Construction of Quaternary Stereocenters by Palladium‐Catalyzed Carbopalladation‐Initiated Cascade Reactions

The enantioselective synthesis of molecules containing quaternary stereocenters is a field of intense research interest and development. Among the known organic transformations, carbopalladation‐initiated domino transformations constitutes a general method for the construction of compounds containing cyclic or spiro quaternary stereocenters. In this Minireview, recent achievements in palladium‐catalyzed domino Heck/C?H functionalizations and developments in enantioselective carbopalladation‐initiated domino processes are summarized.     

Selective Palladium(II)‐Catalyzed Carbonylation of Methylene β‐C−H Bonds in Aliphatic Amines

Palladium(II)‐catalyzed C−H carbonylation reactions of methylene C−H bonds in secondary aliphatic amines lead to the formation of trans ‐disubstituted β‐lactams in excellent yields and selectivities. The generality of the C−H carbonylation process is aided by the action of xantphos‐based ligands and is important in securing good yields for the β‐lactam products.     

The Discovery of a Palladium(II)‐Initiated Borono‐Catellani Reaction

Reported is a novel palladium(II)‐initiated Catellani‐type reaction that utilizes widely accessible aryl boronic acids as the substrates instead of aryl halides, thereby greatly expanding the existing scope of this powerful transformation. This borono‐Catellani reaction was promoted by cooperative catalysis between Pd(OAc)₂ and the inexpensive 5‐norbornene‐2‐carbonitrile. Practicality is the striking feature of the reaction: it is run open to air at ambient temperature and no phosphine ligand is needed. This mild, chemoselective, and scalable protocol is compatible with a large range of readily available functionalized aryl boronic acids and bromides, as well as terminating olefins (50 examples, 39–97 % yields). Moreover, the orthogonal reactivity between the borono‐Catellani and classical Catellani reaction was demonstrated. This work is expected to open new avenues for developing novel Catellani‐type reactions.     

Stereospecific Palladium‐Catalyzed Acylation of Enantioenriched Alkylcarbastannatranes: A General Alternative to Asymmetric Enolate Reactions

We report the development of a Pd‐catalyzed process for the cross coupling of unactivated primary, secondary, and tertiary alkylcarbastannatrane nucleophiles with acyl electrophiles. Reactions involving optically active alkylcarbastannatranes occur with exceptional stereofidelity and with net retention of absolute configuration. Because the stereochemistry of the resulting products is entirely reagent‐controlled, this process may be viewed as a general, alternative approach to the preparation of products typically accessed via asymmetric enolate methodologies. Additionally, we report a new method for the preparation of optically active alkylcarbastannatranes, which should facilitate their future use in stereospecific reactions.     

Auto‐Tandem Cooperative Catalysis Using Phosphine/Palladium: Reaction of Morita–Baylis–Hillman Carbonates and Allylic Alcohols

Auto‐tandem catalysis (ATC), in which a single catalyst promotes two or more mechanistically different reactions in a cascade pattern, provides a powerful strategy to prepare complex products from simple starting materials. Reported here is an unprecedented auto‐tandem cooperative catalysis (ATCC) for Morita–Baylis–Hillman carbonates from isatins and allylic carbonates using a simple Pd(PPh₃)₄ precursor. Dissociated phosphine generates phosphorus ylides and the Pd leads to π‐allylpalladium complexes, and they undergo a γ‐regioselective allylic–allylic alkylation reaction. Importantly, a cascade intramolecular Heck‐type coupling proceeds to finally furnish spirooxindoles incorporating a 4‐methylene‐2‐cyclopentene motif. Experimental results indicate that both Pd and phosphine play crucial roles in the catalytic Heck reaction. In addition, the asymmetric versions with either a chiral phosphine or chiral auxiliary are explored, and moderate results are obtained.     

Nitroarenes as the Nitrogen Source in Intermolecular Palladium‐Catalyzed Aryl C–H Bond Aminocarbonylation Reactions

A three‐component palladium‐catalyzed aminocarbonylation of aryl and heteroaryl sp² C−H bonds using nitroarenes as the nitrogen source was achieved using Mo(CO)₆ as the reductant and origin of the CO. This intermolecular C−H bond functionalization does not requires any exogenous ligand to be added, and our mechanism experiments indicate that the palladacycle catalyst serves two roles in the aminocarbonylation reaction: reduce the nitroarene to a nitrosoarene and activate the sp² C−H bond.     

Copper‐Catalyzed C(sp3)−H Amidation: Sterically Driven Primary and Secondary C−H Site‐Selectivity

Undirected C(sp³)?H functionalization reactions often follow site‐selectivity patterns that mirror the corresponding C?H bond dissociation energies (BDEs). This often results in the functionalization of weaker tertiary C?H bonds in the presence of stronger secondary and primary bonds. An important, contemporary challenge is the development of catalyst systems capable of selectively functionalizing stronger primary and secondary C?H bonds over tertiary and benzylic C?H sites. Herein, we report a Cu catalyst that exhibits a high degree of primary and secondary over tertiary C?H bond selectivity in the amidation of linear and cyclic hydrocarbons with aroyl azides ArC(O)N₃. Mechanistic and DFT studies indicate that C?H amidation involves H‐atom abstraction from R‐H substrates by nitrene intermediates [Cu](κ²‐N,O‐NC(O)Ar) to provide carbon‐based radicals R^. and copper(II)amide intermediates [Cu^II]‐NHC(O)Ar that subsequently capture radicals R^. to form products R‐NHC(O)Ar. These studies reveal important catalyst features required to achieve primary and secondary C?H amidation selectivity in the absence of directing groups.