Enantioselectivity reduction of prochiral ketones

Enantioselective reductions of prochiral ketones by means of oxazaborolidines 97CLY9. 

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... 

Hydrogenation The enantioselective reduction of prochiral ketones to chiral alcohols has been intensely investigated. The highest enantioselectivity has been found for 2-acetylpyridine, which was reduced in buffered EtOH (pH 4.5), in the presence of strychnine to l-(2-pyridyl[-ethanol with 48% ee. The selectivity was... 

By analogy with the enantioselective reduction of prochiral ketones to chiral alcohols an attractive method for producing enantiomerically pure amines would be enantioselective reductive amination of a ketone via enzymatic reduction of an imine intermediate (Scheme 6.11). Unfortunately the required enzymes-amine... 

Some chiral oxazaphospholididine-borane catalysts can be used for enantioselective reduction of prochiral ketones by borane-THF or bor-ane-dimethyl sulfide complex (Scheme 19) (44). 

The use of oxazaborolidines as asymmetric reduction catalysts257 and the enantioselectivity of diphcnyloxazaborolidinc reduction of ketones have been reviewed.258 Large-scale practical enantioselective reduction of prochiral ketones has been reviewed with particular emphasis on the Itsuno-Corey oxazaborolidinc and Brown s 5-chlorodiisopinocampheylborane (Ipc2BCl) as reagents.259 Brown himself has also reviewed the use of Ipc2BCl.260 Indolinoalkylboranes in the form of dimers have been confirmed by 11B NMR as the products of the reduction of trifluoroacetylindoles by diborane.261... 

This article will focus on new developments on the field of NAD(P)-depen-dent dehydrogenases, in particular on new alcohol dehydrogenases applicable for preparative chemistry. Biochemical properties of dehydrogenases useful for the synthesis of chiral hydroxy esters and alcohols are summarized in this contribution with respect to more recent studies on enantioselective reduction of prochiral ketones and to new enzymes for this purpose. Reviews covering earlier works in this field can be found in [42-44],... 

Enantioselective reduction of prochiral ketones by transfer hydrogenation is catalysed by amino acid derivatives. A mechanistic suggestion for the origin of enantioselective induction has been proposed.306 ,/M Jnsaluralcd nitriles are efficiently reduced by a Cu(I)-H species in the presence of bisphosphine ligands. The active Cu(I)-H species was generated by the reaction of copper(II) acetate and polymethylhydrosilane.307... 

Similarly, the enantioselective reduction of prochiral ketones catalyzed by whole cells of Geotrichum candidum proceeded smoothly in scC02 in a semi-continuous flow system (Fig. 7.27) [94]. 

Several novel catalysts in which borohydride is complexed with a difiinctional chiral ligand have been developed and used for the enantioselective reduction of prochiral ketones to chiral alcohols. Corey-Bakshi-Shibatareduction (CBS reduction) is an organic reaction which reduces ketones enantioselectively into alcohols by using chiral oxazaborolidines and BHs-THF or catecholborane as stoichiometric reductants (CBS reagent, 1.64) (also see Chapter 6, section 6.4.2). 

Corey demonstrated that oxazaborolidine (6) can be used cat-alytically (2.5-100 mol %) with excess borane (60-200 mol %) for the enantioselective reduction of prochiral ketones (eq 3 Table 1). ... 

In general, structural variations to the backbone of the Chirald ligand have not led to the development of more selective or reliable LAH complexes for use in asymmetric reductions. Other complexes of amino alcohols with LAH have been studied for their ability to achieve enantioselective reduction of prochiral ketones. However, in most cases the selectivities observed have been moderate. The complex of LAH with the amino alcohol (IS) reduces some enones, such as cyclohexenone and cyclopentenone, to the corresponding (5)-alcohols in high optical purities (100% and 82% ee, respectively). ... 

Enantioselective Ketone Reduction. The major application of chiral oxazaborolidines has been the stoichiometric (as the oxazaborolidine-borane complex) (eq 1) and catalytic (in the presence of a stoichiometric borane source) (eq 2) enantioselective reduction of prochiral ketones. These asymmetric catalysts work best for the reduction of aryl alkyl ketones, often providing very high (>95% ee) levels of enantioselectivity. 

Enzymes provide an alternative to chemical methods for the enantioselective reduction of prochiral ketones. These reductions are usually carrried out in water or buffered aqueous suspensions with sugars as nutrients. 

The catalytic enantioselective reduction of 1-ketophosphonates has recently been developed. This approach takes advantage of a development in the enantioselective reduction of prochiral ketones to chiral alcohols by means of catalytic amounts of oxazaborolidines with borane as reducing agent. Thus, the enantioselective reduction of 1-ketophosphonates is accomplished by treatment with different boranes, BH. THF (0.9 eq), BII3Me2S (0.66 eq),5 545 qj- catccholborane (1.1 eq)5° 5 6 in different solvent systems in the presence of a catalytic amount of freshly prepared B-n-butyloxazaborolidine, (5) or (R) (Scheme 7.93). The reaction is complete in about 5 h and produces the expected dialkyl 1-hydroxyalkylphosphonates in satisfactory yields (53-98%). 

In order to discover new modifiers in the hydrogenation of both C=0 and C=C bonds we have tested fS7-Qr,a-diphenil-2-pyrrolidinmethanol (DPPM) (Scheme 1), which was used as a ligand in the transition metal complex catalyzed enantioselective reduction of prochiral ketons, like acetophenone and pinacolone [8, 9, 10]. 

Oxidoreductases are of special interest for the enantioselective reduction of prochiral ketones [49]. Formate dehydrogenase from Candida boidinii was found to be stable and active in mixtures of [MMIM][MeS04] with buffer. The apphcation of alcohol dehydrogenases for enzyme-catalyzed reactions in the presence of water-miscible ionic liquids could make use of another advantage of these solvents they increase the solubility of hydrophobic compounds in aqueous systems. By addition... 

One of the outstanding discoveries of recent years is the enantioselective reduction of prochiral ketones with borane in the presence of catalytic amounts of oxazaborolidenes obtained from L-proline (reaction 9.10), and termed... 

Methods for achieving enantioselective reduction of prochiral ketones are always of interest. This can be achieved by asymmetric hydrogenation of corresponding enol diphenylphosphinates using a cationic rhodium complex of (/ )- -[(5)-r,2-bis(diphenylphosphino)-ferrocenyl]ethanol. Although optical yields of up to 78% are reported, only simple ketonic substrates were used further developments, therefore, would be welcome. 

Alternatively, solutions of HSi(OEt)3 with lithium ethoxide or pinacolate may be used to convert aldehydes and ketones to alcohols. Enantioselective reduction of prochiral ketones is achieved by use of a mixture of HSi(OEt)3 and the dilithium salt of a chiral diol or amino alcohol. 

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