Catalytic Asymmetric Synthesis. Группа авторов

Michael addition of glycine imines to acrylates catalyzed by 23.

      Source: [63].

Misaki, Sugimura, and co‐workers developed chiral bicyclic guanidine 24 bearing a hydroxy group as a hydrogen bond donor unit. This catalyst was highly effective in a series of enantioselective reactions of 5H‐oxazol‐4‐ones as a pronucleophile, such as direct aldol reaction and the 1,4‐addition to alkynyl carbonyl compounds (Scheme 3.36) [65].

Scheme 3.36. Enantioselective reactions of 5H‐oxazol‐4‐ones as a pronucleophile catalyzed by 24.

      Source: [65].

Nagasawa and co‐workers developed a series of guanidine‐(thio)urea bifunctional catalysts 25 having conformationally flexible chiral linkers [66]. The catalyst design was based on the idea of using the formation of a double hydrogen bonding network, where a guanidine and a (thio)urea simultaneously activate a pronucleophile and an electrophile, respectively. The adequacy of the catalyst design was verified by applying them to a variety of enantioselective reactions. For instance, guanidine‐bisthiourea catalyst 25a was successfully utilized in the ortho‐selective alkylation of phenols through the enantioselective addition with nitroalkenes (Scheme 3.37) [67].

Scheme 3.37. Enantioselective addition of phenols to nitroalkenes catalyzed by 25a.

      Source: Based on [67].

On the other hand, the use of guanidine‐bisthiourea catalyst 25b enabled the solvent‐dependent enantiodivergent Mannich‐type reaction (Scheme 3.38) [68]. The authors concluded that the origin of solvent‐dependent stereodiscrimination was controlled by the enthalpy–entropy compensation. This type of catalysts was utilized not only in carbon–carbon bond formations but also in carbon‐heteroatom bond formations [69], such as α‐hydroxylation of tetralone‐derived β‐ketoesters [70].

Scheme 3.38. Solvent‐dependent enantiodivergent Mannich‐type reaction catalyzed by 25b.

      Source: Based on [68].

Feng and co‐workers designed bifunctional guanidine catalyst 26a featuring a chiral amino amide backbone, in which an amide moiety functions as a hydrogen bond donor unit [71]. The catalytic activity was demonstrated in the enantioselective addition of β‐ketoesters to nitroalkenes (Scheme 3.39).

Scheme 3.39. Enantioselective addition of β‐ketoesters to nitroalkenes catalyzed by 26a. Source: Based on [71].

Liu, Feng, and co‐workers later developed related guanidine‐amide bifunctional catalysts, such as 26b, 26c, and 26d, and successfully utilized them in several enantioselective reactions (Scheme 3.40) [72].

Scheme 3.40. Enantioselective reactions catalyzed by 26.

      Source: [72].

Wang, Qu, and co‐workers developed tartaric acid‐derived seven‐membered cyclic chiral guanidine 27, and utilized the catalyst in the enantioselective α‐hydroxylation of β‐ketoesters and β‐diketones with oxaziridine (Scheme 3.41) [73]. This type of chiral guanidine catalyst was also used in the Michael addition of 3‐substituted oxindoles to nitroalkenes [74].

Scheme 3.41. Enantioselective α‐hydroxylation of β‐ketoesters catalyzed by 27.

      Source: Based on [73].

Tan and co‐workers developed an aminoindanol‐derived chiral guanidine 28. The catalyst was utilized in the desymmetrization of meso‐aziridines with thiols and carbamodithioic acids as a pronucleophile, providing the ring‐opening products in high yields with high enantioselectivities (Scheme 3.42) [75].

Scheme 3.42. Desymmetrization of meso‐aziridines with thiols catalyzed by 28.

      Source: Based on [75].

Aforementioned all chiral guanidine catalysts control the stereoselectivity of the bond‐forming process based on the central chirality of the catalyst molecule. In contrast, Terada and co‐workers introduced, for the first time, the methodology based on axial chirality of the catalyst molecule into the field of chiral guanidine catalysis [76]. Specifically, the group designed two types of axially chiral guanidines having an axially chiral binaphthyl backbone (Figure 3.9). One is the nine‐membered cyclic guanidines 29, in which an N‐C‐N guanidine subunit is involved in the ring structure. The other is the seven‐membered cyclic guanidines 30, in which one nitrogen atom of guanidine is involved in the ring structure.

Figure 3.9. Axially chiral guanidine catalysts.

The high catalytic activity of nine‐membered 29 was demonstrated in the enantioselective Michael addition of β‐dicarbonyl compounds and diphenyl phosphite to nitroalkenes [77].