AND S — --Phenylethylamine

The diastereoselective and enantioselective synthesis of optically active 2-amino-3,3-dimethylbutanes was achieved as follows pinacolone was reacted individually with ( + )-(/ )-and ( —)-(S)-phenylethylamine to afford the corresponding chiral ( )-imines. Reduction of the imines with borane-tetrahydrofuran complex resulted in addition of hydride to the less hindered face of the azomethine to give (R,R)- and (S. -benzylamine, respectively, which, on hydrogenolysis (10% Pd/C), afforded (7 )- and (5 )-2-amino-3,3-dimethyl butane, respectively, with high enantiomeric purity (ee >99.5%)3. 

Acid (S)-12 was separated as its brucine salt [20,21] and subsequently converted into ketone (S)-ll. Hydroxyketones (K)-IO [22] and (S)-ll [23] were obtained by separation of the mixture of diastereoisomeric imines obtained from rac-10 or rac-ll and (-)-(S)-phenylethylamine. 

Further reactions of allyl organometallics with a-alkoxyaldimines 1, prepared from (S)-2-(methoxymcthoxy)propionaldehyde and (R)- and (S)-l-phenylethylamine, illuminate the difference in the influence of the nitrogen chiral auxiliary and the x-alkoxy center7. 

The addition of 2-nitropropene to the chiral imine derived from 2-methylcyclopentanone and (S )-l-phenylethylamine gives the adduct in high regio- and stereoselectivity (Eq. 4.71).90 The product is converted to a chiral 1,4-diketone via the Nef reaction. 

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... 

This Mulheim chemistry has been highlighted by the discovery of the highly enantioselective hydrovinylation of styrene to produce chiral 2-phenyl-1-butene in 95.2% ee for a 10 kg-scale reaction (Scheme 60) (132). The Ni catalyst is very reactive and contains the unique chiral dimeric aminophosphine ligand derived from (R)-myrtenal and (S)-1-phenylethylamine. Computer simulations suggest that in this chiral Ni complex, the phenyl substituent of the chiral phenylethyl group acts as a windshield wiper across the catalytically active metal center. This... 

Cyclization of chiral imines.1 Asymmetric induction to the extent of 36-65% is observed on cyclization of chiral imines derived from (R)- and (S)- a-phenylethylamine. Example ... 

Harada and Matsumoto studied the effect of solvents on the % ee of the amino acids formed in asymmetric transamination.56 Generally, the optical activity of alanine prepared from benzyl pyruvate and (S )-)-)-1-phenylethylamine decreased with increasing polarity of the solvents used. From the finding that sodium a-phenylglycinate was hydrogenolyzed easily to ammonia and phenylacetate over palladium catalyst, Harada prepared optically active alanine, butyrine, glutamic acid, and aspartic acid in 40-60% optical purities from the corresponding a-oxo... 

R) - and (S)-l-phenylethylamine to the diethyl esters of fumaric and maleic acid which are carried out by heating the pure compounds, without solvent, to 115-120 °C for three days (see Table 1). The reaction mixtures are then hydrolyzed and hydrogenated to give aspartic acids in high yields (85-87%) but very low optical purities (6.3-12.2%). A number of intermediates and by-products arc isolated, especially amides and imides of the dicarboxylic acids participating in the reaction. This may explain the low overall diastereoselectivity which can be calculated from the low optical rotation of the isolated aspartic acids. However, any discussion of the reaction mechanism remains difficult because the structures of the substrates and products of the actual addition step itself are not known with certainty. It is known that... 

Optically pure (+)-6a (MGS0008) (64% yield) and its enantiomer (-)-6b (73% yield) were produced by acidic hydrolysis of carboxylic acids (+)-19 and (-)-19, respectively. Compounds (+)-19 and (-)-19 were obtained through selective saponification of the ester moiety of (+)-18 under basic conditions (93% yield), followed by optical resolution of the resulting (+)-19 with (R)- and (S)-l-phenylethylamine [(+)-19 39% yield, (—)-19 36% yield], respectively (see Scheme 3.1). 

Yamamoto et al. ° have examined the addition of allyl organometallic reagents to a-alkoxyaldimines (40) derived from (S)-2-methoxy(methoxy)propionaldehyde and (/ )- and (S)-l-phenylethylamine (equation 10). The results are summarized in Table 10. Chelation control with allyl-AlEtaMgCl, -MgCTl and -ZnBr (entries 1-3, Table 10) and nonchelation (Cram) control with allyl-Ti(Pi O)3, -B(OMe)2 and -9-BBN (entries 4-6, Table 10) parallels that observed in the allyl metal-a-alkoxyaldimine additions (involving aldimines that lack a chiral nitrogen substituent) shown in Table 6. The chirality of the a-alkoxy... 

The 4CC of benzoic acid (58), isobutyraldehyde (59) and (S)-a-phenylethylamine (60), or their imine (61), with r-butyl isocyanide (26) has been studied quite extensively as a model reaction for stereoselective 4CC. " ... 

Yashima et al. [88] investigated the interaction of poly(phenylacetylene) modified with fi-CD moieties with guest molecules, including 1-adamantanol, (-)-borneol, and R)- and (S)-l-phenylethylamine. They observed a color change upon complex-ation because of a change in the helicity pitch arising from helicity inversion. 

Singh et al. [73] used a methyl silicone fused silica column to separate the amides formed from NSAIDs and S(—)-l-phenylethylamine or R(- -)/S(—)amphet-amine. 

The degree of racemization was also monitored through the experiment of a simple carboxylic add used in peptide synthesis, 2-phenylbutyric acid. The penta-fluorophenyl ester of (R)-2-phenylbutyric acid and (S)-l-phenylethylamine reacts with the corresponding amino acid via an EDCI coupling [5]. In a control experiment, (R)-2-phenylbutyric acid and (R)-l-phenylethylamine were reacted as well. For the amino acid formation of (R)-2-phenylbutyric acid and (S)-1 -phenylethylamine, a 4.2% racemization was found [6], Athigher concentration (0.5 M instead ofO.l M), a higher degree of racemization was observed (7.8%). 

Twro diastereomeric salts (R)-lactic acid plus (5)-1-phenylethylamine and (S)-lactic acid plus (5)-l-phenylethylamine... 

Instead, the reaction of TMS cyanide with the chiral imine prepared from racemic 2-benzoylaminocyclohexanone and (fi)-l-phenylethylamine or (S)-l-phenylethylamine in the presence of zinc chloride occurred with low stereocontrol, and the two enantiomers of fra s-l,2-diaminocyclohexane car-boxyhc acid were isolated with low yields after several steps [88]. 

By heating 2-benzyloxycyclohexanone 208 and (R)-l-phenylethylamine in refluxing toluene for 4 days in a Dean-Stark apparatus, the imine 209 was formed, then a rearrangement occurred to give first the a-aminocyclohexanone derivative 210 and finally the Q, o -disubstituted imine 211 with moderate diastereoselectivity. Reduction of this imine with sodium borohydride gave a mixture of two trans diamines (S,S)-212 and (R,R)-212, which were separated by chromatography. The enantiomers of 1-benzyl-1,2-diaminocyclohexanes 213 were then obtained by hydrogenolysis [99] (Scheme 31). 

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