Cinchonidine-derived catalysts addition with

Use of the preformed Z-silyl enol ether 18 results in quite substantial anti/syn selectivity (19 20 up to 20 1), with enantiomeric purity of the anti adducts reaching 99%. The chiral PT-catalyst 12 (Schemes 4.6 and 4.7) proved just as efficient in the conjugate addition of the N-benzhydrylidene glycine tert-butyl ester (22, Scheme 4.8) to acrylonitrile, affording the Michael adduct 23 in 85% yield and 91% ee [10]. This primary product was converted in three steps to L-ornithine [10]. The O-allylated cinchonidine derivative 21 was used in the conjugate addition of 22 to methyl acrylate, ethyl vinyl ketone, and cydohexenone (Scheme 4.8) [12]. The Michael-adducts 24-26 were obtained with high enantiomeric excess and, for cydohexenone as acceptor, with a remarkable (25 1) ratio of diastereomers (26, Scheme 4.8). In the last examples solid (base)-liquid (reactants) phase-transfer was applied. 

Asymmetric nucleophilic addition to C=C double bonds (see also Chapter 4) can also proceed highly stereoselectively. Several examples of enantio- and diastereo-selective Michael additions with 99% ee for the resulting products have been described by the Corey group [19]. A cinchonidine-derived phase-transfer organo-catalyst (10 mol%) was used. 

Asymmetric Michael additions can also be performed under phase-transfer conditions with an achiral base in the presence of a chiral quaternary ammonium salt as a phase-transfer agent. Conn and coworkers conducted the Michael addition of 2-propyl-l-indanone (13) to methyl vinyl ketone under biphasic conditions (aq 50% NaOH/toluene) using the cinchonine/cinchonidine-derived chiral phase-transfer catalysts (PTCs), 14a and 14b, as a catalyst (Scheme 9.5). However, only low to... 

In 2009, Bernadi and Adamo designed 4-nitro-5-sttyrylisoxazole (66) as a novel Michael acceptor. The asymmetric conjugate addition of nitroalkanes to 66 in the presence of cinchonidine-derived PTC catalyst 8o afforded the addition adduct 67 with high enantioselectivity (97% enantiomeric excess). The 4-nitroisoxazole eore serves as an activator of the conjugated alkene and is readily derivatised to pharmaceutically valuable compounds, such as y-nitroesters and y-amino acids (Scheme 16.20). " ... 

A combined system of PhjP and a cinchonidine-derived primary amine has been identified as an ideal catalyst for the Michael addition of aliphatic aldehydes to iV-aryl maleimides (with <99% ee). Mechanistic investigation, involving UV-vis, fluoreseenee emission (FL), NMR, circular dichroism (CD), and ESI-MS, revealed the existenee of the molecular assembly of phosphine and amine (248) with an arene-arene staeking, which is believed to play the key role ... 

Complementary to the above-presented enantioselective sequences Michael addition/a-alkylation of bromomalonates, a related powerful gem-dialkylative process was also proposed recently [38]. a-Dialkylation of imines 25 with 1,4-dihalo-but-2-ene 26 using a cinchonidine derivative J as phase-transfer catalyst proceeded smoothly in the presence of aqueous NaOH to give the (l/ ,25)-l-amino-2-vinylcyclopropanecarboxylic acid derivatives 27 with generally good diastereose-lectivity but with enantiomeric excesses not exceeding 80% (Scheme 5.10). 

In 2005, Chen and coworkers found that the epi-cinchonidine/cinchonine-derived thiourea catalysts, 79a,b, can serve as highly active promoters of the Michael addition ofthiophenol to the a,P-unsaturated imide 80 however, the reaction proceeded with low enantioselectivity (up to 17% ee) (Scheme 9.28) [22]. 

As the cinchona alkaloids contain a nucleophilic nitrogen center, they can be alkylated at this position. Thus, cinchonidine reacts with benzyl chlorides to form quaternary salts, e.g., 9 and 108, which are useful as chiral phase-transfer catalysts (see Section D.1.5.2.4. for enantioselec-tive additions to azaenolates, and D.4.1. for the oxidation of enolates). Further modification by catalytic reduction of the double bond (hydrogen/platinum) leads to the corresponding dihydrocinchonidine derivatives. 

Quintard and Alexakis examined the catalysis of the addition of cydic ketones to (Z)-l,2-bis(sulfone)vinylene 78 with their aminal secondary amine catalysts and obtained moderate enantioselectivities (64—73% ee) [75] while Lu s group used the more reactive and less sterically sensitive primary amines. The latter group [76] had shown that the primary amine derived from cinchonidine (94) was very efficient in this reaction with six-membered cyclic ketones 95 or prochiral ketones 96 (Scheme 34.34). Unprecedented enantioselectivity was obtained with this catalytic system on combining catalyst 94 and benzoic acid as additive under mild conditions while in the case of prochiral ketones 95 moderate diastereoselectivity was observed. 

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