Lithium aluminum hydride reductions chirally modified

Chiral Ligand of L1A1H4 for the Enantioselective Reduction of Alkyl Phenyl Ketones. Optically active alcohols are important synthetic intermediates. There are two major chemical methods for synthesizing optically active alcohols from carbonyl compounds. One is asymmetric (enantioselective) reduction of ketones. The other is asymmetric (enantioselective) alkylation of aldehydes. Extensive attempts have been reported to modify Lithium Aluminum Hydride with chiral ligands in order to achieve enantioselective reduction of ketones. However, most of the chiral ligands used for the modification of LiAlHq are unidentate or bidentate, such as alcohol, phenol, amino alcohol, or amine derivatives. 

A convenient route to highly enantiomerically enriched a-alkoxy tributylslannanes 17 involves the enanlioselective reduction of acyl stannanes 16 with chiral reducing agents10. Thus reaction of acyl stannanes with lithium aluminum hydride, chirally modified by (S)-l,l -bi-naphthalene-2,2 -diol, followed by protection of the hydroxy group, lead to the desired a-alkoxy stannanes 17 in optical purities as high as 98 % ee. 

In summary, many attempts have been made at achieving enantioselective reduction of ketones. Modified lithium aluminum hydride as well as the ox-azaborolidine approach have proved to be very successful. Asymmetric hydrogenation catalyzed by a chiral ligand-coordinated transition metal complex also gives good results. Figure 6-7 lists some of the most useful chiral compounds relevant to the enantioselective reduction of prochiral ketones, and interested readers may find the corresponding applications in a number of review articles.77,96,97... 

The most general way to obtain chiral a-stannylated ethers today consists of the asymmetric reduction of acylstannanes34,35,36 using the 2,2 -dihydroxy-l,T-binaphthyl-modified lithium aluminum hydride (BINAL-H) reagent37 and etherification of the crude alcohol with chloro-methoxymethane. 

The enantioselective reduction of unsymmetrical ketones to produce optically active secondary alcohols has been one of the most vibrant topics in organic synthesis.8 Perhaps Tatchell et al. were first (in 1964) to employ lithium aluminum hydride to achieve the asymmetric reduction of ketones9 (Scheme 4.IV). When pinacolone and acetophenone were treated with the chiral lithium alkoxyaluminum hydride reagent 3, generated from 1.2 equivalents of 1,2-0-cyclohexylidene-D-glucofuranose and 1 equivalent of LiAlHzt, the alcohol 4 was obtained in 5 and 14% ee, respectively. Tatchell improved the enantios-electivity in the reduction of acetophenone to 70% ee with an ethanol-modified lithium aluminum hydride-sugar complex.10... 

In 1979, Noyori and co-workers invented a new type of chiral aluminum hydride reagent (1), which is prepared in situ from LiAlEE, (S)-l, E-bi-2-naphthol (BINOL), and ethanol. The reagent, called binaphthol-modified lithium aluminum hydride (BINAL-H), affects asymmetric reduction of a variety of phenyl alkyl ketones to produce the alcohols 2 with very high to perfect levels of enantioselectivity when the alkyl groups are methyl or primary1 (Scheme 4.3a). 

In 1951 Bothner-By first attempted asymmetric reductions based on the conversion of lithium aluminum hydride (LAH) into a chiral alkoxy derivative by reaction with (+)-camphor. Since this pioneering work, the use of chirally modified LAH reagents has been the focus of much attention. In 1979, the first virtually complete enantiofacial recognition of prochiral carbonyl compounds was accomplished by using LAH modified with optically pure 2,2 -dihydroxy-1,1 -binaphthyl and a simple alcohol (BINAL-H). Asymmetric reduction with chiral 2,5-dimethylborolane also gave alcohols in high optical yields." Recently, excellent results have been obtained using a chirally modified sodium borohydride... 

Two asymmetric synthesis approaches to chiral cyclopentenone derivatives can be envisaged. The first, reduced to practice by Noyori (43), involved reduction of cyclopentene-l,4-dione with lithium aluminum hydride chirally modified with binaphthol to give R-4-hydroxycyclopent-2-en-l-one in 94% e.e. Alternatively, manganese dioxide oxidation of allylic alcohol [40] (Fig. 7), in analogy to the cis isomer (54), would be expected to give the same enone. 

A recent report by Chan and Chong describes the enantioselective reduction of acylstannanes to the oi-alkoxy organostannanes by the chiral 2,2 -dihydroxy-l,l -binaphthyl modified lithium aluminum hydrides. Matteson has also described a possible route to such chiral organostannanes utilizing the chiral a-chloroboronic esters. ... 

Both enantiomers of binaphthol have found many uses as chiral reagents and catalysts. Thus, they modify reducing agents (e.g., lithium aluminum hydride) for the reduction of ketones to chiral secondary alcohols (Section D.2.3.3.2.) or react with aluminum, titanium or boron compounds to give chiral Lewis acids for asymmetric Diels-Alder reactions (Section D. 1.6.1.1.1.3.) and ene reactions (Section D.I.6.2.). They have also been used as chiral leaving groups in the rearrangement of allyl ethers (Section D.l.1.2.2.) and for the formation of chiral esters with a-oxo acids (Section D. 1.3.1.4.1, and many other purposes. 

Pioneers in the asymmetric reduction area developed suitable reagents by modifying lithium aluminum hydride (LAH) (7) or by developing chiral versions of Meerwdn-Ponndorf-Verley reductions with chiral aluminum alkoxides (8) or chiral Giignard reductions with chiral alkyl magnesium halides (9). 

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