Hydride transfer intramolecular

Closely related to, but distinct from, the anionic boron and aluminum hydrides are the neutral boron (borane, BH3) and aluminum (alane, A1H3) hydrides. These molecules also contain hydrogen that can be transferred as hydride. Borane and alane differ from the anionic hydrides in being electrophilic species by virtue of the vacant p orbital and are Lewis acids. Reduction by these molecules occurs by an intramolecular hydride transfer in a Lewis acid-base complex of the reactant and reductant. 

Suitable dialdehydes can also undergo intramolecular hydride transfer, as in the Cannizzaro reaction of ethan- 1,2-dial (55, glyoxal ) — hydroxyethanoate ( glycollate, 56) anion,... 

This facilitates intramolecular hydride transfer resulting in a Ru-hydroxy ester complex (66) which readily releases the chiral product. When an (R)-BINAP-Ru catalyst is used, the R enantiomer is obtained in >99% ee. The chirality of the BINAP ligand accounts for the difference in energy between the possible transition states TS and TS. ... 

Scheme 16.2 illustrates the catalytic mechanism proposed by Muetterties and coworkers [13]. Salient features of this mechanism are the coordination of benzene in the -fashion, to give a transient Col I( 4-C, iH, i)(PR3)2 complex, and the intramolecular hydride transfer to form the allylic intermediate Co(//3-Ctl l7) (PR3)2. Hydrogen addition would give an 4-1,3-cyclohexadiene complex that ultimately releases cyclohexane via H2 addition/hydride migration steps. Complete cis stereoselectivity of hydrogen addition was demonstrated by replacing H2 with D2. 

New chiral oxazaborolidines that have been prepared from both enantiomers of optically active inexpensive a-pinene have also given quite good results in the asymmetric borane reduction of prochiral ketones.92 Borane and aromatic ketone coordinate to this structurally rigid oxazaborolidine (+)- or (—)-94, forming a six-membered cyclic chair-like transition state (Scheme 6-41). Following the mechanism shown in Scheme 6-37, intramolecular hydride transfer occurs to yield the product with high enantioselectivity. With aliphatic ketones, poor ee is normally obtained (see Table 6-9). 

In the aldol-Tishchenko reaction, a lithium enolate reacts with 2 mol of aldehyde, ultimately giving, via an intramolecular hydride transfer, a hydroxy ester (51) with up to three chiral centres (R, derived from rYhIO). The kinetics of the reaction of the lithium enolate of p-(phenylsulfonyl)isobutyrophenone with benzaldehyde have been measured in THF. ° A kinetic isotope effect of fee/ o = 2.0 was found, using benzaldehyde-fil. The results and proposed mechanism, with hydride transfer rate limiting, are supported by ab initio MO calculations. 

The mechanism of the aldol-Tishchenko reaction has been probed by determination of kinetics and isotope effects for formation of diol-monoester on reaction between the lithium enolate of p-(phenylsulfonyl)isobutyrophenone (LiSIBP) and two molecules of benzaldehyde. ". The results are consistent with the formation of an initial lithium aldolate (25) followed by reaction with a second aldehyde to form an acetal (26), and finally a rate-limiting intramolecular hydride transfer (Tishchenko... 

Trifluoroalanine has also been prepared by reducing trifluoropyruvate imines (ethyl trifluoropyruvate is available commercially it is prepared either from per-fluoropropene oxide or by trifluoromethylation of ethyl or f-butyl oxalate). These imines are obtained by dehydration of the corresponding aminals or by Staudinger reaction. They can also be obtained by palladium-catalyzed carbonylation of trifluoroacetamidoyl iodide, an easily accessible compound (cf. Chapter 3) (Figure 5.4). Reduction of the imines affords protected trifluoroalanines. When the imine is derived from a-phenyl ethyl amine, an intramolecular hydride transfer affords the regioisomer imine, which can further be hydrolyzed into trifluoroalanine. ... 

The cyclization of 1 proceeded with 72 28 diastereoselectivity, leading, after hydrolysis, to the crystalline diketone 8 as the major product Reduction of the ketones to the axial alcohols was followed by spontaneous lactonization, allowing easy differentiation of the several functional groups. Homologation to 10 followed by condensation with methyl carbonate and subsequent O-mcthylation then gave 11. C-Methylation of 11 then set the third quaternary center of the C ring. The deuteriums were introduced to minimize an unwanted intramolecular hydride transfer in a later step. 

Fig. 14. 90.4-MHz 13C MAS spectra of styrene- -l3C reacting on zeolite HZSM-5. The methylindanyl cation 12 (251 ppm), formed through the cracking of the cyclic dimer (cf. Fig. 6) followed by intramolecular hydride transfer, was converted to naphthalene at 523 K. This is the clearest example of a free carbenium ion as a reaction intermediate on a zeolite.

From a mechanistic viewpoint this group of enzymes is best described as oxidoreductases where intramolecular hydride transfer is mediated by enzyme bound NAD+ (Table IV). Different enzymatic end products for these enzymes are a consequence of different ways of stabilization of the 4-ulose intermediates or the 4 carbonium ion. The stabilization of the 4-ulose derivative can occur in several ways as shown by the various examples mentioned. During the molecular rearrangement, initiated by the formation of the 4-ulose, the reaction intermediates are held bound to the enzyme until at the final step enzyme-NADH donates the hydrogen to the last intermediate and enzyme-NAD+ releases the end product from the enzyme. 

