Reduction using borane

E.J. Corey and co-workers synthesized the cdc25A protein phosphatase inhibitor dysidiolide enantioselectively. In the last phase of the total synthesis, the secondary alcohol functionality of the side-chain was established with a highly diastereoselective oxazaborolidine-catalyzed reduction using borane-dimethylsulfide complex in the presence of the (S)-6-methyl CBS catalyst. Finally, a photochemical oxidation generated the y-hydroxybutenolide functionality. This total synthesis confirmed the absolute stereochemistry of dysidiolide. 

Reduction using boranes. A practical modification of the oxazaborolidine-catalyzed reduction of ketones with borane is to replace the trialkylborane component with trimethyl borate. For the reduction of (3-silyl and ( -stannyl enones the use of 80 is advocated. ... 

Scheme 17 Reduction of nitriles using borane dimethyl sulfide and microwave irradiation...

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-... 

Kragl and Wandrey made a comparison for the asymmetric reduction of acetophenone between oxazaborolidine and alcohol dehydrogenase.[59] The oxazaborolidine catalyst was bound to a soluble polystyrene [58] and used borane as the hydrogen donor. The carbonyl reductase was combined with formate dehydrogenase to recycle the cofactor NADH which acts as the hydrogen donor. Both systems were run for a number of residence times in a continuously operated membrane reactor and were directly comparable. With the chemical system, a space-time yield of 1400 g L"1 d"1 and an ee of 94% were reached whereas for the enzymatic system the space-time yield was 88 g L 1 d"1 with an ee of >99%. The catalyst half-life times were... 

The reduction using oxazaborolidine borane needs to be done in anhydrous... 

Other reagents used for reduction are boranes and complex borohydrides. Lithium borohydride whose reducing power lies between that of lithium aluminum hydride and that of sodium borohydride reacts with esters sluggishly and requires refluxing for several hours in ether or tetrahydrofuran (in which it is more soluble) [750]. The reduction of esters with lithium borohydride is strongly catalyzed by boranes such as B-methoxy-9-bora-bicyclo[3.3.1]nonane and some other complex lithium borohydrides such as lithium triethylborohydride and lithium 9-borabicyclo[3.3.1]nonane. Addition of 10mol% of such hydrides shortens the time necessary for complete reduction of esters in ether or tetrahydrofuran from 8 hours to 0.5-1 hour [1060],... 

Introduction of the C2 sulfonamide is accomplished via sulfonylation with chlorosulfonic acid, conversion to the sulfonyl chloride using thionyl chloride, and amidation using concentrated ammonium hydroxide in tetrahydrofuran. Reduction of the 4-acetamido compound using borane-tetrahydrofuran complex provides the 4-ethylamino derivative. The 45,65-frans diastereomer is selectively crystallized as its maleate salt from acetone in the presence of the unwanted 4R,6S-cis diastereomer. Neutralization of the maleate salt and extraction of the free base in ethyl acetate, followed by formation of the hydrochloride salt, yields crude dorzolamide hydrochloride. 

M, Ek, P. J. Garegg, H. Hultberg, and S. Oscarson, Reductive ring openings of carbohydrate benzylidene acetals using borane-trimethylamine and aluminium chloride. RegioSelectivity and solvent dependence, J. Carbokydr. Chem. 2 305 (1983). 

The enantioselective reduction of ketones using borane and a chiral oxazaborolidine as catalyst (CBS Catalyst). Usually, MeCBS... 

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. 

Corey originally used borane-THF as a stoichiometric reducing agent [2, 5]. The use of more robust borane sources, borane-N,N-diethylaniline [6, 7] and borane-N-ethyl-N-isopropylaniline [8, 9], rendered the CBS reduction easier to handle without sacrificing enantioselectivity. Borane-THF prepared in situ from NaBH4 and (CHalaSiCl in THF [10] was also shown to be useful for this type of reduction [11]. 

Lane CF, Myatt HL, Daniels J, Hopps HB (1974) Organic synthesis using borane-methyl sulfide II Reduction of aromatic carboxylic acids in the presence of tnmethyl borate J Org Chem 39 3052-3054... 

C. The reported procedure provides a practical preparation of (S)-tetrahydro-i-methyl-3,3-diphenyl-lH,3H-pyrrolo[i,2-c][l,3,2]oxazaboroie and conversion to its more stable borane complex.13 The oxazaborolidine-borane complex has also been prepared by treatment of a toluene solution of the free oxazaborolidine with gaseous fiborane followed by recrystallization from a dichloromethane-hexane bilayer.14 This nd other chiral oxazaborolidines have been used to catalyze the enantioselective eduction of prochiral ketones.15 The yield and enantioselectivity of reductions using catalytic amounts of the oxazaborolidine-borane complex are equal to or greater than those obtained using the free oxazaborolidine.13... 

D. The use of chiral oxazaborolidines as enantioselective catalysts for the reduction of prochiral ketones, imines, and oximes, the reduction of 2-pyranones to afford chiral biaryls, the addition of diethylzinc to aldehydes, the asymmetric hydroboration, the Diels-Alder reaction, and the aldol reaction has recently been reviewed.15b d The yield and enantioselectivity of reductions using stoichiometric or catalytic amounts of the oxazaborolidine-borane complex are equal to or greater than those obtained using the free oxazaborolidine.13 The above procedure demonstrates the catalytic use of the oxazaborolidine-borane complex for the enantioselective reduction of 1-indanone. The enantiomeric purity of the crude product is 97.8%. A... 

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). 

Reduction using 0.25 mol equiv of the catalyst with excess borane-THF. Reduction using the catalyst derived from (5)-diphenyl-O-benzyltyrosenol. AICI3 added to the ketoxime O-ether prior to reduction. 

Enantioselective Ketone Reduction. Following Itsuno s lead for enantioselective reductions using diphenylvalinol, Kraatz was the first to describe the use of a 1 2 mixture of (5)-diphenylprolinol (1) and Borane-Tetrahydrofuran for the stoichiometric enantioselective reduction of ketone (2) to obtain the plant growth regulator triapenthenol (3) (eq 1). Although not characterized at the time, the species responsible for the enantiose-lectivity observed was presumed to be an oxazaborolidine-borane complex. ... 

Alkali-metal hydrides, boranes or alanes react with alkoxysilanes or silanols to form Si—H bonds in reactions that often are preferred syntheses, depending on the availability of the silane reactant "Lithium hydride or alanate reductions used are ... 

Reduction of a ketoxime is a very useful procedure for introducing a primary amine. Many reducing agents will perform this reduction, including borane, lithium aluminum hydride, and... 

Saturated ketones are not readily reduced by Alpine-Borane. However, the intramolecular version of this reduction using (Ipc)2BH proceeds with good yield and facial selectivity. ... 

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