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(Difluoromethylated cyclopropane represents an important motif, which is widely found in bioactive and functional molecules. Despite significant progress in modern chemistry, the atom‐economic and enantioselective synthesis of difluoromethylated cyclopropanes is still challenging. Herein, an Rh2(II)‐catalyzed asymmetric enyne cycloisomerization is described to construct chiral difluoromethylated cyclopropane derivatives with up to 99% yield and 99% ee in low catalyst loading (0.2 mol%), which can be easily transformed into highly functionalized difluoromethylated cyclopropanes with vicinal all‐carbon quaternary stereocenters by ozonolysis. Mechanistic studies and the crystal structures of alkyne‐dirhodium complexes reveal that the cooperative weak hydrogen bondings between the substrates and the dirhodium catalyst may play key roles in this reaction.) [ABSTRACT FROM AUTHOR]

Abstract (Difluoromethylated cyclopropane represents an important motif, which is widely found in bioactive and functional molecules. Despite significant progress in modern chemistry, the atom‐economic and enantioselective synthesis of difluoromethylated cyclopropanes is still challenging. Herein, an Rh2(II)‐catalyzed asymmetric enyne cycloisomerization is described to construct chiral difluoromethylated cyclopropane derivatives with up to 99% yield and 99% ee in low catalyst loading (0.2 mol%), which can be easily transformed into highly functionalized difluoromethylated cyclopropanes with vicinal all‐carbon quaternary stereocenters by ozonolysis. Mechanistic studies and the crystal structures of alkyne‐dirhodium complexes reveal that the cooperative weak hydrogen bondings between the substrates and the dirhodium catalyst may play key roles in this reaction.)

Chiral biscyclopropanes are an important skeleton in many bioactive molecules. However, there are few routes to synthesize these molecules with high stereoselectivity due to the nature of multiple stereocenters. Herein, we report the first example of Rh2(II)‐catalyzed enantioselective synthesis of bicyclopropanes with alkynes as dicarbene equivalents. The bicyclopropanes with 4–5 vicinal stereocenters and 2–3 all‐carbon quaternary centers were constructed in excellent stereoselectivity. This protocol features high efficiency and excellent functional group tolerance. Moreover, the protocol was also extended to the cascaded cyclopropanation/cyclopropenation with excellent stereoselectivities. In these processes, both sp‐carbons of alkyne were converted into stereogenic sp3‐carbons. Experimental and density functional theory (DFT) calculations revealed that the cooperative weak hydrogen bonds between the substrates and the dirhodium catalyst may play key roles in this reaction. [ABSTRACT FROM AUTHOR]

Artificial metalloenzymes (ArMs) are commonly used to control the stereoselectivity of catalytic reactions, but controlling chemoselectivity remains challenging. In this study, we engineer a dirhodium ArM to catalyze diazo cross‐coupling to form an alkene that, in a one‐pot cascade reaction, is reduced to an alkane with high enantioselectivity (typically >99 % ee) by an alkene reductase. The numerous protein and small molecule components required for the cascade reaction had minimal effect on ArM catalysis. Directed evolution of the ArM led to improved yields and E/Z selectivities for a variety of substrates, which translated to cascade reaction yields. MD simulations of ArM variants were used to understand the structural role of the cofactor on ArM conformational dynamics. These results highlight the ability of ArMs to control both catalyst stereoselectivity and chemoselectivity to enable reactions in complex media that would otherwise lead to undesired side reactions. [ABSTRACT FROM AUTHOR]

Dirhodium(II) complex-catalyzed [3 + 2] reactions between N-arylaminocyclopropanes and alkyne derivatives are described. The cycloaddition products proved to be versatile synthetic intermediates. trans-Cyclic β-amino acids and derivatives thereof can be conveniently synthesized using this cycloaddition protocol.

