Lithium tris borohydride

Enantiomerically pure 3-tolyl-2-sulfinyl-2-cyclopentenone 37 undergoes smooth, mild and diastereoselective conjugate hydride addition with lithium tri(sec-butyl)borohydride to afford ultimately 3-tolylcyclopentanone 38 in 93% enantiomeric purity (equation 35)78. The absolute stereochemistry of product 38 is consistent with a chelated intermediate directing hydride addition from that diastereoface containing the sulfoxide lone pair. 

The key intermediate 124 was prepared starting with tryptophyl bromide alkylation of 3-acetylpyridine, to give 128 in 95% yield (Fig. 37) [87]. Reduction of 128 with sodium dithionite under buffered (sodium bicarbonate) conditions lead to dihydropyridine 129, which could be cyclized to 130 upon treatment with methanolic HC1. Alternatively, 128 could be converted directly to 130 by sodium dithionite if the sodium bicarbonate was omitted. Oxidation with palladium on carbon produced pyridinium salt 131, which could then be reduced to 124 (as a mixture of isomers) upon reaction with sodium boro-hydride. Alternatively, direct reduction of 128 with sodium borohydride gave a mixture of compounds, from which cyclized derivative 132 could be isolated in 30% yield after column chromatography [88]. Reduction of 132 with lithium tri-f-butoxyaluminum hydride then gave 124 (once again as a mixture of isomers) in 90% yield. 

Replacement of hydrogen by alkyl groups gives compounds like lithium triethylborohydride (Super-Hydride ) [100], lithium tris sec-butyl)borohydride [101] (L-Selectride ) and potassium tris sec-butyl)borohydride (K-Selectride ) [702], Replacement by a cyano group yields sodium cyanoborohydride [103], a compound stable even at low pH (down to 3), and tetrabutylammonium cyanoborohydride [93],... 

Transformation of ketones to alcohols has been accomplished by many hydrides and complex hydrides by lithium aluminum hydride [55], by magnesium aluminum hydride [89], by lithium tris tert-butoxy)aluminum hydride [575], by dichloroalane prepared from lithium aluminum hydride and aluminum chloride [816], by lithium borohydride [750], by lithium triethylboro-hydride [100], by sodium borohydride [751,817], by sodium trimethoxyborohy-dride [99], by tetrabutylammonium borohydride [771] and cyanoborohydride [757], by chiral diisopinocampheylborane (yields 72-78%, optical purity 13-37%) [575], by dibutyl- and diphenylstannane [114], tributylstanrume [756] and others Procedure 21, p. 209). 

Reduction of unsaturated ketones to saturated alcohols is achieved by catalytic hydrogenation using a nickel catalyst [49], a copper chromite catalyst [50, 887] or by treatment with a nickel-aluminum alloy in sodium hydroxide [555]. If the double bond is conjugated, complete reduction can also be obtained with some hydrides. 2-Cyclopentenone was reduced to cyclopentanol in 83.5% yield with lithium aluminum hydride in tetrahydrofuran [764], with lithium tris tert-butoxy)aluminium hydride (88.8% yield) [764], and with sodium borohydride in ethanol at 78° (yield 100%) [764], Most frequently, however, only the carbonyl is reduced, especially with application of the inverse technique (p. 21). 

Other reagents used for the preparation of lactones from acid anhydrides are lithium borohydride [1019], lithium triethylborohydride (Superhydride ) [1019] and lithium tris sec-butyl)borohydride (L-Selectride ) [1019]. Of the three complex borohydrides the last one is most stereoselective in the reduction of 3-methylphthalic anhydride, 3-methoxyphthalic anhydride, and 1-methoxynaphthalene-2,3-dicarboxylic anhydride. It reduces the less sterically hindered carbonyl group with 85-90% stereoselectivity and is 83-91% yield [1019]. 

Although sodium borohydride appears to be the most popular reducing agent, a significantly better endo selectivity was achieved in the reduction of bicyclo[3.2.0]hept-2-en-6-ones using lithium tri-fer -butoxyaluminum hydride instead, e.g. formation of 3.251 In another study,99 lithium tri-sec-butylborohydride was found to reduce (la,4a,5a)-4-benzy)oxycarbonyl-2-oxabi-cyclo[3.2.0]heptan-6-one to (la,4oc,5a,6/i)-4-benzyloxycarbonyl-2-oxabicyclo[3.2.0]heptan-6-ol (4) with complete stereoselectivity. 

Oxidation reactions r-Butyl hydroperoxide-Dialkyl tar-trate-Titanium(IV) isopropoxide, 51 m-Chloroperbenzoic acid, 76 Reduction reactions Chlorodiisopinocampheylborane, 72 Diisobutylaluminum hydride-Tin(II) chloride- (S) -1 - [ l-Methyl-2-pyrrolidi-nyljmethylpiperidine, 116 Lithium borohydride, 92 Lithium tri-sec-butylborohydride, 21 B-3-Pinanyl-9-borabicyclo[3.3.1]-nonane, 249... 

Triethylaluminum, 204 Triisobutylaluminum, 205 Trimethylaluminum, 22, 205 Vilsmeier reagent-Lithium tri-r-butoxy-aluminum hydride, 342 Boron Compounds Alkyldimesitylboranes, 8 Allenylboronic acid, 36 9-Borabicyclo[3.3.1]nonane, 92 Borane-Dimethylamine, 42 Borane-Dimethyl sulfide-Sodium borohydride, 25... 

