Reduction with boranes

The aziridine carbinols are also effective ligands in the preparation of oxazaborolidine catalysts for the asymmetric ketone reduction with borane (Fig. 4) [551. 

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

Scheme 5.13 Chiral sulfoxide preparation and olefin reduction with borane.

Tertiary amines have been prepared in good yield by a repetitive generation of imida-zolides and subsequent reduction with borane/dimethylsulfide, 1361 as the following examples show ... 

Decomposition of the reaction mixtures with water followed by dilute acids applies also to the reductions with boranes and alanes. Modifications are occasionally needed, for example hydrolysis of esters of boric acid and the alcohols formed in the reduction. Heating of the mixture with dilute mineral acid or dilute alkali is sometimes necessary. 

REDUCTION WITH BORANE IN SITU Reduction of Esters to Alcohols [738]... 

Comparison of Products and Reactivities of Functional Groups for Reduction with Borane and Metal Hydrides3,6... 

Reduction of the nitro compounds (193 R = R = H, or R = Me, R = OH) with lithium aluminum hydride affords the corresponding saturated amine.556 Similar reduction of carboxamides with the general formula (194) affords the corresponding amines143,8n 313, 568,569. jn t,]ie Case of 194 (R = H, R = 6-OMe), reduction with borane tetrahydrofuranate is more satisfactory.312... 

Reduction with borane/tetrahydrofuran8 regenerated enantiomerically pure (S)-(-)-2-methyl-1 -butanol, as shown by esterification with Mosher s acid and subsequent NMR analysis of the ester (see Note 1). 

An asymmetric synthesis of 3,4,5-trisubstituted-tetrahydro-l-benzazepines has been reported based on a type a ring construction process mediated by triethylaluminium with a chiral amino ester followed by lactam reduction with borane <2006OL2667>. Dynamic thermodynamic resolution in a lithiation-substitution sequence was integral to the preparation of the amino ester. An acid-catalyzed ring construction approach to the asymmetric synthesis of 4,5,6-trisubstituted- and 3,4,5,6-tetrasubstituted azepanes based on chiral acyclic precursors has also been described <2006JA2178>. 

The workers at Merck were able to go from start to finish in a single vessel. Base treatment of 22 + 23 led to attack at the epoxide end of 22 to give the anion 24. This is in equilibrium with the carbanion stabilised by Ar and CN and cyclises to an epoxide that gives a 15 85 mixture of the diastereoisomers 25 and 20. Reduction with borane gave a mixture of the amino alcohols... 

Radical methods are useful for the synthesis of highly functionalized enantiomerically pure cyclopentane derivatives [95SL918]. Reductive cyclization of the arabinolactone 88 furnished the eir-lactone 89 in quantitative yield. Exhaustive reduction with borane-dimethylsulfide gave the functionalized cyclopentane 90. 

Table 6.1.1. HPLC elution volumes of lignin acidolysis products after reduction with borane-dimethyl sulfide and acetylation...

Addition of phenylmagnesium chloride to methyl pyroglutamate followed by reduction with borane to give racemic a,a-diphenyl-2-pyrrolidinemelhanol (3 steps, 51% yield from pyrroglutamic acid) that was then resolved as its O-acetylmandelate salt 10 give (R)- or (S)-a,a-diphenyl-2-pyrrolidinemethanol (2 steps, 3 recrystallizations, 30% yield from racemic a,a-diphenyl-2-pyrrolidinemethanol ref. 5f). 

Nitro-4-(trifluoromethyl)-phenol 42 (Scheme 17) in reaction with 2-bromo-2-methyl-propionamide in the presence of cesium carbonate and cesium iodide in acetonitrile afforded 2-hydroxy-2-methylpropionamide 43, apparently via derivative 44 as the intermediate [32]. Amide 44, prepared on a circuitous route, on reduction with borane-dimethylsulfide complex, gave amine 45 as the only isolated product. The parent 2-hydroxy-2-methyl-W-(2-... 

The use of hydride reagentsfor the reduction of carboxylic acids requires vigorous conditions because the carboxylatc anion, once formed, is resistant to further nucleophilic attack. An interesting exception to this is reduction with borane. A triacyloxyborane may be formed. Re.sonance involving the vacant orbitals of the boron and the lone pairs on the oxygen has the effect of making the attack of a nucleophilic hydride on the carbonyl carbon of the acid easier (see 3.21). 

Aldrichimica Acta 1977, 10,A Brown, H.C. Krishnamurthy, S. Aldrichimica Acta 1979,12, 3. For reviews of reduction with borane derivatives, see Pelter, A. Smith, K. Brown, H.C. Borane Reagents, Academic Press, NY, 1988, pp. 125-164 Pelter, A. Chem. Ind. (London) 1976, 888. 

Rogic, M. M. Conformational Analysis and the Transition State in Asymmetric Reductions with Boranes Based on (+)-a-Pinene. 1. Benzaldehyde Reduction with Alpine Borane and Other B-Alkyl-9-borabicyclo[3.3.1]nonanes. ASemiempirical Study. J. Org. Chem. 1996, 61, 1341-1346. 

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. 

Valinol 27 and phenylalaninol 29 are used to make the Evans chiral auxiliaries used in asymmetric aldol reactions (chapter 27) and Evans prefers reduction with borane itself as its complex with Me2S. The phenylalanine based auxiliary 30 is generally preferred as the compounds are more likely to be crystalline and can easily be made11 on a 150 g scale. 

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