Lithium tris borohydride reduction

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. 

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... 

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. 

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). ... 

Tamm found the reagent useful for reduction of carbonyl groups in the bufadien-olide series. Thus reduction of the ketone (11) with sodium borohydride suffered from the fact that the unsaturated lactone ring is attacked to some extent and the yield of (12) was only 40-50%. Reduction with lithium tri-f-butoxyaluminum hydride in tetrahydrofurane at 0° proceeded rapidly (15 min.), the lactone ring was... 

Such a phenol keto-tautomer equivalent strategy was used for conjugate reduction of cyclic enones (equation 5). The quinone monoketals 9 and para-quinol ethers 10 were used as precursors to keto-tautomer equivalents of substituted phenols, namely enones 11, which were prepared by action of bis(2,6-di-fert-butyM-methylphenoxy)methylaluminium (MAD), followed by addition of lithium tri-iec-butyl borohydride (L-Selectride). The enones 11 obtained are reasonably stable at a freezer temperature without aromatization. ... 

Lithium tri-fert-Butoxyaluminohydride is a bulky chemo- and stereoselective hydride reducing agent. Aldehydes are reduced chemoselectively in the presence of ketones and esters at low temperature. Ethers acetals, epoxides, chlorides, bromides, and nitro compounds are unaffected by this reagent. Reviews (a) Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in Organic Synthesis Wiley-VCH NewYork, 1997, 2" edition, (b) Malek, J. Org. React. 1985, 34, 1-317. 

Mercury(II) compounds are less effective as catalysts for Cope and oxy-Cope rearrangements777- 783, 84. Treatment of tertiary alcohol 14 with stoichiometric amounts of mereury(II) trilluoroacetate primarily leads to a mercurated ketone 15, from which the mercury is removed by sodium borohydride reduction, 85. The same overall result is obtained by using catalytic amounts of mercury(II) trifluoroacetate in the presence of an excess of lithium tri-fluoroacetate783. 

The reduction of iV-diphenylphosphinyl imines of substituted cycloalkanones with lithium tri-sw-butylborohydride (L-Selectride) provides highly diastereoselective conversions to protected axial primary amines in 83-96% yield17. The reduction of cyclohexylidene diphenylphos-phinyl imines with sodium borohydride is less diastereoselective17. 

In two separate routes the aminoepoxides were obtained by highly stereoselective methods. Chlorination of iV -benzoylquinotoxine (5) with iV -chlorodiisopropylamine in 100% phosphoric acid in the dark gave an amorphous mixture of the epimeric a-chloroketones 85 and 86 (Scheme 8) [10). Reduction with sodium borohydride or with lithium tri-i-butoxyaluminum hydride afforded stereoselectively a mixture of the threo chlorohydrins 87 and 88. Treatment of 87 and 88 with aqueous potassium hydroxide at 20°C gave smoothly a mixture of the erythro iV-benzoylepoxides 89 and 90. The benzoyl groups were removed reductively with diisobutylaluminum hydride to give the aminoepoxides 81 and 82 which were cyclized in refluxing toluene-methanol (100 1). This reaction yielded 9-ep -quinine (12) and 9-epi-quinidine (13) in a ratio of 2 1. The overall yield of 12 and 13 from 87 and 88 was 50%. Only traces of the erythro products quinine and quinidine were observed. 

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