1<2-Naphthyl ethanol

The high catalyst loading typical of sol gel entrapped catalysts ensures a desirably high substrate/catalyst (S/C) ratio as the major part of the heterogeneous catalyst weight originates from the silicate matrix. For example, in a preparative-scale reaction of the alcohol raol-(2-naphthyl)-ethanol only 250 mg of sol-gel CaLB immobilizate could be used per 10 g of substrate. For comparison, all this makes the process based on sol-gel immobilized lipase very competitive with the commercial BASF process using lipase immobilized on Amberlite to produce the amine at a scale of 1000 tons per year. 

The most successful modifier is cinchonidine and its enantiomer cinchonine, but some work in expanding the repertoire of substrate/modifier/catalyst combinations has been reported (S)-(-)-l-(l-naphthyl)ethylamine or (//)-1 -(I -naphth T)eth Tamine for Pt/alumina [108,231], derivatives of cinchona alkaloid such as 10,11-dihydrocinchonidine [36,71], 2-phenyl-9-deoxy-10, 11-dihydrocinchonidine [55], and O-methyl-cinchonidine for Pt/alumina [133], ephedrine for Pd/alumina [107], (-)-dihydroapovincaminic acid ethyl ester (-)-DHVIN for Pd/TiOz [122], (-)-dihydrovinpocetine for Pt/alumina [42], chiral amines such as 1 -(1 -naphtln I)-2-(I -pyrro 1 idiny 1) ethanol, l-(9-anthracenyl)-2-(l-pyrrolidinyl)ethanol, l-(9-triptycenyl)-2-(l-pyrrol idi nyl)cthanol, (Z )-2-(l-pyrrolidinyl)-l-(l-naphthyl)ethanol for Pt/alumina [37,116], D- and L-histidine and methyl esters of d- and L-tryptophan for Pt/alumina [35], morphine alkaloids [113],... 

The CSAs that have been used most widely are 2,2,2-trifluoro-l-phenylethanol (TFPE, la), 2,2,2-trifluoro-l-(l-naphthyl)ethanol (TFNE, lb), 2,2,2-trifluoro-l-(9-anthryl)ethanol (TFAE, Ic), 1-phenylethylamine (PEA, 2a), and l-(l-naphthyl)ethylamine (NEA, 2b). Both enantiomers of TFPE, TFAE (9), PEA, and NEA are commercially available. The fluoroalcohols are relatively acidic and interact strongly with solutes having one or more basic sites (Sect. IV-B). Amines 2 have been used most often as CSAs for organic acids or other acidic solutes (Sect. IV-C). A number of analogs of TFAE have been studied (Sect. III-C). 

A higher enantioselectivity is obtained at a lower temperature. The enantioselectivity by 31b/(5,5)-DPEN is higher than that by ( )-10b/(5,5)-DPEN at the same temperature and pressure. The tropos 31b/(5,5)-DPEN catalyst affords (f )-l-(l-naphthyl) ethanol with 92% ee in quantitative yield (entries 3 and 4). 31b/(5,5)-DPEN is also effective for o-methylacetophenone 22a to afford (7 )-l-(l-o-methylphenyl)ethanol quantitatively with 88% ee, higher than 86% ee obtained by ( )-10b/(5,5)-DPEN (entries 5 and 6). 

The reduction of methyl 6-methoxy-2-naphthyl acetate with lithium aluminium hydride in refluxing ether gives 2-(6-methoxy-2-naphthyl)ethanol, which by treatment with PBr3 in refluxing benzene is converted into 2-(6-methoxy-2-naphthyl)ethyl bromide. Further reaction with KCN in refluxing ethanol-water affords 3-(6-methoxy-2-naphthyl) propionitrile, which is finally treated with methylmagnesium iodide in refluxing ethanol. 

These chiral acyl donors can be used for quite effective kinetic resolution of racemic secondary alcohols. For example, enantiomeric aryl alkyl ketones are es-terified by the acyl pyridinium ion 8 with selectivity factors in the range 12-53 [10], In combination with its pseudo-enantiomer 9, parallel kinetic resolution was performed [11], Under these conditions, methyl l-(l-naphthyl)ethanol was resolved with an effective selectivity factor > 125 [12]. Unfortunately, the acyl donors 8 and 9 must be preformed, and no simple catalytic version was reported. Furthermore, over-stoichiometric quantities of either MgBr2 or ZnCI2 are required to promote acyl transfer. In 2001, Vedejs and Rozners reported a catalytic parallel kinetic resolution of secondary alcohols (Scheme 12.3) [13]. 

High reactivity was observed for 21b, and 21a was found to be the most selective. In the presence of 10 mol% 21a selectivity factors as high as 6.5 were observed with racemic 1-(1-naphthyl)ethanol as substrate (Scheme 12.6) [18]. The TBS analog of 21a was found to be good catalyst for asymmetric addition of methanol to a variety of prochiral aryl alkyl ketenes [18]. The catalytic asymmetric addition of achiral alcohols to prochiral ketenes is discussed in Section 13.2. 

