Reductions, selective, with diborane

The resulting acetate 116 is formulated as the tawis-isomer, too. The carboxylic group was then converted by selective reduction with diborane to the alcohol 117. The alcohol function was converted to the nitrile 119 via the tosylate 118 and displacement of the tosylate group with sodium cyanide. Methanolysis led to the methylester 120 because the acetate moiety was not cleaved under these conditions (MeOH/HCl). Hydrolysis with base yielded the deprotected lactone acid alcohol 121, which was purified by converting it into the methylester 122. 

A new application of the Schmidt rearrangement is to give unnatural aminoacids <91BMC125>. Treatment of the optically active cyclic -ketoester (266) with hydrazoic acid gives the optically active azepinone (267) which upon selective reduction with diborane furnishes the novel cyclic amino acid ester (268) (Scheme 36). 

The main methods of reducing ketones to alcohols are (a) use of complex metal hydrides (b) use of alkali metals in alcohols or liquid ammonia or amines 221 (c) catalytic hydrogenation 14,217 (d) Meerwein-Ponndorf reduction.169,249 The reduction of organic compounds by complex metal hydrides, first reported in 1947,174 is a widely used technique. This chapter reviews first the main metal hydride reagents, their reactivities towards various functional groups and the conditions under which they are used to reduce ketones. The reduction of ketones by hydrides is then discussed under the headings of mechanism and stereochemistry, reduction of unsaturated ketones, and stereochemistry and selectivity of reduction of steroidal ketones. Finally reductions with the mixed hydride reagent of lithium aluminum hydride and aluminum chloride, with diborane and with iridium complexes, are briefly described. 

To avoid the production of diastereomers during reductive alkylation of Pro residues, the corresponding dipeptide should be first synthesized and the central amide bond subsequently selectively reduced with diborane (see Section 10.7.1.2.1). 

Direct reduction of a peptide bond with diborane 59 or a thioamide bond with several reductive procedures 60 is an alternative route for the production of a reduced peptide bond in a peptide. In some cases the reductive amination does not give satisfactory results. As described earlier, preparation of Boc-Pher )[CH2N]Pro-OH by reductive amination yields two diastereomers (Scheme ll). 57 In this case treatment of Boc-Phe-Pro-OBzl by diborane yielded the reduced pseudodipeptide Boc-Pher )[CH2N]Pro-OBzl without epimerization (Scheme 12). However, in some cases diborane is not entirely selective for the amide bond and can reduce ester functions when they are present. Another procedure is to prepare endothiopeptides directly from protected dipeptides 61-66 followed by their selective reduction. 60 ... 

Selective protection of an aldehyde.1 Selective reduction of 4-acetylbenzaldehyde (1) to 4-(l-hydroxyethyl)benzaldehyde (3) is possible by conversion to the sodium bisulfate adduct (2), which is absorbed on silica to increase the stability. The dried adduct is then reduced with diborane. Use of alumina as support is less satisfactory. 

Selective reduction of progesterone at C s) with diborane M. Stefa-Novid AND S. Tetrahedron Letters, No. 19 (1967) 1777. 

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. 

Primary Amines. - Reductive methods in the preparation of amines continue to be popular. In particular, anilines can be prepared under mild conditions and in good yields by reduction of nitrobenzenes with the new system of diborane-nickel (II) chloride." Selective reduction in the presence of a number of functional groups is the chief advantage of the method. Nitrobenzenes are also... 

Attempts to prepare the required bicyclic azetidines by selective reduction of the C-7 carbonyl bond in penicillins failed [66, 67,68] treatment with diborane in THF gave exclusively the aminoalcohols 107 resulting from the cleavage of the four-membered ring (Scheme 34). However, 3-hydroxypropylamine derivatives can be transformed into azetidines, using for instance a modified Mitsonobu reaction [69, 70]. Nevertheless, this transformation was unsuccessful with compound 107b because cyclisation occurred onto the acylamino side-chain to yield dihydrooxazole 108 (Scheme 35). 

There is, however, a major disadvantage in using boron trifluoride or tetrafluoroborates in the preparation of diborane, for they result in a product that is contaminated with BF3, which is not readily removed (29). Particularly when the diborane is required for selective reductions, this is a most undesirable impurity traces of BF3 enhance the reducing powers of B2Hg and catalyze hydrogenolysis at centers that would not otherwise be attacked (24). 

Diborane is also a useful reagent for reducing amides. Tertiary and secondary amides are quite easily reduced, but primary amides react only slowly. Amides require vigorous conditions for complete reduction by LiAlH4. Selective reduction of amides in the presence of such functional groups as ester and nitro are therefore best done with diborane. 

Amides require vigorous reaction conditions for reduction by LiAlH4 so that little selectivity can be achieved with this reagent. Diborane, however, permits the reduction of amides in the presence of ester and nitro groups. 

There are several reports of methods that will selectively reduce a tertiary amide in the presence of a secondary amide[59]. The secondary lactam of 101 was protected as the lactim ether 107 and treated with diborane however, the spectral characteristics of the major products isolated were consistent with reduction of both the tertiary amide and the lactim ether. In 1991 Martin et al. [60] successfully used alane to reduce a tertiary amide in the presence of an oxindole (secondary amide) relying on the known rate difference for reduction between these two groups [61]. 

BROWN, HERBET C. (1912-). An English-born chemist who was the recipient of the Nobel prize for chemistry with Wuug. Georg in 1979. Via his work in organic synthesis, he discovered new routes to arid substituents to olefins selectively. His early education was irregular and disjointed as a result of family circumstances and the economic depression of the 1930s. He eventually received his Ph.D. from the University of Chicago. The reduction of carbonyl compounds with diborane was the topic of... 

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