Effect of Substituent on the Mechanism and Chemoselectivity of the

15 Mar 2017 - Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, ... from propargyl esters catalyzed by an organometallic Au(I) c...
0 downloads 0 Views 3MB Size
Article pubs.acs.org/Organometallics

Effect of Substituent on the Mechanism and Chemoselectivity of the Gold(I)-Catalyzed Propargyl Ester Tandem Cyclization Yunhe Li,† Alexander M. Kirillov,‡ Ran Fang,*,† and Lizi Yang*,† †

State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China ‡ Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisbon, Portugal S Supporting Information *

ABSTRACT: This study reports a detailed theoretical analysis of the mechanisms and chemoselectivity for the formation of benzo[b]fluorenes or benzofulvenes from propargyl esters catalyzed by an organometallic Au(I) complex. Three different substitution patterns within the 1,5-diyne ester substrates were explored to rationalize the reaction mechanism and chemoselectivity. DFT calculations reveal that the title reaction proceeds through four main steps: (i) 1,3-acyl-shift, (ii) 6-endodig or 5-exo-dig cyclization, (iii) Friedel−Crafts-type, and (iv) proton transfer, with step (ii) being rate-determining in all studied pathways. In the absence of substituents at the aromatic rings of the substrate (R = H), the 6-endo-dig cyclization is favored. In turn, in the presence of one strong electrondonating substituent at the backbone (R = OCH3) of the substrate, the 5-exo-dig cyclization is favored. Besides, a modification of the substrate’s acetyl group by a pivaloyl group leads to an activation barrier difference between the 6-endo-dig and 5-exo-dig cyclizations, which increases and suppresses the formation of benzofulvenes. The obtained theoretical data are in a very good agreement with prior experimental evidence, suggesting that the substituent plays a crucial role in the outcome of the final product. High chemoselectivity can be explained by the hindrance (torsional strain) along the forming C−C bond and the carbocation stability provided by substituents.

1. INTRODUCTION Rearrangement/tandem cyclization of propargyl esters is an exclusive class of reactions not only in organic synthesis but also in gold chemistry.1 Among a variety of investigated substrates, the diynes or yne-allene containing propargyl esters play a significant role in constructing diverse organic molecules.2 Yne-allenes can undergo two main thermal diradical cyclization pathways, namely, Myers−Satio cyclization3 or Schmittel cyclization.4 Various gold catalysts, including those based on organometallic complexes, are known to activate propargyl esters for an initial 1,3-acyloxy migration process to form an yne-allene intermediate.5 Thermal cycloaromatization of yne-allenes (Myers−Satio/Schmittel cyclization) has been extensively studied both experimentally and theoretically, since it can afford a variety of useful molecules.6 In particular, the chemoselectivity in such cycloisomerization reactions has been an important issue.7 Various attempts have been made to regulate chemoselectivity by modifying the substrates and/or experimental conditions.8 For example, Hashmi and co-workers have reported a detailed experimental and theoretical study on the influence of the diyne backbone on the cyclization mode, demonstrating that the cyclization selectivity is controlled by an electronic and not a steric nature of the diyne backbone.9 It is well-established that the remote © XXXX American Chemical Society

substituents are capable of enhancing chemoselectivity of the ring closure step.10 Zhong et al. have showed that the degree of amine−amine electronic coupling through the dibenzo[a,e]pentalene bridge greatly depends on the substitutent position.11 Basak et al. have subsequently reported that Garratt− Braverman (GB) cyclization depends on the nature of the substituent at the propargyl arm, as well as on the reaction conditions.12 Another interesting type of cycloaromatization involves a selective gold(I)-catalyzed rearrangement of aromatic methoxypropynyl acetals, leading to fused catechol ethers.13 Generally, the usual paradigm for applying electronic effects in organic chemistry is based on the concept that an efficient orbital overlap is required to transmit conjugation and hyperconjugation.14 Alabugin and co-workers have provided an experimental evidence for the utility of this concept in cycloaromatization reactions involving enediynes.15 Hashmi et al. demonstrated that vinylcation intermediates are accessible from such enediynes.16 More recently, Hashmi and co-workers have reported a very remarkable study wherein the substituted propargyl esters are transformed to benzo[b]fluorenes and benzofulvenes via a Received: January 16, 2017