The design of the peptide implies that interaction of the catalyst with its substrate relies heavily on hydrogen bonding. Initial studies indeed revealed that, in particular, N-acyl amino alcohols such as 25 and ent-25 were efficiently differentiated whereas both enantiomers of l-(l-naphthyl)ethanol were acetylated at identical rates [28]. Catalyst 23b, shown in Scheme 12.12, was the most efficient from a series of ten peptides. For best performance, proper matching of the sense of chirality of all three chiral amino acids is necessary, and the type of amino acid present at the carbon terminus enables further tuning (for example, L-Phe was found to be better than, e.g., L-Val, selectivity factor 21) [29]. 

The 2-(2-naphthyl)ethanol is treated with 138 L of concentrated hydrobromic acid. The mixture is refluxed for 5 h and allowed to return to room temperature, with stirring, and the product obtained is then filtered off and washed with water. The moist product is dissolved in 147 L of isopropanol under reflux, about 75 L of solvent are removed by distillation and the mixture is allowed to cool overnight. The product which has crystallized is filtered off, washed with previously cooled isopropanol and dried under vacuum at 40°C. So the 2-(2-bromoethyl)naphthalene is obtained (yield ... 

Enantiomer separation of various compounds such as barbituric acids, benzoin, MTH-proline, glutethimide, a-methyl-oc-phenyl-succinimide, y-phenyl-y-butyrolac-tone, methyl-mandelate, l-(2-naphthyl)ethanol, mecoprop methyl, diclofop methyl and fenoxaprop methyl by pressure supported CEC on a permethyl-P-cyclodextrin modified stationary phase was described by Wistuba and Schurig [42-44]. Three different separation beds were used (i) permethyl-P-cyclodextrin was covalently attached via a thioether to silica (Chira-Dex-silica) [42], permethyl-P-cyclodextrin was linked to a dimethylpolysiloxane and thermally immobilized (ii) on silica (Chirasil-Dex-silica) [43] or (iii) on a silica monolith (Chirasil-Dex-monolith) [44], respectively. 

Alkylated barbituric acids, 6-chloro-a-methylcarbazole-2-aceticacid, 1-phenylethanol, 1-phenyl-1-propanol, dimethyl, 3,4,5,6-pentafluoro-benzyl alcohol, l-(2-naphthyl)-ethanol, 1 -(p-biphenyl)-ethanol Chirasil-Dex coated column, 0.15 pm... 

Minder et al. studied various modifiers containing a nitrogen base for the enantioselective hydrogenation of ethyl pyruvate.223,224 Up to 82% ee with (R)-l-(l-naphthyl)ethylamine and up to 75% ee with (/ )-2-( 1 -pyrrolidinyl)-1 -(1 -naphthyl)-ethanol as modifiers were achieved in the hydrogenation of ethyl pyruvate to (R)-ethyl lactate over Pt-Al203 in acetic acid. 

Further increase in enantioselectivity was attained at a lower reaction temperature (Run 3). The enantioselectivity by the RuCl2(dmbiphep) (4b)/(5,5)-dpen was higher than that by the ( )-RuCl2(dmbinap) (3b)/(S,5)-dpen complex at the same low temperature and high pressure (Run 4). Thus, (R)-l-(l-naphthyl)ethanol was obtained with 92% ee in quantitative yield. RuCl2(dmbiphep) (4b)/(5,S)-dpen was also useful in the reduction of o-methylacetophenone. 

Ester-based chiral auxiliaries have also beat used in other settings. P-Alk-oxyesters 1.27 of (R)-1 -phenylethanol 1.1 (R = Me, Ar = Ph) or (5)-1-naphthyl-ethanol 1.1 (R = Me, Ar = 1-Np) are transformed into dural synthons by reactions with a lithiated carbanion a to phosphorous followed by hydrogenolysis [194], Ethers 1.28 of chiral alcohols 1.1 undergo selective alkylations or hydroxyalkyla-tions [169]. The auxiliaries can be removed by hydrogenolysis. Enol or dienol ethers 1.29 and 1 JO suffer [2+2] [195, 196] or [4+2] cycloadditions [49, 197,198, 199], The best stereoselectivities are obtained when the chiral auxiliary is 1.1 (R = r-Pr, Ar=Ph), 1.4 (R=Ph), 1.5 (R = Ph), 1.10 or 1.13. These auxiliaries are cleaved either by acid treatment [199] or by other means in subsequent steps. Acetylene ethers G OC=CR derived from 1.5 (R=Ph) [199a] can undergo stereoselective Pauson-Khand reactions [200, 201], The auxiliaries are removed by treatment of the products with Sml2 in THF-MeOH. 

---