Phenethylamines diastereoselectivity

Addition of Grignard and organolithium reagents to imines 2. derived from enantiomerically pure (S)-valinol (1), provides a-substituted phenethylamines 3 in moderate to good yield and excellent diastereoselectivity (in each case only one diastereomer can be detected by NMR)15. By appropriate selection of imine and organometallic reagent both diastereomeric amines are accessible (see also refs 16 and 17). 

Amino acid synthesis (cf. 12,15). The reaction of 1 with chiral a-imino esters provides an enantio- and diastereoselective synthesis of amino acid derivatives. The imine (2), prepared from (S)-phenethylamine, reacts with 1 to give 3, which... 

The origin of the observed 1,4-asymmetric induction in Michael reactions of chiral imines (Scheme 28) has been rationalized by conformational transmission of chirality. Thus, the phenethylamine auxiliary forces the cyclohexene part of the intermediate enamine into a half-chair conformation (140) that is 0.8 kcal mol-1 lower in energy than (141). Axial attack as shown then leads to the major product the energy difference between (140) and (141) roughly correlates with the observed diastereoselectivity ( 9 l).105... 

Allylation. Allyl halides are converted to allyltitanium compounds by r-PrMgBr/jr-PrOj Ti, which can be used for allylation of carbonyl compounds and aldimines. With imines derived from a chiral a-phenethylamine, the reaction is highly diastereoselective following the Cram pattern exhibiting a 1,3-asymmetric induction. 

For investigating diastereoselectivity, Mannich reactions of calix[4]resorcinarene with chiral primary amines were studied (95TL4905, 95TL6221). In a representative case of the reaction of R-(+)-l-phenethylamine, formation of two diastereomers 131 and 132 is possible but only one of these is formed with high stereoselectivity as shown by H- and C-NMR spectra and X-ray confirmed structure 131 with... 

Until the early 1990s, there was no practical use of the hydroxychlorination of alkenes. Recently, Dai and co-workers have enhanced the synthetic utility of this reaction by employing allylic amines and sulfides as the substrate. When a combination of DMF or THF with H2O is used as the solvent, the hydroxychlorination of these substrates proceeds smoothly and regioselectively to give chlorohydrins in high yields (Scheme 3). The product chlorohydrins serve as the precursors of epoxides. Unfortunately, with allyl amines bearing chiral moieties such as (/ )-phenethylamine, the diastereoselectivities of... 

Reaction of 10a and 11a with the aluminum amide prepared from MejAl and the (R)-phenethylamine and subsequent reduction step occurred with the same excellent anti/syn diastereoselection as precedently, leading respectively to anti amino alcohols 8a and 9a. These amino alcohols were obtained in an excellent purity from 10a (8a/9a = 93/7) and from 11a (9a/8a = 90/10). The stereoisomeric excess is the same as the enantiomeric excess of starting epoxy ethers. No racemization occurred in the reaction ring opening does not involve a carbenium ion, and no enolization occurs from intermediate A or B. Both enantiommc amino alcohols 12a and 13a were obtained by debenzylation with palladium hydroxide imfortunately, we have not been able to assign the absolute configuration of the asymmetric carbons of 8a and 9a (Scheme 7). 

Although the asymmetric Staudinger reaction, controlled by a chiral iV substituent on imines, is seldom diastereoselective, because of the relatively long distance between chiral and reaction centers," we turned all the same towards the [2+2] ketene-imine cycloaddition with the chiral trifluoroacetaldimine 25, prepared from trifluoroacetaldehyde hemiketal and the (iS)-phenethylamine. Tlie reaction of benzyloxyketene with imine 25 was efficient leading to flie mixture of azetidinones 26 and 27 in 90 % yield. High cis/trans stereoselectivity was observed, with only 3-5 % of trans azetidinones formed. As expected, the cWrality transfer was low with a diastereoisomeric excess of only 10 %. Fortunately, it was possible to easily separate the two diastereoisomers by crystallization in ethanol of the crude mixture. Stereoisomer 26 crystallized in ethanol and was obtained in an excellent diasteroisomeric purity (> 99 %). Stereoisomer 27 could be isolated in 95 % diastereoisomeric purity after SiOj chromatography and crystallization (Scheme 12). 

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