Lithium borohydride synthesis

The success of the halo ketone route depends on the stereo- and regio-selectivity in the halo ketone synthesis, as well as on the stereochemistry of reduction of the bromo ketone. Lithium aluminum hydride or sodium borohydride are commonly used to reduce halo ketones to the /mm-halohydrins. However, carefully controlled reaction conditions or alternate reducing reagents, e.g., lithium borohydride, are often required to avoid reductive elimination of the halogen. 

J.M. Lalancette et al., Reduction of Functional Groups with Sulfurated Borohydrides, Synthesis 1972, 526. J. Malek u. M. Cerny, Reduction of Organic Compounds by Alkoxyaluminohydrides, Synthesis 1972, 217. S.-C. Chen, Molecular Rearrangements in Lithium Aluminium Hydride Reduction, Synthesis 1974, 691. 

Liquid injection molding, for silicone rubbers, 3, 674—675 Liquid ligands, in metal vapor synthesis, 1, 229 Liquid-phase catalysis, supported, for green olefin hydroformylation, 12, 855 Lithiacarbaboranes, preparation, 3, 114 Lithiation, arene chromium tricarbonyls, 5, 236 Lithium aluminum amides, reactions, 3, 282 Lithium aluminum hydride, for alcohol reductions, 3, 279 Lithium borohydride, in hydroborations, 9, 158 Lithium gallium hydride, in reduction reactions, 9, 738 Lithium indium hydride, in carbonyl reductions, 9, 713—714... 

Lilly has used an Evans auxiliary in its synthesis of LY309887 (32), a dideazafolate antitumor agent (Scheme 23.8).2 The de of the key step, reaction of the titanium-derived enolate, was >98%. It was noted that the auxiliary could be recycled after cleavage with lithium borohydride. 

Enantioselective reduction of an a, -enone. One of the final steps in a synthesis of palytoxin, a toxin of marine soft corals containing 115 carbon atoms and 60 chiral centers, involves, in addition to the usual deprotections, enantioselective reduction of an enone to an allylic alcohol. A mixture (1 1) is obtained with borohydrides, but lithium borohydride combined with EuC13 provides an 8 1 mixture, with the desired isomer being favored. 

In 1972 Link and Bernauer (69) published a synthesis of (+)-isopilosine and of (+)-pilocarpine, and then obtained (—)-epiisopilosine as a by-product. The readily available ester 53 was converted in two steps to the aldehyde (54), which on Stobbe condensation with succinic ester gave the half-ester acid salt 55. Lithium borohydride reduction followed by prolonged acid treatment gave ( )-pilosinine [( )-32], together with 2,3-dehydropilosin-... 

A starting material for the synthesis of 9 is the 7-methoxymethyl ether of fraxetin (41), which was prepared by different workers using alternative methods. Tanaka et al. found it convenient to prepare it from fraxetin (35) by dropwise addition of a solution of chloromethyl methyl ether to a solution of 35 in a suspension of sodium hydride in THF. The reaction of this fraxetin derivative 41 with ethyl 2-bromo-3-(4-benzyloxy-3-methoxyphenyl)-3-oxopropionate (40) yielded an ether (42), which on lithium borohydride reduction yielded a mixture of diastereomers with threo- and erythro-Aio %, 43. Cyclization of this compound with sulphuric acid (5%) afforded cleomiscosin A monoacetate (44), which gave cleomiscosin A (9) on mild alkaline... 

In aprotic solvents, such as dichloromethane and THF, potassium boro-hydride [10], lithium borohydride [8b], lithium triethylborohydride [8a, 11], and diisobutylaluminum hydride (DIBALH) [11] have been used instead of NaBH4. NaBH4 also reduces elemental selenium in alcohol or water to sodium hydrogen selenide or sodium diselenide (Na2Se2) depending on the stoichiometry of the reactants (Scheme 8) [12]. These anions are useful for the synthesis of selenides or diselenides, respectively, via nucleophilic substitution with various electrophiles. 

Lithium hydride Lithium hydride is manufactured from metallic lithium and hydrogen. It is industrially important as a source of hydrogen and as a reducing agent in organic synthesis, particularly in the form of its derivatives lithium aluminum hydride and lithium borohydride. 

Lithium borohydride is more reactive than sodium borohydride, but less reactive than LiAlH4. Reviews (a) Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in Organic Synthesis Wiley-VCH New York, 1997, 2" edition, (b) Brown, H. C. Krishnamurthy, S. Tetrahedron 1979, 35, 567-607. 

