Chiral alcohols hydrogenolysis

In contrast to phenolic hydroxyl, benzylic hydroxyl is replaced by hydrogen very easily. In catalytic hydrogenation of aromatic aldehydes, ketones, acids and esters it is sometimes difficult to prevent the easy hydrogenolysis of the benzylic alcohols which result from the reduction of the above functions. A catalyst suitable for preventing hydrogenolysis of benzylic hydroxyl is platinized charcoal [28], Other catalysts, especially palladium on charcoal [619], palladium hydride [619], nickel [43], Raney nickel [619] and copper chromite [620], promote hydrogenolysis. In the case of chiral alcohols such as 2-phenyl-2-butanol hydrogenolysis took place with inversion over platinum and palladium, and with retention over Raney nickel (optical purities 59-66%) [619]. 

Ester-based chiral auxiliaries have also beat used in other settings. P-Alk-oxyesters 1.27 of (R)-1 -phenylethanol 1.1 (R = Me, Ar = Ph) or (5)-1-naphthyl-ethanol 1.1 (R = Me, Ar = 1-Np) are transformed into dural synthons by reactions with a lithiated carbanion a to phosphorous followed by hydrogenolysis [194], Ethers 1.28 of chiral alcohols 1.1 undergo selective alkylations or hydroxyalkyla-tions [169]. The auxiliaries can be removed by hydrogenolysis. Enol or dienol ethers 1.29 and 1 JO suffer [2+2] [195, 196] or [4+2] cycloadditions [49, 197,198, 199], The best stereoselectivities are obtained when the chiral auxiliary is 1.1 (R = r-Pr, Ar=Ph), 1.4 (R=Ph), 1.5 (R = Ph), 1.10 or 1.13. These auxiliaries are cleaved either by acid treatment [199] or by other means in subsequent steps. Acetylene ethers G OC=CR derived from 1.5 (R=Ph) [199a] can undergo stereoselective Pauson-Khand reactions [200, 201], The auxiliaries are removed by treatment of the products with Sml2 in THF-MeOH. 

Asymmetric hydrogenolysis of epoxides has received relatively little attention despite the utility such processes might hold for the preparation of chiral secondary alcohol products. Chan et al. showed that epoxysuccinate disodium salt was reduced by use of a rhodium norbornadiene catalyst in methanol/water at room temperature to give the corresponding secondary alcohol in 62% ee (Scheme 7.31) [58]. Reduction with D2 afforded a labeled product consistent with direct epoxide C-O bond cleavage and no isomerization to the ketone or enol before reduction. 

Significantly better results in addition of non-stabilized nucleophiles have come from hydrogenolysis reactions using formate as a hydride donor as shown in Scheme 8E.46. The racemic cyclic acetate and prochiral linear carbonates were reduced in good enantioselectivities by monophosphine ligands (/ )-MOP (16) and (Zf)-MOP-phen (17), respectively [195]. The chirality of the allylsilane can be efficiently transferred to the carbinol center of the homoallylic alcohol by the subsequent Lewis acid catalyzed carbonyl addition reaction 1196], The analogous... 

A very high degree of stereoselectivity was observed when certain chiral amino alcohols were used as the amine component (Scheme 7.9) [34]. For example, either enantiomer of homo-phenylalanine (61 and 64) could be efficiently prepared beginning with one of the two enantiomers of 2-phenylglycinol (59 and 62), followed by hydrogenolysis of the corresponding intermediate (60 and 63). 

The ethers are stable to aqueous or alcoholic base, to hydrogenolysis (H2 Pd), and to mild chemical reduction (Zn-CH OH). The dimethyl-/-butylsilyl group is an alternative to the tetrahydropyranyl group but has the advantage that it does not have a chiral... 

Photochemical conversion of an amino(cyclopropyl)carbene (obtained from cyclopro-pyl(methoxy)carbene with optically pure D,i.-erythro amino alcohols) gave a cyclopropyl-substituted lactone, e.g. formation of 13, which upon hydrogenolysis gave a chiral cyclopropyl-glycine system.The reaction proceeds via a ketene complex. 

Simultaneously and independently, Cullis and Lowe developed a second general methodology for the synthesis of, 0, 0-labeled chiral phosphate monoesters (76, 77). This synthesis relies upon the synthesis of a cyclic hydrobenzoin triester of the alcohol or phosphoric acid followed by hydrogenolysis to liberate the isotopically labeled monoester product (Fig. 2). Hydrobenzoin, chiral by virtue of stereospecific labeling with 0 and 0, is the source of the two specified oxygen isotopes, and O is derived from H2 0 via P OCL. The reader is referred to the articles by Cullis and Lowe for details of the synthesis. 

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