Intramolecular hydride transfer under MPV reduction conditions occurs in substrate (25) with complete stereospecificity to generate (26).275 A 2 1 mixture of product to reactant was observed, irrespective of reaction tune or relative excess of Al(0 Pr)3, indicative of an equilibrium, hitennolecular hydride transfer to give (27) does not occur and the absence of the epimer of (25) implies that complete stereodifferentiation also occurs in the reverse process (Oppenhauer oxidation). Stereodifferentiation under... 

The conversion of nitrocoumarins into the amino compounds has been achieved by hydrogen transfer (95JCR(S)372) and an intramolecular hydride transfer features in the formation of Mannich bases of 4-aminocoumarins from 4-alkylaminocoumarin-3-carbaldehyde (95S633). Amine derivatives of coumarin-3-carboxaldehyde undergo a thermal 1,3-cycloaddilion involving an oxime nitrone isomerisation on reaction with Al-methyl-hydtoxylamine yielding hetero-fused coumarins (95JCS(P1)1857). 

Effective molarity measurements for intramolecular hydride transfers are scarce, and a conclusion that high effective molarities are a feature of hydride shifts would be premature. Only two other measurements are available, a low value of 13 for the Cannizarro reaction of phthalaldehyde (McDonald and Sibley, 1981), discussed below, and a larger value, 200, for... 

An effective concentration for the second aldehyde group of 13 has been quoted, obtained by taking the value of (kobs/[NaOH]) at low [NaOH] and comparing it with the third-order rate coefficient for the intermolecular Cannizzaro reaction of benazaldehyde under the same conditions. This does not compare inter- and intramolecular hydride transfer steps. 

Lithium aluminium hydride reduction of 1,2-disubstituted cyclopropene-3-carboxy-lates occurs initially at the ester group, but with additional reagent good yields of cis-1,2-disubstituted-rranj-3-methanols are obtained 176). The reduction of the double bond is regioselective, leading to the more stable carbanion, and the attack of the hydride ion exclusively cis to the 3-substituent may be explained in terms of initial formation of an alkoxyaluminium complex followed by intramolecular hydride transfer 176). In the case of cyclopropene-1-carboxylates, direct reduction to the saturated alcohol occurs thus (253) is converted to the rranj-alcohol177) ... 

As can be seen from Table 2, very high stereoselectivities could be observed for both syn and anti substrates, depending on the 2-alkyl substituent (R). In the absence of ZnCl2, a nonchelated chairlike transition state was anticipated, following the Solladie model, with intramolecular hydride transfer. This process was expected to lead to an opposite sense of selectivity to that observed for the chelation-controlled model (with DIBAL/ZnCl2). This reversal in stereoselectivity was indeed observed... 

The 18 —> 20-hemiacetal (160) gave novel dimers (163) on reaction with toluene-p-sulphonic acid in benzene, through attack of the vinyl ether (161) on the oxonium ion (162), followed by an intramolecular hydride transfer from C-16 to C-20.16°... 

Creation of the 8-membered ring 3 3 of IhxoL by an intramolecular directed aldol reaction failed when the thionium ion intermediate 3 2 underwent intramolecular hydride transfer from a neighbouring p-methoxy benzyl ether instead [Scheme 1.38]. Loss of p-methoxybenzaldehyde and hydrolysis of the enol silane occurred on workup to give the hemiacetal 38,5 in 48% yield. Benzyl ethers can also transfer hydride to proximate carbocationic intermediates.71... 

The rearrangement of [13] bears a close resemblance to the transannular reactions observed in medium sized rings that have been reviewed by Prelog and Traynham (1963) and Cope et al. (1966). Recently Sorensen and coworkers have studied medium sized cycloalkyl cations under stable ion conditions in non-nucleophilic media and demonstrated that their structures are ji.-hydrido-bridged. The bonding situation in these ions contrasts sharply with that in the ions described above and rather corresponds to that of transition states (or intermediates) for intramolecular hydride transfer in these ions. 

Mechanism The Wilkinson catalyst (6.9), a 6-electron complex, loses one or two triph-enylphosphine ligands and converts into a 14- or 12-electrons complex. The activation of hydrogen occurs by uptake on the metal complex catalyst via an oxidative addition. This is followed by ir-complexation of alkene to metal. Intramolecular hydride transfer and subsequent reductive elimination release the alkane and complete the cycle (Scheme 6.2). 

This observation led to the proposal that tethering two rhodium centers together via the bisphosphine ligands was producing some sort of bimetallic cooperativity between the two metal centers. An intramolecular hydride transfer, analogous to the intermolecular hydride transfer proposed by Heck (Scheme 1), enhanced by the proximity of the two metal centers, seemed a very likely possibility. 

The mixed Tishchenko reaction involves the reaction of the aldol prodnct 113 from one aldehyde with another aldehyde having no a-hydrogens to yield an ester The products were proposed to be formed through an aldol step (equation 33), followed by addition of another aldehyde (equation 34) and an intramolecular hydride transfer (equation 35). However, several aspects of this mechanism need to be clarified. As part of the continuing mechanistic studies carried out by Streitwieser and coworkers on reactions of alkali enolates ", it was found that the aldol-Tishchenko reaction between certain lithium eno-lates and benzaldehyde proceeded cleanly in thf at room temperature". Reaction of the lithium enolate of isobutyrophenone (Liibp) with 1 equiv of benzaldehyde in thf at — 65 °C affords a convenient route to the normal aldol product 113 (R = R" = Ph, R = Me). At room temperature, however, the only product observed after acid workup was the diol-monoester 116, apparently derived from the corresponding lithium ester alcoholate (115, R = R" = Ph, R = Me), which was quantitatively transformed into 116 after quenching. As found in other systems", only the anti diol-monoester diastereomer was formed. 

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