Asymmetric Cyanation of Activated Olefins with Ethyl Cyanoformate Catalyzed by Ti(IV)-Catalyst: A Theoretical Study

The reaction mechanism and origin of asymmetric induction for conjugate addition of cyanide to the C=C bond of olefin were investigated at the B3LYP-D3(BJ)/6-31+G**//B3LYP-D3(BJ)/6-31G**(SMD, toluene) theoretical level. The release of HCN from the reaction of ethyl cyanoformate (CNCOOEt) and isopropanol (HOiPr) was catalyzed by cinchona alkaloid catalyst. The cyanation reaction of olefin proceeded through a two-step mechanism, in which the C-C bond construction was followed by H-transfer to generate a cyanide adduct. For non-catalytic reaction, the activation barrier for the rate-determining C-H bond construction step was 34.2 kcal mol−1, via a four-membered transition state. The self-assembly Ti(IV)-catalyst from tetraisopropyl titanate, (R)-3,3′-disubstituted biphenol, and cinchonidine accelerated the addition of cyanide to the C=C double bond by a dual activation process, in which titanium cation acted as a Lewis acid to activate the olefin and HNC was orientated by hydrogen bonding. The steric repulsion between the 9-phenanthryl at the 3,3′-position in the biphenol ligand and the Ph group in olefin raised the Pauli energy (ΔE≠Pauli) of reacting fragments at the re-face attack transition state, leading to the predominant R-product.

Nickel-Catalysed Allylboration of Aldehydes

A nickel catalyst for the allylboration of aldehydes is reported, facilitating the preparation of homoallylic alcohols in high diastereoselectivity. The observed diastereoselectivities and NMR experiments suggest that allylation occurs through a well-defined six-membered transition state, with nickel acting as a Lewis acid.

Metal-Free Aryl Cross-Coupling Directed by Traceless Linkers

<div>The metal-free, highly selective synthesis of biaryls poses a major challenge in organic synthesis. We report the scope and mechanism of a promising new approach to (hetero)biaryls by the photochemical fusion of aryl substituents tethered to a traceless linker (photosplicing). Interrogating photosplicing with varying reaction conditions and comparison of diverse synthetic probes (40 examples, including a suite of heterocycles) showed that the reaction has a surprisingly broad scope and involves neither metals nor radicals. Quantum chemical calculations revealed that the C–C bond is formed by an intramolecular photochemical process that involves an excited singlet state and the traverse of a five-membered transition state, thus warranting consistent <i>ipso</i>‑<i>ipso</i>‑coupling fidelity. These results demonstrate that photosplicing is a unique aryl cross-coupling method in the excited state that can be applied to synthesize a broad range of biaryls. </div>

Metal-Free Aryl Cross-Coupling Directed by Traceless Linkers

<div>The metal-free, highly selective synthesis of biaryls poses a major challenge in organic synthesis. We report the scope and mechanism of a promising new approach to (hetero)biaryls by the photochemical fusion of aryl substituents tethered to a traceless linker (photosplicing). Interrogating photosplicing with varying reaction conditions and comparison of diverse synthetic probes (40 examples, including a suite of heterocycles) showed that the reaction has a surprisingly broad scope and involves neither metals nor radicals. Quantum chemical calculations revealed that the C–C bond is formed by an intramolecular photochemical process that involves an excited singlet state and the traverse of a five-membered transition state, thus warranting consistent <i>ipso</i>‑<i>ipso</i>‑coupling fidelity. These results demonstrate that photosplicing is a unique aryl cross-coupling method in the excited state that can be applied to synthesize a broad range of biaryls. </div>

Facile difluoromethylation of aliphatic alcohols with an S-(difluoro-methyl)sulfonium salt: reaction, scope and mechanistic study

Facile difluoromethylation of alcohols is herein described, and the mechanistic study reveals that the difluorocarbene pathway is rational via a five-membered transition state with the participation of water.

