Optically active secondary alcohols

With optically active secondary alcohols the reaction proceeds with predominant, but incomplete, inversion of configuration. 

Allylsilanes are available by treatment of allyl acetates and allyl carbonates with silyl cuprates17-18, with antarafacial stereochemistry being observed for displacement of tertiary allyl acetates19. This reaction provides a useful asymmetric synthesis of allylsilanes using esters and carbamates derived from optically active secondary alcohols antarafacial stereochemistry is observed for the esters, and suprafacial stereochemistry for the carbamates20,21. 

Catalytic asymmetric hydrosilylation of prochiral olefins has become an interesting area in synthetic organic chemistry since the first successful conversion of alkyl-substituted terminal olefins to optically active secondary alcohols (>94% ee) by palladium-catalyzed asymmetric hydrosilylation in the presence of chiral monodentate phosphine ligand (MOP, 20). The introduced silyl group can be converted to alcohol via oxidative cleavage of the carbon-silicon bond (Scheme 8-8).27... 

Menthol ester (20) with (l/ S)-frans-2,2-dimethyl-3-(2,2-dichloroethenyl) cyclopropanecarboxylic acid (19) has been utilized to produce ( R)-trans-2, 2-dimethyl-3-(2,2-dichloroethenyl) cyclopropanecarboxylic acid (21), an acid moiety of transfluthrin (22) [9]. Matsuo et al. surveyed various optically active secondary alcohols for their potential in the optical resolution of (lRS)-trans-chrysanthemic acid [10] (Scheme 2). 

It is well known that bakers yeast is capable of reducing a wide range of ketones to optically active secondary alcohols. A recent example involves the preparation of the (R)-alcohol (7) (97 % ee) (a key intermediate to ( norephedrine) from the corresponding ketone in 79 % yield1281. Other less well-known organisms are capable of performing similar tasks for instance, reduction of 5-oxohexanoic acid with Yamadazyma farinosa furnishes (R)-5-hydroxyhexanoic acid in 98 % yield and 97 % ee[29]. 

It is possible to use isolated, partially purified enzymes (dehydrogenases) for the reduction of ketones to optically active secondary alcohols. However, a different set of complications arises. The new C H bond is formed by delivery of the hydrogen atom from an enzyme cofactor, nicotinamide adenine dinucleotide (phosphate) NAD(P) in its reduced form. The cofactor is too expensive to be used in a stoichiometric quantity and must be recycled in situ. Recycling methods are relatively simple, using a sacrificial alcohol, or a second enzyme (formate dehydrogenase is popular) but the real and apparent complexity of the ensuing process (Scheme 8)[331 provides too much of a disincentive to investigation by non-experts. 

The enantioselective addition of alkyllithium to aldehyde in the presence of the lithium salt of diaminoalcohol (94) yielded optically active secondary alcohols as shown in Table 2. 

One popular method that has been apphed to industrial processes for the enantio-selective reduction of prochiral ketones, leading to the corresponding optically active secondary alcohols, is based on the use of chiral 1,3,2-oxazaborolidines. The original catalyst and reagent system [diphenyl prolinol/methane boronic acid (R)] is known as the Corey-Bakshi-Shibata reagent. Numerous examples... 

Microbial reduction of ketones is a useful method for the preparation of optically active secondary alcohols. Recently, both enantiomers of secondary alcohols were prepared by reduction of the corresponding ketones with a single microbe.Thus, reduction of aromatic ketones with Geotrichum candidum IFO 5767 afforded the corresponding 5-alcohols in an excellent ee when Amberlite XAD-7, a hydro-phobic polymer, was added to the reaction system the same microbe afforded... 

The transesterification reaction does not involve fission of the C—O bond of the alcohol, and therefore optically active secondary alcohols yield optically active orthoformates [34, 38, 45-48]. 

As a consequence of steric congestion in the transition state, ketones generally require high pressures to increase the reaction rate but yield optically active secondary alcohols in high . Thus, acetophenone yields 100% . of (S -l-phenylethanol at 2000 atm ... 

