Other Catalysts for the Strecker Reaction

In 2007, Kunz presented a new class organocatalysts that consists of glycosyl amines and planar-chiral [2.2]paracyclophane derivatives [51]. Within this new class, N-galactosyl[2.2]paracyclophane carbaldimine 97 proved to be a valuable catalyst for the enantioselective Strecker reaction of aromatic (entries 1, 5) and aliphatic aldi-mines 96 (entries 2—4) (Table 30.13). Aromatic products were obtained in good yields (55-87%) and reasonable enantiopurities (71-82% ee), aliphatic substrates instead led to higher yields (84—89%) and better enantiopurities (88-99% ee). 

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%). 

46 Reingruber, R., Baumann, T., Dahmen, S., and Braese, S. (2009) Adv. Synth. Catal, 351,1011U1024. 

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Several catalysts have been developed for the asymmetric organocatalyzed hydrocyanation of carbonyls and for the Strecker reaction. This chapter divides the catalysts into several subgroups, defined according to important structural motifs responsible for catalytic activity. Each catalyst group will be discussed in detail with regard to substrate scope, hmitations, and other important factors. In addition, mechanistic insights will be provided, if transition states are satisfyingly revealed by experimental work or in silica studies. 

Shibasaki and co-workers applied (BINOL)Al(III)-derived catalyst 5a, previously developed for the cyanation of aldehydes [28], to the asymmetric Strecker reaction. This catalyst proved to be highly enantioselective for both aromatic and a,p-unsaturated acyclic aldimines (>86% ee for most substrates) (Scheme 8) [63-65]. Aliphatic aldimines underwent cyanide addition with lower levels of enantioselectivity (70-80% ee). A significant distinction of 5 relative to other catalysts is, undoubtedly, its successful application to the hydrocyanation of quinolines and isoquinolines, followed by in situ protection of the sensitive cx-amino nitrile formed (this variant of the Strecker reaction is also known as the Reissert reaction [66]). Thus, Shibasaki has shown that high enantioselectivities (>80% ee for most substrates) and good yields are generally obtainable in the Reissert reaction catalyzed by 5b [67,68]. When applied to 1-substituted... 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Two other types of catalysts have been investigated for the enantioselective Strecker-type reactions. Chiral N-oxide catalyst 24 has been utilized in the trimethylsilyl cyanide promoted addition to aldimines to afford the corresponding aminonitriles with enantioselectivities up to 73% ee [14]. Electron-deficient aldimines were the best substrates, but unfortunately an equimolar amount of catalyst 24 was used in these reactions. The asymmetric Strecker addition of trimethylsilyl cyanide to a ketimine with titanium-based BINOL catalyst 25 gave fast conversions to quarternary aminonitriles with enantiomeric excesses to 59%... 

To create stereochemical diversity within MCRs there is need for stereoselective (or -specific) reactions. Since many MCRs involve flat intermediates, like imines and a,p-unsaturated ketones, they result in the formation of racemic products. Moreover, often mixtures of diastereomers are obtained if more than one stereo-genic centre is formed. However, there are several examples known of asymmetric induction, by the use of chiral building blocks (diastereoselective reactions). For example, it has been successfully applied to the Strecker, Mannich, Biginelli, Petasis, Passerini, Ugi, and many other MCRs, which has been excellently reviewed by Yus and coworkers [33]. Enantioselective MCRs, which generally proved to be much harder, have been performed with organometaUic chiral catalysts and orga-nocatalysts [33, 34]. 

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 1998, Jacobsen reported an asymmetric metal-catalyzed Strecker reaction that employs aluminium salen complex 145 (Equation 20) [105], Interestingly, the salen(aluminum) complex 145 proved superior to a wide range of other salen(metal) complexes both in terms of conversion and of enantioselectivity. This constituted the first example of successful use of a main group salen(metal) catalyst for asymmetric synthesis. The N-allylated imine 144 was thus converted into the trifluoroacetyl derivative 146 in 91 % yield and 95 % ee. 

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