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Despite the enormous potential for the use of stereospecific cross-coupling reactions to rationally manipulate the three-dimensional structure of organic molecules, the factors that control the transfer of stereochemistry in these reactions remain poorly understood. Here we report a mechanistic and synthetic investigation into the use of enantioenriched alkylboron nucleophiles in stereospecific Pd-catalyzed Suzuki cross-coupling reactions. By developing a suite of molecular descriptors of phosphine ligands, we could apply predictive statistical models to select or design distinct ligands that respectively promoted stereoinvertive and stereoretentive cross-coupling reactions. Stereodefined branched structures were thereby accessed through the predictable manipulation of absolute stereochemistry, and a general model for the mechanism of alkylboron transmetallation was proposed.
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Catalytic Asymmetric Synthesis of Zinc Metallacycles
Transition-metal-catalyzed reductive coupling reactions of alkynes and imines are attractive methods for the synthesis of chiral allylic amines. Mechanistically, these reactions involve an oxidative cyclization of the alkyne and the imine to generate a metallacyclic intermediate, which then reacts with H2 or an H2 surrogate to form the product. As an alternative to this hydrogenolysis pathway, here we show that transmetallation to zinc can occur, forming a zinc metallacycle product. This organozinc product serves as a versatile nucleophile for carbon–carbon and carbon–heteroatom coupling reactions. Mechanistic studies based on isotopic labelling experiments and DFT calculations suggest that the key transmetallation step occurs between a Co(II) species and ZnCl2.
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- Award ID(s):
- 2101931
- PAR ID:
- 10507120
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- Journal of the American Chemical Society
- Volume:
- 145
- Issue:
- 37
- ISSN:
- 0002-7863
- Page Range / eLocation ID:
- 20152 to 20157
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/jacs.3c05885
