Regioselective Allylic Alkylation Research Articles

Tunable Regioselective Allylic Alkylation/Iodination of Imidazoheterocycles in Water.

The switchable roles of allylic alcohol and molecular iodine as reagents and catalysts have been demonstrated in the regioselective allylic alkylation and iodination of imidazoheterocycles employing the mixture of allylic alcohol-I2. First, we have explored the catalytic activity of iodine for the allylation of imidazoheterocycles using allylic alcohol in an aqueous medium. The allylation of a library of imidazoheterocycles and other electron-rich heterocycles like indole, pyrazole, 4-hydroxy coumarin, and 6-amino uracil has been achieved by employing this methodology. The efficiency of the I2 catalyst for N-allylation of azoles has also been demonstrated. Next, we have shown that this mixture of allylic alcohol and I2 could be beneficial for the iodination of imidazoheterocycles under room temperature. Mechanistic studies indicate that the activation of allylic alcohol by molecular iodine took place probably through halogen bonding, and NMR studies show that the reaction did not proceed through allylic ether formation.

Experimental and Computational Studies on Cobalt(I)‐Catalyzed Regioselective Allylic Alkylation Reactions

AbstractHere, we report the development of cobalt(I)‐catalyzed regioselective allylic alkylation reactions of tertiary allyl carbonates with 1,3‐dicarbonyl compounds. A family of well‐defined tetrahedral cobalt(I) complexes bearing commercially available bidentate bis(phosphine) ligands [(P,P)Co(PPh3)Cl] are synthesized and explored as catalysts in allylic alkylation reactions. The catalyst [(dppp)Co(PPh3)Cl] (dppp=1,3‐Bis(diphenylphosphino)propane) enables the alkylation of a large variety of tertiary allyl carbonates with high yields and excellent regioselectivity for the branched product. Remarkably, this methodology is selective for the activation of tertiary allyl carbonates even in the presence of secondary allyl carbonates. This contrasts with the selectivity observed in cobalt‐catalyzed allylic alkylations enabled by visible light photocatalysis. Mechanistic insights by means of experimental and computational investigations support a Co(I)/Co(III) catalytic cycle.

Experimental and Computational Studies on Cobalt(I)-Catalyzed Regioselective Allylic Alkylation Reactions.

Here, we report the development of cobalt(I)-catalyzed regioselective allylic alkylation reactions of tertiary allyl carbonates with 1,3-dicarbonyl compounds. A family of well-defined tetrahedral cobalt(I) complexes bearing commercially available bidentate bis(phosphine) ligands [(P,P)Co(PPh3 )Cl] are synthesized and explored as catalysts in allylic alkylation reactions. The catalyst [(dppp)Co(PPh3 )Cl] (dppp=1,3-Bis(diphenylphosphino)propane) enables the alkylation of a large variety of tertiary allyl carbonates with high yields and excellent regioselectivity for the branched product. Remarkably, this methodology is selective for the activation of tertiary allyl carbonates even in the presence of secondary allyl carbonates. This contrasts with the selectivity observed in cobalt-catalyzed allylic alkylations enabled by visible light photocatalysis. Mechanistic insights by means of experimental and computational investigations support a Co(I)/Co(III) catalytic cycle.

Nickel-Catalyzed Regioselective Allylic Alkylation of Unsymmetric Ketones at the Higher-Substituted α-Site

Nickel-Catalyzed Regioselective Allylic Alkylation of Unsymmetric Ketones at the Higher-Substituted α-Site

Squaramide-catalyzed asymmetric regioselective allylic alkylation of 4-aminopyrazolones with Morita-Baylis-Hillman carbonates.

An efficient squaramide-catalyzed asymmetric allylic alkylation of 4-aminopyrazolones with various MBH carbonates via different pathways has been described. This method provides access to a series of pyrazolone derivatives bearing a nitrogen-containing quaternary stereocenter in high yields with excellent enantioselectivities and regioselectivities under mild conditions. In addition, we utilized the target products to construct a range of bi-heterocyclic skeletons through [3 + 2] cycloadditions. These novel hybrid heterocycles would be promising candidates for drug-discovery programs and chemical biology.

Synthesis of a Seco iso-Secologanin Aglycone Analogue of Interest toward Secoiridoids and Monoterpene Indole Alkaloids.

We report the access to an acyclic iso-secologanin aglycone analogue relevant to secoiridoids and monoterpene indole alkaloids. Its synthesis involved the regioselective allylic alkylation of a linear dienyl carbonate with dimethyl malonate, which was catalyzed by an iridium complex, and an anti-Markovnikov Wacker-type oxidation of the terminal alkene of the branched product that was obtained. The thus-formed aldehyde was engaged in a Pictet-Spengler reaction with tryptamine toward monoterpene indole alkaloids.

Organocatalytic Asymmetric Allylic Alkylations of Sulfoximines.

An enantio- and regioselective allylic alkylation of sulfoximines with Morita-Baylis-Hillman carbonates was developed. The asymmetric reaction is directed by a quinidine-derived organocatalyst providing a range of optically active α-methylene β-sulfoximidoyl esters in high yields (up to 93%) with good to excellent enantiomeric excesses (up to 95%) under mild reaction conditions.

Intermolecular Stereoselective Iridium-Catalyzed Allylic Alkylation: An Evolutionary Account.

