Xiaotian Qi

Visible‐Light‐Mediated Decarboxylation/Oxidative Amidation of α‐Keto Acids with Amines under Mild Reaction Conditions Using O2

Photochemistry has ushered in a new era in the development of chemistry, and photoredox catalysis has become a hot topic, especially over the last five years, with the combination of visible-light photoredox catalysis and radical reactions. A novel, simple, and efficient radical oxidative decarboxylative coupling with the assistant of the photocatalyst [Ru(phen)3 ]Cl2 is described. Various functional groups are well-tolerated in this reaction and thus provides a new approach to developing advanced methods for aerobic oxidative decarboxylation. The preliminary mechanistic studies revealed that: 1) an SET process between [Ru(phen)3 ](2+) * and aniline play an important role; 2) O2 activation might be the rate-determining step; and 3) the decarboxylation step is an irreversible and fast process.

Transition-Metal-Assisted Radical/Radical Cross-Coupling: A New Strategy to the Oxidative C(sp3)–H/N–H Cross-Coupling

A transition-metal-assisted oxidative C(sp(3))-H/N-H cross-coupling reaction of N-alkoxyamides with aliphatic hydrocarbons is described. During the reaction, nitrogen radicals were generated from the oxidation of N-alkoxyamides. Experiments and DFT calculations revealed that transition-metal catalyst could lower the reactivity of the generated nitrogen radical by the coordination of the transition metal, which allowed the selective radical/radical cross-coupling with the transient sp(3) carbon radical to construct C(sp(3))--N bonds. Various C(sp(3))-H bonds could be transformed into C(sp(3))-N bonds through this radical amidation strategy.

Catalytic N-radical cascade reaction of hydrazones by oxidative deprotonation electron transfer and TEMPO mediation

Compared with the popularity of various C-centred radicals, the N-centred radicals remain largely unexplored in catalytic radical cascade reactions because of a lack of convenient methods for their generation. Known methods for their generation typically require the use of N-functionalized precursors or various toxic, potentially explosive or unstable radical initiators. Recently, visible-light photocatalysis has emerged as an attractive tool for the catalytic formation of N-centred radicals, but the pre-incorporation of a photolabile groups at the nitrogen atom largely limited the reaction scope. Here, we present a visible-light photocatalytic oxidative deprotonation electron transfer/2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediation strategy for catalytic N-radical cascade reaction of unsaturated hydrazones. This mild protocol provides a broadly applicable synthesis of 1,6-dihydropyradazines with complete regioselectivity and good yields. The 1,6-dihydropyradazines can be easily transformed into diazinium salts that showed promising in vitro antifungal activities against fungal pathogens. DFT calculations are conducted to explain the mechanism.

Nickel-Catalyzed Selective Oxidative Radical Cross-Coupling: An Effective Strategy for Inert Csp3–H Functionalization

An effective strategy for inert Csp(3)-H functionalization through nickel-catalyzed selective radical cross-couplings was demonstrated. Density functional theory calculations were conducted and strongly supported the radical cross-coupling pathway assisted by nickel catalyst, which was further confirmed by radical-trapping experiments. Different arylborates including arylboronic acids, arylboronic acid esters and 2,4,6-triarylboroxin were all good coupling partners, generating the corresponding Csp(3)-H arylation products in good yields.

Reactivity for the Diels-Alder reaction of cumulenes: a distortion-interaction analysis along the reaction pathway.

Cumulenes, including allene, ketenimine, and ketene, can be employed as dienophiles in Diels-Alder type reactions. The activation energies of a Diels-Alder reaction between cyclopentadiene and either the C ═ C bond or the other C ═ X (X = C, N, or O) bond in cumulenes have been calculated by G3B3, CBS-QB3, M06-2X, and B3LYP methods. The reactivity trend for the C ═ C bond in cumulenes is allene > ketenimine > ketene and that of the C ═ X bond in cumulenes is ketene > allene > ketenimine. Application of distortion-interaction analysis only at transition states does not give a satisfactory explanation for these reactivities. By employing distortion-interaction analysis along reaction pathways, we found that the reactivity of the C ═ C and C ═ X bond in cumulenes is controlled by both of its distortion and interaction energies. The lowest distortion energy of allene leads to its highest reactivity; the higher interaction energy results in higher activation energy of ketene than that of ketenimine. Compared with the reactivity of the C ═ X bond in cumulenes, the C ═ O bond in ketene has the lowest activation energy to react with cyclopentadiene, due to its lowest interaction energy, whereas the lower distortion energy of ketenimine than that of allene leads to a higher reactivity. The distortion energy of the reactants can be attributed to folding ability and molecule strain. The corresponding interaction energy of the reactants is controlled by orbital interaction, closed-shell repulsion, and static repulsion.

