Jianbiao Liu

On the mechanism of carbonyl hydrogenation catalyzed by iron catalyst.

Density functional theory calculations have been performed to investigate the detailed mechanism of the carbonyl hydrogenation catalyzed by the first well-defined bifunctional iron catalyst. The catalytic reaction proceeds by hydrogen transfer and dihydrogen activation. The hydrogen transfer reaction occurs via the bifunctional mechanism in which the two hydrogen atoms attached on the Fe and O of the catalyst are transferred to the oxygen and carbon atom of the carbonyl compound concertedly. Both the alcohol-mediated and nonalcohol-mediated dihydrogen activation processes are explored.

Density Functional Theory Study of Rh(III)-Catalyzed C–H Activations and Intermolecular Annulations between Benzamide Derivatives and Allenes

Density functional theory has been applied to gain insight into the Cp*Rh(OAc)2-catalyzed C-H activation and intermolecular annulation of benzamide derivatives with allenes. The study shows that the reactions proceed in three steps: (1) C-H activation induced by Rh catalyst reacting with benzamide derivatives, (2) carborhodation of allene, and (3) regeneration of Rh catalyst. The results indicate that the N-H deprotonation makes the following C-H activation much easier. The regio- and stereoselectivities of 1a (N-pivaloyloxy benzamide)/2a (cyclohexylallene) and 1b (N-pivaloyloxy-4-methyl-benzamide)/2b (1,1-dimethyl allene) depend on the allene carborhodation step. The steric hindrance effect is the dominant factor. We also discuss the reaction mechanism of 1c (N-methoxy benzamide)/2a. The chemoselectivity between 1c/2a is determined by the N-O cleavage step. Replacement of OPiv by OMe leads to loss of the stabilization effect provided by C=O in OPiv. Additionally, Cp*Rh(OAc)(OPiv) is produced in the Cp*Rh(OAc)2 regeneration step, which can work as catalyst as well.

Tandem Synthesis of Pyrrolo[2,3-b]quinolones via Cadogen-Type Reaction

A tandem [3 + 2] cycloaddition/reductive cyclization of nitrochalcones with activated methylene isocyanides for the efficient synthesis of pyrrolo[2,3-b]quinolones is reported. In this reaction, the in situ generated dihydropyrroline acts as the internal reductant to convert the nitro into an electrophilic nitroso group, which undergoes subsequent C-N bond formation. Transition-metal-free, simple experimental procedure and ready accessibility of starting materials characterize the present transformation.

Theoretical characterization of the conformational features of unnatural oligonucleotides containing a six nucleotide genetic alphabet

The addition of the unnatural P:Z base pair to the four naturally occurring DNA bases expands the genetic alphabet and yields an artificially expanded genetic information system (AEGIS). Herein, the structural feature of oligonucleotides containing a novel unnatural P:Z base pair is characterized using both molecular dynamics and quantum chemistry. The results show that the incorporation of the novel artificial base pair (P:Z) preserves the global conformational feature of duplex DNA except for some local structures. The Z-nitro group imparts new properties to the groove width, which widens the major groove. The unnatural oligonucleotides containing mismatched base pairs exhibit low stability. This ensures efficient and high-fidelity replication. In general, the incorporation of the P:Z pair strengthens the stability of the corresponding DNA duplex. The calculated results also show that the thermostability originates from both hydrogen interaction and stacking interaction. The Z-nitro group plays an important role in enhancing the stability of the H-bonds and stacking strength of the P:Z pair. Overall, the present results provide theoretical insights in the exploration of artificially expanded genetic information systems.

The stabilizing effect of the transient imine directing group in the Pd(II)-catalyzed C(sp3)–H arylation of free primary amines

A transient directing group (DG) has been successfully applied to assist the activation of C–H bonds. In this paper, we have performed density functional theory (DFT) calculations to investigate the mechanism of ligand-assisted Pd(II)-catalyzed C(sp3)–H arylation. In the presence of a quinoline-8-carbaldehyde (ArQCHO) ligand, the reaction starts with the nucleophilic addition of 2-butylamine with the ligand to generate the transient imine DG, which binds to the Pd(II) center via bidentate coordination. The sequential C(sp3)–H activation, oxidative addition of [Ph2I]+ with a palladacycle, and C–C reductive elimination yield the final product of arylation. Instead of the traditional inner-sphere concerted metalation deprotonation (CMD) mechanism, a novel deprotonation mechanism for the rate-determining C(sp3)–H activation is discovered; that is, the methyl group is deprotonated by an outer-sphere pivalate. A comparison with the results of the reaction without the ligand indicates that the square planar geometry formed by the transient DG with Pd(II) significantly reduces the distortion energies, which ultimately makes the C(sp3)–H activation kinetically favorable.

