Development of Chiral Organosuperbase Catalysts Consisting of Two Different Organobase Functionalities

Abstract

In the field of chiral Brønsted base catalysis, a new generation of chiral catalysts has been highly anticipated to overcome the intrinsic limitation of pronucleophiles that are applicable to the enantioselective reactions. Herein, we reveal conceptually new chiral Brønsted base catalysts consisting of two different organobase functionalities, one of which functions as an organosuperbase and the other as the substrate recognition site. Their prominent activity, which stems from the distinctive cooperative function by the two organobases in a single catalyst molecule, was demonstrated in the unprecedented enantioselective direct Mannich‐type reaction of α‐phenylthioacetate as a less acidic pronucleophile. The present achievement would provide a new guiding principle for the design and development of chiral Brønsted base catalysts and significantly broaden the utility of Brønsted base catalysis in asymmetric organic synthesis.

Spotting trends in organocatalysis for the next decade

“…and, consequently, a considerable portion of the contributions in organocatalysis focuses on enantioselective transformations. After the initial explosive expansion, the following years witnessed the consolidation of the field with the development of concepts such as bifunctional catalysis 3 , biomimetic cascade reactions 4 , the implementation of open-shell reactivity (SOMO activation) 5 , the introduction of organosuperbases for the activation of weakly acidic nucleophiles 6 , or the activation by frustrated Lewis pairs (FLPs) 7 , among others, and the discipline passed also the test as a key tool in challenging total syntheses 8 . The evolution of the field was quantified in 2008 9 as follows: the word organocatalysis or its derivatives had appeared in ca.…”

Development of Chiral Organosuperbase Catalysts Consisting of Two Different Organobase Functionalities

“…The absolute configuration of the major diasteromer of 4 aa was unambiguously determined to be (2S,3R) by single-crystal X-ray diffraction analysis. [22] The scope of imines is summarized in Scheme 1. A variety of aromatic imines including those having an electrondonating group or an electron-withdrawing group at the para position, 3 b-3 e, and sterically hindered ortho-tolyl imine 3 g, were applicable to this reaction, providing the corresponding adducts in high yields with a good level of diastereoselectivities and high enantioselectivities.…”

DBU-catalyzed Michael addition of bulky glycine imine to α,β-unsaturated isoxazoles and pyrazolamides

“…These substrates with an acidic H and low pKa values are easily deprotonated to be carbon anions to take apart in Michael reactions. However, substrates with high pKa values, for examples, glycine imines, aromatic ketones, nitroalkanes are challenging Michael donors for base-catalyzed Michael additions because of their low acidity [17][18][19] [20][21][22][23][24][25]. On one hand, the benzophenoneprotected glycine derivatives (glycine imines) as readily available starting materials were used in many tranformations including alkylation [26,27], [3+2] cycloaddition [28][29][30] and Michael addition [31][32][33][34][35][36][37][38][39].…”