Reduction Using LiAlH

The mixture was passed through a short plug of silica gel to separate the catalyst from the alcohol/acetate mixture (EtOAc/hexanes, 1/1 —> 3/1 then Et N/EtOAc, 1/9). The solution of alcohol and acetate was concentrated in vacuo and the residue purified by FC on silica gel (EtjO/pentane, 1/20 1/4) to afford the (R)-acetate (639 mg, 44%, 90.2% eeby chiral-GC on the alcohol obtained by reduction using LiAlH ) and the (5)-alcohol (517 mg, 47%, 92.9% ee by chiral-GC). The calculated selectivity value at 50.7% conversion was s = 65.9. The recovered catalyst was purified by FC on silica gel (EtOAc/hexanes, 1/1 EtOAc/ hexanes/EtjN, 9/9/2), which provided 24.9 mg of pure catalyst 16 (90%). 

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. 

Determined following reduction to the alcohol using LiAlH Average of 2-3 runs... 

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... 

The reaction of 2-acetylphenothiazine with ethyl magnesium bromide led to 2-(but-2-enyl)phenothiazine (156) A-substituted ketones gave ethynyl derivatives (157) on treatment with acetylene. Reduction of 2-acyl derivatives to alcohols has been performed by the Meerwein-Ponndorf reaction and by using LiAlH. - - Polarographic one-electron reduction of the keto group in 10-acetyl-2-()3-piperidinopropionyl)phenothiazine has been reported. ... 

Boranes may be prepared by reduction of B—O bonds using LiAlH, e.g., C Hj-B(OCjHj)2 or (CjHjBOj reacts with LiAlH., in (CjHj) containing xs CjHjN at 70°C to form the air-stable pyridine—borane ... 

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. 

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.,. ... 

B. The conversion is a reduction reaction, and can be accomplished by using LiAlH,. 

In the last steps, all that remained was to reduce the azide and methylate the resulting amine. Reduction of azide was cleanly effected by hydrogen over Pd/C. The problem of selectivity in reduction of carbamate to Me group was circumvented, however, by using LiAlH(OMe3) in refluxing THE. 

It is worth pointing out that a reductive treatment using LiAlH followed by a hydrogenolysis with Raney nickel affords the corresponding amines [13], while the treatment of the hydrazones with propan-l,3-dithiol in the presence of BFj.EtjO leads to the corresponding dithianes [14]. 

Lithium aluminium hydride, LiAlH, is a very active reducing agent, and is used particularly for the ready reduction of carboxylic acids (or their esters) to primary alcohols R-COOH -> R CH,OH. 

Lithium aluminium hydride LiAlH is a useful and conveuient reagent for the selective reduction of the carbonyl group and of various other polar functional groups. It is obtained by treatment of finely powdered lithium hydride with an ethereal solution of anhydrous aluminium chloride ... 

Another possibility for asymmetric reduction is the use of chiral complex hydrides derived from LiAlH. and chiral alcohols, e.g. N-methylephedrine (I. Jacquet, 1974), or 1,4-bis(dimethylamino)butanediol (D. Seebach, 1974). But stereoselectivities are mostly below 50%. At the present time attempts to form chiral alcohols from ketones are less successful than the asymmetric reduction of C = C double bonds via hydroboration or hydrogenation with Wilkinson type catalysts (G. Zweifel, 1963 H.B. Kagan, 1978 see p. 102f.). 

Constmction of multilayers requires that the monolayer surface be modified to a hydroxylated one. Such surfaces can be prepared by a chemical reaction and the conversion of a nonpolar terminal group to a hydroxyl group. Examples of such reactions are the LiAlH reduction of a surface ester group (165), the hydroboration—oxidation of a terminal vinyl group (127,163), and the conversion of a surface bromide using silver chemistry (200). Once a subsequent monolayer is adsorbed on the "activated" monolayer, multilayer films may be built by repetition of this process (Fig. 8). 

The reduction of (aLkylarnino)haloboranes using hydride reagents can provide a convenient route to (aLkylamino)boranes for example, LiAlH has been utilized to prepare bis (dimethyl amino)borane [23884-11-9] from chi orobis (dimethyl amino)borane [6562-41-0] (68). When this same strategy is appHed to (bis(trimethylsi1y1)amino)ch1oro((trimethylsi1y1)amino)borane [10078-93-0] the expected compound is obtained along with the formation of two... 

Reduction with Metals and Metal Hydrides. Practically any ester can be reduced by Na—C2H OH, Li or Na—NH, LiAlH, LiBH, or NaBH to give alcohols in excellent yield (35,36). Carbon-carbon double bonds are usually preserved using these reducing reagents. 

LiAlH —(C2H )2NH. The use of BH or LiAlH —BE 0(C2H )2 as a reducing reagent converts esters to ethers. Thus, reduction of esters can be manipulated by the judicious selection of metal-containing reducing reagents. 

Aldehyde (4) can be made by chloromethylation (P 9), the condensation with nitromethane with mild base gives an excellent yield of crystalline (3) and LiAlH can be used for the reduction. 

The first reductive kinetic resolution of racemic sulphoxides was reported by Balenovic and Bregant. They found that L-cysteine reacted with racemic sulphoxides to produce a mixture of L-cystine, sulphide and non-reduced optically active starting sulphoxide (equation 147). Mikojajczyk and Para reported that the reaction of optically active phosphonothioic acid 268 with racemic sulphoxides used in a 1 2 ratio gave the non-reduced optically active sulphoxides, however, with a low optical purity (equation 148). It is interesting to note that a clear relationship was found between the chirality of the reducing P-thioacid 268 and the recovered sulphoxide. Partial asymmetric reduction of racemic sulphoxides also occurs when a complex of LiAlH with chiral alcohols , as well as a mixture of formamidine sulphinic acid with chiral amines, are used as chiral reducing systems. ... 

Chemoselectivity between aldehydes and ketones is demonstrated by this method in the competitive reduction of a mixture of pentanal and cyclohexanone. The ratios of primary and secondary alcohols are 75 25 when catechol is used at 0° and 79 21 when 2,2/-dihydroxybiphenyl is used at room temperature. These regents are not as chemoselective as other reducing agents such as LiAlH(OBu-i)3 (87 13) and LiAlH(OCEt3)3 (94 6) at 0°.93... 

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