Naphthyl ethylamine

In the modified procedure for reactions carried out at —30 °C, a solution of the organozinc reagent (2.4 mmol) in THF and the ally chloride (2.0 mmol) were added simultaneously over 3 h. 

Knochel, P. Duebner, F. Copper-Catalyzed Enantioselective Allylic Substitution Reactions, PCT Int. Appl. 2000. 

Form Supplied in clear liquid both enantiomers and the racemate are all widely available. 

Analysis of Reagent Purity the enantiomeric purity of the reagent can be determined by either NMR or HPLC analysis of derivatives produced from a-methoxy-a-(trifluoromethyl)benzyl isocyanate, a-methoxy-a-(trifluoromethyl)benzyl acid chloride, or 2 -methoxy-l,l -binaphthyl-2-carboxylic acid chloride.  

Preparative Methods racemic l-(l-naphthyl)ethylamine can be resolved with camphoric acid, tartaric acid, L-menthyl hydrogen phthalate, di-O-isopropylidene-2-ketogulonic 

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Synthesis of (A) started with the combination of 2,4,6-trimethylphenol and allyl bromide to give the or/Ao-allyl dienone. Acid-catalyzed rearrangement and oxidative bydroboration yielded the dienone with a propanol group in porlactone ring were irons in the product as expected (see p. 275). Treatment with aqueous potassium hydroxide gave the epoxy acid, which formed a crystalline salt with (R)-l-(or-naphthyl)ethylamine. This was recrystallized to constant rotation. 

The method described is rather general. With appropriate modifications for the purification of the aim ne the method yields a- -tolylethylamine (72 per cent), a-p-chlorophenylethyl-amine (65 per cent), a -/)-bromophenylethylamine (63 per cent), a- -xenylethylamine (66 per cent), and a-(/9-naphthyl)-ethylamine (84 per cent) from the corresponding ketones. 

The ci i-fused lactone A was resolved using (-t-)-l-(l-naphthyl)ethylamine to give the enantiomer required for the synthesis of prostanoids (Ref. 3). 

Fig. 7-6). Two unichiral amides which have been known capable of this reaction are 1-phenylethylamine [15] and l-(l-naphthyl)ethylamine [16]. Marfey s reagent [N-a-(2,4-dinitro-5-fluorophenyl)-L-alaninamide] was introduced as a reagent to deriva-tize amino acids with cyclopentane, tetrahydroisoquinoline or tetraline structures [17]. Simple chiral alcohols such as 2-octanol can also be used to derivatize acids such as 2-chloro-3-phenylmethoxypropionic acid [18]. 

A. fi(-)-a-(l-Naphthyl)ethylamine. A mixture of 58.44 g. (0.20 mole) of (-)-2,3 4,6-di-0-isopropylidene-2-keto-L-gulonic acid hydrate [(-)-DAG] (Note 1) and 1.7 1. of acetone (Note 2) is placed in a 3-1. Erlenmeyer flask. A boiling chip is added, and the mixture is heated to a gentle boil. To the resulting hot solution is added cautiously but rapidly, over a 1 minute period, 34.24 g. (0.20 mole) of racemic y.- 1 -naphthyl)et hylamine (Note 3) in 100 ml. of acetone. The mixture is allowed to stand at room temperature for approximately 4 hours. The (-)-amine (-)-DAG salt is filtered with suction, washed with 100 ml. of acetone, and dried in a vacuum oven at 60° to constant weight. The yield of the crude (-)-amine (-)DAG salt is 73-76 g., m.p. 205-207° (decomp.) (Note 4), [a]p —14.2° (c 1.01%, methanol). For crystallization, the crude salt and 4.2 1. of ethanol (Note 5) are placed in a 5-1. round-bottomed flask fitted with a reflux condenser and a mechanical stirrer. The mixture is stirred and heated at reflux... 

Practical-grade racemic a-(l-naphthyl)ethylamine (purchased from Norse Laboratories, Inc., Santa Barbara, Calif. 93103) was distilled before use, b.p. 117—118° (2 mm.). 

S(-)-x-(l-Naphthyl)ethylamine has been prepared by resolution of the racemic amine with camphoric acid in unspecified yield.2,3... 

The spiro compound 206 was prepared in five steps from (S)-l-naphthyl-ethylamine and was composed of a mixture of imine and enamine tautomers. Reduction of the imine function by sodium borohydride occurred on the less hindered si face, leading to the diamine with the R configuration of the newly formed stereo center, then the N-benzyl substituent was removed by hydrogenolysis to give 207 with good overall yield [98] (Scheme 30). 

An attractive alternative to these novel aminoalcohol type modifiers is the use of 1-(1-naphthyl)ethylamine (NEA, Fig. 5) and derivatives thereof as chiral modifiers [45-47]. Trace quantities of (R)- or (S)-l-(l-naphthyl)ethylamine induce up to 82% ee in the hydrogenation of ethyl pyruvate over Pt/alumina. Note that naphthylethylamine is only a precursor of the actual modifier, which is formed in situ by reductive alkylation of NEA with the reactant ethyl pyruvate. This transformation (Fig. 5), which proceeds via imine formation and subsequent reduction of the C=N bond, is highly diastereoselective (d.e. >95%). Reductive alkylation of NEA with different aldehydes or ketones provides easy access to a variety of related modifiers [47]. The enantioselection occurring with the modifiers derived from NEA could be rationalized with the same strategy of molecular modelling as demonstrated for the Pt-cinchona system. 

Naphthyl)ethylamine, chiral derivatizing reagent, 6 76t 1 -N aphthylethylcarbamoy la ted... 

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],... 

In a 50-mL, round-bottomed flask, equipped with a rubber septum and a magnetic stirring bar and filled with argon, are placed citronellic acid (112 mg, 0.658 mmol) and a solution of (R)-1-(1-naphthyl)ethylamine (140 mg, 0.818 mmol) (Note 29) in dry DMF (4 mL) (Note 5). To this mixture in an ice bath are added a solution of diethyl cyanophosphonate (224 mg, 1.37 mmol) (Note 30) in dry DMF (2 mL) and then dry triethylamine (0.1 mL). The mixture is stirred and the reaction is followed by TLC. When the carboxylic acid has been consumed, which takes approximately 2 hr at room temperature, the reaction mixture is dissolved in a mixture of benzene (5 mL) and ethyl acetate (5 mL). The mixture is washed successively with cold 5% hydrochloric acid,... 

R)-(+)-1-(1-Naphthyl)ethylamine is purchased from Aldrich Chemical Company, Inc. The reagent is purified by recrystallization of its tartaric acid salt three times from 94% aqueous methanol followed by treatment with base and distillation of the free amine. 

Using cyclohexylamine, as M ef, the data for various enantiomeric mixtures ofl-(l-naphthyl)ethylamine (M) display a linear relationship between RPIj /RPP and ee. Enantiomeric impurieties as small as about 2% can currently be detected with this method." " Variable-temperature FT-ICR-MS measurements of the ligand... 

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). 

The required chirally substituted indoloazepine 219 was prepared by reaction of (5)-l-(l-naphthyl)ethylamine with the methiodide of 4-piper-idone (223), followed by a Fischer indole reaction leading to the V-carboline 224 (Scheme 56). Chlorination and reaction with thallium dimethylmalonate, followed by decarbomethoxylation of the resulting in-... 

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