Ilya D. Gridnev

Rigid P-Chiral Phosphine Ligands with tert-Butylmethylphosphino Groups for Rhodium-Catalyzed Asymmetric Hydrogenation of Functionalized Alkenes

Both enantiomers of 2,3-bis(tert-butylmethylphosphino)quinoxaline (QuinoxP*), 1,2-bis(tert-butylmethylphosphino)benzene (BenzP*), and 1,2-bis(tert-butylmethylphosphino)-4,5-(methylenedioxy)benzene (DioxyBenzP*) were prepared in short steps from enantiopure (S)- and (R)-tert-butylmethylphosphine-boranes as the key intermediates. All of these ligands were crystalline solids and were not readily oxidized on exposure to air. Their rhodium complexes exhibited excellent enantioselectivities and high catalytic activities in the asymmetric hydrogenation of functionalized alkenes, such as dehydroamino acid derivatives and enamides. The practical utility of these catalysts was demonstrated by the efficient preparation of several chiral pharmaceutical ingredients having an amino acid or a secondary amine component. A rhodium complex of the structurally simple ligand BenzP* was used for the mechanistic study of asymmetric hydrogenation. Low-temperature NMR studies together with DFT calculations using methyl α-acetamidocinnamate as the standard model substrate revealed new aspects of the reaction pathways and the enantioselection mechanism.

A method for the synthesis of substituted quinolines via electrophilic cyclization of 1-azido-2-(2-propynyl)benzene.

A new and efficient strategy for the synthesis of substituted quinolines via electrophilic cyclization is developed. The intramolecular cyclization of 1-azido-2-(2-propynyl)benzene 1 proceeds smoothly in the presence of electrophilic reagents (I(2), Br(2), ICl, NBS, NIS, and HNTf(2)) in CH(3)NO(2) at room temperature or in the presence of catalytic amounts of AuCl(3)/AgNTf(2) in THF at 100 degrees C to afford the corresponding quinolines 2 in good to high yields. In the case of the electrophilic reagents, E of 2 is either I, Br, or H, depending on the reagent type, while E of 2 is H in the case of the electrophilic catalyst.

Reflections on spontaneous asymmetric synthesis by amplifying autocatalysis

Spontaneous generation of chirality was observed in the course of studying the mechanism of asymmetric autocatalysis by NMR in ZnR2 alkylation of pyrimidin-5-aldehydes. A systematic study was carried out in order to discover its origins. Even in clean fresh non-glass reaction vessels spontaneous ee was clearly observed, and was not dependent on any single reaction parameter. For comparison it was demonstrated that enantiomerically pure Zn alkoxide catalyst could control the configuration of the reaction product even when present at below micromolar concentrations. The high propensity of the Soai reaction system to produce an enantiomerically enriched product without initial bias is suggested to result from stochastic effects. These are especially important in autocatalysis because all the final products can be derived by breeding from a small number of initial events. The statistical excess of one enantiomer in that set is sufficient to generate a measurable ee in the product. The process is aided by the requirement for dimerisation before the product is an active catalyst. An enumeration that rationalises these observations is provided.

Palladium-Catalyzed Allylic Alkylation of Simple Ketones with Allylic Alcohols and Its Mechanistic Study†

Allylic alcohols were directly used in Pd-catalyzed allylic alkylations of simple ketones under mild reaction conditions. The reaction proceeded smoothly at 20 °C by the concerted action of a Pd catalyst, a pyrrolidine co-catalyst, and a hydrogen-bonding solvent, and does not require any additional reagents. A computational study suggested that methanol plays a crucial role in the formation of the π-allylpalladium complex by lowering the activation barrier.

Enantioselective Direct Amination of α-Cyanoacetates Catalyzed by Bifunctional Chiral Ru and Ir Amido Complexes

The bifunctional chiral amido Ir complex catalyzed asymmetric electrophilic direct amination of α-substituted α-cyanoacetates using azodicarboxylates proceeds rapidly to provide the corresponding hydrazine adducts in high yields and with excellent ee values.

Bifunctional transition metal-based molecular catalysts for asymmetric C-C and C-N bond formation.

