Cinchona DHQD 2PYR

In 2005, the application of cinchona alkaloid derivatives as catalysts for enantiose-lective a-sulfenylation of activated C—H bonds in lactones, lactams, and P-dicarbonyl compounds 146 by electrophilic sulfur reagent 147 was reported by Jorgensen and coworkers (Scheme 6.44) [73]. Optically active a-sulfenylated products 148 were obtained in good to excellent yields and up to 86% ee in the presence of 10 mol% (DHQD)2PYR in toluene solvent at —30 or —40°C. Furthermore, the diastereose-lective reduction of a-sulfenylated (3-keto esters to give optically active a-sulfenylated (5-hydroxy esters was also demonstrated. 

Sharpless bis-cinchona alkaloids such as [DHQD]2PYR (163a) have proved to serve as highly efficient catalysts for the asymmetric vinylogous Michael addition of the electron-deficient vinyl malonitriles 164 as the nucleophilic species to nitroole-fins 124 [50], This process exhibited exclusive y-regioselectivity and high diastereo-and enantioselectivity. Only the anti-products 165 were observed in all reactions (Scheme 9.57). Of note, 1-tetralone did not react with nitroolefins under these... 

In a model reaction, Deng et al. reached enantioselectivities up to 99% with (DHQD)2PYR at —60 °C inferior results were obtained at room temperature. Natural alkaloids showed usable enantioselectivities with chalcones as substrates, " and more recently, excellent enantioselectivities (61-99%) have been reported using Cinchona squaramide-type catalysts, also with acrylates. Enantioselectivities of CiracAoraa-sulfonamides were low compared to the Cinchona-AetweA ureas (see Chapter 19). Nitro-olefins turned out to be slightly more demanding substrates, both for natural alkaloids and their squaramides. ... 

Several derivatives of cinchona alkaloids 1—4 were prepared and used in the asymmetric sulfa-Michael addition. The first highly efficient method, based on the catalyst (DHQD)2PYR 5, was presented by the Deng group in 2002 [18]. Especially high ees were observed in the conjugated addition of 2-thionaphthol to several six-to nine-membered cyclic enones at low temperature (Scheme 14.3). Although 2-cyclopentenone reacted with moderate enantioselectivity (41% ee), the ee was increased dramatically with 4,4-dimethyl-2-cyclopentenone (92% ee). 

Halogenation reactions were also shown to be catalyzed by bis-cinchona alkaloids, for example, (DHQ)2PHAL (PHAL 1,4-phthalazinediyl) (50) was reported to catalyze the fluorocyclization of indoles [123] and (DHQD)2PYR (PYR 2,5-diphenyl-4,6-pyrimidinediyl) (51) [124] as well as (DHQD)2PYDZ (PYDZ 3,6-pyridazinediyl) (52) [125] were shown to catalyze halogenation/semipinacol rearrangements (Scheme 6.59). 

Skarzewski reacted acyclic enones with thiols catalyzed by cinchona alkaloids [114]. Cinchonine was the best catalyst evaluated and the Michael adducts were obtained in excellent yields albeit with moderate enantioselectivities. Similar approximations were made by Mukaiyama and coworkers using hydroxyl-proUne derivatives, affording the thio adducts in good yields and good enantioselectivities (up to 88% ee) [115], However, the most effective thiol addition to enones was reported by Deng [116]. In this report (DHQD)2PYR (hydroquinidine-2,5-diphenyl-4,6-pyrimidinediyl diether) was used as catalysts, affording the final compounds in excellent yields and enantioselectivities (Scheme 33.37). 

Shibata successfully adapted the asymmetric transfer fluorination to cyclic silyl enol ethers, cyclic allyl silanes and oxindoles, illustrated in Schemes 13.1-13.3, as a catalytic method (Scheme 13.6) [16]. Similar reaction conditions were identified for all three substrates, including the use of stoichiometric NFSI as the electrophilic fluorine source and a stoichiometric inorganic base additive. It was observed that bis-Cinchona alkaloid (DHQ)2PHAL was best for cyclic silyl enol ethers (X = 0), (DHQ)2PYR (Scheme 13.2) was best for cyclic allyl silanes (X = CH2), while (DHQD)2AQN was best for oxindoles. A similar method was applied to cyclic enol ethers, providing products in modest ee s [17]. 

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