Primary-tertiary diamine catalyst, aldol

The aldol reaction of cyclic ketones and acetone with aromatic aldehydes were carried out in combination with triflic acid in water at 25°C [250]. Other chiral primary-tertiary diamine catalyst such as compound 167 (20 mol%) was used in combination with solid polyoxometalate acid support (6.67% mol) in the aldol reaction between dihydroxyacetone (149a) and aromatic aldehydes in NMP as solvent at 25°C to afford mainly iyn-aldol products in good yields (59-97%) and high diastereo- and enantioselectivities (78-99% de, 84-99% ee). The combination of catalyst 167 with triflic acid was used in the reaction of acyclic ketones and a-hydroxyketones 8 with aromatic aldehydes also with good results [251]. Simple chiral diamine 168 (10 mol%) in the presence of Iriflic acid (20 mol%) was applied as catalyst in the reaction between acetone and cyclohexanone with aromatic aldehydes in water at 25°C, giving aldol adducts 4 in low yields (15-58%) and moderate diastereo- and enantioselectivities (50-98% de, 45-93% ee) [252]. 

Amino acid-derived primary-tertiary diamine catalysts have been used extensively in aldol reactions. Lu and Jiang [34] documented a direct asymmetric aldol reaction between acetone and a-ketoesters catalyzed by an L-serine-derived diamine 17. Sels et al. [35] found that several primary amino acid-based diamines (18) were efficient catalysts for the syn-aldol reaction of linear aliphatic ketones with aromatic aldehydes. Luo and Cheng utilized L-phenylalanine-derived diamine catalyst 15a for the enantioselective syn-aldol reaction of hydroxyl ketones with aromatic aldehydes [36]. Moreover, a highly enantioselective direct cross aldol reaction of alkyl aldehydes and aromatic aldehydes was realized in the presence of 15a (Scheme 3.8) [37]. Very recently, the same group also achieved a highly enantioselective cross-aldol reaction of acetaldehyde [38]. Da and coworkers [39] discovered that catalyst 22, in combination with 2,4-dinitrophenol, provided good activation for the direct asymmetric aldol reaction (Scheme 3.9). 

DFT calculations, focusing on the C-C bond forming steps, have been used to rationalize the high regio- and stereo-selectivities found for direct aldol reactions of aliphatic ketones (propanone, butanone, and cyclohexanone) with a chiral primary-tertiary diamine catalyst (trans-N,N-dimethy diaminocyclohexane). ... 

Inspired by the primary aminocatalytic motif in nature, our group is interested in developing simple and efficient chiral primary amine catalysts. With Hine s pioneering contribution as a starting point, we developed simple primary-tertiary diamine catalysts derived from chiral tran -cyclohexanediamine such as 24 for asymmetric aldol reaction with excellent efficiency and enantioselectivity. 

The use of an (5)-threonine/a,a-(5)-diphenylvalinol-derived ionic liquid 81 gave comparable results to the 0-iBu-L-tyrosine-catalyzed reaction, but the recovery of the catalyst was simpler [100]. The simple primary-tertiary diamine 38 proved syn-selective, though it works only for aromatic aldehydes [76]. For the synthesis of iy -aldols derived from active benzaldehydes, other catalysts bearing primary amine functionalities also gave satisfactory results [90b, 60, 100, 101]. 

Polyoxometalates (POMs) are transition metal oxygen clusters with well-defined atomic coordination structures. POMs are used as functional nano-colloidal materials and also as supports for catalysts via ion-pair interactions due to their acidic properties. Combinations of chiral diamines and POM 225 effectively catalyze enamine-based aldol reactions. Less than 1 mol% of chiral amine loading is suf-ficientto catalyze the reaction (Table 28.10, entries 1 and 2) [114]. Highly diastereo-and enantioselective cross-aldol reactions of aldehydes are accomplished using chiral diamine-POM 226 under emulsion conditions (entries 3 and 4) [115]. Sul-fonated polystyrene or fluoropolymer Nafion NR50 are also good supports for the immobilization of primary-tertiary diamines. The catalyst 227 can be recovered by filtration and reused for at least four cycles with no loss of stereoselectivity (entries 5 and 6) [116]. 

Luo S, Xu H, Li J, Zhang L, Cheng JP. A simple primary-tertiary diamine-Brpnsted acid catalyst for asymmetric direct aldol reactions of linear aliphatic ketones. J. Am. Chem. Soc. 2007 129 3074 3075. 

The simple primary-tertiary diamine salts can be successfully applied in the aldol reactions of a-hydroxyketones with good activity and excellent stereoselectivity. Notably, the catalyst enabled the reaction of dihydroxyacetone (DHA), a versatile C3-building block in the chemical and enzymatic synthesis of carbonhydrates. By employing either free or protected DHA, syn- or anh-diols could be selectively formed with excellent enantioselectivity (Scheme 5.7). Since enantiomers of diamine 26 and 29 are readily available, this class of chiral primary amine catalysts thus functionally mimics four types of DHA aldolases in nature [17b]. Later, simple chiral primary-tertiary diamine 27 derived from amino acid was also found to be a viable catalyst for the iyn-selective aldol reactions of hydroxyacetone and free DHA (Scheme 5.7) [18]. 

Mesoporous silica functionalized by chiral primary-tertiary diamine/Bronsted acid conjugates was successfully synthesized by Xiaobing et al. Two functionalities of this material, that is, the chiral organofunctional group and the mesoporous support, provided the chiral enhancement in the asymmetric aldol reaction of acetone with various aldehydes. The catalyst exhibited good activity and enantioselectivity without loss of activity. Particularly, the catalytic activity of SBA-15 with an immobilized chiral organic group increased in enantiomeric excess value of the reaction product as compared with silica gel as the support [89]. 

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