Carbonyl Addition Diethylzinc has been added to benzaldehyde at room temperature in the presence of an ephedra-derived chiral quat (8) to give optically active secondary alcohols, a case in which the chiral catalyst affords a much higher enantioselectivity in the solid state than in solution (47 to 48, Scheme 10.6) [30]. Asymmetric trifluoromethylation of aldehydes and ketones (49 to 50, Scheme 10.6 [31]) is accomplished with trifluoromethyl-trimethylsilane, catalyzed by a quaternary ammonium fluoride (3d). Catalyst 3d was first used by the Shioiri group for catalytic asymmetric aldol reactions from silyl enol ethers 51 or 54 (Scheme 10.6) [32]. Various other 1,2-carbonyl additions [33] and aldol reactions [34] have been reported. 

Optically active amino thiocyanate derivatives of (—)-norephedrine [e.g. (44)] have been found to act as effective aprotic ligands for enantioselective addition of diethylzinc to aldehydes.115 This reaction has provided optically active secondary alcohols with ee up to 96%. 

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... 

Starting with the optically active secondary alcohol sec-butanol (or butan-2-ol, but we want to emphasize that it is secondary), the secondary cation can be made by the usual method and has a characteristic 13C NMR shift. Quenching this cation with water regenerates the alcohol but without any optical activity. Water has attacked the two faces of the planar cation with exactly equal probability as we described in Chapter 16. The product is an exactly 50 50 mixture of (S)-butanol and (R)-butanol. It is racemic. 

The reaction of optically active secondary alcohols with DCC in dioxane or toluene affords O-alkyhsoureas 447, which react with formic acid to produce the ester 448 with complete inversion of configuration. Hydrolysis of 448 produces the secondary alcohol 449 with inversion of configuration." ... 

Chiral carbamates were prepared from racemic or optically active secondary alcohols A H and used to determine the induced diastereoselectivity of the osmium-catalyzed hydroxyamination reaction93. 

Asymmetric Reductions. Asymmetric reductions of prochiral ketones to optically active secondary alcohols have been extensively studied. The most common method involves the use of chiral unidentate or bidentate ligands in conjunction with Lithium Aluminum Hydride. However, an (5)-aspartic acid derived tridentate ligand has been shown to be very effective in certain cases, presumably due to the rigidity of aluminum complex (4) (eq 5-7). ... 

Enantioselective Addition of Dialkylzincs to Aldehydes Using Chiral Amino Alcohols Derived from Ephedrine. Nucleophilic addition of dialkylzinc to aldehydes is usually very slow. Amino alcohols facilitate the addition of Diethylzinc to benzalde-hyde to afford l-phenylpropanol. When chiral amino alcohols possessing the appropriate stracture are used as a precatalyst, optically active secondary alcohols are obtained. Highly enantioselective chiral catalysts derived from ephedrine are known. (lR,25)-N-Isopropylephedrine functions as a precatalyst for the enantioselective addition of diethylzinc to benzaldehyde to afford (R)-l-phenylpropanol with 80% ee in 72% yield. The use of an excess amount of diethylzinc increases the enantioselectivity up to 97% ee (eq 17). ... 

Asymmetric lactonization of prochiral diols has been performed vsdth chiral phosphine complex catalysts (Ru2Cl4((-)-DIOP)3 and [RuCl((S)-BINAP)(QH6)]Cl [17, 18]. Kinetic resolution of racemic secondary alcohol was also carried out with chiral ruthenium complexes 7 and 8 in the presence of a hydrogen acceptor, and optically active secondary alcohols were obtained with >99% e.e. (Eqs. 3.7 and 3.8) [19, 20]. 

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. ... 

Extension of this methodology to the use of chiral acetals such as (72 equation 19) to produce optically active secondary alcohols is found to be less efTicient than the ketal series. Alkyl Grignard reagents in ether (Table 18) provide the best selectivities (up to 90 10), while aryl and alkynyl organometallics show very little diastereofacial differentiation. ... 

The enantioselective addition of organometallics to aldehydes is a useful approach to optically active secondary alcohols. Diorganozinc reagents add with excellent enantioselectivity to aldehydes in the presence of a chiral catalyst such as 1,2- or 1,3-amino alcohols (see equation 14 and Table 2). In most cases, diethylzinc has been used, but the reaction could be extended to some other dialkylzinc reagents and to divinylzinc. Alkylzinc halides afford secondary alcohols with a substantially lower enantiomeric excess. Many aldehydes are good substrates, "- but the best results are usually obtained with aromatic aldehydes. ... 

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