Reduction reactions Lithium borohydride

There is a surprisingly large stereodirecting effect for an alkoxy substituent (ca. 4 kcal mol ) in the amidomercuriation cyclization of the 2-(3-butenyl)-l,3-benzoxazin-4-ones (36). Thus, there is competition between the stereoselective effect of the aminal center and that of the allylic alkoxy group. For example, reaction of (36 R = OBn) with mercury(II) acetate and trifluoroacetate, followed by reduction with lithium borohydride, affords only the tricyclic compound (37 R = OBn), whereas similar treatment of (36 R = H) gives a mixture of the cycloadducts (37 R = H) and (38) in the ratio 1 12.4, respectively <90TL6765>. 

Thiomethyl-PS 6b, prepared from Merrifield s resin la by reaction with thioacetate followed by reduction, can be acylated to give thioesters [263]. The resin-bound thioesters have been converted to silyl enol ethers, which were shown to form aldol products that could be released from the resin by three methods [264], Thus, reduction with lithium borohydride or diisobutylaluminum hydride (DIBAL) gave diols and aldehydes, respectively alternatively, base hydrolysis afforded carboxylic acids. Resin 6b thereby extends the range of functional groups available compared with cleavage of related molecules from an ester anchor. 

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. ... 

In many cases, the carboxyl portion of the amino acid starting material is converted to an aldehyde, allowing several reactions that are not available to carboxylic acids. An example of this approach is the conversion of N-Boc alanine (5.4) to N-Boc alinal (5.5X via conversion to the ester and reduction with lithium borohydride. The next step will be a common feature of this and succeeding chapters. Oxidation of the alcohol moiety in 5.5 to an aldehyde, in this case using S03 pyridine in DMSO, allowed condensation with sodium cyanide to give a cyanohydrin. Hydrol-... 

Good yields of phenylarsine [822-65-17, C H As, have been obtained by the reaction of phenylarsenic tetrachloride [29181-03-17, C H AsCl, or phenyldichloroarsine [696-28-6], C3H3ASCI25 with lithium aluminum hydride or lithium borohydride (41). Electrolytic reduction has also been used to convert arsonic acids to primary arsines (42). Another method for preparing primary arsines involves the reaction of arsine with calcium and subsequent addition of an alkyl haUde. Thus methylarsine [593-52-2], CH As, is obtained in 80% yield (43) ... 

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. 

Brimble and coworkers176 studied the asymmetric Diels-Alder reactions of cyclopentadiene with chiral naphthoquinones 272 bearing different chiral auxiliaries. The highest endo and facial selectivities were obtained using zinc dichloride as the Lewis acid catalyst and (—)-pantolactone as the chiral auxiliary. Thus, the reaction between cyclopentadiene and 272 afforded a 98 2 mixture of 273 and 274 (equation 76). The chiral auxiliary was removed easily by lithium borohydride reduction. 

This is not strictly correct, in that hydride, from say sodium hydride, never acts as a nucleophile, but because of its small size and high charge density it always acts as a base. Nevertheless, there are a number of complex metal hydrides such as lithium aluminium hydride (LiAlHj LAH) and sodium borohydride (NaBH4) that deliver hydride in such a manner that it appears to act as a nucleophile. We have already met these reagents under nucleophilic substitution reactions (see Section 6.3.5). Hydride is also a very poor leaving group, so hydride reduction reactions are also irreversible (see Section 7.1.2). 

Chemical reduction of aromatic aldehydes to alcohols was accomplished with lithium aluminum hydride [5i], alane [770], lithium borohydride [750], sodium borohydride [757], sodium trimethoxyborohydride [99], tetrabutylam-monium borohydride [777], tetrabutylammonium cyanoborohydride [757], B-3-pinanyl-9-borabicyclo[3.3.1]nonane [709], tributylstannane [756], diphenylstan-nane [114], sodium dithionite [262], isopropyl alcohol [755], formaldehyde (crossed Cannizzaro reaction) [i7i] and others. 

The CD fragment 1s synthesized starting with resolved bicyclic acid 129. Sequential catalytic hydrogenation and reduction with sodium borohydride leads to the reduced hydroxy acid 1. The carboxylic acid function is then converted to the methyl ketone by treatment with methyl-lithium and the alcohol is converted to the mesylate. Elimination of the latter group with base leads to the conjugated olefin 133. Catalytic reduction followed by equilibration of the ketone in base leads to the saturated methyl ketone 134. Treatment of that intermediate with peracid leads to scission of the ketone by Bayer Villiger reaction to afford acetate 135. The t-butyl protecting... 

The benzotriazole moiety of iV-(a-aminoalkyl)benzotriazoles is readily replaced by hydride upon reduction with sodium borohydride, or with a carbanion by reaction with Grignard or lithium reagents. These are two most important reactions of benzotriazole derivatives from which versatile routes have been developed for the synthesis of primary, secondary, and tertiary amines. 