A

DOI: 10.1021/acs.organomet.7b00042 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Scheme 1. Gold(I)-Catalyzed Tandem Cyclization Showing Typical Substrates (a) for the Synthesis of Benzo[b]fluorenes (b) and Benzofulvenes (c)

Scheme 2. Three Proposed Reaction Mechanisms (Pathways a−c) for the Gold(I)-Catalyzed Tandem Cyclization of Propargyl Esters

fragment that acts as a nucleophile to attack the allenyl acetate to give intermediate vinyl cation C1 (Scheme 2, pathway c). This species is trapped by an acetate moiety, presumably generated via an elimination of HOAc from another molecule of the starting material, thus giving rise to byproduct C. Furthermore, depending on the electronic properties of the phenyl group and the influence of different substituents at the backbone, a distinct product selectivity can be observed (Scheme 1). Given these very interesting experimental results obtained by Hashmi and co-workers, an in-depth mechanistic understanding of the tandem cyclization sequence and the influence of various substituents on the reactivity and chemoselectivity of propargyl esters is crucial for further development of such tandem cyclization processes. Hence, the main objectives of this work consisted of performing a thorough mechanistic study that would address the following essential issues of the tandem cyclization, namely, (1) to fully understand the mechanism of the reaction, (2) to unveil possible reasons for an unfavorable character of pathway c, and (3) to rationalize the experimental selectivities influenced by a remote substituent.

gold-catalyzed rearrangement/tandem cyclization sequence: Myers−Satio versus Schmittel-type cyclization (Scheme 1 shows three typical substrates and the corresponding products).17 The proposed mechanisms for these reactions are depicted in Scheme 2. An initial activation of an acetate alkynyl moiety in the substrate affords a gold complex I. This can lead to a 1,3-acyl shift generating yne-allene gold intermediate II, which shows diverse reactivities in the functionalization reactions.18 Subsequently, the reaction diverges into pathway a, b, or c. Activation of an alkyne unit via its coordination to a gold center initiates two potential cyclization pathways: (1) 6-endo-dig cyclization to form naphthyl intermediate A119 and (2) 5-exo-dig cyclization to generate fulvene intermediate B1 (Scheme 2, pathways a and b, respectively).20 In both cases, further functionalization generates the benzo[b]fluorine (A2) and benzofulvene (B2) cores, followed by aromatization and a series of 1,2-H migration steps, thus yielding products A and B, respectively. For cycloaromatization reactions, both regioisomers are generated from common intermediate, II, which was proposed to be responsible for the formation of A and B. In specific cases, an organometallic gold(I)-complex-catalyst [IPrAuCl] can also activate an electron-rich allene moiety, leading to an alkyne B

DOI: 10.1021/acs.organomet.7b00042 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Figure 1. Full energy profile calculated for the gold(I)-catalyzed propargyl ester tandem cyclization sequence (pathways a and b).

2. COMPUTATIONAL DETAILS

3. RESULTS AND DISCUSSION The gold(I)-catalyzed rearrangement of 1a (R1 = CH3, R2 = R3 = H, Scheme 1) was first considered as a model reaction to explore mechanistic details and the origin of the chemoselectivity (Scheme 2). Then, by increasing the electron density through an introduction of a methoxy group on the backbone of substrate 2a (R2 = OMe, R3 = H, Scheme 1), we investigated an electronic effect of the substituents on the product distribution (2b vs 2c). Finally, a similar cycloisomerization reaction of 3a was used to study high selectivity to give exclusive 3b product containing electron-donating (R3 = OMe) and electron-withdrawing (R2 = F) groups. It is interesting to highlight that the three different backbones in substrates 1a−1c represent the three converging scenarios that favor different cyclization pathways (Scheme 2). Energy profiles for the reaction pathways a−c are shown in Figures 1 and 3. The optimized geometries for the reactants, intermediates, transition states, and reaction products are depicted schematically in Figures 2 and 4, along with selected key geometry parameters (e.g., bond lengths). Unless otherwise noted, the relative energies discussed in subsequent sections refer to the values in CH2Cl2 solvent. Detailed structural parameters and energies for the calculated structures are collected in the Supporting Information. 3.1. General Reaction Pathway. Figure 1 shows that the catalytic cycle starts via an interaction of the gold-complex catalyst with a propargyl ester, giving preliminary intermediate

