Asymmetric squaramides

Xn et al. have carried ont asymmetric Michael addition reaction in ball mill using squaramide catalyst (Scheme 2.32) [23]. Optimal reaction conditions in planetary ball mill feature milling of 1,3-diones 83 and aryl styrenes in the presence of the cinchona-derived squaramide catalyst CA (5mol%). In these conditions, high yields... 

In 2011, Wu and co-workers [118] designed and synthesized a new bifunctional catalyst 66 that is comprised of phosphine and squaramide units and fliat efficiently promoted the asymmetric intramolecular BH reaction in modest to good yields with good to excellent enantioselectivities (Scheme 9.33). 

Polysubstituted 3,4-dihydro-3-nitro-2ff-chromans are obtained from the enantioselective Michael—Michael cascade reaction of chalcone enolates and nitromethane catalyzed by bifunctional thiourea 19 (Scheme 31) (13JOC6488) and tandem Friedel—Crafts alkylation—Michael addition reaction of nitroolefin enoates and 1-methylindole promoted by Zn(OTf)2 (13S601).A squaramide-tertiary amine catalyst promotes the asymmetric sulfa-Michael—Michael cascade reaction of thiosalicylates with nitroalkene enoates which leads to polysubstituted chromans in high yields with excellent stereoselectivities (13OL1190). 

Wang, X., Yao, W., Yao, Z., Ma, C. (2012). Bifunctional amino-squaramides catalyzed asymmetric spiroannulation cascades with aliphatic p,Y-unsaturated a-keto esters controlling an aldehyde enolate. Journal of Organic Chemistry, 77, 2959-2965. 

In 2003, Rawal reported the use of TADDOLs 177 as chiral H-bonding catalysts to facilitate highly enantioselec-tive hetero-Diels-Alder reactions between dienes 181 and different aldehydes 86 (Scheme 6.29A) [82], and also BINOL-based catalysts 178 were found to facilitate this reaction with excellent selectivities [83]. TADDOLs were also successfully used as organocatalysts for other asymmetric transformations like Mukaiyama aldol reactions, nitroso aldol reactions, or Strecker reactions to mention a few examples only [84]. In addition, also BINOL derivatives have been employed as efficient chiral H-bonding activators as exemplified in the Morita-Baylis-Hilhnan reaction of enone 184 with different carbaldehydes 86 [85]. The use of chiral squaramides for asymmetric reactions dates back to 2005 when Xie et al. first used camphor-derived squaric amino alcohols as ligands in borane reductions [86]. The first truly organocatalytic application was described by Rawal et al. in 2008 who found that minute amounts of the bifunctional cinchona alkaloid-based squaramide 180 are... 

Comparable results were obtained for asymmetric conjugate addition of aromatic and aliphatic thiols to chalcones [88]. For this reaction it was also observed that 31 was a more suitable catalyst than derivatives with, for example, a 4-CH3OQH4, a 3,5-(CH3)2QH3, or a cydohexyl group, which is in line with the expectation that the acidity of the squaramide N-H groups is related to the stereoselectivity and yield of the catalytic reaction. 

Scheme 21.32 Squaramides as an organocatalyst for asymmetric Michael additions.

A chiral quinine-derived squaramide catalysed the highly enantioselective Michael addition of malononitrile to chalcones. The reactions take place at a very low catalyst loading (0.5 mol%) and provide the Michael adducts with high yields and good enan-tioselectivities (up to 96% ee). Chiral bifunctional squaramides have also been used as multiple hydrogen-bond donor-acceptor organocatalysts for the asymmetric Michael addition of nitroolefins to 1,3-dicarbonyl compounds. ... 

The asymmetric formal 3 + 2-cycloaddition reaction of a-isocyanoacetates with A-aryl maleimides produced optically active, substituted l,3fl,4,5,6,6a-hexahydropyrrolo[3,4-cjpyrrole derivatives in high yields, high diastereoselectivities, and good to excellent enantioselectivities. A cinchona-derived squaramide/AgSbFg catalyst (68) was used in this reaction. 

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