Organocatalysts cinchonidine-derived

Michael addition of thioacetic acid to a series of a-substituted (V-acryloyloxazolidin-2-ones, followed by enantioselective protonation, catalysed by the cinchonidine-derived thiourea (288a), has been reported to proceed with <97% ee The pseudo-enantiomeric, cinchonine-derived thiourea (289a) can catalyse the Michael addition of dimedone to enone RCH=CHCO( -Py) with <98% ee The isosteviol-derived thiourea (290) represents yet another variation this organocatalyst has been reported to facilitate the Michael addition of a-substituted cyanoacetates NCCH(Ar)C02R and maleimides in toluene at -30 °C (with <93% ee and <98 2 dr) as a method for the construction of quaternary chiral centres " ... 

Making use of the stereochemically matched combination of a chiral auxiliary and a chiral ammonium catalyst, Minakata and coworkers succeeded in developing a highly diastereoselective aziridination of electron-deficient alkenes with iV-carbamate chloramine salts [60]. For example, in the presence of a cinchonidine-derived ammonium salt as an organocatalyst, the reaction of the enone that has L-mentho-pyrazole moiety as an auxiliary with iV-Boc chloramine salt gave diastereochemicaUy pure aziridine in 77% yield (Scheme 2.39). 

The use of Merrifield resin-bound alkaloid-based organocatalysts has also been reported [66-67]. The best results were obtained when attachment to the Merrifield resin was made via the hydroxy moiety of a (cinchonidine) alkaloid derivative [67]. The immobilization of alkaloid-derived catalysts on poly(ethylenglycol) (and modifications thereof) was also developed [68a, b]. Furthermore, asymmetric catalytic alkylations under micellar conditions were reported [68c],... 

Aldol reactions using a quaternary chinchona alkaloid-based ammonium salt as orga-nocatalyst Several quaternary ammonium salts derived from cinchona alkaloids have proven to be excellent organocatalysts for asymmetric nucleophilic substitutions, Michael reactions and other syntheses. As described in more detail in, e.g., Chapters 3 and 4, those salts act as chiral phase-transfer catalysts. It is, therefore, not surprising that catalysts of type 31 have been also applied in the asymmetric aldol reaction [65, 66], The aldol reactions were performed with the aromatic enolate 30a and benzaldehyde in the presence of ammonium fluoride salts derived from cinchonidine and cinchonine, respectively, as a phase-transfer catalyst (10 mol%). For example, in the presence of the cinchonine-derived catalyst 31 the desired product (S)-32a was formed in 65% yield (Scheme 6.16). The enantioselectivity, however, was low (39% ee) [65],... 

Replacing 30a by the bulky alkyl enolate 30b as nucleophile led to an improved enantioselectivity (up to 62% ee) (Scheme 6.16). In both reactions the (S) enantiomer was preferably formed. The organocatalyst derived from cinchonine 31 was more efficient than that derived from cinchonidine [66],... 

Total synthesis of (—)-nakadomarin A 31, a marine alkaloid of the manzamine family, " was reported by Dixon and co-workers In their synthesis, a bifunctional organocatalyst derived from cinchonidine was effective for the Michael addition reaction of 27 and 28, and stereochemistries at C7 and C8 were efficiently controlled. In this reaction, low selectivity or decomposition of the nitroolefin was observed with the stoichiometric use of lithium 1,1,1,3,3,3-hexamethyIdisiIazide, (or lithium bis(trime-thylsilyl)amide) (LHMDS), potassium 1,1,1,3,3,3-hexam-ethyldisilazide [potassium bis(trimethylsilyl)amide] (KHMDS), or I,4-diazabicycIo[2.2.2]octane (DABCO) (Scheme 27.5). 

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