Bimetallic Catalysis in Stereodivergent Synthesis

Abstract

Bimetallic catalysis has emerged as an efficient strategy for the development of new chemical reactions. Importantly, this strategy also provides a simple and powerful platform for stereodivergent synthesis, whereby all the possible stereoisomers of products bearing two stereocenters can be easily prepared from the same set of starting materials. In this Minireview, the development of stereodivergent allylic substitution, propargylic substitution, hydrofunctionalization, and annulation based on bimetallic catalysis has been summarized. It is expected that more bimetallic catalytic systems will be developed and applied for the stereodivergent synthesis of valuable molecules.

Simultaneous Dual Cu/Ir Catalysis: Stereodivergent Synthesis of Chiral β-Lactams with Adjacent Tertiary/Quaternary/Tertiary Stereocenters

“…Contiguous stereogenic centers are common in natural products, bioactive molecules, and drugs and can greatly enhance the molecular complexity and diversity of chemicals. − The three-dimensional orientation of substituents at carbon stereogenic centers plays an important role in the properties of bioactive molecules, affecting for example their binding to proteins or other targets. − Enantioselective construction of these stereogenic centers in organic synthesis has gained great attention in recent years and has been advanced by transition-metal- or organo-catalysis. The enantioselective creation of all-carbon quaternary carbon stereocenters is challenging due to the steric congestion associated with such centers. − When other tertiary carbon stereocenters adjacent to the quaternary stereocenter are present, efficient methods to install the two stereocenters in a single step are extremely limited. − A further challenge lies in the stereodivergent synthesis of all stereoisomers and the precise control of multiple chiral centers. − In traditional sequential reactions, the existing chiral center can have a steric effect on the formation of new chiral centers, favoring one isomer and making access to other isomers difficult. Novel transformations offering precise control of multiple chiral centers are underexplored but highly desirable, primarily because of the demands of biochemistry and medicinal chemistry.…”

Diastereodivergentcis- andtrans-fused [4 + 2] annulations of cyclic 1,3-dienes and 1-azadienesvialigand-controlled palladium catalysis

“… 1 Diastereodivergent synthesis, which enables producing diverse diastereomers from the same set of starting materials just by varying reaction conditions, has emerged as a flourishing area owing to its high efficiency and great versatility. 2 Several strategies, including tuning the catalysts, 3 ligands, 4 solvents 5 and additives, 6 etc , 7 have demonstrated to be useful for furnishing divergently many diastereomers with linear and cyclic structures. However, there have been few well-developed studies showing an ability to switch the stereochemistry of the bridgehead atoms in fused structures, and only a few examples have been uncovered for constructing both cis - and trans -fused bicyclic or polycyclic frameworks ( Scheme 1a ).…”

Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2-Substituted Cyclopentyl Aryl Ketones

“…Some bioactive molecules bearing chiral cyclopentanes with two contiguous stereogenic centers possess trans -dihydrogen scaffolds, and the reported hydrogenation reaction only delivers the cis -dihydrogen as products. To expand the versatility of the developed method in the synthesis of chiral cyclopentanes bearing two contiguous stereogenic centers, and considering our group’s interest in stereodivergent systhesis, − we intended to synthesize all four stereoisomers of the hydrogenated products. We speculated that the hydrogenated product could be transformed into the trans -products via epimerization, as the cyclopentanes bearing two trans -dihydrogen stereogenic centers are thermodynamically stable.…”