All calculations were conducted using the Gaussian 09 program package.21 The geometries of all species were fully optimized by DFT22 with the M06-2X23 method and using the 6-31G (d, p) basis set for all atoms except for Au; the Lanl2dz24 basis set (BS1) was applied for Au. This computational method was successfully applied in various mechanistic studies.25 Vibrational frequency calculations conducted at the M06-2X/6-31G (d, p) theoretical level were used to characterize all the stationary points as either minima (number of imaginary frequencies, NIMAG = 0) or transition states (NIMAG = 1). In several significant cases, calculation of intrinsic reaction coordinates (IRC)26 was performed to unambiguously connect the transition states with the reactants and products. Thus, the relative energies were corrected to the vibrational zero-point energies (ZPE, not scaled). The solvent effect was taken into consideration by using the M06-2X/6-311++G (d, p) level. For Au, the small core Los Alamos (LANL2TZ(f)) pseudopotentials and basis sets (these include the Dunning−Huzinaga full TZ and Los Alamos ECPs plus TZ) were employed with an extra f polarization function (BSII),27 using a singlepoint calculation with the integral equation formalism polarizable continuum model (IEF-PCM) in CH2Cl2 (ε = 8.9). The radii and nonelectrostatic terms were taken from the universal solvation model (SMD).28 1,5-diyne esters were used as model substrates (for formulas, see Scheme 1), whereas a methyl analogue of the organometallic Au(I) complex [IPrAuCl] (the IPr groups have been substituted by CH3 groups in our calculations) was applied as a model catalyst (Figure 1). C

DOI: 10.1021/acs.organomet.7b00042 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Figure 2. Optimized structures with selected structural parameters for the intermediates and transition states shown in Figure 1.

I, which is stabilized by the CC bond binding to Au.29 In I, similar lengths of the two Au−C bonds (2.381 and 2.405 Å, Figure 2) indicate an almost symmetrical coordination. In fact, an increased electrophilicity of the triple CC bond is expected upon symmetrical to asymmetrical deformation of the CC coordination to gold, which in turn enhances the electronic charge subtracted from the substrate facilitating the nucleophilic attack.30 This leads to cyclization of the O1 onto C2 atom and gives an oxonium ion intermediate, II, via a sixmembered ring transition structure, TS1. The calculated activation energy for this step is 5.8 kcal/mol. The free energy of the reaction for the formation of intermediate III is −6.8 kcal/mol with respect to I. Due to a strain of the six-membered ring, intermediate III converts to allenyl derivative II via fourelectron rearrangement transition structure TS2. The activation free energy for the second step is 9.8 kcal/mol, and the formation of II is an endothermic process (the free energy of the reaction for II is 2.3 kcal/mol with respect to that of III).

After the formation of II, three different cyclization pathways were located in our study. In pathway a, gold activates a lower alkyne unit and initiates the 6-endo-dig cyclization to generate naphthyl intermediate A1. In pathway b, gold activates the same moiety and initiates the 5-exo-dig cyclization to form fulvene intermediate B1 (Figures 1 and 2). In pathway c, gold activates an electron-rich allene moiety, and an alkyne fragment acts as a nucleophile to attack a gold-activated allenyl acetate to generate intermediate C1 (Figures 3 and 4). For pathway a, the 6-endo-dig cyclization occurs via the formation of the C1−C5 bond through TSa. This cyclization leads to naphthyl intermediate A1 and is exothermic by 25.3 kcal/mol due to the generation of a conjugated system and thermodynamic stability of two atom bonding interactions. Aromatization of the C1−C5 bond in allenyl intermediate II proceeds via TSa and requires an activation free energy of 12.6 kcal/mol. A1 is a reactive intermediate with an unsaturated C3 atom and benzene ring. A subsequent Friedel−Crafts-type reaction will form dibenzopentalene intermediate A2. The D

DOI: 10.1021/acs.organomet.7b00042 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Figure 3. Energy profile calculated for the chemoselective gold(I)-catalyzed formation of the byproduct C (pathway c).

