Chiral hydride reagents asymmetric reduction

In an attempt to prepare alkylamines by asymmetric reduction of imines with chiral hydride reagents, diphenylphosphinyl imines (38), prepared by reaction of ketoximes (39) with chlorodiphenylphosphine [(Cg 115)2 PCI], were reduced in the presence of a variety of chiral aluminum and boron hydride reagents43. Among the most promising reagents was BINAHL-H44 (40), a chiral hydride compound prepared by the modification of lithium... 

Table 1 Optical Yields for Asymmetric Reduction of Typical C=X Compounds with Selected Chiral Hydride Reagents... 

Asymmetric reduction of prochiral a,p-unsaturated ketones with chiral hydride reagents derived from LiAlH4 and (5)-4-anilino- and (S)-4-(2,6-xylidino)-3-methylamino-l-butanol gives (S)- and ( )-allylic alcohols, respectively, in high chemical and optical yields (Scheme 44).2° ... 

The asymmetric reduction of prochiral ketones employing chiral hydride reagents has been the subject of extensive work, and a number of methods have been reported. 

Relatively high optical yields were achieved in the asymmetric reduction of acetophenone by these chiral hydride reagents however, the optimum enantiomeric excess (e.e.) achievable was 83% at that time. Two effective methods have been reported since then Thus, we initiated a study on the exploration of a new and efficient chiral ligand suitable for the asymmetric reduction of prochiral ketones, and found that a chiral hydride reagent formed in situ from LiAlHj and the chiral diamine (S)-2-(anilinomethyI)pyrrolidine la) is efficient for the reduction of acetophenone, affording (S)-l-phenylethanol in 92% e.e. . Examination of the effect of the N-substituent in the diamine la-m) on the enantioselectivity in the asymmetric reduction of acetophenone, revealed that when a phenyl or 2,6-xylyl substituent was employed, 1-phenylethanol was obtained in 95% e.e. (Table 1)... 

Other results obtained by the asymmetric reduction of various ketones, in ether, using the chiral hydride reagent prepared from LiAlH and la or lb are summarized in Table 2 . ... 

Asymmetric syntheses based on chiral diamines. Optically active secondary alcohols are obtained by reduction of prochiral ketones with the chiral hydride reagent 1 prepared from lithium aluminium hydride and ( )-2-(N-substituted aminomethyl)-... 

Asymmetric reduction of prochiral ketones, A chiral hydride reagent formed by treating the chiral diamine 1 with LiAlH was postulated to assume a cis-fused five-membered bicyclic ring structure Highly enantiomerically pure alcohols were obtained when the reaction was carried out in ether at low temperature (-100 C) by employing diamines 1 having 2,6-xylyl or phenyl substituents on nitrogen, ... 

Haubenstock, H., Asymmetric Reductions with Chiral Complex Aluminum Hydrides and Tricoordinate Aluminum Reagents, 14, 231. 

Asymmetric reduction of ketones or aldehydes to chiral alcohols has received considerable attention. Methods to accomplish this include catalytic asymmetric hydrogenation, hydrosilylation, enzymatic reduction, reductions with biomimetic model systems, and chirally modified metal hydride and alkyl metal reagents. This chapter will be concerned with chiral aluminum-containing reducing re-... 

In the fourth and final chapter, Howard Haubenstock discusses asymmetric reduction of organic molecules. Within this general topic of wide and continuing interest, Haubenstock s chapter deals with chiral derivatives of lithium aluminum hydride, their preparation from suitable amino or hydroxy compounds, and their use in reducing carbonyl groups. Related reactions of the Meerwein-Ponndorf-Verley type or involving tri-alkylaluminum reagents are also presented. 

ASYMMETRIC REDUCTIONS WITH CHIRAL COMPLEX ALUMINUM HYDRIDES AND TRICOORDINATE ALUMINUM REAGENTS 231... 

Reviews on stoichiometric asymmetric syntheses M. M. Midland, Reductions with Chiral Boron Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 2, Academic Press, New York, 1983 E. R. Grandbois, S. I. Howard, and J. D. Morrison, Reductions with Chiral Modifications of Lithium Aluminum Hydride, in J. D. Morrison, ed.. Asymmetric Synthesis, Vol. 2, Chap. 3, Academic Press, New York, 1983 Y. Inouye, J. Oda, and N. Baba, Reductions with Chiral Dihydropyridine Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 4, Academic Press, New York, 1983 T. Oishi and T. Nakata, Acc. Chem. Res., 17, 338 (1984) G. Solladie, Addition of Chiral Nucleophiles to Aldehydes and Ketones, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 6, Academic Press, New York, 1983 D. A. Evans, Stereoselective Alkylation Reactions of Chiral Metal Enolates, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 1, Academic Press, New York, 1984. C. H. Heathcock, The Aldol Addition Reaction, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 2, Academic Press, New York, 1984 K. A. Lutomski and A. I. Meyers, Asymmetric Synthesis via Chiral Oxazolines, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 

Asymmetric reduction of prochiral ketones. Chiral metal hydrides previously investigated have been effective only for asymmetric reduction of aromatic or a,p-ucclylenic ketones. This new reagent unexpectedly reduces straight-chain aliphatic ketones such as 2-bulanonc and 2-octanone to the corresponding (S)-alcohols in 76%... 

