Ranjan Jana

A Palladium-Catalyzed Three-Component Cross-Coupling of Conjugated Dienes or Terminal Alkenes with Vinyl Triflates and Boronic Acids

A three-component coupling of vinyl triflates and boronic acids to alkenes catalyzed by palladium is reported. Using 1,3-dienes, selective 1,2-alkene difunction-alization is observed, whereas the use of terminal alkenes results in 1,1-alkene difunctionalization. The reaction outcome is attributed to the formation of stabilized, cationic Pd-π-allyl intermediates to regulate β-hydride elimination.

Formation of N-Alkylpyrroles via Intermolecular Redox Amination

A wide variety of aldehydes, ketones, and lactols undergo redox amination when allowed to react with 3-pyrroline in the presence of a mild Brønsted acid catalyst. This reaction utilizes the inherent reducing power of 3-pyrroline to perform the equivalent of a reductive amination to form alkyl pyrroles. In doing so, the reaction avoids stoichiometric reducing agents that are typically associated with reductive aminations. Moreover, the redox amination protocol allows access to alkyl pyrroles that cannot be made via standard reductive amination.

Palladium(II)-Catalyzed Enantio- and Diastereoselective Synthesis of Pyrrolidine Derivatives

A palladium-catalyzed enantio- and diastereoselective synthesis of pyrrolidine derivatives is described. Initial intramolecular nucleopalladation of the tethered protected amine forms the pyrrolidine moiety and a quinone methide intermediate. A second nucleophile adds intermolecularly to afford diverse products in high enantio- and diastereoselectivity.

Pd(0)-Catalyzed 1,1-Diarylation of Ethylene and Allylic Carbonates

An efficient protocol for the one-step synthesis of biologically relevant 1,1-diarylalkanes has been described. This reaction introduces two different aryl groups across the terminal end of simple feedstock alkenes such as ethylene and allylic carbonates. The propensity to generate π-benzylpalladium intermediates dictates the exclusive 1,1-regioselectivity observed in the product.

A Homogeneous, Recyclable Rhodium(I) Catalyst for the Hydroarylation of Michael Acceptors

A robust and practical polymer-supported, recyclable biphephos rhodium(I) catalyst has been developed. Control of polymer molecular weight allowed the tuning of solubility such that the polymer-supported catalyst is soluble in nonpolar solvents and not soluble in polar solvents. Thus, catalytic addition of aryl- and vinylboronic acids to enones occurs under completely homogeneous conditions and catalyst recycle can be achieved by simple precipitation and filtration.

Merging C–H Activation and Alkene Difunctionalization at Room Temperature: A Palladium-Catalyzed Divergent Synthesis of Indoles and Indolines

A palladium-catalyzed 1,2-carboamination through C-H activation at room temperature is reported for the synthesis of 2-arylindoles, and indolines from readily available, inexpensive aryl ureas and vinyl arenes. The reaction initiates with a urea-directed electrophilic ortho palladation, alkene insertion, and β-hydride elimination sequences to provide the Fujiwara-Moritani arylation product. Subsequently, aza-Wacker cyclization, and β-hydride elimination provide the 2-arylindoles in high yields. Intercepting the common σ-alkyl-Pd intermediate, corresponding indolines are also achieved. The indoline formation is attributed to the generation of stabilized, cationic π-benzyl-Pd species to suppress β-hydride elimination.

Migratory Decarboxylative Coupling of Coumarins: Synthetic and Mechanistic Aspects**

