BROWN Stereoselective reduction

BREDERECK Imidazole synthesis 48 BROOK Sitaketona rearrangement 49 BROWN Stereoselective reduction 50 BROWN Hydroboiation 51-52 Bnirmer 104... 

Brown Stereoselective reduction 10( ketones to alcohols by means ot boiohydnde reagents l°r formation ol chiral alcohols)... 

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

In a totally different approach, Noyori et al. have used binaphthol-modifled aluminum hydride reagent for enatioselective reduction of alkynyl ketones. Suitably modified boranes can be used for stereoselective reduction of ketones. Along these same lines. Midland" has developed Alpine borane (1, Scheme 21.5), which is excellent for several acetylenic ketones but has been found inefficient for hindered ot,p-acetylenic ketones. To overcome this problem, Brown et al." have introduced P-chlorodiisopinocamphenyl borane 2(-)-DIP-Cl (2, (Scheme 21.5), which reacts well with hindered ketones to provide the corresponding propargyl alcohols in 96 to 99% e.e. 

A stereoselective total synthesis of ( )-hirsutine has been developed by Brown et al. (179). Catalytic hydrogenation of hydroxycyclopentenone 327, prepared previously (180), afforded a mixture of isomeric diols 328, which were quantitatively cleaved by sodium periodate to supply 329. Reductive amination of 329 with tryptamine resulted in tetrahydropyridine 330, which upon treatment with aqueous methanol in the presence of hydrochloric acid gave indolo-[2,3-a]quinolizine 321 with pseudo stereochemistry. Conversion of 321 to ( )-hirsutine was accomplished in a similar manner by Wenkert et al. (161) via selective reduction with diisobutylaluminum hydride and methylation with methanol (179). 

U. Kazmaier, J. M. Brown, A. Pfaltz, P. K. Matzinger, H. G. W. Leuenberger, Formation of C-H Bonds by Reduction of Olefinic Double Bonds Hydrogenation, in Methoden Org. Chem. (Houben-Weyl) 4th ed. 1952-, Stereoselective Synthesis (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), Vol. E21d, 4239, Georg Thieme Verlag, Stuttgart, 1995. 

The stereoselectivities of the carbonyl group reductions with Alpine-Borane (Figure 10.24) or with Brown s chloroborane (Figure 10.25) are explained as shown in the for-... 

In an investigation of meso- and c/,/-3,4-dibromohexane and of meso- and d,1-2,5-dimethyl-3,4-dibromohexane. Brown and coworkers [74] found that the meso compounds are easier to reduce than the dj species. Moreover, for the reduction of 3,4-dibromohexane in DMF at less negative potentials, the meso isomer affords trans-h.QX-3-QnQ exclusively, whereas the d,l compound gives only cw-hex-3-ene however, at more negative potentials, the stereoselectivity is lost, and the trans-cis product ratios are 50 50 for the meso isomer and 70 30 for the d,l isomer. Evans and coworkers [75,76] employed cyclic voltammetry to probe the temperature-dependent conformational equilibrium for a number of vicinal dibromides, and Lexa and coworkers [77] have discussed inner- and outer-sphere processes for the reduction of vicinal dibromides. 

Rogic, M. M., Ramachandran, P. V., Zinnen, H., Brown, L. D., Zheng, M. The origins of stereoselectivity in asymmetric reductions with boranes based on (+)-a-pinene. II. The geometries of competing transition-states and the nature of the reaction. A semiempirical study. 

Selective reductions. Brown et al.2 conducted an extensive study of reductions with diborane in THF. Most aldehydes and ketones are readily reduced unusually high stereoselectivity was realized in the case of norcamphor, which was reduced to 98% endo-norbornanol and 2% exo-norbornanol. p-Benzoquinone is reduced to hydroquinone at a moderate rate, but reduction of anthraquinone is sluggish. Carboxylic acids are reduced very rapidly indeed this group can be reduced selectively in the presence of many other substituents. Acid chlorides react much more slowly than carboxylic acids. Esters and ketones are reduced relatively slowly. Reactions with epoxides are relatively slow and complex. 

Hydroboration. Hydroborations with this reagent have been reviewed Brown concludes that the regio- and stereoselectivity of 9-BBN surpass those of other hydroboration reagents. An example of the marked stereospecificity of hydroboration with 9-BBN is the reduction of 1-substituted cycloalkenes to trc/i5-2-methylcycloalkanols (equation I). The same selectivity is shown in the hydroboration of 1,3-dimethylcycloalkenes (equation II). In fact this method is... 

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