Article pubs.acs.org/Organometallics
DFT Study on the Mechanism of Tandem Oxidative Acetoxylation/ Ortho C−H Activation/Carbocyclization Catalyzed by Pd(OAc)2 Hui Li,†,‡ Xuelu Ma,†,§ Baohua Zhang,∥ and Ming Lei*,† †
State Key Laboratory of Chemical Resource Engineering, Institute of Materia Medica, College of Science, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China ‡ College of Chemistry and Chemical Engineering, Beifang University of Nationalities, Yinchuan, Ningxia 750021, People’s Republic of China § Department of Chemistry and Key Laboratory of Organic Optoelectronics & Molecular Engineering of Ministry of Education, Tsinghua University, Beijing 100084, People’s Republic of China ∥ Supercomputing Center, Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China S Supporting Information *
ABSTRACT: A density functional theory (DFT) study has been conducted to unveil the mechanisms of tandem oxidative acetoxylation/ortho C−H activation/ carbocyclization catalyzed by Pd(OAc)2. The potential competitive reaction pathways between oxidative acetoxylation and ortho C−H activation, C−H activation with outer-sphere and inner-sphere acetate ligands, and the role of DMSO in the reaction have been discussed in detail. The calculated results indicate that the oxidative acetoxylation proceeds before ortho C−H activation in this tandem reaction in a neutral system without DMSO as a ligand coordinated to Pd. A six-membered transition state is proposed in the oxidative acetoxylation step, and a six-membered transition state is proposed in the palladium carboxylate catalyzed sp2 C−H activation step. The coordination of outer-sphere acetate ion to Pd decreases the energy barrier of the step of ortho sp2 C−H activation. In addition, this theoretical work demonstrates that the cosolvent DMSO as a ligand coordinated with Pd decreases the energy barrier of C−H activation. Also, the reaction tandem sequence changes to ortho C−H activation/oxidative acetoxylation/carbocyclization induced by DMSO as a ligand coordinated with Pd.
1. INTRODUCTION
Pd(II)-catalyzed oxidative carbocyclizations represent a general class of reactions, which provide influential and atomeconomical approaches to construct a new C−X bond.8 Pd(II)catalyzed oxidative carbocyclizations have been identified as a potential technology for the synthesis of more complex structures in natural products and pharmaceuticals.8d,9 In the last few decades, Bäckvall and co-workers have developed a wide variety of Pd(OAc)2-catalyzed oxidative carbocyclizations of enallenes, dienallenes, allenynes, and enynes.8d,9d,f,10 They suggested new patterns of Pd(II) catalyst oxidative carbocyclization, in which allenynes are regarded as directing groups. The directing group guides the ortho sp2 C−H activation on aryl, which is followed by carbocyclization. C−H activation is the rate-determining step usually resulting in C−C bond formation. Recently, Bäckvall et al.11 reported the Pd(II)catalyzed tandem oxidative acetoxylation/ortho C−H activation/carbocyclization of arylallenes (shown in Scheme 1), in which the allene moiety acts as a directing group for aryl sp2 C−H activation. Pd-catalyzed tandem oxidative acetoxylation/
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Palladium-catalyzed C−H activation and oxidative carbocyclization reactions represent an atom-economical approach to the construction of new C−C bonds, in a selective and controlled manner, in the organic synthesis of natural products and pharmaceuticals.2 The development of new methods to create new C−C and C−O bond connections in a rapid and practical fashion has been the focus of numerous organic chemists.3 The versatility of C−C bond formation stems from the activation of C−H bonds that is catalyzed by transitionmetal complexes. Research on palladium-catalyzed reactions to achieve selective sp2 C−H activation has been broadly investigated. The mechanism of C−H activation catalyzed by a carboxylate-assisted Pd(II) complex has attracted a great deal of attention.4 Ortho sp2 C−H activation contains three principally different mechanisms for the C−H cleavage transition state catalyzed by Pd(II):5 electronic palladation,6 oxidative addition,4a and proton abstraction.7 In proton abstraction, Davies and Macgregor pointed to a six-membered transition state, which is thought to operate via an agostic interaction rather than in a Wheland intermediate.4a,5d,7 © XXXX American Chemical Society
Received: June 19, 2016
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DOI: 10.1021/acs.organomet.6b00503 Organometallics XXXX, XXX, XXX−XXX
Article
Organometallics Scheme 1. Reactions of Palladium(II)-Catalyzed Carbocyclization and Dimerization of Arylallenes
Scheme 2. Mechanism of Pd-Catalyzed Tandem Oxidative Acetoxylation/Ortho C−H Activation/Carbocyclization of Arylallene Provided by Bäckvall11
of the vinyl Pd(II) intermediate B. Subsequent acetate-assisted C−H activation of the ortho arene C−H bond via TSB-C with concomitant loss of HOAc generates intermediate C. Oxidative carbocyclization from C finally gives product 2 and Pd(0). The latter is reoxidized to Pd(II) by BQ, thus closing the catalytic cycle. The purpose of this study is to elucidate the mechanism of tandem oxidative acetoxylation/ortho C−H activation/carbocyclization catalyzed by Pd(OAc)2. In this work, we conduct a detailed investigation of the mechanism for the Pd(II)catalyzed tandem oxidative acetoxylation/ortho C−H activation/carbocyclization of arylallenes using density functional theory (DFT).5b,14 We have focused on the following critical issues: (i) the mechanism of Pd-catalyzed tandem oxidative acetoxylation/ortho C−H activation/carbocyclization of arylallene, (ii) the competitive reaction between oxidative acetoxylation and ortho C−H activation,6,7b,c,15 (iii) C−H activation with outer-sphere and inner-sphere acetate ligands,16
ortho C−H activation/carbocyclization in the aryl group of arylallene generates carbocyclization products as the major species, while sp3 C−H activation in the methyl group of the allene moiety generates dimerization products as byproducts. It is worth mentioning that dimethyl sulfoxide (DMSO) as an additive in coordination with Pd(OAc)2 decreases the energy barrier of C−H activation. The essential role of DMSO appears to be associated with its palladium-coordination ability.12 A certain amount of DMSO (2 equiv) well controls the catalytic activity of the transition-metal complex in situ.13 Bäckvall and co-workers also explained the formation of carbocyclization, as shown in Scheme 2. The reaction involves coordination of Sub to 1 to form A. Initial allene activation by Pd(OAc)2 is expected to form chelate complex A, which is followed by a nucleophilic attack by acetate on the coordinated allene. Another possibility is generation of a dimerization intermediate via sp3 C−H activation on the allene moiety in intermediate chelate complex A. This attack leads to formation B
DOI: 10.1021/acs.organomet.6b00503 Organometallics XXXX, XXX, XXX−XXX
Article
Organometallics
Figure 1. Mechanism for palladium(II)-catalyzed tandem oxidative acetoxylation/ortho C−H activation/carbocyclization of arylallenes.