We report the first Rh2(II)-catalyzed asymmetric cycloisomerization of activated enynes to provide cyclopropane-fused tetra-hydropyridines in good yields and excellent enantioselectivities under mild conditions. The activated group, CHZ (Z is electron-withdrawing group (EWG)), in the enyne substrates exerts two synergetic roles, one is to activate alkyne for the cyclopropanation reaction; the other is to introduce the C-H···O interaction between substrate and catalyst (reducing the energy barrier of the reaction). This double-mode activation was supported by both density functional theory (DFT) calculations and experimental tests. This strategy was also extended to other CH2Z (Z can be OH, OMe, F) as activating groups that made the CH2 more acidic so that the substrates could also form increased C-H···O interaction with the catalyst. [ABSTRACT FROM AUTHOR]

A RhII-catalyzed direct and stereospecific N-H- and N-alkyl aziridination of olefins is reported that uses hydroxylamine-O-sulfonic acids as inexpensive, readily available, and nitro group-free aminating reagents. Unactivated olefins, featuring a wide range of functional groups, are converted into the corresponding N-H or N-alkyl aziridines in good to excellent yields. This operationally simple, scalable transformation proceeds efficiently at ambient temperature and is tolerant towards oxygen and trace moisture. [ABSTRACT FROM AUTHOR]

Highly functionalized cyclopropanecarboxylates were readily prepared by rhodium-catalyzed cyclopropanation of alkenes with aryldiazoacetates and styryldiazoaceates, in which the ester functionality is either trimethylsilylethyl (TMSE) or trichloroethyl (TCE). By having labile protecting groups on the ester, chiral triarylcyclopropane carboxylate ligands were conveniently prepared. The asymmetric induction during cyclopropanation is dependent on the nature of the ester group and the chiral dirhodium tetracarboxylate catalyst. The prolinate catalyst Rh 2 ( S -DOSP) 4 was the optimum catalyst for asymmetric intermolecular cyclopropanation of TMSE diazoesters with styrene, while Rh 2 ( R -BPCP) 4 was the optimum catalyst for TCE diazoesters. [ABSTRACT FROM AUTHOR]

Abstract: Catalytic enantioselective methods for the generation of cyclopropanes have been of long standing pharmaceutical interest. Chiral dirhodium(II) catalysts prove to be an effective means for the generation of diverse cyclopropane libraries. Rh2(R-DOSP)4 is generally the most effective catalyst for asymmetric intermolecular cyclopropanation of methyl aryldiazoacetates with styrene. Rh2(S-PTAD)4 provides high levels of enantioinduction with ortho-substituted aryldiazoacetates. The less-established Rh2(R-BNP)4 plays a complementary role to Rh2(R-DOSP)4 and Rh2(S-PTAD)4 in catalyzing highly enantioselective cyclopropanation of 3-methoxy substituted aryldiazoacetates. Substitution on the styrene has only moderate influence on the asymmetric induction of the cyclopropanation. [Copyright &y& Elsevier]

Abstract: Rh2(S-PTAD)4 is an effective catalyst for the asymmetric cyclopropenation of aryl alkynes using a siloxyvinyldiazoacetate as the carbenoid precursor. Upon deprotection of the silyl protecting group, highly enantioenriched cyclopropenes bearing geminal acceptor groups can be accessed. These cyclopropenes undergo regioselective rhodium(II)-catalyzed ring expansion to furans. [Copyright &y& Elsevier]

Keywords: artificial metalloenzymes; cascade catalysis; directed evolution; dirhodium catalysis; molecular dynamics simulations EN artificial metalloenzymes cascade catalysis directed evolution dirhodium catalysis molecular dynamics simulations 1 1 1 10/20/21 20211025 NES 211025 B Directed Evolution b In their Research Article on page 23672, Benoit Roux, Jared C. Lewis et al. use directed evolution to improve dirhodium artificial metalloenzyme (ArM)-catalyzed diazo cross-coupling yield and selectivity. Artificial metalloenzymes, cascade catalysis, directed evolution, dirhodium catalysis, molecular dynamics simulations. [Extracted from the article]

Dirhodium(II) complex-catalyzed [3 + 2] reactions between N -arylaminocyclopropanes and alkyne derivatives are described. The cycloaddition products proved to be versatile synthetic intermediates. trans -Cyclic β-amino acids and derivatives thereof can be conveniently synthesized using this cycloaddition protocol.

A Rh II -catalyzed direct and stereospecific N-H- and N-alkyl aziridination of olefins is reported that uses hydroxylamine-O-sulfonic acids as inexpensive, readily available, and nitro group-free aminating reagents. Unactivated olefins, featuring a wide range of functional groups, are converted into the corresponding N-H or N-alkyl aziridines in good to excellent yields. This operationally simple, scalable transformation proceeds efficiently at ambient temperature and is tolerant towards oxygen and trace moisture., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)