Our lab has long been interested in the development of methods for the creation of enantioenriched all-carbon quaternary stereocenters. Historically, our interest has centered on palladium-catalyzed allylic alkylation, though recent efforts have moved to include the study of iridium catalysts. Whereas palladium catalysts enable the preparation of isolated stereocenters, the use of iridium catalysts allows for the direct construction of vicinal stereocenters via an enantio-, diastereo-, and regioselective allylic alkylation. This account details the evolution of our research program from inception, which focused on the first iridium-catalyzed allylic alkylation to prepare stereodyads containing a single quaternary center, to our most recent discovery that allows for the synthesis of vicinal quaternary centers.

Transfer of Chirality in the Rhodium-Catalyzed Chemoselective and Regioselective Allylic Alkylation of Hydroxyarenes with Vinyl Aziridines.

By taking advantage of chirality-transfer strategy, a chemo- and regioselective allylic alkylation of naphthols and phenols with vinylaziridines provides an atom-economic and efficient method for the synthesis of enantioenriched 2-vinyl-2-arylethylamine derivatives. Use of readily available starting materials, a broad substrate scope, high selectivity, mild reaction conditions, as well as versatile functionalizations of the aromatic ethylamine products make this approach very practical and attractive.

ChemInform Abstract: Iridium‐Catalyzed Diastereo‐, Enantio‐, and Regioselective Allylic Alkylation with Prochiral Enolates

AbstractReview: 33 refs.

Regioselective synthesis of functionalized dihydroquinolines via organocatalytic allylic alkylation

The regioselective allylic alkylation of 1,2-dihydroquinolines and Morita-Baylis-Hillman(MBH) adducts has been developed. By surveying various reaction parameters, we summarize the effects of temperatures, relative reactant doses, catalysts, solvents and N-protected groups on the regioselectivity of this transformation. This method provides a facile protocol for the preparation of allylic α-substituted dihydroquinolines.

A Regioselective Palladium-Catalyzed Allylic Alkylation Cascade with Dihydropyrans

A Regioselective Palladium-Catalyzed Allylic Alkylation Cascade with Dihydropyrans

ChemInform Abstract: Controllable Regioselective Construction of Both Functional α‐Methylene‐β‐ and ‐γ‐amino Acid Derivatives Through an Organocatalyzed Tandem Allylic Alkylation and Amination.

AbstractA controllable regioselective allylic alkylation and amination reaction is developed using α‐amino nitriles.

ChemInform Abstract: A Simple Diamine as Ligand in Iron‐Catalyzed Regioselective Allylic Alkylation.

AbstractTMEDA is found to be an efficient ligand in the process.

Controllable Regioselective Construction of Both Functional α‐Methylene‐β‐ and ‐γ‐amino Acid Derivatives Through an Organocatalyzed Tandem Allylic Alkylation and Amination

AbstractA new controllable and regioselective allylic alkylation and amination reaction has been developed for the highly selective construction of compounds containing α‐alkylidene‐β‐amino acid and α‐methylene‐γ‐butyrolactam moieties. Furthermore, on the basis of this controllable strategy, multicomponent tandem reactions have also been accomplished. The subsequent transformations of the densely functionalized products have readily afforded a range of useful building blocks, which have potential utility in organic synthesis.

A simple diamine as ligand in iron-catalyzed regioselective allylic alkylation

A simple and efficient diamine was found to be an efficient ligand for the iron-catalyzed regioselective allylic alkylation between various allyl carbonates and nucleophiles, affording excellent yields and good regioselectivity (up to 94% and >20 : 1).

ChemInform Abstract: Highly Regioselective Allylic Alkylation of Dienyl Acetates and Enynyl Acetates Catalyzed by an Iridium Complex.

ChemInform Abstract: Highly Regioselective Allylic Alkylation of Dienyl Acetates and Enynyl Acetates Catalyzed by an Iridium Complex.

Calix[4]arene bisphosphite ligands bearing two distal 2,2′-biphenyldioxy or 2,2′-binaphthyldioxy moieties: conformational flexibility and allyl–palladium complexes

Achiral and chiral calix[4]arene bisphosphite ligands ( 2 and 3) bearing two distal 2,2′-biphenyldioxyphosphinoxy and 2,2′-binaphthyldioxyphosphinoxy moieties, respectively, have been synthesized. Each of these ligands exists in two pairs of interconverting conformations in solution. The partial cone conformer (A) of the (bis)biphenyldioxyphosphinoxy ligand 2 has been separated by fractional crystallization and its structure established by X-ray crystallography. The mechanism of interconversion of the pairs of conformers (A/B and C/D) has been probed by two-dimensional NMR spectroscopy. The 1H and 31P NMR evidence strongly supports a similar kind of exchange mechanism for ligand 3. Freezing of the cone conformer from the interconverting C/D pair of conformers of ligand 2 has been achieved by complexation with (allyl)palladium moieties. The methyl–allyl complex ( 2d) is moderately effective for catalytic regioselective allylic alkylation of crotyl acetate.

Iridium-Catalyzed Enantioselective Allylic Alkylation

Combination of [Ir(cod)Cl]2 and phosphoramidite 1 is shown to be a very effective catalytic system for enantio- and regioselective allylic alkylation. The advantage of the methodology described here is the use of readily available starting material, mild conditions to yield branched products exclusively.

Ligand‐Dependent Mechanistic Dichotomy in Iron‐Catalyzed Allylic Substitutions: σ‐Allyl versus π‐Allyl Mechanism

Iron at the crossroads: A remarkable mechanistic dichotomy in iron-catalyzed allylic substition increases not only the scope of regioselective allylic alkylation but could also herald the development of asymmetric allylic substitution (see Scheme, MTBE=methyl tert-butyl ether). Depending on the ligand used, either a σ- or a π-allyl mechanism is observed.