Organocatalysts squaramide

Several chiral organocatalysts such as chiral squaramide 31, chiral phosphoric acid (S)-32a, and binaphthyl-based chiral sulfonimide (i )-33 have also been successfully applied in the AFC reaction of indoles with N-sulfonyl imines (Scheme 6.14). 

The addition of diphenyl phosphite to ketimines derived from isatin was attempted using several Cinchona derived organocatalysts. The best results were achieved with a quinine-derived bifunctional squaramide (Q-SQ 1),... 

Nitrocyclopropanation of a,p-unsaturated ketones 16usingbromonitromethaneas an ambiphilic substrate in the presence of organocatalysts E-I allows the preparation of several interesting trisubstituted cyclopropanes 17 in high levels of both diastereo and enantioselectivities. A general scheme compiling selected recent achievements on this purpose is depicted in Scheme 5.7. Chiral primary [25] and secondary [26, 27] amines as well as thiourea [28] and squaramide [29] derivatives E-I (all of them as bifunctional catalysts) were capable of catalyzing the transformation. 

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... 

The concept of bifunctional catalysis as advanced for the natural cinchona alkaloids and cuprei(di)nes has resulted in the design and synthesis of a range of new cinchona derivatives. The major part of these novel organocatalysts are urea and thiourea cinchona derivatives together with cinchona alkaloids modified with, for example, a sulfonamide, squaramide, or guanidine group (Figure 6.8). 

Squaramide-based dimeric cinchona alkaloid organocatalysts have also been described [92] and shown to be highly suitable for the dynamic kinetic resolution of racemic azlactones (Scheme 6.43). The dimeric squaramide derivatives were free from self-association, as indicated by the observation that the enantioselectivity was not influenced to any significant extent by the concentration of the dimeric squaramide, in contrast to the monomeric species that showed a decline in ee upon an increase in concentration. 

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. ... 

Malonates, malononitrile, and anthranone, can be added to -nitroalkenes RCH=CHN02 (R = alkyl, Ar) in the presence of the original Takemoto s thiourea organocatalyst (421) (5 mol%) in liquid CO2 (100 bar, room temperature) with 67-89% ee The same reaction, with an extended portfolio of substrates, catalysed by 0 the cinchona alkaloid-based squaramides (lmol%) in CH2CI2 at 15 C exhibited <96% ee ... 

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