Diastereodivergent Catalysis

Abstract

Alongside enantioselective catalysis, synthetic chemists are often confronted by the challenge of achieving catalyst control over the relative configuration to stereodivergently access desired diastereomers. Typically, these approaches iteratively or simultaneously control multiple stereogenic units for which dual catalytic methods comprising sequential, relay, and synergistic catalysis emerged as particularly efficient strategies. In this Perspective, the benefits and challenges of catalyst-controlled diastereodivergence in the construction of carbon stereocenters are discussed on the basis of illustrative examples. The concepts are then transferred to diastereodivergent catalysis for atropisomeric systems with twofold and higher-order stereogenicity as well as diastereodivergent catalyst control over E-and Z-configured alkenes.

Catalytic stereodivergent and simultaneous construction of axial and point chirality

“…This observation adds a new entry to the intriguing ligand-induced diastereodivergent reactions. 9 Notably, this is the first time to report that Trost ligands could be successfully employed in catalytic asymmetric reactions of isocyanoacetates, 13 c thus expanding the choice of chiral ligands in this field. With the optimal ligands being identified, further evaluation of other parameters such as metal salts and solvents was carried out; however, it did not lead to better results (see the ESI† for details).…”

“…7,8 In this context, both issues of diastereo- and enantioselectivity need to be addressed properly to prevent the generation of a complex mixture of stereoisomers. Furthermore, it would be ideal and extremely desirable to establish catalyst-controlled diastereodivergent processes 9,10 that allow access to different diastereomers from identical starting materials (scenario III ), since individual diastereomers may exhibit significantly distinct biological activities against the same target. 11 For example, ( S )-atropisomer A was found to be 200-fold more potent than its corresponding ( R )-epimer A′ as APJ receptor agonists.…”

Synergistic Catalysis Involving Palladium for Stereodivergent Csp3–Csp3 Coupling Reactions

“…In the field of asymmetric synthesis, a stereodivergent process refers to one that allows access to any given stereoisomer of a product with multiple stereocenters from the same set of starting materials. − This can sometimes be achieved by altering the catalyst, reagents, or reaction conditions, and such stereodivergent reactions have been demonstrated over the past 30 years. However, there is still a high demand for developing effective strategies for catalytic stereodivergent synthesis. , …”

Diastereodivergent and Regioselective Synthesis of Tetrahydrofuro[2,3-b]furans with Four Consecutive Stereocenters

“…Realizing precise control of the relative configuration of two or more stereocenters in a transformation is challenging and often results in a mixture of diastereomers. The synthetic potential of stereodivergent reactions has been proved in many momentous transformations during the past 30 years . Therefore, developing novel catalytic stereodivergent methods to selectively synthesize diastereomers under the same starting material and small variation of reaction conditions is highly desirable.…”