Highly Efficient Asymmetric Direct Intermolecular Aldol Reaction Promoted By Novel And Green Catalysts Based On (R,R)-1,2-cyclohexandiamine

In the 20th century, the discovery and development of asymmetric catalysis was the one of the most important achievements in chemistry. These years witnessed the rapid development of organocatalysis as a new branch of asymmetric catalysis. Organocatalysis has provided a new avenue to explore the fundamental chemical parameters. Novel modes of substrate activation have been achieved using organocatalyst that can deliver unique, orthogonal, or complementary selectivities comparable to many established metal-catalyed and enzyme-catalyzed transformations. Otherwise, the aldol reaction is one of the most powerful methods for the formation of C-C bonds for the synthesis of the complex nature product and drug. The design and synthesis of high efficient and green chiral organocatalysts are of great importance. In this thesis, we designed and prepared two series of prolinamide derivates based on (R, R)-1,2-cyclohexandiamine. Their application in direct intermolecular Aldol reaction was investigated. The catalysts are outlined as below: 1. Highly Efficient Asymmetric Direct Intermolecular Aldol Reaction Employing L-Prolinamide (Part 1)A novel simple bifunctional, recoverable and reusable L-prolinamide organocatalyst that promotes aldol reactions achieving excellent enantioselectivity was reported. The catalyst 1b was applicable to the aldol reactions of a wide range of aromatic and heteroaromatic aldehydes with cyclic and acyclic ketones, and the anti-aldol products could be obtained with up to 99:1 anti/syn ratio and 98% ee. Furthermore, the desired product can be obtained successfully from low reactive aldhydes such as p-anisaldehyde and benzalhyde in good yields with high enantioselectives. The catalyst could be easily recovered and reused, and only slightly decrease of enantioselectivity was observed for five cycles. Meanwhile, we demonstrated that the prolinamide lb could be used in gram scale synthesis with the enantioselective maintaining at the same level, which remains a great possibility to apply in industry.2. High Efficient Asymmetric Direct Intermolecular Aldol Reaction Promoted by L-Prolinamide (Part 2)There are two kinds of N-H units in second series of catalyst which involved in the binding of electrophilic aldehydes via two N-H..O hydrogen bonds when they were used to catalyse Aldol reaction. Among them, 2a afford aldol products in excellent isolated yields (up to 97%) with high diastereo-(up to 99:1) and enantioselectivites (up to 99%). The catalyst 2a can be easily recovered and reused, and only slightly decrease of enantioselectivity was observed for five cycles. When only 2 mol% 2a was used in large-scale reactions, the aldol products could be achieved efficiently without obviously decrease of enantiomeric excess and yield, which remains a great possibility to apply in industry.