Cinchona sulfonamide catalysts

Scheme 2.10 Enantioselective Michael addition of ketones to nitroalkenes catalyzed by primary amine-sulfonamide catalysts 27a-b and by 9-epi amino cinchona alkaloid 28a.

The Song group has also developed monobasic cinchona alkaloid catalysts [24] such as the bulky sulfonamide 77 that do not display self-aggregation behavior. These catalysts are highly useful for the enantioselective alcoholysis of meso anhydrides [25], as demonstrated in Scheme 6.11. 

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. ... 

Yeung et al. used amino-thiocarbamate catalysts 6 (Scheme 15.4), 8 and 9 derived from Cinchona alkaloids for enantioselective bromoaminocyclisa-tions of unsaturated sulfonamides to pyrrolidines (Scheme 15.42), 2-substituted 3-bromopyrolidines, and 2-substituted 3-bromopiper-idines in good yield and with high enantioselectivity. 

Finally, the methanolytic desymmetrisation of a variety of cyclic anhydrides was also achieved by using a thermally robust sulfonamide-based bifunctional cinchona alkaloid as the organocatalyst. Under these conditions, an unprecedented catalytic activity combined with an excellent level of enantioselectivity of up to 98% ee were obtained at a catalyst loading of 5 mol %, as shown in Scheme 9.5. No appreciable effects of the concentration and temperature on the reactivity and enantioselectivity were observed with this catalyst. 

New cinchona derivatives are continuously being developed for appUcation in asymmetric organocatalysis. Examples of catalysts obtained by further modification of existing derivatives include an N-oxide of dihydrocupreidine [127], a C6 -N-Boc-glycine-P-isocupreine (53) [128], a C9 thiourea substituted at a remote site with a sulfonamide group (54) [129, 130], and catalysts with an amine as well as a thiourea group (55) [131] (Figure 6.16). 

The tetrahedral intermediate is generated by a nucleophilic attack on the carbonyl carbon atom of the activated nucleophile, which in the case of chymotrypsin and trypsin is the catalytic Serl95. The mechanism of chymotrypsin can be compared to that of Song catalyst 77 that catalyzes the nucleophilic ring opening of acid anhydrides. The role of the sulfonamide group is played by the oxyanion hole amide NH groups, and the role of the cinchona alkaloid-derived base is played by the Asp-His-(Ser) dyad/triad. 

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