Rhodium(II)-Catalyzed Asymmetric Cyclopropanation and Desymmetrization of [2.2]Paracyclophanes

Ly, Duc; Bacsa, John; Davies, Huw M. L.

doi:10.1021/acscatal.4c01292

Cited by 1 publication

(1 citation statement)

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“…On the other hand, there has been a resurgence of substantial interest in the development of processes able to modify the skeleton of organic molecules in carbon–carbon and carbon–heteroatom bonds. , Such types of reactions and strategies categorized as skeletal editing complement the established retrosynthetic logic by providing new and simple disconnection approaches. Within this context, skeletal editing processes have recently been developed for single-carbon, -nitrogen, and -oxygen atom insertions in C( sp 2 )–C( sp 2 ) bonds of cyclic and acyclic molecules including alkenes, − indoles, − arenes, or indenes. − Methodologies that provide asymmetric induction during the C( sp 2 )–C( sp 2 ) bond cleaving process are largely unexplored and currently limited to the Büchner reaction. − …”

Section: Introductionmentioning

confidence: 99%

Rh-Catalyzed Enantioselective Single-Carbon Insertion of Alkenes

Teo,

Esteve Guasch,

Jiang

et al. 2024

J. Am. Chem. Soc.

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The interest in the discovery and development of skeletal editing processes that selectively insert, exchange, or delete an atom in organic molecules has significantly increased over the last few years. However, processes of this class that proceed through the creation of a chiral center with high asymmetric induction have been largely unexplored. Herein, we report an enantioselective single-carbon insertion in aryl-and alkyl-substituted alkenes mediated by a catalytically generated chiral Rhcarbynoid and phosphate nucleophiles that produce enantioenriched allylic phosphates (enantiomeric ratio (e.r.) = 89.5:10.5− 99.5:0.5). The key to the process was a diastereo-and enantioselective cyclopropanation of the alkene with a chiral Rh-carbynoid and the formation of a transient cyclopropyl−I (III) intermediate. The addition of the phosphate nucleophile provided a cyclopropyl− I (III) -phosphate intermediate that undergoes disrotatory ring opening following the Woodward−Hoffmann−DePuy rules. This process led to a chiral intimate allyl cation−phosphate pair that evolved with excellent enantioretention. The evidence of an S N 1-like S N i mechanism is provided by linear free-energy relationship studies, kinetic isotope effects, X-ray crystallography, and control experiments. We demonstrated the utility of the enantioenriched allylic phosphates in late-stage N−H allylations of natural products and drug molecules and in cross-coupling reactions that occurred with excellent enantiospecificity.

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