Strain-Releasing Ring-Opening Diphosphinations for the Synthesis of Diphosphine Ligands with Cyclic Backbones.

Diphosphine ligands based on cyclobutane, bicyclo[3.1.1]heptane, and bicyclo[4.

γ-Butyrolactone Synthesis from Allylic Alcohols Using the CO Radical Anion.

γ-Butyrolactone structures are commonly found in various natural products and serve as crucial building blocks in organic synthesis. Consequently, the development of methods for synthesizing γ-butyrolactones has garnered significant interest within the organic synthesis community. In this study, we present a direct and highly efficient approach for the synthesis of γ-butyrolactones from allylic alcohols.

Quantum chemical calculations for reaction prediction in the development of synthetic methodologies.

Quantum chemical calculations have been used in the development of synthetic methodologies to analyze the reaction mechanisms of the developed reactions. Their ability to estimate chemical reaction pathways, including transition state energies and connected equilibria, has led researchers to embrace their use in predicting unknown reactions. This perspective highlights strategies that leverage quantum chemical calculations for the prediction of reactions in the discovery of new methodologies.

Revisiting the Electrochemical Carboxylation of Naphthalene with CO: Selective Monocarboxylation of 2-Substituted Naphthalenes.

Numerous remarkable reactions based on electrochemical carboxylations using CO have recently attracted considerable attention. In contrast to more recent examples, the electrochemical carboxylation of naphthalene had already been established in 1959, whereby a dearomative dicarboxylation selectively produces 1,4-dicarboxylated 1,4-dihydronaphthalene derivatives. Here, we report that the use of electron-deficient naphthalene derivatives in the presence of a redox mediator such as -terphenyl and HO under CO bubbling affords -1,2-disubstituted 1,2-dihydronaphthalene derivatives.

Synthesis of Bicyclo[1.1.1]pentane (BCP)-Based Straight-Shaped Diphosphine Ligands.

[1.1.1]Propellane, which is structurally simple and compact, exhibits promising potential for the synthesis of disubstituted straight-shaped bicyclo[1.

Toward Ab Initio Reaction Discovery Using the Artificial Force Induced Reaction Method.

Predicting the whole process of a chemical reaction while solving kinetic equations presents an opportunity to realize an on-the-fly kinetic simulation that directly discovers chemical reactions with their product yields. Such a simulation avoids the combinatorial explosion of reaction patterns to be examined by narrowing the search space based on the kinetic analysis of the reaction path network, and would open a new paradigm beyond the conventional two-step approach, which requires a reaction path network prior to performing a kinetic simulation. The authors addressed this issue and developed a practical method by combining the artificial force induced reaction method with the rate constant matrix contraction method.

Prediction of High-Yielding Single-Step or Cascade Pericyclic Reactions for the Synthesis of Complex Synthetic Targets.

Pericyclic reactions, which involve cyclic concerted transition states without ionic or radical intermediates, have been extensively studied since their definition in the 1960s, and the famous Woodward-Hoffmann rules predict their stereoselectivity and chemoselectivity. Here, we describe the application of a fully automated reaction-path search method, that is, the artificial force induced reaction (AFIR), to trace an input compound back to reasonable starting materials through thermally allowed pericyclic reactions via product-based quantum-chemistry-aided retrosynthetic analysis (QCaRA) without using any a priori experimental knowledge. All categories of pericyclic reactions, including cycloadditions, ene reactions, group-transfer, cheletropic, electrocyclic, and sigmatropic reactions, were successfully traced back via concerted reaction pathways, and starting materials were computationally obtained with the correct stereochemistry.

A theory-driven synthesis of symmetric and unsymmetric 1,2-bis(diphenylphosphino)ethane analogues via radical difunctionalization of ethylene.

