Design And Synthesis Of Tartaric Acid Derived Chiral Guanidines And Their Application In Asymmetric Catalysis

In the field of asymmetric organocatalysis, chiral guanidines represent a preeminent catalyst class, which have enabled a broad spectrum of asymmetric organic reactions. Although a wide array of structurally diverse chiral guanidines have been developed, there still exists a paucity in this field of more general guanidine catalysts capable of catalyzing a broader scope of asymmetric transformations. One major problem that hampered the development of guanidine-based chiral organic catalysts is the lack of a skeleton that is both synthetically easily accessible and readily tunable. As a consequence, the development of chiral guanidines from simple precursors with readily tunable steric and electronic factors for more asymmetric applications is highly desirable.Tartaric acid has played a prominent role in the development of chiral auxiliaries and chiral catalysts for use in asymmetric organic synthesis due to its rich abundance and ready-diversification. In the context of the flourishing development of asymmetric organocatalysis over the past decade, a number of tartaric acid derivatives have been introduced as organocatalysts including, for example, TADDOLs, TADDOL-based phosphoric acids, TADDOL-derived phase transfer catalysts. Despite these sporadic reports, however, the potential of tartaric acid as a parent scaffold for the development of chiral organocatalysts is far from being fully exploited. Given the readily tunable nature of the TADDOL backbone, we envisioned that tartaric acid could serve as a promising scaffold for the construction of a library of guanidine catalysts. With this purpose, we developed a novel method to synthesise30chiral guanidines featuring a tartaric acid skeleton from diethyl L-tartrate and constructed a library of guanidine catalysts which are easily accessed with different steric and electronic properties.With the guanidine library established, we firstly evaluated the catalytic activity and enantioselectivity on the a-hydroxylation of (3-dicarbonyl compounds which afforded excellent enantioselectivities and high yields (up to99%yield,94%ee). And their application to the catalytic hydroxylation of3-substituted oxindoles was also successful, giving the highly enantioselective switch process and both enantiomers of the product with good result. To further highlight the utility of our guanidine catalysts, we consequently developed a chiral guanidine catalyzed asymmetric Michael addition of3-Substituted oxindoles to nitroalkenes in excellent yields (82-99%), diastereoselectivities (dr=92/8->99/1), and with high to excellent enantioselectivities (83->99%ee). This method showed an extraordinarily broad substrate scope in terms of both reaction partners. Lastly, an application of tartrate-derived chiral guanidines to catalytic asymmetric fluorination reaction of1,3-dicarbonyl and a-cyano carbonyl compounds was also effected with good enantioselectivity in high yields.