A review describing the major advances in the field of asymmetric reduction of achiral ketones using borohydrides, exemplified by oxazaborolidines and /9-chlorodiisopino- camphenylborane, has appeared. Use of sodium borohydride in combination with chiral Lewis acids has been discussed.298 The usefulness of sodium triacetoxyboro-hydride in the reductive amination of aldehydes and ketones has been reviewed. The wide scope of the reagent, its diverse and numerous applications, and high tolerance for many functional groups have been discussed.299 The preparation, properties, and synthetic application of lithium aminoborohydrides (LABs) have been reviewed. 

H. Haubenstock, Asymmetric Reductions with Chiral Complex Aluminium Hydrides and Tricoordinate Aluminium Reagents, Top. Stereochem. 1983, 14, 213. 

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). 

Reaction with chiral acetals. The chiral ketals derived from (2R,4R)-(-)-2,4-pentanediol (1) can be cleaved with high diastercoselectivity by aluminum hydride reagents, in particular DIBAH, CI2AIH, and Br,AlH. Oxidative removal of the chiral auxiliary affords optically active alcohols. This process provides a useful method for highly asymmetric reduction of dialkyl ketones. ... 

Asymmetric reduction of ketones. Chiral ketals 2, obtained by reaction of 1 with prochiral ketones, are reduced diastereoselectively to 3 by several aluminum hydride reagents, the most selective of which is dibromoalane (LiAIHj-AIBr, 1 3). Oxidation and cleavage of the chiral auxiliary furnishes optically active alcohols (4) in optical yields of 78-96% ee (equation 1). 

Reduction of Prochiral Ketones. BINOL has been used as the chiral ligand of the reagent BINAL-H (see Lithium Aluminum Hydride-2,2 -Dihydroxy-1,1 -binaphthyl, Vol. B) for asymmetric reduction. The reagent reduces prochiral unsaturated ketones to the corresponding secondary alcohols in up to 90% yield and >90% ee (eq 7) (f )-BINAL-H leads to the (i )-alcohols while (S)-BINAL-H gives the (S)-alcohols. 

Asymmetric Alkene Isomerization. The chiral titanocene reagent (1) serves as precatalyst for the isomerization of alkene (4) (eq 3). Active isomerization catalyst is obtained by in situ reduction of (1) with Lithium Aluminum Hydride (164 °C, 30 min). Treatment of the achiral substrate (4) with 2 mol % catalyst produced axially dissymmetric product (5)-(5) in 44-76% ee (100% yield). The reaction is slow at room temperature (120 h required for complete reaction) faster rates are obtained at higher temperatures, but at the expense of lower product enantiomeric purity. 

The enantioselective synthesis of optically active secondary amines via asymmetric reduction of prochiral ketimines was studied by screening various chiral hydrides. In this case, K-glucoride gave only disappointing results and was inferior to other reagents. Better results were obtained in the asymmetric reduction of prochiral Af-diphenylphosphinylimines to chiral N-(diphenylphosphinyl)amines (eq 1), which can then be readily converted into optically active primary amines. For this reaction the stereochemical course depends dramatically on the relative bulkiness of the groups R and R. The reaction conditions for reduction of C=N double bonds are the same as used for ketones, but the high reactivity of diphenylphosphinylimines dramatically reduces the reaction time. 

The modification of aluminum or boron hydrides with chiral protic substances, such as R OH or RR NH, generates useful reagents for the asymmetric reduction of prochiral ketones or imines leading to optically active secondary alcohols and amines, respectively. Some reviews have appearered in the literature. ... 

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... 

Although -3-pinanyl-9-borabicyclo[3.3.1]nonane and related substances have also been developed as efficient asymmetric reducing agents for carbonyl compounds (Volume 8, Chapter 1.3), we discuss here only asymmetric reductions using chirally modified metal hydride reagents. The asymmetric hydrosilyl-ation of a carbonyl group catalyzed by a chirally modified transition metal is mentioned briefly. 

The properties of complex metal hydrides, particularly those of aluminum, and their use in organic synthesis have been compared in a number of papers, review articles and monographs. " ° Useful tables, listing the most appropriate hydride reagents for selective reduction of various polyfunctional compounds, have been published. " Use of chiral metal alkoxyaluminum hydride complexes in asymmetric synthesis has also been reviewed. ... 

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