Phenylethyl alcohol, enantioselective

Highly enantioselective oxidation of phenylethyl alcohol was achieved by using a TEMPO-modified graphite felt electrode in the presence of (—(-sparteine, where the enan-tiopurity of the unreacted (//(-alcohol was >99% ee and the current efficiency was >90% (equation 24( . However, this selectivity has been questioned . 

Zeolite-encapsulated perfluorinated ruthenium phthalocyanines catalyze the oxidation of cyclohexane with t-BuOOH [146]. A dioxoruthenium complex with a D4-chiral porphyrin ligand has been used for the enantioselective hydroxylation of ethylbenzene to give a-phenylethyl alcohol with 72% e.e. [147]. 

Chiral modification is not limited to boronate and aluminate complexes. Boranes or alanes are partially decomposed with protic substances such as chiral amines, alcohols or amino alcohols to form useful reagents for enantioselective reduction of carbonyl compounds. For example, reduction of acetophenone with borane modified with the amines (65) to (67) gives (5)-l-phenylethyl alcohol with 3.5-20%... 

Several optically active polymers of acrylates and methacrylates have been obtained by enantioselective polymerization of a racemic monomer initiated by a Grignard compound complexed with chiral reagent. Complexing agents for the polymerization of (K,S)-a-methylbenzyl methacrylate include chiral alcohols, such as quinine and cinchonine [63], (— )-sparteine and its derivatives [64-67], and other axially disymmetric biphenyl compounds [68,69]. Other racemic monomers used include (/ ,S)-a-methylbenzyl acrylate [70], (K,S)-l-phenylethyl acrylate, methacrylate and a-ethylacrylate [71], and 1,2-diphenylethylmethacrylate [72]. 

The popularity of the poly(saccharide) derivatives as chiral stationary phases is explained by the high success rate in resolving low molecular mass enantiomers. It has been estimated that more than 85% of all diversely structured enantiomers can be separated on poly(saccharide) chiral stationary phases, and of these, about 80% can be separated on just four stationary phases. These are cellulose tris(3,5-dimethylphenyl carbamate), cellulose tris(4-methylbenzoate), amylose tris(3,5-dimethylphenyl carbamate), and amylose tris(l-phenylethyl carbamate). Typically, n-hexane and propan-2-ol or ethanol mixtures are used as the mobile phase [111]. Both the type and concentration of aliphatic alcohols can affect enantioselectivity. Further mobile phase optimization is restricted to solvents compatible with the stationary phase, such as ethers and acetonitrile, as binary or ternary solvent mixtures, but generally not chloroform, dichloromethane, ethyl acetate, or tetrahydrofuran. Small volumes of acidic (e.g. tri-fluoroacetic acid) or basic (n-butylamine, diethylamine) additives may be added to the mobile phase to minimize band broadening and peak tailing [112]. These additives, however, may be difficult to remove from the column by solvent rinsing to restore it to its original condition. 

Acid zeolites have also been tested for the racemisation of alcohols under biphasic conditions.Their scope was found, however, to be limited to benzylic alcohols, since electron-rich benzylic alcohols were not suitable substrates because of the formation of dimers. Under optimised conditions, based on the use of H-Beta zeolite, CALB lipase, and an excess of vinyl octanoate at 60 °C, enantiopure (R)-l-phenylethyl octanoate (>99% ee) was obtained in 90% yield from 1-phenylethanol. In addition, Lozano et al. have recently performed the DKR of this alcohol in the presence of acidic zeolite catalysts (CBV400) in an ionic liquid-supercritical carbon dioxide system with a continuous reaction system. Therefore, when Novozym 435 was employed at 50 °C and 100 bars in the presence of vinylpropanoate as the acyl donor, the expected (R)-phenylethylpropionate was produced in excellent yield of 98% with enantioselectivity of 97% ee and without any activity loss during 14 days of operation. 

In the first preparations of 128 and 129, 191 reacted with TMSNCO to give adducts 192, which were transformed to cyclic imines 193 upon dehydratation. Reaction of 193 with lithium cyclopropylacetylenide gave racemic 128 and 129, which were subjected to chiral stationary phase HPLC to isolate 128 and 129 as pure enantiomers [136, 137]. Several improvements were reported for this synthetic scheme. In particular, diastereoselective additions of lithium cyclopropyl acetylenide to the derivatives of 193 containing residues of a-phenylethyl amine or campheic acid were developed [154,155]. Moreover, an enantioselective modification of this method employing amino alcohol 194 as an asymmetric catalyst was discovered [156, 157]. Another enantioselective method involved reaction of the derivatives of 193 and cyclopropyl acetylene itself, catalysed by amino alcohol derivatives (e.g. 195) and Zn(OTf)2 [158]. 

Synthesis of BMY-14802 (228) commenced from pyrimidine derivative 243 which reacted with piperazine 244 to give derivative 245 (Scheme 58) [215, 216]. Reduction of the compound 245 followed by deprotection gave amine 246, which was alkylated with chloride 247 and then subjected to acidic hydrolysis to form ketone 248. Reduction of 248 allowed BMY-14802 (228) to be obtained. Pure enantiomers of 228 were also obtained. To achieve this, the following methods were used resolution of 228 with using reaction with a-phenylethyl isocyanate [217] or lipase-catalyzed acetylation or hydrolysis [218], alkylation of 245 with enantiopure alcohols 249 [219] and microbial reduction [305] or Ru-catalyzed enantioselective hydrogenation [220] of 248. 

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