It is well-documented that a side product arises from the formal addition of acetate, which is presumably generated by the elimination of HOAc from another molecule of starting material.16 In order to investigate this assertion, pathway c was calculated. Herein, gold catalyst activates an electron-rich allene moiety, and the alkyne fragment acts as the nucleophile to attack the gold-activated allenyl acetate to generate intermediate C1 (Figures 3 and 4). In this pathway, the allene moiety binds to the Au center via its CC π bond, implying that the electrophilicity of the C3 atom and the nucleophilicity of the C4 atom result in the generation of intermediate C1. The activation free energy for this step is 15.4 kcal/mol. After the formation of C1, there are two pathways that can complete the catalytic cycle, namely, a direct intramolecular proton transfer or a HOAc-assisted proton transfer. Figure 3 indicates that the direct intramolecular proton transfer proceeds via the C1 → TSc1 → C3 → TSc4 → C4 → TSc5 → C5 → TSc6 → C transformation. The activation free energy of the TSc1, TSc4, TSc5, and TSc6 transition states is 12.1, 35.0, 22.5, and 26.0 kcal/mol, respectively. On the basis of the computational results, the proton migration (TSc4) becomes a rate-limiting step for pathway c with a high barrier. Except for the direct intramolecular proton transfer, the HOAc-assisted 1,2-H shift process was also investigated.31 The calculated energy profile (Figure 3, outlined in red) shows that the HOAc-assisted 1,2-H shift process occurs via transition states TSc2 and TSc3 with a free energy barrier of 9.3 and 1.6 kcal/mol, respectively. Lower activation free energies found for the 1,2-H shift process indicate an important role of HOAc. Given the HOAc-assisted 1,2-H shift process, it is obvious that the step for the formation of C1 through TSc is rate-determining for this pathway. 3.2. Explanation of Chemoselectivity in the Au(I)Catalyzed Reactions. The catalytic cycles illustrated in Figures 1 and 3 summarize the results of our theoretical

Gibbs activation barrier and exothermic energy for this step were calculated (3.8 and 12.3 kcal/mol, respectively). As shown in Figure 2, in II, TSa, A1, TSa1, and A2, the C4−Au bond lengths are 2.371, 2.164, 2.077, 2.061, and 2.055 Å, respectively, indicating that the C4−Au bond is more stable in the latter three structures. The fact that the Au center is stabilized by the hyperconjugation may account for such bond stability. A subsequent protodeauration to close the catalytic cycle is favorable, showing the barriers of 11.0, 7.9, and 2.7 kcal/mol, respectively. A comparison of these steps in pathway a indicates that the barrier of the 6-endo-dig step is higher than those of other steps; thus, 6-endo-dig is a rate-determining step. Apart from pathway a involving naphthyl intermediate A1, gold catalyst can activate the same moiety and initiate an alternative pathway b, namely, the 5-exo-dig cyclization to form fulvene intermediate B1. The activation free energy for the 5exo-dig cyclization step is 14.3 kcal/mol (Figure 1), and the formation of B1 is an exothermic process (the free energy of the reaction for B1 is 19.3 kcal/mol with respect to that of II). An attack of the C1 atom on the positively charged C4 atom leads to C1−C4 (2.228 Å) bond formation in TSb. It is evident that the C1−C4 bond in B1 becomes completely formed. In contrast to the 6-endo-dig process, the interaction between the C1 and C4 atoms is weakened during the 5-exo-dig process due to a decreased electrophilicity of the C4 atom. Similar to pathway a, the next step of a Friedel−Crafts-type reaction will lead to intermediate B2 (with the activation free energy of 8.5 kcal/mol). Subsequent protodeauration steps lead to the formation of final product B, which is accompanied by the regeneration of the gold catalyst (the corresponding Gibbs activation energies are 12.1 and 3.5 kcal/mol, respectively). Analysis of pathway b indicates that the 5-exo-dig cyclization is a rate-limiting step. E

DOI: 10.1021/acs.organomet.7b00042 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Figure 4. Optimized structures with selected structural parameters for the intermediates and transition states shown in Figure 3.