This paper describes the recent advances in the conceptually new bifunctional Ir and Ru catalysts for asymmetric catalytic reactions. These reactions include the enantioselective Michael addition of 1,3-dicarbonyl compounds to cyclic enones and nitroalkenes, and the enantioselective direct amination of alpha-cyanoacetates with diazoesters. The outcome of these reactions in terms of reactivity and selectivity was delicately influenced by the catalyst structures and the reaction conditions including the solvents used. Even with a 1 : 1 molar ratio of donors to acceptors, the reactions proceeded smoothly to give the corresponding chiral adducts with an excellent yield and enantiomeric excess (ee). Preliminary mechanistic studies showed that the key stage of the catalytic cycle is the interaction of the bifunctional catalyst with a pronucleophilic reagent that leads to stereoselective formation of C-, O-, or N-bound complexes. The resulting protonated catalyst bearing metal-bound nucleophiles readily reacts with electrophiles to provide C--C and C--N bond formation products in a highly stereoselective manner.

Mechanism of the Asymmetric Hydrogenation of Exocyclic α,β‐Unsaturated Carbonyl Compounds with an Iridium/BiphPhox Catalyst: NMR and DFT Studies

The mechanism of the asymmetric hydrogenation of exocyclic α,β-unsaturated carbonyl compounds with the (aS)-Ir/iPr-BiphPhox catalyst was studied by NMR experiments and DFT computational analyses. Computed optical yields of the asymmetric hydrogenation proceeding by an iridium(I)/iridium(III) mechanism involving a transition state stabilized through two intramolecular hydrogen bonds are in good accordance with the experimental ee values.

Pd(II)-catalyzed asymmetric addition of arylboronic acids to cyclic N-sulfonyl ketimine esters and a DFT study of its mechanism

A palladium-catalyzed asymmetric arylation of cyclic N-sulfonyl ketimine esters is described. The desired products could be prepared with excellent yields (up to 99%) and enantioselectivities (up to 99% ee) under mild reaction conditions. Furthermore, a possible reaction mechanism was determined using DFT calculations.

Mechanism of Enantioselective C−C Bond Formation with Bifunctional Chiral Ru Catalysts: NMR and DFT Study

The mechanism of Michael addition reactions of 1,3-dicarbonyl compounds to cyclic enones catalyzed by bifunctional Ru catalysts bearing N-sulfonylated (R,R)-DPEN ligands (DPEN = (R,R)-1,2-diphenylethylenediamine) was studied by NMR and DFT computational analyses. NMR investigation of the stoichiometric reactions of chiral amido Ru complexes, Ru(N-sulfonylated dpen)(η(6)-arene) 1a-c, with dimethyl malonate 2 and β-keto ester 3 revealed that at decreased temperatures deprotonation proceeds in a stereoselective manner to provide amine complexes. The reaction with malonic ester 2 provided exclusively C-bound amino Ru complexes 6a,c, while the reaction of β-keto ester 3 gave an equilibrium mixture of rapidly interconverting C- and O-bound complexes. The structures of C-bound Ru complex 6c and O-bound Ru complex 9c were determined by single crystal X-ray analysis. A computational study showed that the enatioselective C-C bond formation proceeds through intermediate formation of chelating ion pairs that coordinate a molecule of enone via the Ru metal center producing a highly organized environment for the C-C bond formation, yielding selectively only one enantiomer of the product. Systematic study of a series of the catalyst-substrate combinations revealed that the experimentally observed sense of enantioselection was consistently explained by computational analysis. The tendency of increasing ee with the bulk of the coordinated arene in Ru complex is reproduced computationally by changes in the difference of either ZPPE-corrected energies or Gibbs free energies for S- and R-pathways.

Asymmetric Autocatalysis with Organozinc Complexes; Elucidation of the Reaction Pathway

This review describes the development of mechanistic understanding of amplifying asymmetricautocatalysis. After a brief description of kinetics, the main body of the work discusses theapplication of a variety of NMR techniques to the structure of the resting state in solution.The results are consistent with a dominant square Zn–O bonded dimer at ambient temperature.Furthermore, the energies of homo- and heterochiral dimers is comparable; they exchange slowly onthe NMR timescale but fast enough for the lifetime of an individual molecule to be established. Theassociation of alkylzinc with this dimer can be quantified and located, and dynamic alkyl exchangesdefined. DFT calculations have been carried out, which underpin the dimer structure and provide furtherinsight into the steric control of autocatalysis by the bulk of diisopropylzinc. NMR, kinetics andcomputation converge in supporting the role of dimers of the indicated structure, and in pointingto a mechanism whereby the unique reactivity of the homochiral dimer is the driving force, atleast at ambient temperature.