Asymmetric Yttrium‐Catalyzed C(sp3)−H Addition of 2‐Methyl Azaarenes to Cyclopropenes

An enantioselective C−H addition to a C=C bond represents the most atom‐efficient route for the construction of chiral carbon–carbon skeletons, a central research topic in organic synthesis. We herein report the enantioselective yttrium‐catalyzed C(sp³)−H bond addition of 2‐methyl azaarenes, such as 2‐methyl pyridines, to various substituted cyclopropenes and norbornenes. This process efficiently afforded a new family of chiral pyridylmethyl‐functionalized cyclopropane and norbornane derivatives in high yields and high enantioselectivities (up to 97 % ee ).     

Rhodium‐Catalyzed Asymmetric Intramolecular Hydroamination of Allenes

The rhodium‐catalyzed asymmetric intramolecular hydroamination of sulfonyl amides with terminal allenes is reported. It provides selective access to 5‐ and 6‐membered N‐heterocycles, scaffolds found in a large range of different bioactive compounds. Moreover, gram scale reactions, as well as the application of suitable product transformations to natural products and key intermediates thereof are demonstrated.     

An Enantioselective CpxRh(III)‐Catalyzed C−H Functionalization/Ring‐Opening Route to Chiral Cyclopentenylamines

A chiral Cp^xRh^III catalyst system in situ generated from a Cp^xRh^I(cod) precatalyst and bis(o‐toluoyl) peroxide as activating oxidant was developed for a C?H activation/ring‐opening sequence between aryl ketoxime ethers and 2,3‐diazabicyclo[2.2.1]hept‐5‐enes. This transformation provides access to densely functionalized chiral cyclopentenylamines in excellent yields and enantioselectivities of up to 97:3 er. The reported method is also well suitable for asymmetric alkenyl C?H functionalizations of α,β‐unsaturated oxime ethers, furnishing skipped dienes with high levels of enantiocontrol.     

Asymmetric Alkenyl C−H Functionalization by CpxRhIII forms 2H‐Pyrrol‐2‐ones through [4+1]‐Annulation of Acryl Amides and Allenes

An efficient Cp^xRh^III‐catalyzed enantioselective alkenyl C?H functionalization/[4+1] annulation of acryl amides and allenes is reported. The described transformation provides straightforward access to enantioenriched α,β‐unsaturated‐γ‐lactams bearing a quaternary stereocenter. The reaction operates under mild conditions, displays a broad functional‐group tolerance, and provides 2H‐pyrrol‐2‐ones with excellent selectivity of up to 97:3 er. Such scaffolds are frequently found in natural products and synthetic bioactive compounds and are of significant synthetic value. It is noteworthy that the allene serves as a one‐carbon unit in the [4+1]‐annulation.     

Rhodium‐Catalyzed Enantioselective Oxidative [3+2] Annulation of Arenes and Azabicyclic Olefins through Twofold C−H Activation

C?H bond activation is mostly limited to ortho selectivity. Activation of both ortho and meta C?H bonds constitutes a particularly important strategy for annulation, but has rarely been studied in enantioselective systems. Reported herein is rhodium(III)‐catalyzed asymmetric [3+2] transannulation of arenes with 7‐azabenzonorbornadienes. Two distinct classes of arenes have been identified as substrates, and the coupling proceeded with high enantioselectivity and excellent diastereoselectivity through sequential activation of ortho and meta C?H bonds.     

Enantioselective Formal C(sp3)−H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives

Herein, we report the first enantioselective annulation of α‐arylidene pyrazolones through a formal C(sp³)?H activation under mild conditions enabled by highly variable Rh^III‐Cp^x catalysts. The method has a wide substrate scope and proceeds with good to excellent yields and enantioselectivities. Its synthetic utility was demonstrated by the late‐stage functionalization of drugs and natural products as well as the preparation of enantioenriched [3]dendralenes. Preliminary biological investigations also identified the spiropyrazolones as a novel class of Hedgehog pathway inhibitors.     

Squaramide‐Catalyzed Asymmetric aza‐Friedel–Crafts/N,O‐Acetalization Domino Reactions Between 2‐Naphthols and Pyrazolinone Ketimines

N‐Boc ketimines derived from pyrazolin‐5‐ones were explored to develop an unprecedented domino aza‐Friedel–Crafts/N,O‐acetalization reaction with 2‐naphthols. The novel method requires a catalyst loading of only 0.5 mol % of a bifunctional squaramide catalyst, is scalable to gram amounts, and provides a new series of furanonaphthopyrazolidinone derivatives bearing two vicinal tetra‐substituted stereogenic centers in excellent yields (95–98 %) and stereoselectivity (>99:1 d.r. and 97–98 % ee ). A different reactivity was observed in the case of 1‐naphthols and other electron‐rich phenols, which led to the aza‐Friedel–Crafts adducts in 70–98 % yield and 47–98 % ee .     

Enantioselective Synthesis of C−N Axially Chiral N‐Aryloxindoles by Asymmetric Rhodium‐Catalyzed Dual C−H Activation

The first enantioselective Satoh–Miura‐type reaction is reported. A variety of C?N axially chiral N‐aryloxindoles have been enantioselectively synthesized by an asymmetric rhodium‐catalyzed dual C?H activation reaction of N‐aryloxindoles and alkynes. High yields and enantioselectivities were obtained (up to 99 % yield and up to 99 % ee). To date, it is also the first example of the asymmetric synthesis of C?N axially chiral compounds by such a C?H activation strategy.     

Efficient Kinetic Resolution of Sulfur‐Stereogenic Sulfoximines by Exploiting CpXRhIII‐Catalyzed C−H Functionalization

Chiral sulfoximines with stereogenic sulfur atoms are promising motifs in drug discovery. We report an efficient method to access chiral sulfoximines through a C?H functionalization based kinetic resolution. A rhodium(III) complex equipped with a chiral Cp^x ligand selectively participates in conjunction with phthaloyl phenylalanine in the C?H activation of just one of the two sulfoximine enantiomers. The intermediate reacts with various diazo compounds, providing access to chiral 1,2‐benzothiazines with synthetically valuable substitution patterns. Both sulfoximines and 1,2‐benzothiazines were obtained in high yields and excellent enantioselectivity, with s‐values of up to 200. The utility of the method is illustrated by the synthesis of the key intermediates of two pharmacologically relevant kinase inhibitors.     

Kinetic Resolution and Dynamic Kinetic Resolution of Chromene by Rhodium‐Catalyzed Asymmetric Hydroarylation

A highly efficient kinetic resolution and dynamic kinetic resolution of chromene is reported for the first time and they procced by a rhodium‐catalyzed asymmetric hydroarylation pathway. This new approach offers versatile access to various chiral 2,3‐diaryl‐chromanes containing vicinal stereogenic centers, as well as the recovered chiral flavenes, in high yields with excellent ee values (s factor up to 532). Particularly noteworthy is that this strategy can be further extended to the establishment of a dynamic version of the kinetic resolution of chromene acetals and allows complete access to chiral isoflavanes and α‐aryl hydrocoumarins.