxane, dihydrofuran, aldehydes, formic acid, cyclohexene orV-benzylaniline are some of the other compounds that already have been employed as alternatives. ... 

Wiswall, R.H., Hydrogen Storage, in Hydrogen in Metals II Application Oriented Properties, G. Alefeld and Volkl, J., Editors, Springer Berlin, 1978. p. 201. Snape, E., Huston, E.L. and Sandrock, G.D., Development of solar-hydrogen systems using metal hydrides, in 2nd Miami Int. Conference on Alternative Energy Sources. 

Reductive aldol reaction of a,(5-unsaturated esters and enones with aldehyde mediated by a transition metal hydride complex and a hydride source, such as hydrosilane, is a versatile process to produce p-hydroxy carbonyl compounds (Scheme 15a) [21]. This reaction is thought to be an alternative transformation of Lewis acid-catalyzed Mukaiyama-type aldol reaction with silyl enol ethers or silyl ketene acetals (Scheme 15b). 

---