Stereoselective reductions based on complexed borohydrides have also proved of value in many instances in particular they have been of use in the synthesis of epimeric cyclic alcohols. For example, the reduction of 4-t-butylcyclo-hexanone to the cis-alcohol [99.5%, arising from equatorial hydride ion attack (i)] is effected by L-Selectride (lithium tri-s-butylborohydride, cf. Section 4.2.49, p. 448), or LS-Selectride53 (lithium trisiamylborohydride, cf. Section 4.2.49, p. 448) but to the trans-alcohol [98%, arising from axial hydride ion attack (ii)] with lithium butylborohydride.54 The experimental details of these reductions are given in Expt 5.34. 

REDUCTION, REAGENTS Aluminum amalgam. Borane-Dimethyl sulfide. Borane-Tetrahydrofurane. t-Butylaminoborane. /-Butyl-9-borabicyclo[3.3.1]nonane. Cobalt boride— f-Butylamineborane. Diisobutylaluminum hydride. Diisopropylamine-Borane. Diphenylamine-Borane. Diphenyltin dihydride. NB-Enantrane. NB-Enantride. Erbium chloride. Hydrazine, lodotrimethylsilane. Lithium-Ammonia. Lithium aluminum hydride. Lithium borohydride. Lithium bronze. Lithium n-butylborohydride. Lithium 9,9-di-n-butyl-9-borabicyclo[3.3.11nonate. Lithium diisobutyl-f-butylaluminum hydride. Lithium tris[(3-ethyl-3pentylK>xy)aluminum hydride. Nickel-Graphite. Potassium tri-sec-butylborohydride. Samarium(II) iodide. Sodium-Ammonia. Sodium bis(2-mcthoxyethoxy)aluminum hydride. 

Stereoselective reduction of 3-ketogibberellin adds.1 The 3-ketogibberellin acid 1 is reduced by this borohydride almost entirely to the 3/(-alcohol. Reduction with lithium tri-.wr-hutylhorohydride proceeds with the opposite stereoselectivity. The dilfcrence is considered lo be the result of differences in size between potassium and lithium borate complexes with the carboxylic acid group. 

Then lithium tris-sec-butyl-borohydride (L-Selectride ) 38 is added and the ketone is selectively transformed to get 9.14... 

Secondary enamino sulphoxides were reduced through their imino forms, with L-selectride [lithium tri(s-butyl)borohydride] to give jS-aminosulphoxides of R, R configuration with high stereoselectivity120 (Scheme 89). 

The sodium borohydride reduction of l-[j8-(3-indolyl)ethyl]-3-hydroxymethylpyridinium bromide (100, R = H) affords a 73% yield-of the 3-piperideine (101), but with the use of lithium aluminum hydride a 50% yield of the diene (102) is obtained. The lithium tri-f-butoxy aluminum hydride reduction of (100) leads to a mixture... 

Stereoselective reduction of ketones. This borohydride (1) is comparable to lithium tri-.ver-butylborohydride (4. 312-313) for stereoselective reduction of cyclic ketones to the less stable alcohols, but less stereoselective than lithium trisiamylborohydride (7, 216-217). The by-product formed in reductions with I can be removed as an insoluble ate complex formed by addition of water, simplifying isolation of the reduction product. 

REDUCTION, REAGENTS Bis(N-methylpi-perazinyl)aluminum hydride. Borane-Di-methyl sulfide. Borane-Tetrahydrofurane. Borane-Pyridine. n-Butyllithium-Diisobu-tylaluminum hydride. Calcium-Amines. Diisobutylaluminum hydride. 8-Hydroxy-quinolinedihydroboronite. Lithium aluminum hydride. Lithium 9-boratabicy-clo[3.3.1]nonane. Lithium n-butyldiisopro-pylaluminum hydride. Lithium tri-j c-butylborohydride. Lithium triethylborohy-dride. Monochloroalane. Nickel boride. 2-Phenylbenzothiazoline. Potassium 9-(2,3-dimethyl-2-butoxy)-9-boratabicy-clo[3.3.1]nonane. Raney nickel. Sodium bis(2-methoxyethoxy)aluminum hydride. Sodium borohydride. Sodium borohy-dride-Nickel chloride. Sodium borohy-dride-Praeseodymium chloride. So-dium(dimethylamino)borohydride. Sodium hydrogen telluride. Thexyl chloroborane-Dimethyl sulfide. Tri-n-butylphosphine-Diphenyl disulfide. Tri-n-butyltin hydride. Zinc-l,2-Dibromoethane. Zinc borohydride. 

Reduction of acid chlorides to aldehydes One of the most useful synthetic transformations in organic synthesis is the conversion of an acid chloride to the corresponding aldehyde without over-reduction to the alcohol. Until recently, this type of selective reduction was difficult to accomplish and was most frequently effected by catalytic hydrogenation (the Rosenmund reduction section 6.4.1). However, in the past few years, several novel reducing agents have been developed to accomplish the desired transformation. Among the reagents that are available for the partial reduction of acyl chlorides to aldehydes are bis(triphenylphosphine)cuprous borohydride , sodium or lithium tri-terf-butoxyaluminium hydride, complex copper cyanotrihydridoborate salts °, anionic iron carbonyl complexes and tri-n-butyltin hydride in the presence of tetrakis(triphenylphosphine)palladium(0). ... 

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