Amines chiral bifunctional primary

Chiral bifunctional primary amine-thiourea/ f-BuNH2.TFA/DCM/25 °C (09MI1) 12/EtOH/rt (09MI2)... 

Scheme 19.55 Direct vinylogous aldol reaction promoted by a chiral bifunctional primary amine-thiourea.

Miao, Chen, and coworkers have reported an efficient enantioselective Biginelli reaction catalyzed by a chiral bifunctional primary amine-thiourea derivative 43 with a carbohydrate in the catalyst skeleton and using an external Brpnsted acid in a cooperative way, with t-BuNH TFA as additive (Scheme 9.15) [54]. This protocol renders a wide range of optically active DHPMs 44 in high yields and with good to excellent enantioselectivities (up to 99% ee). 

Biginelli reaction (combining ArCHO, MeCOCH2COEt, and urea) has been catalysed by a combination of a chiral bifunctional primary amine-pyridine and HCl in dioxane/CHCl3 to form dihydropyrimidines with up to 99% ee Lewis-acid-promoted formations of dihydropyrimidinones via Biginelli reactions catalysed by imidazolium-based ionic liquids have been found by NMR, ESI-MS, and theoretical studies to proceed via stabilized charged intermediates. ... 

There is an interesting variant of this reaction which involves the use of tert-butyldimethylsilyloxyacetaldehyde as Michael donors and chiral primary amine thiourea bifunctional catalyst 37b (Scheme 2.13). In this case, the diastereoselectivity of the reaction changed from the usually observed syn relative stereochemistry at the final Michael adduct to the formation of the anti diastereoisomer as the major product. This change in diastereoselectivity was explained in terms of the generation of a Z-enamine intermediate assisted by the formation of an intramolecular hydrogen bond between the secondary... 

Axial-to-central chirality transfer in cyclization processes 13CSR8434. Bifunctional primary amine-thioureas in asymmetric organocatalysis 13OBC7051. 

Wang et al. s synthesis In 2011, a simple chiral primary amine thiourea bifunctional catalyst was introduced to the asymmetric Michael addition of 4-hydroxycoumarin to enones (Table 9.15). With Wang et al. s catalyst, l-[(15, 25)-2-amino-l,2-diphe-nylethyl]-3-benzylthiourea, all Michael additions could be smoothly performed to afford Michael... 

Mei RQ, Xu XY, Li YC, Fu JY, Huang (JC, Wang LX. Highly effective and enantioselective Michael addition of 4-hydroxy-coumarin to a, p-unsaturated ketones promoted by simple chiral primary amine thiourea bifunctional catalysts. Tetrahedron Lett. 2011 52(14) 1566-1568. 

The higher activity of primary amines in the reaction involving enones as Michael acceptors has also been extended to the use of different bifunctional catalysts (Scheme 3.19), which usually contain a primary amine functionality connected to a basic site by means of a chiral scaffold, as is the case in the use of 280 and 55. These diamine catalysts have been found to be excellent promoters of the Michael reaction of enones with cyclic 1,3-dicarbonyl compounds and malonates respectively, the tertiary amine basic site present at the catalyst structure being responsible for assisting in the deprotonation of the Michael donor in order to increase the concentration of the nucleophile species. In a different approach, bifunctional thiourea-primary amine catalyst 56a has also... 

Using the bifunctional chiral primary amine thiourea catalyst 41 (20 mol%) in CH Clj and in the presence of five equivalents of H O as additive, a highly enanti-oselective direct conjugate addition of a wide range of a,a-unsymmetrically dis-ubstituted aldehydes (only a twofold excess of aldehyde relative to nitroaUcene) to nitroolefins is obtained (see Table 2.1, entry 15, for a representative example) [61], The beneficial role of water is proposed to lie in increasing turnover by eliminating potential catalyst deactivation pathways, and accelerating the final imine hydrolysis. 

The first primary amine-thioureas as effective bifunctional organocatalysts were reported in 2006. Tsogoeva and Wei synthesised a thiourea based on (l5,25)-diphenylethylene-l,2-diamine and a chiral arylethyl moiety, for the Michael reaction between aliphatic ketones and aromatic nitro-olefins (Scheme 19.36). Utilising catalyst 29 (15 mol%) and acetone as the Michael donor, the Michael products were obtained in high yields (84-99%) and enantioselectivities (90-91% enantiomeric excess). When cyclohexanone 31 was employed, product 33 was obtained in high yields (82 and 89%, respectively), good diastereoselectivity (up to 83 17 symanti) and excellent enantioselectivity (96 and 98% enantiomeric excess, respectively). 

Asymmetric addition of diorganozincs to aldehydes and ketones has been reviewed, focusing on bifunctional catalysts such as those prepared from salens or BINOLs. Regioisomeric chiral amine-sulfonamide organocatalysts give >99% yield and up to 98% ee in addition of diethylzinc to aldehydes. Switching between regioisomers effectively switches the direction of selectivity. Amino-acid-derived (15,l 5)-4,4 -biquinazoline primary amines catalyse ethylation of aryl aldehydes in up to 95%... 

The aldolisation of cyclic ketones with benzaldehydes performed in water was carried out by using a novel bifunctional trara-cyclohexyldiamine-derived primary amine, which bore both central and axial chiral elements. The aldol products were isolated with excellent levels of diastereo- and enantioselectivities and high yields, as shown in Scheme 2.34. Moreover, the high efficiency of this binaphthyl catalyst could be extended to aliphatic ketones such as acetone, which led to the corresponding aldol adduct in 71% yield and 87% ee in similar conditions. 

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. 

The majority of the organocatalysts that are commonly employed are chiral Lewis or Brpnsted bases, and the catalytic potential of base functionalities has been referred to in previous chapters to some extent already. As discussed before, the use of chiral primary or secondary amines for enamine or iminium activation belongs to the most important applications of asymmetric organocatalysts nowadays. In addition, also the interplay between an acidic (thio)urea and a basic amine separated by a chiral linker was shown to enable the simultaneous activation of both the electrophile and nucleophile. In addition to such bifunctional thiourea-containing acid-base catalysts, chiral catalysts containing a (Lewis or... 

---