Catalytic asymmetric phase-transfer Michael addition

Catalytic Asymmetric Phase-Transfer Michael Addition to a,f -Unsaturated Esters 119... 

Scheme 6.3 Catalytic asymmetric phase-transfer Michael addition and counter anion effects.

The catalytic enantioselective synthesis of ( )-paroxetine (69, Paxil GlaxoSmithKline, London, U.K.), which is a selective serotonin reuptake inhibitor being used for the treatment of depression, anxiety, and panic disorders, was executed as an application of the catalytic asymmetric mono -a-alkylation of 1,3-amide esters (Scheme 4.16). The characteristic feature of this protocol is the introduction of the C3-stereocenter first by the asymmetric phase-transfer alkylation before installing the C4-center by a diastereoselective Michael addition. Af,A -Di-p-methoxyphenyl malonamide... 

Acrylonitrile, polymerization, 120 Activity of phase-transfer catalysts Sjj2 reactions, 170-175 weak-nucleophile Sj.Ar reactions, 175-182 Acyltetracarbonyl cobalt compound, cleavage in the carboxyalkylation of alkyl halides, 150 Addition reactions, Michael, catalytic asymmetric, 69,70f... 

Catalytic Michael additions of a-nitroesters 38 catalyzed by a BINOL (2,2 -dihydroxy-l,r-bi-naphthyl) complex were found to yield the addition products 39 as precursors for a-alkylated amino acids in good yields and with respectable enantioselectivities (8-80%) as shown in Scheme 9 [45]. Asymmetric PTC (phase transfer catalysis) mediated by TADDOL (40) as a chiral catalyst has been used to synthesize enantiomeri-cally enriched a-alkylated amino acids 41 (up to 82 % ee) [46], A similar strategy has been used to access a-amino acids in a stereoselective fashion [47], Using azlactones 42 as nucleophiles in the palladium catalyzed stereoselective allyla-tion addition, compounds 43 were obtained in high yields and almost enantiomerically pure (Scheme 9) [48]. The azlactones 43 can then be converted into the a-alkylated amino acids as shown in Scheme 4. 

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