Reduction with LiAlH

Table 5. Yields of Organosilanes via Reduction with LiAlH and LiH ...

Harrison, J. Fuller, J.C. Goralski, C.T. Singaram, B. Tetrahedron Lett., 1994, 35, 5201. Boireau, G. Deberly, A. Toneva, R. Synlett, 1993, 585. In this study, reduction with LiAlH(Or-Bu)3 was shown to give primarily the trans-alcohol. 

We have previously (13) reported a rapid two step synthesis of 4-(pyrrolidino)pyridine copolymers via the reaction of commercially available maleic anhydride copolymers with 4-aminopyridine followed by reduction with LiAlH, yielding polymers with a high degree of functionalization. 

In analogy to imidazolides, both triazolides and pyrazolides have been converted into aldehydes by reduction with LiAlH ... 

The parent compound, 69, has been synthesized and characterised <2003ZFA1475>. 4-Chloro-hepta-l,6-diene was reacted with Mg. No Grignard rearrangement was noticed but instead the Grignard reagent was converted into l-allyl-3-butenylphosphonous dichloride by reaction with PC13. Reduction with LiAlH. produced l-allyl-3-butenyl-phosphane. Radical-initiated cyclization led to the product, l-phosphabicyclo[3.3.0]octane. Four derivatives were similarly prepared and characterized (70-73). Compound 74 was similarly prepared via a radical reaction < 1997PS(123)141 >. 

The 3,4-dihydrodiol was also synthesized via Method IV (74). Oxidation of 3-hydroxy-MBA with Fremy s salt gave the 3,4-quinone which underwent reduction with LiAlH to give 19a. The yield in the reduction step was only 15%, but it is likely that this could be substantially improved by the use of the NaBH /02 system (18) developed after these studies were completed. 

Reduction with LiAlH(OBu )3293 or LAH292 also gives selective hydride addition to the less substituted allyl end (equations 317 and 318). In contrast, formate reductions selectively deliver hydride to the more substituted allyl terminus (equations 319 and 320).302-303 Si—H-mediated reduction, conveniently performed with polymethylhydrosiloxane (PMHS), demonstrates no clear pattern of regioselectivity (equation 321).320 LiHBEt3 delivers hydride regioselectivity to the less substituted allyl terminus (equation 322)289-291... 

The most important reactions involve addition of nucleophiles to the phenoxenium salts 14a-c or to the observed deep blue very reactive intermediates 12 via an SN1 or by an acid supported SN2 reaction. Reduction with LiAlH or NaBH4 may also occur by adding a hydride ion to any of the possible cationic centers of the mesomeric formulas 2 (p. 151) to give the phenol. 

So far, we have considered protocols that result in chiral centres in the C and position (actnally always with the same substiment). Let us now turn to satnrated carbenes that have only one chiral centre in the backbone. Figure 5.15 shows a procedure that utilises a chiral diamine derived from proline, a naturally occurring a-amino acid. Reaction with aniline to the corresponding amide and reduction with LiAlH yields the diamine used [60]. The actual synthesis of the chiral carbene then calls for reaction of the proUne derived diamine with thiophosgene and subsequent S/Cl exchange with oxalyl chloride [50]. The... 

Steric protection can be provided by adamantyl wingtip groups that are introduced by the reaction of the l,r-diaminobiphenyl to the Schiff base (with 2-adamantone) followed by reduction with LiAlH [79,80] (see Figure 5.24). Ring closure with triethyl orthoformate to the corresponding azolium salt proceeds as usual and subsequent reaction with [Pd(allyl)Cl]j in the presence of a suitable auxiliary base (potassium tcrt-butylate) yields the respective palladium allyl complex. The paUadium(II) allyl complex can then be reacted with hydrochloric acid to form the [Pd(NHC)Cy dimer. Subsequent reaction with a silver(I) salt predictably breaks up the dimer under chloride abstraction and anion transfer from silver to palladium. 

Epoxide reduction with LiAlH (abnormal cis-3,4-epoxy-5-ols 4,5-diols) E. Glotter, Sk Greenfield and D. Lavie, Teimhedron Letters, No. 52 (1967) 5261. 

In uncontrolled reductions, lactones are reduced by lithium trialkyoxyaluminum hydrides to diols but the reduction with LiAlH(OBu )3 is very slow and advantage can be taken of this to stop the reaction at... 

