Mechanisms of the Thermal Cyclotrimerizations of Fluoro

ARTICLE pubs.acs.org/JACS Mechanisms of the Thermal Cyclotrimerizations of Fluoro- and Chloroacetylenes: Density Functional Theory Investigation and Intermediate Trapping Experiments Zhong-Ke Yao and Zhi-Xiang Yu* Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China bS Supporting Information ABSTRACT: Theoretical studies of the mechanisms of the thermal cyclotrimerization of fluoro- and chloroacetylenes, which were reported by Viehe and Ballester, respectively, were conducted with the aid of density functional theory calculations of the (U)B3LYP functional, indicating that the thermal cyclotrimerizations of fluoro- and chloroacetylenes involve tandem processes of regioselectively stepwise [2þ2] and stepwise [4þ2] cycloadditions. These tandem processes generate 1,2,6-trihalo-Dewar benzenes and 1,2,4-trihalo- Dewar benzenes, which then isomerize to the corresponding benzenes when heated. The rate-determining step of the cyclotrimerizations of haloacetylenes is the dimerization step involving open-shell singlet diradical transition states and intermediates. The substituent effects in the thermal cyclotrimerization of haloacetylenes have been rationalized using frontier molecular orbital theory. The higher reactivity of fluoroacetylenes compared to that of chloroacetylenes is due to the fact that fluoroacetylenes have lower singletÀtriplet gaps than chloroacetylenes and more easily undergo dimerization and cyclotrimerization. In this report, additional experiments were performed to verify the theoretical prediction about the cyclotrimerization of chloroacetylene and to trap the proposed 1,4-dichlorocyclobutadiene intermediate. Experiments revealed that the thermal reaction of phenylchloroacetylene at 110 °C gave 1,2,3-triphenyltrichlorobenzene and 1,2,4-triphenyltrichlorobenzene together with a tetramer, cis-1,2,5,6-tetrachloro- 3,4,7,8-tetraphenyltricyclo[4.2.0.02,5]octa-3,7-diene. The proposed 1,4-diphenyldichlorocyclobutadiene intermediate in the thermal cyclotrimerization of phenylchloroacetylene was successfully trapped using dienophiles of maleic anhydride and dimethyl acetylenedicarboxylate. ’ INTRODUCTION reported by Viehe and co-workers.6a,b This reaction was found to be spontaneous below 0 °C, yielding Dewar benzene 2, Alkyne cyclotrimerization to form benzene derivatives is one fi of the most intensely studied reactions because of the ubiquitous benzvalene 3, and an unidenti ed tetramer 4. The trimers 2 presence of substituted benzenes in molecular sciences.1 Alkyne and 3 were roughly equal in yield, and their total yield accounted for two-thirds of the entire reaction products. Tetramer 4 (its cyclotrimerization reactions are typically performed in the pre- À sence of catalysts, which can be transition metals,2 Lewis acids,3 structure was not determined) accounted for 1 3% of the entire amines,4 or disilanes.5 Uncatalyzed thermal cyclotrimerization of reaction products. When 2 and 3 were heated at a higher 6 temperature (100 °C), they isomerized to 1,2,3-tri-tert-butyltri- alkynes to give benzene derivatives was rarely reported, though fl fl the first uncatalyzed thermal cyclotrimerization of acetylene7 was uorobenzene 5 and 1,2,4-tri-tert-butyltri uorobenzene 6, re- ∼ fi spectively (Scheme 1). discovered 80 years before the rst report of its catalytic 9 version.2a The process of uncatalyzed thermal cyclotrimerization The proposed mechanism of the thermal cyclotrimerization described by Viehe is shown in Scheme 2. The cyclotrimerization of alkynes to benzene derivatives was usually conducted at a very fl high temperature to overcome the high reaction barrier. In 1866, was believed to start with the dimerization of two uoroalkynes, Berthelot reported the first example of the thermal transforma- giving rise to tetrahedrane 7a, which was proposed to be in equilibrium with planar 1,4-difluorocyclobutadiene derivative tion of acetylene to benzene. The reaction was conducted at fl 400 °C, giving a complex mixture of products.7 A concerted 7b, and 1,3-di uorocyclobutadiene derivative 7c. Intermediate 7b/7c could also exist in a diradical form of 7b0/ 7c0. Then 7b and pathway was proposed for the cyclotrimerization of acetylene, fl and the computed activation energy of the reaction was higher 7c reacted with the third uoroalkyne to give trimers 2 and 3, than 50 kcal/mol at different calculation levels.8 An interesting exception to all uncatalyzed and catalyzed alkyne cyclotrimeriza- Received: March 9, 2011 tions is the cyclotrimerization of tert-butylfluoroacetylene 1, Published: June 23, 2011 r 2011 American Chemical Society 10864 dx.doi.org/10.1021/ja2021476 | J. Am. Chem. Soc. 2011, 133, 10864–10877 Journal of the American Chemical Society ARTICLE