Synthesis from L-threitol The L-threitol derivative 24, obtained from D-(-)-diethyl tartarate in three steps and 90% overall yield, was used as a starting material for the synthesis of nectrisine (1) (Scheme 5). " Swern oxidation of 24 produced the L-threose derivative 25, which was transformed into the aminonitrile 26 in 96% overall yield from 24, as an inseparable diastereomeric mixture. Removal of the silyl protecting group from 26 followed by oxidation of the resulting primary hydroxyl group with TPAP afforded the lactam 27, which was treated with sodium methoxide to produce the methyl ester 28 in 62% yield from 26. Lithium borohydride reduction of 28 afforded a chromatographically separable mixture of the lactams 29 and 30 in a ratio of 56 44 and 87% total yield. Silylation... 

Synthesis from aldonolactone Syntheses of casuarines 249, 253, 261 and 262 from lactone 245 have been reported (Schemes 24 and 25). The triflate in 245 was displaced with azide ion to give the inverted azide, which on reduction with lithium borohydride... 

The use of TEMPO to effect oxidative demercuration was originally demonstrated by Whitesides [16], and is attractive because it gives a functional handle for further structural elaboration. This technique was invoked by Kang in the syntheses of (-t-)-lactacystin and (-l-)-furanomycin [17]. For example, alkene 10 was subjected to mercurioamidation conditions to afford the cyclized organomercury intermediate 11 (Scheme 4). Treatment with lithium borohydride in the presence of TEMPO forms the unstable organomercury hydride. This fragments to release the primary carbon radical, which is trapped by TEMPO to yield the masked alcohol product 12, an intermediate in the synthesis of the neurotropic factor (-l-)-lactacystin. 

Another method for the synthesis of the lithium borohydride (59) is the reaction of (3) with Bu Li 2-methylpropene is the second product of the reaction (Equation (6)) <80JOM(188)1>. 

Chloroboranes are another class of heteroatom-substituted boranes. Dichloroborane (CI2BH) and mono-chloroborane (CIBH2) are formed by the reaction of diborane with varying proportions of boron trichloride etherate (BCl3 OEt2). In ether solvents, both reagents are formed as the etherate.23 An alternative synthesis was the reaction of HCl with borane THF,24 but reduction of boron trichloride with lithium borohydride in ether proved to be the most useful route.23... 

The interesting conversion of nornarceine (181) into the rhoeadine analogues (187) and (188) has been carried out as shown in Scheme 9. Nornarceine (181), obtained from (— )-a-narcotine, was heated in base to afford the enamine (182) which readily cyclized in dilute acetic acid to the y-lactone (183). Upon standing, (183) was oxidized to the ketone (184). Lithium borohydride reduction led to the c/.s-acid (185). The derived ds-fused lactone (186) was then reduced to the hemi-acetal (187) which upon O-methylation with trimethyl orthoformate gave (188). The structure of the methiodide salt of (187) was confirmed by an X-ray analysis. The phthalideisoquinoline alkaloid (— )-bicuculline (189) was then converted into naturally occurring (+ )-rhoeadine (190) by an analogous route. Since (— )-bicuculline was obtained from (—)-)3-hydrastine, whose synthesis had been reported in 1950, this transformation represents the first total synthesis of a rhoeadine alkaloid. ... 

Gold nanoparticles (2.5-7.5 nm diameter) were obtained by Martino and others [402] by reduction of AUCI4 via lithium borohydride in tetrahydrofuran in the reverse micelle system DDAB (didodecyldimethylammonium bromide)/toluene. A purple-colored gold colloid was observable. The particles were encapsulated by silica gels formed in the micellar system by hydrolysis-condensation of TEOS or a prehydrolyzed TEOS, already added in the system. Gelation of silica was achieved by the addition of tetrabutylammonium hydroxide (quicker in case of pre-hydrolyzed TEOS). The particle size was found to be independent of reaction stoichiometry, gel precursor type (TEOS/pre-hydrolyzed TEOS) and the washing step after synthesis. 

A modern and relatively convenient borazine synthesis uses lithium borohydride and ammonium chloride instead as the starting materials ... 

Similarly, a key strategy in an elegant synthesis of (-)-cribostatin was the use of a chiral auxiliary to fix the stereochemistry of C3 and C4 of the lactam, which subsequently determined the stereochemical outcome of a Pictet-Spengler reaction on the aryl ether. Subsequently, the 3-lactam was used to set the stereochemistry of the pentacyclic fiximework of (-)-cribrostatin by reduction with lithium borohydride and spontaneous cyclization. ... 

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