1,2-Bis(diphenylphosphino)ethane (DPPE) and its synthetic analogues are important structural motifs in organic synthesis, particularly as diphosphine ligands with a C-alkyl-linker chain. Since DPPE is known to bind to many metal centers in a bidentate fashion to stabilize the corresponding metal complex via the chelation effect originating from its entropic advantage over monodentate ligands, it is often used in transition-metal-catalyzed transformations. Symmetric DPPE derivatives (ArP-CH-CH-PAr) are well-known and readily prepared, but electronically and sterically unsymmetric DPPE (ArP-CH-CH-PAr; Ar≠Ar) ligands have been less explored, mostly due to the difficulties associated with their preparation.

Oxidation and Reduction Pathways in the Knowles Hydroamination via a Photoredox-Catalyzed Radical Reaction.

Systematic reaction path exploration revealed the entire mechanism of Knowles's light-promoted catalytic intramolecular hydroamination. Bond formation/cleavage competes with single electron transfer (SET) between the catalyst and substrate. These processes are described by adiabatic processes through transition states in an electronic state and non-radiative transitions through the seam of crossings (SX) between different electronic states.

Electrochemical Dearomative Dicarboxylation of Heterocycles with Highly Negative Reduction Potentials.

The dearomative dicarboxylation of stable heteroaromatics using CO is highly challenging but represents a very powerful method for producing synthetically useful dicarboxylic acids, which can potentially be employed as intermediates of biologically active molecules such as natural products and drug leads. However, these types of transformations are still underdeveloped, and concise methodologies with high efficiency (e.g.

Radical Difunctionalization of Gaseous Ethylene Guided by Quantum Chemical Calculations: Selective Incorporation of Two Molecules of Ethylene.

Ethylene, of which about 170 million tons are produced annually worldwide, is a fundamental C feedstock that is widely used on an industrial scale for the synthesis of polyethylenes and polyvinylchlorides. Compared to other alkenes, however, the direct use of ethylene for the synthesis of fine chemicals such as pharmaceuticals and agrochemicals is limited, probably due to its small and gaseous character. We, herein, report a new radical difunctionalization strategy of ethylene, aided by quantum chemical calculations.

Carboxylation of a Palladacycle Formed via C(sp )-H Activation: Theory-Driven Reaction Design.

Theory-driven organic synthesis is a powerful tool for developing new organic transformations. A palladacycle(II), generated from 8-methylquinoline via C(sp )-H activation, is frequently featured in the scientific literature, albeit that the reactivity toward CO , an abundant, inexpensive, and non-toxic chemical, remains elusive. We have theoretically discovered potential carboxylation pathways using the artificial force induced reaction (AFIR) method, a density-functional-theory (DFT)-based automated reaction path search method.

Synthesis of Difluoroglycine Derivatives from Amines, Difluorocarbene, and CO : Computational Design, Scope, and Applications.

Invited for the cover of this issue are Satoshi Maeda, Tsuyoshi Mita, and co-workers at ICReDD (Hokkaido University). The image depicts an Artificial Force Induced Reaction (AFIR) conducted on a supercomputer, which predicts a new chemical transformation and its application. Read the full text of the article at 10.

Discovery of a synthesis method for a difluoroglycine derivative based on a path generated by quantum chemical calculations.

The systematic exploration of synthetic pathways to afford a desired product through quantum chemical calculations remains a considerable challenge. In 2013, Maeda introduced 'quantum chemistry aided retrosynthetic analysis' (QCaRA), which uses quantum chemical calculations to search systematically for the decomposition paths of a target product and proposes a synthesis method. However, until now, no new reactions suggested by QCaRA have been reported to lead to experimental discoveries.

Synthesis of Difluoroglycine Derivatives from Amines, Difluorocarbene, and CO : Computational Design, Scope, and Applications.

A three-component reaction (3CR) for the synthesis of difluoroglycine derivatives has been achieved by using amines, difluorocarbene (generated in situ), and the abundant, inexpensive, and nontoxic C source CO . Various tert-amines and pyridine, (iso)quinoline, imidazole, thiazole, and pyrazole derivatives were incorporated, and the corresponding products were isolated in solid form without purification by column chromatography on silica gel. Detailed reaction profiles of the 3CR were obtained from computational analysis using DFT calculations, and the results critically suggest that simple ammonia is not applicable to this reaction.