Comprehensive Mechanistic Insight into Cooperative Lewis Acid/Cp*CoIII-Catalyzed C–H/N–H Activation for the Synthesis of Isoquinolin-3-ones

The mechanism of B(C6F5)3 promoted Cp*CoIII-catalyzed C-H functionalization was investigated in detail employing density functional theory (DFT). The formation free energy of every possible species in the multicomponent complex system was explored and the optimal active catalyst was screened out. The results uncover the role of B(C6F5)3 played in forming active catalyst is from the coordination with OAc-, but not from the formation of [I(C6F5)3B]-, and no acceleration effect is found in C-H activation as well as the formation of CoIII-carbene intermediate. Moreover, present theoretical results elucidate the Cp*CoIII-catalyzed C-H activation is mediated by imine N-coordination other than general proposed the sequence of N-deprotonation directed C-H activation. The metal-controlled C-H/N-H selectivity was then elucidated by insighting into [Cp*CoIIIOAc]+/[Cp*RhIIIOAc]+-catalyzed C-H and N-H activations, respectively.

Mechanistic Exploration of Cp*CoIII/RhIII-Catalyzed Carboamination/Olefination of N-Phenoxyacetamides with Alkenes

A computational study of Cp*CoIII/RhIII-catalyzed carboamination/olefination of N-phenoxyacetamides with alkenes was carried out to elucidate the catalyst-controlled chemoselectivity. The reaction of the two catalysts shares a similar process that involves N-H and C-H activation as well as alkene insertion. Then the reaction bifurcates at the generated seven-membered metallacycle. For Cp*CoIII catalyst, the resulting metallacycle undergoes oxidation addition, reductive elimination, and protonation to yield the carboamination product exclusively. However, the Cp*RhIII catalyst could promote the subsequent olefination pathway via sequential β-H elimination, reductive elimination, oxidation addition, and protonation, which enables the experimentally observed mixtures of both carboamination and olefination products. Our results uncover that the higher propensity for the β-H-elimination of the Cp*RhIII than the Cp*CoIII catalyst in the olefination pathway could be responsible for the different selectivity and reactivity of the two catalysts.

Solvent Mediating a Switch in the Mechanism for Rhodium(III)-Catalyzed Carboamination/Cyclopropanation Reactions between N-Enoxyphthalimides and Alkenes

Recently, a new synthetic methodology of rhodium-catalyzed carboamination/cyclopropanation from the same starting materials at different reaction conditions has been reported. It provides an efficient strategy for the stereospecific formation of both carbon- and nitrogen-based functionalities across an alkene. Herein we carried out a detailed theoretical mechanistic exploration for the reactions to elucidate the switch between carboamination and cyclopropanation as well as the origin of the chemoselectivity. Instead of the experimentally proposed RhIII-RhI-RhIII catalytic mechanism, our results reveal that the RhIII-RhV-RhIII mechanism is much more favorable in the two reactions. The chemoselectivity is attributed to a combination of electronic and steric effects in the reductive elimination step. The interactions between alkene and the rhodacycle during the alkene migration insertion control the stereoselectivity in the carboamination reactions. The present results disclose a dual role of the methanol solvent in controlling the chemoselectivity.

Mechanistic insight into Ni-mediated decarbonylation of unstrained ketones: the origin of decarbonylation catalytic activity

Mechanistic details of the decarbonylation of unstrained ketones by (IMesMe)Ni and (IMesMe)NiCO complexes with a N-heterocyclic carbene ligand (IMesMe) have been explored by density functional theory calculations. The calculated mechanism sheds light on the origin of realization for the decarbonylation catalytic cycle. (IMesMe)Ni mediates the first decarbonylation cycle and generates a biaryl product and (IMesMe)NiCO, which is inactive for the substrate 4-methyl-4′-trifluoromethyl benzophenone 1. However, (IMesMe)NiCO can mediate the decarbonylation of 3-quinolinyl ketone 2 and realize the catalytic cycle. The decarbonylation step is the rate-determining step controlling whether the transformation can be mediated catalytically. The stabilization energy E(2) of BDC(O)–C(methyl phenyl) → LVNi for the decarbonylation transition state plays a dominant role in the catalytic cycle. In addition, an electron-withdrawing group on the arene can stabilize the orbital energies facilitating the initial C–C(O) oxidative addition step. A moderate linear correlation is observed between the oxidative addition barriers and the charges transferred from (IMesMe)Ni to the benzoyl moiety.

Mechanistic Exploration of the Competition Relationship between a Ketone and C═C, C═N, or C═S Bond in the Rh(III)-Catalyzed Carbocyclization Reactions

The introduction of a C═O, C═C, C═S, or C═N bond has emerged as an effective strategy for carbocycle synthesis. A computational mechanistic study of Rh(III)-catalyzed coupling of alkynes with enaminones, sulfoxonium ylides, or α-carbonyl-nitrones was carried out. Our results uncover the roles of dual directing groups in the three substrates and confirm that the ketone acts as the role of the directing group while the C═C, C═N, or C═S bond serves as the cyclization site. By comparing the coordination of the ketone versus the C═C, C═N, or C═S bond, as well as the chemoselectivity concerning the six- versus five-membered formation, a competition relationship is revealed within the dual directing groups. Furthermore, after the alkyne insertion, instead of the originally proposed direct reductive elimination mechanism, the ketone enolization is found to be essential prior to the reductive elimination. The following C(sp2)-C(sp2) reductive elimination is more favorable than the C(sp3)-C(sp2) formation, which can be explained by the aromaticity difference in the corresponding transition states. The substituent effect on controlling the selectivity was also discussed.