A three-component coupling of vinyl triflates and boronic acids to alkenes catalyzed by palladium is reported. Using 1,3-dienes, selective 1,2-alkene difunctionalization is observed, whereas the use of terminal alkenes results in 1,1-alkene difunctionalization. The reaction outcome is attributed to the formation of stabilized, cationic Pdπ-allyl intermediates to regulate β-hydride elimination. S effort has been afforded to the development of high utility methods involving palladium-catalyzed alkene functionalization as highlighted by the Heck reaction and the Wacker oxidation. Inspired by the key mechanistic motifs of these fundamental reactions, a focus of our research program over the past several years has been the advancement of palladiumcatalyzed alkene difunctionalization reactions with the ultimate goal of selectively introducing two groups across the alkene. 7 As a specific example, we have reported the diarylation of conjugated and terminal alkenes using oxidative palladium catalysis (Scheme 1a). In this reaction, two aryl groups originating from an arylstannane are added across a 1,3-diene (or styrene) to yield the 1,2-diarylation product. Mechanistically, this reaction is thought to initiate by transmetalation to form Pdaryl species A, Heck insertion of a conjugated diene yielding B, and stabilization of the Pd-alkyl as aπ-allylC. Subsequent cross-coupling of a second equivalent of an aryl stannane results in product formation. The success of this reaction is partially attributed to stabilization of the electrophilic Pd-species by formation of either a π-allyl (for dienes) or a π-benzyl (for styrenes) intermediate suppressing β-hydride elimination. The obvious synthetic limitation of this 1,2-alkene difunctionalization reaction is the introduction of two identical aryl groups from the arylstannane as well as reasonably complex reaction conditions. To overcome this significant synthetic drawback, we considered an alternative and perhaps simpler approach. Specifically, the use of Pd(0) initiated catalysis is proposed wherein a vinyl triflate undergoes oxidative addition to yield Pd-vinyl species D. Heck insertion of a diene should produce intermediate B0 which is closely related to the proposed intermediate in the oxidative Pd-catalyzed diarylation reaction and should be stabilized by formation of a π-allyl C0 to suppress β-hydride elimination. It should be noted that vinyl triflates were specifically selected to initiate the catalysis since highly electrophilic Pd-species should result in alkene insertion in preference to the more common Suzuki coupling sequence. To complete the process, transmetalation of a boronic acid derivative and reductive elimination will introduce two different groups into the alkene framework to yield skipped diene products. Reports of related three-component coupling reactions of this type with Pd have been generally limited to substrates that are unable to undergo β-hydride elimination after Heck insertion such as norbornenes, alkynes, and carbene precursors. Allenes as the “alkene” coupling partner have been reported, where a Pd-πallyl species is directly formed viamigratory insertion to presumably avoid β-hydride elimination in a manner similar to our proposal. Herein, we present the successful development of a three-component coupling to achieve the formation of two sp sp carbon carbon bonds from the alkene framework using vinyl triflates as the organic electrophile and boronic acids as the organometallic reagent. Surprisingly, this complexity generating reaction occurs under very simple and mild reaction conditions, where alkene 1, 2-difunctionalization is achieved using conjugated dienes. Extension tomore challenging terminal alkenes, which has not previously been reported, is also presented, yielding the 1,1-alkene difunctionalization products under identical reaction conditions. For optimization, vinyl triflate 1a, diene 2a, and boronic acid 3a were selected (Table 1). Gratifyingly, the optimized conditions Scheme 1. Proposed Three-Component Coupling of Conjugated Dienes with Vinyl Triflates and Aryl Boronic Acids Received: February 16, 2011

A Homogeneous, Recyclable Polymer Support for Rh(I)-Catalyzed C-C Bond Formation

A robust and practical polymer-supported, homogeneous, recyclable biphephos rhodium(I) catalyst has been developed for C-C bond formation reactions. Control of polymer molecular weight allowed tuning of the polymer solubility such that the polymer-supported catalyst is soluble in nonpolar solvents and insoluble in polar solvents. Using the supported rhodium catalysts, addition of aryl and vinylboronic acids to the electrophiles such as enones, aldehydes, N-sulfonyl aldimines, and alkynes occurs smoothly to provide products in high yields. Additions of terminal alkynes to enones and industrially relevant hydroformylation reactions have also been successfully carried out. Studies show that the leaching of Rh from the polymer support is low and catalyst recycle can be achieved by simple precipitation and filtration.

Mechanistic Origin of the Stereodivergence in Decarboxylative Allylation

A stereochemical test has been used to probe the mechanism of decarboxylative allylation. This probe suggests that the mechanism of DcA reactions can change based on the substitution pattern at the alpha-carbon of the nucleophile; however, reaction via stabilized malonate nucleophiles is the lower energy pathway. Lastly, this mechanistic proposal has predictive power and can be used to explain chemoselectivities in decarboxylative reactions that were previously confounding.

Lewis acid-catalyzed diastereoselective hydroarylation of benzylidene malonic esters

Herein we report that simple Lewis acids catalyze the hydroarylation of benzylidene malonates with phenols. Ultimately, 3,4-disubstituted dihydrocoumarins are obtained via a hydroarylation-lactonization sequence. Moreover, the dihydrocoumarins are formed with a high degree of diastereoselectivity favoring the trans stereoisomer.