Chemoselective Cleavage of Si-C(sp) Bonds in Unactivated Tetraalkylsilanes Using Iodine Tris(trifluoroacetate).

Organosilanes are synthetically useful reagents and precursors in organic chemistry. However, the typical inertness of unactivated Si-C(sp) bonds under conventional reaction conditions has hampered the application of simple tetraalkylsilanes in organic synthesis. Herein we report the chemoselective cleavage of Si-C(sp) bonds of unactivated tetraalkylsilanes using iodine tris(trifluoroacetate).

General Synthesis of Trialkyl- and Dialkylarylsilylboranes: Versatile Silicon Nucleophiles in Organic Synthesis.

Compared to carbon-based nucleophiles, the number of silicon-based nucleophiles that is currently available remains limited, which significantly hampers the structural diversity of synthetically accessible silicon-based molecules. Given the high synthetic utility and ease of handling of carbon-based boron nucleophiles, silicon-based boron nucleophiles, i.e.

Syntheses of α-Amino Acids by Using CO as a C1 Source.

The incorporation of CO into organic compounds is currently one of the most active research topics in organic chemistry, because CO is an abundant, inexpensive, nontoxic, and renewable C1 source. However, CO is also a thermodynamically stable and kinetically inert gaseous compound, and as such, special strategies are required to activate CO and incorporate it into organic compounds. In particular, because the carbon atom adjacent to the nitrogen atom of amine derivatives is positively charged, umpolung carboxylation, which is a difficult chemical process, should be considered for the production of α-amino acids by using CO .

Pd-Catalyzed Dearomative Carboxylation of Indolylmethanol Derivatives.

By using a new catalytic system (PdCl[P( n-Bu)] in combination with ZnEt), various 3-indolylmethanol derivatives were successfully carboxylated with CO (1 atm) via dearomatization of the indole nucleus, affording 3-methyleneindoline-2-carboxylates. In contrast, carboxylation of 2-indolylmethanol derivatives afforded unexpected doubly carboxylated products, which are useful synthetic precursors for biologically active compounds.

Cobalt-catalyzed nucleophilic addition of the allylic C(sp)-H bond of simple alkenes to ketones.

We herein describe a cobalt/Xantphos-catalyzed regioselective addition of simple alkenes to acetophenone derivatives, affording branched homoallylic alcohols in high yields with perfect branch selectivities. The intermediate of the reaction would be a nucleophilic allylcobalt(I) species generated via cleavage of the low reactive allylic C(sp)-H bond of simple terminal alkenes.

Co-Catalyzed Direct Addition of Allylic C(sp)-H Bonds to Ketones.

By using Co(acac)/Xantphos with AlMe, the C(sp)-H bonds of allylarene derivatives were cleaved for reaction with various ketones, affording the homoallylic alcohols in moderate to good yields. The branch/linear selectivity depended on the steric and electronic factors of the ketone electrophiles. The intermediate in this reaction is thought to be a low-valent allylcobalt(I) species, which exhibits high nucleophilicity toward ketones.

Palladium-Catalyzed Intramolecular Arylative Carboxylation of Allenes with CO for the Construction of 3-Substituted Indole-2-carboxylic Acids.

Arylative carboxylation of allenes proceeded in an intramolecular manner to afford the corresponding β,γ-unsaturated carboxylic acids in high yields using PdCl/PAr (Ar = CH-p-CF) and ZnEt under 1 atm of CO. The intermediate of the cyclization/carboxylation sequence is thought to be a nucleophilic η-allylethylpalladium, which reacts with CO at the γ-position of palladium. The products obtained could be efficiently converted into 3-substituted indole-2-carboxylate derivatives.