Nucleophilic addition takes place at C-1, and this is considerably enhanced if the reaction is carried out upon an isoquinolinium salt. Reduction with lithium aluminium hydride [tetrahydroaluminate(III)] in THF (tetrahydrofuran), for example, gives a 1,2-dihydroisoquinoline (Scheme 3.15). These products behave as cyclic enamines and if isoquinolinium salts are reacted with sodium borohydride [tetrahy-droboronate(III)] in aqueous ethanol, further reduction to 1,2,3,4-tetrahydroisoquinolines is effected through protonation at C-4 and then hydride transfer from the reagent to C-3. 

Acylmetallocenes undergo many reactions shown by acylbenzenes (35, 87, 91, 116, 124), but a detailed discussion is not presented here. Reductions with either lithium aluminum hydride or sodium borohydride give the corresponding carbinols, while Clemmensen reduction, reduction with lithium aluminum hydride plus aluminum chloride, catalytic hydrogenation, etc., yield corresponding alkyl derivatives. Acetylferrocenes undergo a variety of base condensation reactions and can be oxidized to ferrocenecarboxylic acids without apparent oxidation of the iron atom. 

When the reaction between a trialkylborane and carbon monoxide (8-24) is carried out in the presence of a reducing agent such as lithium borohydride or potassium triisopropoxy-borohydride, the reduction agent intercepts the intermediate 73, so that only one boron-to-carbon migration takes place, and the product is hydrolyzed to a primary alcohol or oxidized to an aldehyde.333 This procedure wastes two of the three R groups, but this problem can be avoided by the use of B-alkyl-9-BBN derivatives (p. 785). Since only the 9-alkyl group... 

Polystyrene-bound carboxylic esters have been reduced with diisobutylaluminum hydride or lithium aluminum hydride. Use of the latter reagent can, however, lead to the formation of insoluble precipitates, which could readily cause problems if reactions are performed in fritted reactors. An alternative procedure for reducing carboxylic esters to alcohols involves saponification, followed by activation (e.g. as the mixed anhydride) and reduction with sodium borohydride (Entries 10 and 11, Table... 

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... 

Stork, Jacobson, and Levitz (51) have recently reported that the reaction of the lithium carbanion 234 with benzaldehyde followed by reduction with sodium borohydride gave the phenylcarbinol 235. The sequence of events in the transformation of 234 to 23S was shown to be as depicted below. Convincing spectral evidence was obtained for 236, 238, and 239. Thus, the hemi-orthoamide tetrahedral intermediate 237 which was generated in situ gave the ami nobenzoate 238, the expected product from stereoelectronic control. 

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... 

An alternate route to substituted tetrahydrobenzazepines (Scheme 33) commenced with the Michael addition of the ester 351 to acrylonitrile in the presence of Triton B, and the intermediate cyanoester was converted to 352 by reduction of the ester function with lithium borohydride and O-benzylation (168). Base-induced hydrolysis of the nitrile group of 352 delivered the corresponding acid, which was transformed to 353 via a Curtius rearrangement. Subjection of 353 to a modified two-step Tschemiac-Einhom reaction involving AMiydroxymethyla-tion and subsequent acid-catalyzed cyclization gave 354. 

A convenient method for the specific introduction of 2H or 3h (or both) into a molecule is by ketone reduction with labeled metal hydride. Beale and MacMillan (10) have utilized this method for the preparation of GAs labeled at the 1, 2 or 3 positions from GA3 or GA7 (Figure 12). One point of interest is the lithium borohydride reduction of the enone formed by manganese dioxide oxidation of GA3 or GA7. When the reaction is carried out in anhydrous tetrahydrofuran it proceeds in two steps. Initially the lithium enolate is formed which incorporates a proton at carbon-2 from the acid used in the work-up, forming the 3 ketone. This ketone is reduced to the 3 -alcohol by the borohydride which is decomposed more slowly than is the lithium enolate. Thus it is possible to introduce two different labels in a single reaction. 

The reduction of 1-hydroxymethyl- and 1-benzoyloxymethyl-benzotriazole (138) with lithium aluminum hydride and sodium borohydride has been investigated by Gaylord and Kay.148 The hydroxymethyl compound failed to undergo reduction with lithium aluminum hydride, apparently as a result of the immediate formation of an insoluble complex by reaction of the metal hydride with the... 

Two large-scale syntheses were reported by Quaedflieg et al. at Tibotec.31 Chiral synthon 20, obtained from ascorbic acid, was converted to a,p-unsaturated ester 21 in 92% yield and E/Z ratio was > 95 5. Michael addition of nitromethane to 21 was carried out with DBU as base to provide 22 in 80% yield and a syn/anti ratio of 5.7 1. A Nef reaction then converted 22 to a mixture of lactone 23 (major, 56%) (a/p = 3.8 1) and ester 24 (minor). The a-23 was obtained via recrystallization in isopropanol (37%), with high enantiomeric purity (> 99%). Isomerization of P-23 followed by recrystallization in isopropyl alcohol gave an additional 9% yield of a-23. It is interesting that most of 24 remained in the aqueous layer. Lithium borohydride reduction of a-23 followed by acid-catalyzed cyclization resulted in (-)-ll. 

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