Chiral metal hydride reagents

C. Reduction of Imines with Chiral Metal Hydride Reagents. 112... 

The diastereoselective hydride addition of a chiral metal hydride reagent to a ketone substrate bearing a stereogenic center is called a substrate-controlled process, and it leads to 1,2-asymmetric induction. Enantioselective hydride addition to a prochiral ketone by metal... 

One approach to enantioselective reduction of prochiral carbonyl compounds is to utilize chiral ligand-modified metal hydride reagents. In these reagents, the number of reactive hydride species is minimized in order to get high chemo-selectivity. Enantiofacial differentiation is due to the introduced chiral ligand. 

Tetr 37 3547 (1981) (organoboron reagents) 42 5157 (1986) (chiral metal hydride complexes) JACS 105 3725 (1983) (Cram and anti-Cram redaction of a-chiral ketones)... 

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%... 

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. 

Several alternative methods with high ee s for various types of ketones are known reductions catalyzed by enzymes or baker s yeast [30] and microbial reagents [31], homogeneous hydrogenation (cf. Chapter 6.1), and stoichiometric reductions with chiral metal hydrides [32]. 

In contrast to the considerable amount of successful attention devoted to the asymmetric reduction of prostereogenic ketones to chiral alcohols with metal hydride reagents (see Section D.2.3 and ref 1), corresponding studies and identification of useful stereoselective conversions of stereo-genic imine derivatives to amines have been sparse, and only limited success has been obtained. 

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-... 

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. 

Optically active aliphatic propargylic alcohols are converted to corticoids (90% ee) via biomimetic polyene cyclization, and to 5-octyl-2(5ii)-furanone. The ee s of propargylic alcohols obtained by this method are comparable with those of the enantioselective reduction of alkynyl ketones with metal hydrides, catalytic enantioselective alkylation of alkynyl aldehydes with dialkyIzincs using a chiral catalyst ((S)-Diphenyl(l-methylpyrrolidin-2-yl)methanol) (DPMPM), and the enantioselective alkynylation of aldehydes with alkynylzinc reagents using A(A-dialkylnorephedrines. °... 

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. ... 

In general, the chiral hydride reagent is generated in situ by reaction of a suitable metal hydride with chiral ligands such as alkaloids , sugar derivatives , amino alcohol chiral oxazolines tartaric acid derivatives chiral amines and chiral diols... 

Hydride reductions of C=N groups are well known in organic chemistry. It was therefore obvious to try to use chiral auxiliaries in order to render the reducing agent enantioselective [41]. The chiral reagent or catalyst is prepared by addition of a chiral diol or amino alcohol and the active species is formed by reaction of OH or NH groups of the chiral auxiliary with the metal hydride. A maj or drawback of most hydride reduction methods is the fact that stoichiometric or higher amounts of chiral material are needed. At this time only two such catalytic systems are useful for preparative purposes (Table 2, entry 2.6, Table 6, entry 6.1) [24,32]. 

Many workers have cleaved chiral acetals with nucleophilic reagents such as metal hydrides, alkyl- or arylmetals, allyl- or alkynylsilanes or enoxysilanes in the presence of Lewis acids [213, 220, 221, 222]. Functionalized hydroxyethers are... 

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