respectively. Finally, upon being heated, Dewar benzene deriva- In 1986, Ballester and co-workers6c found that perchlorophe- tive 2 and benzvalene derivative 3 isomerized to the aromatic nylacetylene 8 can also undergo cyclotrimerization upon being 1,2,3-tri-tert-butyltrifluorobenzene 5 and 1,2,4-tri-tert-butyltri- heated in perchlorostyrene, giving perchloro-1,2,3-triphenylben- fluorobenzene 6, respectively. zene 9, perchloro-1,2,4-triphenylbenzene 10, and an unidentified isomeric C24Cl18 compound 11 (Scheme 3). Formation of 9 and 10 was also thought to proceed via a mechanism involving Scheme 1. Thermally Spontaneous Cyclotrimerization of diradical cyclobutadiene and terahedrane intermediates, similar tert-Butylfluoroacetylene to the mechanism of fluoroacetylene cyclotrimerization proposed by Viehe. In 1993, Hopf and Witulski reported that 1,2,4- and 1,2,3- tricyanobenzenes were formed with other products when cyano- acetylene was heated at 160 °C in a sealed tube.6d Recently, they gave the energies of the products and the proposed intermediates, but no information about the transition states was given.10 The interesting phenomena of these uncatalyzed thermal cyclo- À trimerizations of alkynes have attracted some attention.8,10 12 However, several questions remain unanswered because of the scarce experimental and computational evidence. Why can these alkyne cyclotrimerization reactions occur under thermal reaction conditions? Why are fluoroacetylenes more reactive than chloroacetylenes? What factors control the regioselectivity in the thermal cyclotrimerization that gives different benzene derivatives (Schemes 1 and 3)? In particular, how does this process generate Scheme 2. Mechanism Proposed by Viehe for the Cyclotrimerization of tert-Butylfluoroacetylene Scheme 3. Thermal Cyclotrimerization of Perchlorophenylacetylene 10865 dx.doi.org/10.1021/ja2021476 |J. Am. Chem. Soc. 2011, 133, 10864–10877 Journal of the American Chemical Society ARTICLE Scheme 4. Mechanism of the Cyclotrimerization of Fluoroacetylene Supported by DFT Calculations the uncommon 1,2,3-trisubstituted benzene, which is difficult to states and intermediates, the YJH spin-projection22 scheme has been produce by metal-catalyzed cyclotrimerizations of substituted used to reduce spin contamination. Orbital energies were computed alkynes? Another interesting question remained unanswered. What using the HF/6-31G(d) method,23 and the orbital coefficients listed are is the tetramer in Viehe’s reaction? the 2p orbitals of carbons and fluorines and 3p orbitals of chlorines. ΔG, Δ Δ Here we report the first computational study of the uncata- H, and E0 are the calculated relative free energies, relative enthalpies, lyzed cyclotrimerizations of haloacetylenes, aiming to answer the and zero-point energy (ZPE) corrected relative electronic energies in the questions listed above. We believe that answering these questions gas phase, respectively. Unless otherwise specified, all discussed energies is critical not only to our in-depth mechanistic understanding of in what follows refer to ΔG values. these reactions but also to guiding the future design of other uncatalyzed cyclotrimerizations and studying the potential ap- ’ RESULTS AND DISCUSSION plication of these reactions in material sciences and other disciplines. It is well-known that fluoroacetylene derivatives are Density Functional Theory (DFT) Study of the Cyclotri- highly reactive (sometimes explosive) and difficult to handle.13 merization of Fluoroacetylene. For the sake of calculation Therefore, experimental investigation of fluoroacetylenes’ reac- efficiency, we chose the fluoroacetylene reaction as the model tions and reaction mechanisms and the experimental trapping of reaction instead of the cyclotrimerization reaction of experimen- the proposed intermediates are very difficult. However, experi- tally used tert-butylfluoroacetylene in the first attempt to under- mental studies of cyclotrimerizations of chloroacetylenes, if they stand the reaction mechanisms. Because the used fluoroacetylene can occur thermally, could be easily performed because chloro- is unsymmetric, there are several possible pathways for the acetylenes are stable and can be easily prepared. Because cyclotrimerization of this fluoroacetylene, which had all been of these facts, we investigated experimentally the thermal cyclo- investigated by our DFT calculations. To present the results of trimerization of arylchloroacetylene and trapped one of the our calculation clearly and concisely, we will first elucidate how proposed cyclobutadiene intermediates with the aim of further the cyclotrimerization occurs in its most favored reaction path- confirming or complementing

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