I-a-pHENYLETHYLAMINE

By the method referred to under the benzyl/soquinoline alkaloids (p. 193) Leithe has shown that the configuration of the I- and d-canadines by reference to Z( —)-a-phenylethylamine is l(—) and d(-j-) respectively. 

In the presence of ZrCU or HC1, cyclization of y - a I k o x y a 11 y I s t a n n a n e 158 bearing (i )-(+)-l-phenylethylamine as a chiral auxiliary occurs to produce trans-fi-aminocyclic ether 159 with high de (91%). As shown in Scheme 3-55, asymmetric addition of an allyl group to the imine carbon can be explained by the modified Cram model 160. The attack of the allylic y-carbon approaches... 

FIGURE 5. Proton NMR spectra of solutions prepared from (S)-a-phenylethylamine [(S)-22] (10 pL) (upper spectrum) and a mixture of (R)- and (S)-a-phenylethylamine (R)- and (S)-22] (7 and 5 J-L, respectively) (lower spectrum) in 0.3 mL of a carbon tetrachloride solution of tris[3-(ferf-butylhydroxymethylene)-(i-camphorato]europium(III) (96). The chemical shift scale applies only to the lower spectrum. Reprinted with permission from Reference 82. Copyright (1970) American Chemical Society... 

By using (/ )-. Y, V-dimethyl-l-phenylethylarnine. alkenes of the opposite absolute configuration but, surprisingly, with different enantioselectivity are formed81. However, elimination with ( S i-A. jY-dimeLhyTl-phenylethylamine of the trifluoromethanesulfonate of cfs-cyclohex-ane-l,4-diol monomethoxymethyl ether gives the corresponding alkene with only 5% ee. 

This procedure may be used for the preparation of a variety of a-amino ketones as is indicated in Table I, which summarizes most of the submitters experience with this reaction. Principal deviations from the procedure wifi be in the time required for a negative starch-iodide test and the nature and amount of extraction and recrystallization solvent. It is strongly recommended that any one using the reaction for the first time carry out the preparation on a-phenylethylamine before attempting to use it on other more valuable amines. 

R)-a-Phenylalkylamines. (R)-a-Phenylethylamine (4) can be prepared in about 97% optical purity by addition of methylmagnesium bromide to the chiral hydrazone obtained from benzaldehyde and the N-amino derivative (1) of D-( —)-ephedrine followed by hydrogenolysis (equation I). Acetophenone is not a suitable starting material because it reacts with 1 to form two isomeric hydrazones. ... 

The (S)-(-)-isomer (lb) was the one required for synthesis of the herbicides. Reaction of racemic 2-chloropropionic acid with one equivalent of (//)-(+)-a-phenylethylaminc (2) gave a quantitative yield of the mixture of diastereoisomeric salts, which after 4 recrystallizations gave the required diastereoisomer in 20% yield [i.e., 40% based on the (S)-(-)-isomer present] with a de of 88% (determined by nuclear magnetic resonance, or NMR). The free acid (lb) was obtained quantitatively and without racemization on acidification of the salt, and the (R)-(+)-a-phenylethylamine was also recovered without racemization in 89% yield. 

When salt crystals of the aryl 1-phenylcyclopenty 1 ketone carboxylic acid 40 with chiral amines such as (+ )-bomylamine or (—)-1-phenylethylamine were irradiated, the optically active exo- and endo-oxetanes 41 or 42 were formed in low to moderate enantiomeric excesses (Scheme 10) [57]. The formation of the oxetanes is believed to occur through Norrish type 1 cleavage and hydrogen abstraction, producing an alkene and an aldehyde, followed by a Paterno-Buchi reaction within the crystal lattice cage. In contrast, solution photolysis of 40 in acetonitrile afforded product 43 as the only isolable product via a typical Norrish type I a-cleavage followed by radical coupling. 

Figure 4.5. Schematic representations of the crystal structures of the less and more soluble salts of enantiopure 1 with 1-arylethylamines in success, (a) Less soluble salts, which are stable from the viewpoint of hydrogen-bonding and van der Waals interactions. (,b) More soluble (R)-l (S)-l-(m-methoxyphenyl)ethylamine, in which a stable hydrogen-bond sheet is formed while the close packing of the sheets is not achieved, (c) More soluble (R)-l (i )-l-phenylethylamine, in which a stable hydrogen-bond sheet is not formed while the close packing of the sheets is achieved.

Salts of 2-carboxyphenoxatellurin with nor-c -i -ephedrine, strychnine, cinchonidine, quinine, and r/-a-phenylethylamine were prepared with the hope of resolving 2-carboxyphenoxatellurin into optically active isomers. 2-Carboxyphenoxatellurin samples regenerated from these salts did not have optical activity b 2-Carboxyphenoxatellurin was esterified by heating with /-menthol . 

An altemative synthesis of fosfomycin has been effected by the halohydrin route. 9 Thus, treatment of ( ) (Z)-l-propenylphosphonic acid in aqueous solution with sodium hypochlorite gave t/zreo-l-chloro-2-hydroxypropylphosphonic acid (85%). Resolution is accomplished by means of (-)-a-phenylethylamine to yield (-i-)-chlorohydrin (80%), which is converted with 10 M aqueous NaOH into fosfomycin (85-90%). ... 

A final comment on Table 4 concerns the reaction shown in entry 8. Because the di-TT-methane photorearrangement of benzonorbornadiene derivatives requires triplet energy sensitization, we could not use typical, passive amines such as (/ )-(-I-)-l-phenylethylamine as chiral auxiliaries. We therefore prepared an optically pure amine to which a sensitizing benzophenone moiety was tethered, namely, the 4-benzoylphenyl ester of L-valine [25]. Photolysis of the salt of this amine at wavelengths where only the benzophenone chromophore absorbs led to the photoproduct in 91% ee at 100% conversion, a gratifying vindication of the concept. Optically active photosensitizers have been used in solution with limited success [33], but this represents the first example of simultaneous triplet-triplet energy transfer and asymmetric induction in the crystalline state. 

The asymmetric reductive animation of racemic 2-substituted cyclohexanones (R = CH3, Et, i-Pr, C6H5, Bn) using optically active (S)- or (/ )-a-phenylethylamine yields 2-substituted cis-cy-clohexanamines 23- 25 in 42- 79% yield with 92-99% ee, according to H-NMR data. 

Further reactions may occur after the formation of a Schiff base. Thus aldehydes react with substituted phenylethylamines under mild experimental conditions to form ultimately tetrahydroisoquinolines i . A particular case of this is the reaction between pyridoxal and DOPA [Figure 4.5). A similar reaction occurs between pyridoxal and histidine [Figure 4.5). The observation that DOPA decarboxylase is subject to substrate inhibition aroused... 

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