coordination step of the OAc− with Pd (4a → 5a1), (5) the C−H activation step of the ortho sp2 C−H of aryl (5a1 → 6a1), (6) the HOAc release step (6a1 → 7a), and (7) the reductive elimination step to produce the carbocyclization product (Pro) (7a → 8a). In the coordination step, the catalytic species Pd(OAc)2 (1) coordinates with the arylallene substrate (Sub) and forms intermediate (INT) 2a. In the structure of 2, the allene moiety of arylallene coordinates with the Pd(II) center, in which one of the acetate ligands partially dissociates into a monodentate ligand with carboxylate and another acetate ligand remains coordinated as a bidentate ligand. The Pd1−O1 bond length decreases from 2.061 Å in 1 to 1.990 Å in 2a, and Pd1−O2 cleavage occurs so that the distance increases from 2.061 Å in 1 to 2.801 Å in 2a. In the bidentate ligand, the Pd1−O3 bond length increases from 2.061 Å in 1 to 2.070 Å in 2a and the Pd1−O4 bond length increases from 2.061 Å in 1 to 2.212 Å in 2a. In 2a, the bond lengths of Pd1−C1 and Pd1−C2 are 2.095 and 2.221 Å, respectively. In the oxidative acetoxylation step, O4 in OAc dissociates from Pd and O4 attacks C2 via a six-membered transition state. As the result of oxidative acetoxylation, 3a is generated via TS2a-3a, and C3−C4 in the aryl group coordinates to Pd to form Pd1−C1 and C2−O3 bonds. Meanwhile, O2 recoordinates to Pd and the acetate ligand changes into a bidentate ligand. In the C−C rotation step, the Pd1−C1−C2−O3 dihedral angle changes from 36.2° in 3a to 166.1° in the more stable intermediate 4a due to decreased steric hindrance. According to the source of OAc−, we distinguish the solvent and catalyst by outer sphere and inner sphere. In the OAc− coordination step, OAc− comes from the outer sphere and coordinates to Pd. The Pd1−O1 distance increases from 2.243 Å in 4a to 3.047 Å in 5a1, and the Pd1−O2 bond length decreases from 2.116 Å in 4a to 2.107 Å in 5a1. The Pd1−C1 bond length increases from 1.974 Å in 4a to 2.005 Å in 5a1, and the Pd1−C3/Pd1−C4 distance increases from 2.271/2.306 Å in 4a to 2.377/2.367 Å
and (iv) the function of DMSO in the reaction. The theoretical calculations give a good explanation of the outcome of experiments and provide guidance for experiments.
2. COMPUTATIONAL DETAILS All of the optimized structures and frequency analyses were calculated at the ωB97X-D/BSI level using the hybrid DFT functional17 implemented in the Gaussian09 program package.17c BSI denotes the LANL2DZ basis set for Pd and the 6-31G* basis set for the other atoms. In addition, we have calculated single-point energy data using ωB97X-D/BSII//ωB97X-D/BSI (BSII denotes LanL2DZ for the Pd center and 6-311+G** for other atomes) on the basis of stationary points along the favorable reaction pathways. The hybrid density functional method ωB97X-D18 is reliable and was used in previous work.19 The transition states (TSs) were further confirmed by vibrational analyses and characterized only by imaginary frequencies. Intrinsic reaction coordinate (IRC) calculations were performed in order to confirm intermediates (INTs) along the reaction pathway. Optimized structure and frequency analyses and single-point energy calculations were conducted using the solvation model density model (SMD)20 to evaluate the solvent effects for all of the gas-phase optimized species. Because several TSs did not converge in the calculations, the energies discussed below are corrected free energies (in kcal mol−1) with the SMD model in HOAc solvent (the disparity in energy of optimized and single-point calculations conducted using the SMD controlled over an allowable range (