Cu(II)-Cu(I) synergistic cooperation to lead the alkyne C-H activation.

An efficient alkyne C-H activation and homocoupling procedure has been studied which indicates that a Cu(II)/Cu(I) synergistic cooperation might be involved. In situ Raman spectroscopy was employed to study kinetic behavior, drawing the conclusion that Cu(I) rather than Cu(II) participates in the rate-determining step. IR, EPR, and X-ray absorption spectroscopy evidence were provided for structural information, indicating that Cu(I) has a stronger interaction with alkyne than Cu(II) in the C-H activation step. Kinetics study showed Cu(II) plays a role as oxidant in C-C bond construction step, which was a fast step in the reaction. X-band EPR spectroscopy showed that the coordination environment of CuCl2(TMEDA) was affected by Cu(I). A putative mechanism with Cu(I)-Cu(II) synergistic cooperation procedure is proposed for the reaction.

The Mechanism of NO Bond Cleavage in Rhodium‐Catalyzed CH Bond Functionalization of Quinoline N‐oxides with Alkynes: A Computational Study

Metal-catalyzed C-H activation not only offers important strategies to construct new bonds, it also allows the merge of important research areas. When quinoline N-oxide is used as an arene source in C-H activation studies, the N-O bond can act as a directing group as well as an O-atom donor. The newly reported density functional theory method, M11L, has been used to elucidate the mechanistic details of the coupling between quinoline N-O bond and alkynes, which results in C-H activation and O-atom transfer. The computational results indicated that the most favorable pathway involves an electrophilic deprotonation, an insertion of an acetylene group into a Rh-C bond, a reductive elimination to form an oxazinoquinolinium-coordinated Rh(I) intermediate, an oxidative addition to break the N-O bond, and a protonation reaction to regenerate the active catalyst. The regioselectivity of the reaction has also been studied by using prop-1-yn-1-ylbenzene as a model unsymmetrical substrate. Theoretical calculations suggested that 1-phenyl-2-quinolinylpropanone would be the major product because of better conjugation between the phenyl group and enolate moiety in the corresponding transition state of the regioselectivity-determining step. These calculated data are consistent with the experimental observations.

Carbon‐Centered Radical Addition to OC of Amides or Esters as a Route to CO Bond Formations

Among various types of radical reactions, the addition of carbon radicals to unsaturated bonds is a powerful tool for constructing new chemical bonds, in which the typical applied unsaturated substrates include alkenes, alkynes and imines. Carbonyl is perhaps the most common unsaturated group in nature. This work demonstrates a novel C-O bond formation through carbon-centered radical addition to the carbonyl oxygen of amide or ester, in which amide and ester groups are easily activated through the radical process. EPR spectroscopy and radical clock experiments support the radical process for this transformation, and density functional theory (DFT) calculations support the possibility of carbon-centered radical addition to the carbonyl oxygen of amides or esters.

Radical–Radical Cross-Coupling for C–S Bond Formation

A new method was demonstrated to overcome the selectivity issue of radical-radical cross-coupling toward the synthesis of asymmetric diaryl thioethers. The preliminary mechanism was revealed by radical-trapping experiments, DFT calculations, and kinetics, etc., indicating that the C-S bond formed through cross-coupling of a thiyl radical and an aryl radical cation. Moreover, the formation of an aryl radical cation instead of the C-H bond cleavage was determined as the rate-limiting step.

Iron-Catalyzed Decarboxylative (4+1) Cycloadditions: Exploiting the Reactivity of Ambident Iron-Stabilized Intermediates.

The first example of iron-catalyzed decarboxylative (4+1) cycloaddition reactions is described in this publication. By using this method, a wide range of functionalized indoline products were prepared from easily available vinyl benzoxazinanones and sulfur ylides in high yields and selectivities. A possible reaction pathway involving an allylic iron intermediate is discussed based on a series of control experiments and density-functional theory calculations.