Abstract1,2-Bis(diphenylphosphino)ethane (DPPE) and its synthetic analogues are important structural motifs in organic synthesis, particularly as diphosphine ligands with a C2-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 (Ar12P−CH2−CH2−PAr12) are well-known and readily prepared, but electronically and sterically unsymmetric DPPE (Ar12P−CH2−CH2−PAr22; Ar1≠Ar2) ligands have been less explored, mostly due to the difficulties associated with their preparation. Here we report a synthetic method for both symmetric and unsymmetric DPPEs via radical difunctionalization of ethylene, a fundamental C2 unit, with two phosphine-centered radicals, which is guided by the computational analysis with the artificial force induced reaction (AFIR) method, a quantum chemical calculation-based automated reaction path search tool. The obtained unsymmetric DPPE ligands can coordinate to several transition-metal salts to form the corresponding complexes, one of which exhibits distinctly different characteristics than the corresponding symmetric DPPE–metal complex.
Quantum chemical calculations are mainly regarded as a method for mechanistic studies in organic chemistry, whereas their use for the simulation of unknown reactions could greatly assist in reaction development. Here we report a strategy for developing multicomponent reactions on the basis of the results of computational reaction simulations. In silico screening of multicomponent reactions with difluorocarbene using the artificial force induced reaction method suggested that cycloadditions between an azomethine ylide and a variety of coupling partners would proceed to generate the corresponding α,α-difluorinated N-heterocyclic compounds. The predicted reaction was successfully realized experimentally, leading to a multicomponent N-difluoroalkylative dearomatization of pyridines involving a pyridinium ylide-mediated 1,3-dipolar cycloaddition with a diverse range of electrophiles such as aldehydes, ketones, imines, alkenes and alkynes. Moreover, the performance of the cycloaddition could be explained by comparing the energy barrier of the desired pathway with that of the competitive undesired pathway, which was also identified by the artificial force induced reaction search.
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 C1 source CO2. 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. In addition, as strongly supported by computational predictions, a new reagent that can generate difluorocarbene at 0 °C without any additives was discovered. Finally, radical substitution reactions of the obtained difluoroglycine derivatives under photoredox conditions, as well as a synthetic application as an N‐heterocyclic carbene ligand are shown.
Numerous
remarkable reactions based on electrochemical carboxylations
using CO2 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 p-terphenyl and H2O under CO2 bubbling affords trans-1,2-disubstituted 1,2-dihydronaphthalene derivatives.
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