2- Phenylethylamine, reaction with

L-Pkenylalanine, reaction with phthalic anhydride to yield N-phthalyl-L-phenylalanine, 40,82 Phenyl terf-BUTYL ether, 41, 91 a-Phenylethylamine, N-chlorination of, 41,82... 

In contrast to the allyltitaniums derived from acrolein cyclic acetals, such as 1,2-dicyclo-hexylethylene acetal shown in Scheme 9.8, those derived from acrolein acyclic acetals react with ketones and imines exclusively at the y-position. As shown in Eq. 9.29, the reaction with chiral imines having an optically active 1-phenylethylamine moiety proceeds with high diastereoselectivity, thus providing a new method for preparing optically active 1-vinyl-2-amino alcohol derivatives with syn stereochemistry [53], The intermediate allyltita-nium species has also found use as a starting material for a carbozincation reaction [54],... 

Even if the imine may not be isolated, the transient species may sometimes be trapped by reaction with a suitable nucleophile. This is the basis of the reductive amination reaction in which an amine is formed from the reaction of ammonia with a carbonyl compound in the presence of a reducing agent such as sodium borohydride or formate. Use of a primary or secondary amine results in the specific formation of secondary or tertiary amines respectively (Fig. 5-45). This synthetic method allows the preparation of high yields of amines, in contrast to the unselective and uncontrollable reaction of alkylating agents with amines. A specific example involving the preparation of a-phenylethylamine from acetophenone is presented in Fig. 5-46. 

Despite the results obtained by Emmenegger123 showing that one chelate ring placed in the equatorial plane of the complex may be opened quite easily in a reaction with a monodentate ligand, it seems that the strain of this chelate ring is smaller in complexes of penten compared to EDTA. Contrary to the result with [Ni(PDTA)]2-, it was not possible to coordinate 1-phenylethylamine in a stereoselective way with [Ni((R)-mepenten)]2+113 124. ... 

Protopine has been isolated from Bocconia frutescens,110 Fumaria judaica,111 F. schleicheri,112 and Papaver bracteatum,146 cryptopine from F. schleicheri,112 and allocryptopine from B. frutescens110 and Zanthoxylum nitidum.141 The protopine ring-system has been prepared from tetrahydrobenzindenoazepines (75) by photo-oxidation to the amides (76) followed by reduction with lithium aluminium hydride and re-oxidation with manganese dioxide.148-150 The tetrahydrobenzindenoazepines have been prepared from A-chloroacetyl-/ -phenylethylamines (73) by cyclization to the lactam (74) followed by reaction with a benzyl bromide and phosphorus oxychloride. -Protopine (77 R R2 — CH2)148 and fagarine II (77 R1 = R2 = Me)149 have been synthesized in this way. 

The compound /3-phenylglutaric anhydride, 49, contains enantiotopic ligands. On reaction with ( —)-a-phenylethylamine the two diastereoisomers of the monoamide, 50 and 51, were formed in unequal amounts [67]. In contrast to the earlier statement (the products are usually enantiomers in an enantiodifferentiating process), the products here are diastereoisomers. Of course, if the amine component of the amide were to be removed, the products from the substrate anhydride would be enantiomers. This differentiation between enantiotopic groups was important in the early days of the citrate story. It proved the possibility of differentiation in homogeneous solution, presumably without a three-point attachment. 

The addition of chiral amines to a,/(-unsaturated sulfoximines has been employed for the resolution of racemic sulfoximines 3 utilizing 0.5 equivalents of a chiral amine in chloroform 117. After completion of the reaction, the unreacted starting material is isolated by column chromatography and its optical purity determined by comparison with the reported optical rotation, or by HNMR using a chiral shift reagent. While (—)-(l/f,2.S,)-2-mcthylamino-1-phenyl-l-propanol [(l/ ,2S)-ephedrine] affords material of moderate optical purity, racemic products are isolated from addition reactions with (—)-l-phenyl-2-propanamine [(—)-am-phetamine] or ( + )-( )-l-phenylethylamine. 

Many water-insoluble ketones, aliphatic, aryl aliphatic, and heterocyclic, respond favorably to treatment with ammonium formate or formamide to form with subsequent hydrolysis the primary amines. A typical procedure for the synthesis of a-phenylethylamine (66%) from acetophenone and ammonium formate has been applied to many other ketones (65-84%). Nuclear alkoxyl, halo, and nitro groups are not disturbed. The reaction with formamide as the reducing agent is catalyzed by ammonium formate, ammonium sulfate, or magnesium chloride. ... 

Direct amidation can be carried out if an aromatic compound is heated with a hydroxamic acid (34) in polyphosphoric acid, but the scope is essentially limited to phenolic ethers.The reaction of an aromatic compound with aniline, BU4NF and KMn04 led to the diarylamine. The formation of hydroindole derivatives was accomplished by reaction of a A-carbamoyl phenylethylamine derivative with phenyliodine (III) diacetate, followed by Bu4NF. Direct amidation via ipso substitution by nitrogen was accomplished when a A -methoxy arylethylamide (35) was... 

The most prominent intramolecular reaction of iminium ions with aromatic C-nucleophiles is the long-known Pictet-Spengler condensation of 2-phenylethylamines (8) with reactive carbonyl compounds (9)—by far the most important route to natural and synthetic tetrahydroisoquinolines (10 Scheme 8). 

Another method to prepare tetramisole involves reaction of 2-bromo-l-phenylethylamine (31) with vinyl isothiocyanate in methylene chloride at temperatures below 5 C, followed by treatment with mercuric acetate to form tetramisole (3) [24] (Scheme 5). 

A synthesis of 7,8-dioxygenated isoquinolines (found in cularine alkaloids) requires o-metallation of the Af-protected -phenylethylamine. The primary amine is protected by reaction with two equivalents of trimethylsilyl chloride. Phenylhydroxylamine and the allenic nitrile (53.7) react in boiling ethanol over 48 h to give a high yield of 4-aminoquinoline—an important intermediate for the synthesis of some antimalarial drugs. 

One of the most powerful methods for the construction of tetrahydroisoquinoline systems is the Pictet-Spengler cyclisation. The reaction consists of the condensation of a b-phenylethylamine derivative with a carbonyl compound, generating an imine (Schiffs base), which undergoes cyclisation via an intramolecular electrophilic aromatic substitution yielding the isoquinoline derivative. The Pictet-Spengler reaction is traditionally carried out in a protic solvent with acid catalysts, usually acetic acid or trifluoroacetic acid. 

A very different, but similarly effective, auxiliary is the chiral carbonyl(t/5-cyclopentadienyl)(tri-phenylphosphine)iron moiety. When the z./i-unsaturated acyl-iron complex ( -)-(/ )-11 is treated by a modified Simmons Smith reagent, a 91 9 mixture of cyclopropane diastereomers is isolated in good yield73. Precomplexation of the starting iron complex by the Lewis acid zinc(II) chloride seems to be necessary to obtain good selectivity. The chiral iron moiety can then be removed oxidatively by bromine treatment, and the intermediate acyl bromides converted into amides by reaction with (/ )- -phenylethylamine. 

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