Thiophenes can be prepared from the sultones of ,j8-unsaturated ketones. From the S-sultone of pulegone (89), the thiophene (91) has been obtained through reduction with LiAlH to (90), followed by dehydration of the latter, " ... 

Alternatively, borane in tetrahydrofuran (BH/THF) is a useful reagent for reducing carboxylic acids to primary alcohols. Reaction of an acid with BH3/THF occurs rapidly at room temperature, and the procedure is often preferred to reduction with LiAlH because of its relative ease, safety, and specificity. Borane reacts with carboxylic acids faster than with any other functional group, thereby allowing selective transformations such as that shown below on p-nitrophenylacetic acid. If the reduction of p-nitrophenyl-acetic acid were done with LiAlH4, both nitro and carboxyl groups would be reduced. 

Reduction of ketones. Wheeler and Mateos found that reduction of 3-choles-tanone with mixed hydride gives essentially pure cholestane-3 3-ol, with equatorial hydroxyl, whereas reduction with LiAlH alone was known to give the 3)3- and 3a-epimers in a ratio of approximately 9 1, Eliel and Rerick and Eliel, Martin, and Nasipuri, " seeking a route to pure rrans-4-t-butylcyclohexanol (4), found that... 

Isochroman-3-ones on reaction with HBr/EtOH furnish the bromoesters which on treatment with amines provide isoquinolones. The latter on reduction with LiAlH give 1,2,3,4-tetrahydro isoquinolines... 

Acyl-1,3-thiazolidines-2-ones 1.123 (X = S, R = COOMe), obtained from cysteine methyl ether [261], have been introduced by Mukaiyama and coworkers for use in asymmetric aldol reactions [261, 433, 434, 435], In reactions of related //-acyl-1,3-oxazolidines-2-thiones 1.123 (X = O, R = COOMe), each enantiomer can be obtained either from L- or D-serine [434] and the auxiliaries can easily be recovered by methanolysis. Similarly, //-acyl derivatives of 1.121 (X = S) have been used in asymmetric aldol reactions [429, 436], and //-acyl- 1,3-thiazo-lidinethiones 1.123 (X = S, R = r -Pr) are useful in asymmetric acylation [437] and aldol and related reactions [437, 438], Cleavage of the chiral auxiliary is accomplished by aminolysis with O-benzylhydroxylamine or by reduction with LiAlH.,. ... 

Treatment of 202, prepared from 197 by reduction with LiAlH in dioxane, with formic acid-formaldehyde, gave JV-benzylcycloproto-buxine-C (205), which was characterized by physical means. The same product (205) was obtained when cycloprotobuxine-C (204) was benzoy-lated to give A-benzoylcycloprotobuxine-C (206) and then reduced. 

Reaction of conjugated carbonyls with LiAlH(Ot-Bu)3 gives primarily 1,2-reduction, as in the quantitative reduction of 78 to 79 in Marshall s synthesis of globulol. goth sulfonate esters such as the mesylate group in 78, and halides are resistant to reduction with LiAlH(Of Bu)3. 

Another method of alkylating an amine is to acylate the amine to peld an amide and then carry out a reduction with LiAlH. Although two steps are involved, there is no risk of overalkylafion since acylation can only occur once. 

Quantitative Distribution of Adducts as a Function of Dienophile Stereochemistry. For accurate quantitation of the isomer distribution in the products of cycloaddition to each of the dienophiles 5—8, the entire mixtures of the four stereoisomeric products in each instance were first subjected to sequential Q-deacetylation and periodate oxidation to afford a mixture of two aldehydo esters 29 and 30, which upon reduction with LiAlH afforded trans-2-norbornene-5,6-dimethanol as an unequal mixture of the two enantiomers (only the 5S,6g enantiomer is shown). NMR analysis of the mixture of 29 and 30 showed distinctive resonances for the CH3O and CHO groups in exo and endo orientations, permitting accurate determination of the endo/exo ratio of the products in the mixture. The observed specific rotation of the diol, in comparison with that (+23 ) determined for the enantiomerically pure 5S,6S diol 26 (and its enantiomer), provided a quantitative measure of the si.re diastereofacial selectivity. 

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