Hydride transfer stereochemistry

The regioselective and stereospecific construction of C-20 stereochemistry is explained by the following mechanism. The Pd(0) species attacks the ( )-/3-carbonate 616 from the a-side by inversion to form the Tr-allylpalladium species 620, which has a stable syn structure[392]. Then concerted decarboxylation-hydride transfer as in 621 takes place from the a-side to give the unnatural configuration in 617. On the other hand, the Tr-allylpalladium complex 622... 

The r/zreo-3-deutero-2-trimethylstannylbutane that Hannon and Traylor158 used to determine the stereochemistry of the hydride transfer reaction and to shed light on the mechanism of this reaction was synthesized using the reactions in Scheme 22. Each of the reactions in Scheme 22 is stereo specific and the analysis showed that the product was at least 97% r/rreo-3-deutero-2-trimethylstannylbutane. If the elimination reaction from t/zreo-3-deutero-2-trimethylstannylbutane occurs with an awh -periplanar stereochemistry, the products shown in Scheme 23 will be obtained. Thus, if the elimination occurs by an awft -periplanar stereochemistry, all the fraws-2-butene will be monodeuterated while the ds-2-butene will not be deuterated. A syw-periplanar elimination from f/zreo-3-deutero-2-trimethylstannylbutane, on the other hand, would give the products shown in Scheme 24. If this occurs, the cw-2-butene will contain one deuterium atom and the fraws-2-butene will contain none. 

Hydride Transfer in NAD+- and NADP -Dependent Enzymes. The transfer of the hydride ion in redox reaction of NAD+- and NADP+-dependent enzymes can occur either to the re- or the xi-face of the pyridine ring of the coenzyme . Such stereochemistry is crucial in the characterization of these enzymes. The same enzymes from different sources can express different stereospecificities. For example, E. coli NAD(P)+ transhydrogenase expressed one form of stereospecificity whereas the Pseudomonas aeruginosa enzyme catalyzes the identical reaction with the other NAD form . 

Other methods are also available for generation of boron enolates. Dialkylboranes react with acyclic enones to give Z-enolates by a 1,4-reduction.19 The preferred Z-stereochemistry is attributed to a cyclic mechanism for hydride transfer ... 

Reaction Pathway. The simplest pathway is illustrated by the /3-keto ester substrate in Scheme 50. As suggested by reaction with RuCl2[P(C6H5)3]3 as the catalyst precursor (40c, 96), this hydrogenation seems to occur by the monohydride mechanism. The catalyst precursor has a polymeric structure but perhaps is dissociated to the monomer by alcoholic solvents. Upon exposure to hydrogen, RuC12 loses chloride to form RuHCl species A, which, in turn, reversibly forms the keto ester complex B. The hydride transfer in B, from die Ru center to the coordinated ketone to form C, would be the stereochemistry-determining step. Liberation of the hydroxy ester is facilitated by the al-... 

Table 2. Stereochemistry of the hydrid transfer catalyzed by alcohol dehydrogenases...

Figure 9.4 Proposed reaction sequence to explain why the stereochemistry of the chiral carbon atom is opposite to what is expected from a simple hydride transfer. Note that the stereochemistry of the carbon atom in 9.26 is changed to that of 9.27 by the breakage of the Rh-O bond so that rotation round the Rh-C bond becomes possible. The oxygen atom then occupies the empty coordination site marked by the square, and the Rh-O bond is formed again.

In this synthesis, the reactant was chosen to control stereochemistry and give an equatorial alcohol, due to an intermediate axial radical use of hydride-transfer reagents would tend to afford predominantly the axial alcohol. 

Deoxygenation was realized in the early 1990s, and it was found to be detrimental to the antitumor activity (see also Section 3.2.2.3). A 2-epimerized derivative was prepared by an oxidation-reduction sequence for the transformation of 2ot-OH into 2p-OH through the 2-keto group. The 2-keto group was stereoselec-tively reduced to 2p-OH because of steric hindrance of C-16 and C-19 from the p-face to prevent hydride transfer from this face. Unfortunately, 2-epi-paclitaxel was inactive, which demonstrates the importance of stereochemistry of C-2 substitutions in its activity. 

Gogte, V. N., Salama, M. A., and Tilak. B. D., Synthesis of nitrogen hetcrocyclics. VI. Stereochemistry of hydride transfer in acid catalysed disproportionation of 3,4-disubstituted... 

This reaction is crucial because it establishes the stereochemistry of the a-carbon atom (S absolute configuration) in glutamate. The enzyme binds the a-ketoglutarate substrate in such a way that hydride transferred from NAD(P)H is added to form the 1 isomer of glutamate (Figure 24,6). As we shall see, this stereochemistry is established for other amino acids by transamination reactions that rely on pyridoxal phosphate. 

The additional stereochemical control available in carbanions relative to alkoxides arises both from the extra ligation about carbon and the contributions of the metal. The stereochemistry of hydride transfer from organostannanes has been particularly well investigated. Coordinatively saturated metals like tin function less well as Lewis acids in a cyclic mechanism, and tend to induce hydride loss through an anti-... 

Homer and Balzer had earlier reported 32) that reduction of optically active phosphine oxides with either trichlorosilane (HSiCls), HSiClj/pyridine, or HSiCls/N, N-diethylaniline affords phosphines with overall retention of configuration, whereas reduction with HSiCls/triethylamine affords phosphine with inversion of configuration at phosphorus. In summary, it was suggested 32) that this difference in overall stereochemistry of reduction reflected a difference in the mode of hydride transfer from silicon to phosphorus intra- and intermolecular hydride transfer led to retention and inversion, respectively. The essential features of these mechanistic rationalizations are represented by Eq. (3). The intramolecular hydride transfer mechanism ), which may include pseudorotation (see Sect. 3) if intermediate phospho-HSiClj + O=PR3 - 0 PRj PRj + [ClsSiOH]... 

Steric bulkiness of substituents in ketones (25), for example, makes it possible to differentiate two pairs of lone-pair electrons (a or b in 25) on carbonyl oxygen for coordinating with the Lewis acidic center of boron in oxazaborolidine (28). The complex (29) formed from 28 with catecholborane binds ketone (32) stereospecifically by using the lone-pair electrons at the less hindered side so as to direct the smaller substituent Rs toward the bulky N-tert-butyl group. The intramolecular hydride transfers to the favorably coordinated carbonyl group as shown in 30, Scheme 1.82, results in asymmetric reduction of ketones. Reduction of trifluoromethyl and methyl ketones (25) (R = CF3 or CH3) by this system afforded the corresponding alcohols (26 or 27) with an opposite stereochemistry (Scheme 1.82). 

Figure 15-1. Stereochemistry of the hydride transfer from NAD(P)H to the carbonyl carbon on the substrate (S is a...

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