Rh-Catalyzed Enantioselective Single-Carbon Insertion of Alkenes.

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 Rh-carbynoid 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 SN1-like SNi 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.

Generating Fischer-Type Rh-Carbenes with Rh-Carbynoids.

We describe the first catalytic generation of Fischer-type acyloxy Rh(II)-carbenes from carboxylic acids and Rh(II)-carbynoids. This novel class of transient donor/acceptor Rh(II)-carbenes evolved through a cyclopropanation process providing access to densely functionalized cyclopropyl-fused lactones with excellent diastereoselectivity. DFT calculations allowed the analysis of the properties of Rh(II)-carbynoids and acyloxy Rh(II)-carbenes as well as the characterization of the mechanism.

ß-Diazocarbonyl Compounds: Synthesis and their Rh(II)-Catalyzed 1,3 C-H Insertions.

Herein, we describe the first electrophilic diazomethylation of ketone silyl enol ethers with diazomethyl-substituted hypervalent iodine reagents that gives access to unusual ß-diazocarbonyl compounds. The potential of this unexplored class of diazo compounds for the development of new reactions was demonstrated by the discovery of a rare Rh-catalyzed intramolecular 1,3 C-H carbene insertion that led to complex cyclopropanes with excellent stereocontrol.

Stereodivergent Pd/Cu Catalysis for the Dynamic Kinetic Asymmetric Transformation of Racemic Unsymmetrical 1,3-Disubstituted Allyl Acetates.

A stereodivergent Pd/Cu catalyst system has been developed for the unprecedented dynamic kinetic asymmetric transformation (DyKAT) of racemic unsymmetrical 1,3-disubstituted allylic acetates with prochiral aldimine esters. A series of α,α-disubstituted α-amino acids bearing vicinal stereocenters were easily prepared with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >20:1 dr). Moreover, all four stereoisomers of the product can be readily obtained simply by switching the configurations of the two chiral metal catalysts. Furthermore, the present work highlights the power of synergistic Pd/Cu catalysis consisting of two common bidentate chiral ligands for stereodivergent synthesis.

Catalytic Cleavage of C(sp2)-C(sp2) Bonds with Rh-Carbynoids.

We report a catalytic strategy that generates rhodium-carbynoids by selective diazo activation of designed carbyne sources. We found that rhodium-carbynoid species provoke C(sp2)-C(sp2) bond scission in alkenes by inserting a monovalent carbon unit between both sp2-hybridized carbons. This skeletal remodeling process accesses synthetically useful allyl cation intermediates that conduct to valuable allylic building blocks upon nucleophile attack. Our results rely on the formation of cyclopropyl-I(III) intermediates able to undergo electrocyclic ring-opening, following the Woodward-Hoffmann-DePuy rules.

Highly Diastereo- and Enantioselective Cu-Catalyzed Borylative Coupling of 1,3-Dienes and Aldimines.

A Cu-catalyzed diastereo- and enantioselective borylative coupling reaction of 1,3-dienes with imines was realized. Branched homoallylic amines are readily prepared in a syn-selective manner with high regio-, diastereo- and enantioselectivity. Moreover, these three-component coupling reactions feature good functional-group compatibility and easy access to the substrates and catalyst.

Rhodium-catalyzed asymmetric arylation of ß,γ-unsaturated α-ketoamides for the construction of nonracemic γ,γ-diarylcarbonyl compounds.

A highly regio- and enantioselective rhodium-catalyzed 1,4-addition of arylboronic acids to ß,γ-unsaturated α-ketoamides using a simple new chiral sulfinylphosphine ligand is described. This transformation provides an attractive approach to construct chiral nonracemic γ,γ-diarylsubstituted carbonyl compounds, as exemplified in the concise syntheses of sertraline and tetrahydroquinoline-2-carboxylamide.

Catalytic alkene skeletal modification for the construction of fluorinated tertiary stereocenters.

Herein we describe the first construction of fluorinated tertiary stereocenters based on an alkene C(sp2)-C(sp2) bond cleavage. The new process, that takes advantage of a Rh-catalyzed carbyne transfer, relies on a branched-selective fluorination of tertiary allyl cations and is distinguished by a wide scope including natural products and drug molecule derivatives as well as adaptability to radiofluorination.

Pd-catalyzed enantioselective hydroalkoxylation of alkoxyallenes with phenol for construction of acyclic O,O-acetals.

Palladium-catalyzed asymmetric intermolecular hydroalkoxylation of allenes has been developed by using phenol as a pronucleophile. Acyclic O,O-acetals were obtained in high yields (up to 98%) with good to excellent enantiomeric excesses (up to 94% ee).