Face-selective hydride transfer

This observation has led to the preparation of more effective bicyclic oxaza-borolidines such as 1, prepared from (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine and BH3 (la) or methylboronic acid (lb). Both reagents catalyze borane reduction of alkyl aryl ketones to furnish (R)-alcohols in > 95% ee, by face-selective hydride transfer within a complex such as B. Catalyst lb is somewhat more effective than... 

The first step of the mechanism is the coordination of BFI3 (Lewis acid) to the tertiary nitrogen atom (Lewis base) of the CBS catalyst from the -face. This coordination enhances the Lewis acidity of the endocyclic boron atom and activates the BH3 to become a strong hydride donor. The CBS catalyst-borane complex then binds to the ketone at the sterically more accessible lone pair (the lone pair closer to the smaller substituent) via the endocyclic boron atom. At this point the ketone and the coordinated borane in the vicinal position are cis to each other and the unfavorable steric interactions between the ketone and the CBS catalyst are minimal. The face-selective hydride transfer takes... 

The use of baker s yeast for selective reductions has a long history, while the use of isolated enzymes is more recent. Dehydrogenases and reductases require a nicotinamide cofactor (NADH or NADPH), from which a hydride is transferred to the substrate carbonyl. Enzymes from different species have been classified according to their selectivity (hydride transfer to si- or re-face of the carbonyl) [14]. The cofactors to be used together with isolated enzymes are commercially available (e.g. from Sigma-Aldrich), but are for most applications too costly to use in stoichiometric amounts. However, cofactor in situ regeneration can be... 

The catalytic cycle of the CBS-reduction, proposed by Corey, is shown below. Coordinating the ketone (14) only via its sterically less-hindered electron pair a, the hydride transfer proceeds selectively to the si-face (15,16) of the ketone. 

Enzyme-catalyzed reactions are generally, though not uniformly, characterized by either the stereospecific or stereoselective interconversion of selected stereoisomers of substrates and products via single, well-defined stereochemical pathways. The glycolytic enzyme L-lactate dehydrogenase (LDH) from pig heart illustrates this phenomenon the stereochemical fidelity of hydride transfer between the (S)-enantiomer of lactate and the re face (A side) of the nicotinamide ring of bound NAD is over 99.999998% (27) [Eq. (1)] ... 

The face selectivity in stericaUy unbiased systems, exhibited in 2-adamantyl cation addition and elimination reactions, among others, has been reviewed, " and so have the elecuonic factors governing the diastereofacial selectivity of many reactions, including the nucleophilic capture of 5-substituted adamantyl cations. The standard enthalpy of formation of the 1-adamantyl cation (99) in the gas phase has been determined experimentally to be 162.0 2.0 kcalmoP, and the ab initio calculations on this species have been re-assessed. It has been found that the inuamolecular hydride transfer occurring in the cation derived from (198) is competitive with intermolec-ular processes, and that the rates of the hydride transfers and the reaction products observed were dependent upon R. The direct synthesis of stable adamantylide-neadamantane bromonium salts is reported the anions used contained or Mo, and the resulting salts proved to be more stable than the Brs salts. The synthesis, reactions, and properties of some 2,8-didehydronoradamantane derivatives are reported. " ... 

As noted in Chapter 18, the enzymes that require nicotinamide coenzymes are stereospecific and transfer hydride to either the pro-i or the pro-S positions selectively. The table (facing page) lists the preferences of several dehydrogenases. 

If the catalyst is chiral, it can transfer hydride selectively to one prochiral face of an acceptor to provide an optically active product (Fig. 35.1). 

While the chloroborane transfers a hydride ion to an electrophilic carbon atom, M-iso-propyl ephedrine in reaction B selectively transfers a proton to one of the two faces of a nucleophilic enolate [23]. Co-ordination of the nitrogen of the chiral proton source to the enolate counterion is believed to direct the protonation. As the precursor of the enolate is racemic, this reaction is also called deracemization . Obviously, this offers a clear advantage over a classic resolution procedure, as it can be used to convert the whole racemic mixture into the desired enantiomer. 

Then, the hydride ion is selectively transferred to the f-olefin from the least sterically hindered face to produce the corresponding isomer of the product. Furthermore, although a kinetic preference for (he (Z)-iminium ion formation has been demonstrated, the ( )-iminium ion intermediates, which dominate the equilibrium ratio, react with nucleophiles faster than the ( -isomers when diarylprolinol and imidazohnone-based chiral catalysts are anployed in conjugate additions to a,P-unsaturated aldehydes [20]. 

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