BONDING FEATURES AND REACTION MECHANISM OF THE OXIDATION OF 2-PROPANOL BY A Cp*Ir AMIDO COMPLEX

The mechanistic study on the oxidation of 2-propanol by the model complex CpIr [κ2-(N,C)-( NHCMe2–2-C6H4)] (R) is performed using density functional theory (DFT) calculations. It is found that the rate-determining step is the hydrogen migration from 2-propanol to R via a six-membered transition state. The reaction is calculated to be favorable thermodynamically. To further understand the reaction mechanism, some bonding features are discussed, such as the correlation of the geometry of R and the Ir–N π bond involved, the transformation of the nitrogen hybridization, the variation of Ir–N bond distance, and so on.

Kinetics of catalytic Meerwein-Ponndorf-Verley reduction of aldehydes and ketones using boron triethoxide

Catalytic Meerwein-Ponndorf-Verley (MPV) reduction of various aliphatic, aromatic, and unsaturated aldehydes and ketones to corresponding alcohols (analyzed by GC-MS) in the presence of boron triethoxide (B(OEt)3) were studied. Kinetics of this reduction reaction was also studied and the respective rate constants were determined. It was found that B(OEt)3 catalyzes the reduction of aliphatic aldehydes and ketones to alcohols at room temperature while aromatic aldehydes and ketones were not reduced under the same conditions. In addition, MPV reduction using B(OEt)3 was found to be chemoselective as unsaturated aldehydes and ketones afforded the corresponding alcohols without affecting unsaturated groups. The mechanism proposed involves a six-membered transition state in which both the alcohol and the carbonyl are coordinated to the same boron centre of a boron alkoxide catalyst.

Deprotonation of β,β-disubstituted α,β-unsaturated amides - Mechanism and stereochemical consequences

A detailed study of the lithium dialkylamide induced deprotonation of β,β-disubstituted α,β-unsaturated amides is presented. The preferential γ-Z-deprotonation and stereochemical outcome of substituents on the γ-Z carbon atom are rationalized in terms of a cyclic eight-membered transition state, which is supported by DFT calculations. Analogous deprotonations on cyclohexylidenecarboxamides reveal a delicate balance of the preference for the eight-membered cyclic transition state with the effects of existing substituents on the ring and the intervention of a twist-boat transition state.Key words: dienolate, amide, deprotonation mechanism, transition state, enolization, regioselectivity, stereoselectivity.

Kinetic Study on the Esterification of Hexanoic Acid with N,N-Dialkylamino Alcohols: Evidence for an Activation by Hydrogen Bonding

The pseudo-first order rate constant for the esterification of hexanoic acid (1) and five different N,N-dialkylamino alcohols (2) was determined in comparison to 1-hexanol (k = 0.67 · 10−5 s−1). The values range from 0.60 · 10−5 s−1 to 9.3 · 10−5 s−1. The data suggest a differing reactivity for structurally related compounds, which is directly correlated to the ability of the corresponding amino alcohol to activate the carboxylic acid by hydrogen bonding. A seven-membered transition state C≠ is postulated for reactions of 2-amino alcohols. The fastest reaction was observed for trans-2-(N,N-dimethylamino) cyclohexanol (2e), in which the amino and the hydroxyl groups are in an almost perfect synperiplanar 1,2-position. Attempts to further enhance the rate of the esterification by the addition of potential catalysts failed. Only Cu(OTf)2 (2.5 mol-%) allowed for a moderate rate increase from 7.5 · 10−5 s−1 (uncatalyzed) to 14.8 · 10−5 s−1 (catalyzed) in the esterification of hexanoic acid (1) with 2-(N,N-dimethylamino)ethanol (2a).

Metal–ligand bifunctional catalysis for asymmetric hydrogenation

Chiral diphosphine/1,2-diamine–Ru(II) complexes catalyse the rapid, productive and enantioselective hydrogenation of simple ketones. The carbonyl-selective hydrogenation takes place via a non-classical metal–ligand bifunctional mechanism. The reduction of the C=O function occurs in the outer coordination sphere of an 18e trans -RuH 2 (diphosphine)(diamine) complex without interaction between the unsaturated moiety and the metallic centre. The Ru atom donates a hydride and the NH 2 ligand delivers a proton through a pericyclic six-membered transition state, directly giving an alcoholic product without metal alkoxide formation. The enantiofaces of prochiral ketones are differentiated on the chiral molecular surface of the saturated RuH 2 species. This asymmetric catalysis manifests the significance of ‘kinetic’ supramolecular chemistry.