Asymmetric induction, with phenethylamine

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... 

Amino-l-(3-hydroxyphenyl)ethanol has been prepared by an improved and possibly general method for this class of compounds.16 An interesting report on the partial asymmetric induction in the reduction of acetophenone-N-benzylimine at the mercury cathode with chiral supporting electrolytes may have potential for the chiral synthesis of alkaloids.17 For example, using ( -)-(R, S)-JV-methyI-ephedrine methiodide as the electrolyte resulted in the formation of (—)-(R)-N-benzyl-a-phenethylamine of 7.3% optical purity. Of interest for biosynthetic studies are the reports of the preparation of specifically labelled substituted -phenethylamines18 and of (+)-N-(o-chlorobenzyl)-a-methylphenethylamine hydrochloride 14C-labelled at the -carbon.19... 

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. 

Sodium cyanoborohydride is an effective reagent for the reduction of P-amino-propenoic acid derivatives. Reaction of benzylamine with ethyl acetoacetate gave 1.124 and reduction with cyanoborohydride led to ethyl N-benzyl-3-aminobutanoate, 1.125When R-phenethylamine was used in place of benzylamine, the amino acid product showed asymmetric induction (2-28% ee, see chapter five) after the phen-ethyl group was removed by treatment with hydrogen and Pd(OH)2 on carbon. ... 

An achiral ketone (S OS) was used to prepare protected alcohol 5.206 via condensation with S-phenethylamine, and that protecting group was also an auxiliary Removal of the benzylic group and re-protection with Boc allowed Birch reduction s of the aromatic ring to give 5.207. Ozonolysis in methanol led to methyl 4-(N-Boc amino)-6-methyl-3-oxoheptanoate, 5208. In this synthesis, the phenyl ring functioned as the carboxyl surrogate and asymmetric induction in 5.208 arose from the chiral auxiliary introduced earlier in the sequence. 

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