TADDOL Strecker reaction

Another interesting application of TADDOL derivatives 2 in organocata-lysis was reported by Rueping et in the Strecker reaction although the hydrocyanation of aldimines occurred with only modest enantioselectivities, for the first time the ability of TADDOLs to activate imines was highlighted (Scheme 24.9). 

Scheme 24.9 Asymmetric Strecker reaction catalysed by TADDOLs.

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... 

In addition to the studies mentioned above, chiral alcohols have been used as H-bonding catalysts in a vinylogous aldol reaction of Chan s diene with aldehydes [73], in an enantioselective Strecker reaction [74], and in the enantioselective addition of aza-enamines to imines [75]. Taddol has also found use as a memory of chirality enhancer in the stereoselective synthesis of (i-lactams from amino acid derivatives [76, 77]. 

Experiments showed that TADDOL (2,2-dimethyl-a,a,a, a -tetraphenyl-l,3-dioxolane-4,5-dimethanol) can also be appUed to catalyze the asymmetric Strecker reaction of aromatic N-benzyl aldimines [48]. In initial experiments some asymmetric introduction (22-56% ee) was gained by moderate to high yields (68-93%). 

In 2007, Rueping et al. reported an enantioselective Strecker reaction catalyzed by chiral BINOL phosphate 114 and TADDOL 115 catalysts (Fig. 7.11) [128]. The corresponding amino nitriles were obtained in good isolated yields and enantiose-lectivities (up to 97% ee). 

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