Meanwhile, a negative charge found for the C3 atom makes an attack between the C3 and C4 atoms (TSc) more difficult than that between the C1 and C4 atoms (TSb). Finally, this issue can also be explained by the different activation of the CC triple bond with the gold-complex catalyst. The presence of the electron-donating groups (OCOCH3) should decrease the electron affinity of the alkyne and thus its capacity of accepting back-donation.30 This fact makes the 6-endo-dig cyclization more feasible for TSa than that for TSb. According to experimental results, a very strong electrondonating substituent (methoxy group) at the backbone shifts the reaction toward the 5-exo-dig cyclization.17 Therefore, we calculated the rate-determining steps for two methoxy group substituents at the backbone. The calculated results show that 2TSa is 0.7 kcal/mol higher in energy than 2TSb (see Supporting Information), indicating that the 5-exo-dig cyclization product is a major product. These data suggest that the electron-donating ability of methoxy group on the phenyl moiety is significant, thus consequently resulting in the switch of product selectivity. To probe the reasons for this variation in chemoselectivity, we located an interaction between reactive atoms and natural charges corresponding to transition states. By inspecting the structures of dominant transition states, it is clear that the C1−C5 distance in TSa is shorter than the C1−C4 distance in TSb (2.186 vs 2.228 Å), while the C1−C5 distance in 2TSa is longer than the C1−C4 distance in 2TSb (2.179 vs 2.159 Å). This implies that the binding of the C1 and C5 atoms in 2TSa is weaker than that in TSa due to an increased electron

studies showing that the three catalytic processes are competing with each other to generate benzo[b]fluorenes (A in pathway a), benzofulvenes (B in pathway b), or side products (C in pathway c). A review of these three mechanistic pathways indicates that the alkyne-fragment-attack of a gold-activated allenyl acetate is a rate-limiting step in all of them. The stability of TSa, TSb, and TSc transition structures determines a type of the preferred catalytic cycle. Namely, TSb is 1.7 kcal/mol higher in energy than TSa, while both of them are lower in energy than TSc, which indicates that pathway c is unfavorable. Through examination of transition states, we found three key factors influencing the product selectivity. First, the torsional strains in the intramolecular cyclization transition states are responsible for the experimentally observed chemoselectivity. Transition state TSa possesses a torsional force along the C4− C5 bond, as evidenced by the C4−C5−C6−C7 dihedral angle of 78°. But in the energetically disfavored transition state, TSb, the corresponding C4−C5−C6−C7 dihedral angle is only −41°, suggesting that the torsional strain in TSb is much more severe than that in TSa. This claim is also supported by the C1−C4 bond distance in TSa (2.186 Å) being longer than the C1−C5 bond distance (2.228 Å) in TSb. Second, the NBO charges for the C1, C3, C4, and C5 atoms in III are 0.006, − 0.001, − 0.067, and −0.124 au, respectively. For TSa, a newly formed C−C bond comes from an attack of C1 and C5; however, an attack of C1 and C4 accounts for a newly formed C−C bond in TSb. A more negative charge found for the C5 atom makes the 6-endodig cyclization more feasible for TSa than that for TSb. F

DOI: 10.1021/acs.organomet.7b00042 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Figure 5. Full energy profile calculated for the gold(I)-catalyzed propargyl ester tandem cyclization sequence for 3a substrate.

that pathway a is energetically preferred over pathway b. This calculated result is in accord with the experimental evidence, wherein the change of the acetyl group by the pivaloyl group suppresses the side-product formation and increases the yield of 3b to 83% (Scheme 1). Then, both naphthyl 3A1 and fulvene 3B1 intermediates undergo Friedel−Crafts reaction. Corresponding transition structure 3TSa1 with the barrier of 4.0 kcal/mol leads to benzo[b]fluorene intermediate 3A2, while 3TSb1 with the barrier of 8.3 kcal/mol results in benzofulvene intermediate 3B2. It was also found that the relative Gibbs free energies of 3TSb2, 3B3, and 3TSb3 are far higher (∼16 kcal/ mol) than those of 3TSa2, 3A2, and 3TSa3, which further indicates the preference for the 6-endo-dig over 5-exo-dig process. These data are well consistent with the experimental results and can be also rationalized by analyzing crucial structures. From the structures of 3TSa and 3TSb (Figure S3), it is clear that the C1−C5 distance in 3TSa is shorter than the C1−C4 distance in 3TSb (2.176 vs 2.183 Å), indicating a stronger interaction between the C1 and C5 atoms; this is in excellent agreement with the fact that the reaction favors pathway a. Furthermore, the dihedral C4−C5−C6−C7 angles are 140 and 165° for 3TSa1 and 3A2, respectively. However, in 3TSb1 and 3B2, the dihedral angles are 41 and −25°, respectively. Obviously, the formation of 3A2 or 3B2 overcomes a torsional

density and hindrance at the backbone provided by substituents. In addition, the NBO charge for the C1, C4, and C5 atoms in 2III is 0.0067, − 0.116, and −0.088 au, respectively. These values show that the charge distribution on the C4 and C5 atoms of 2III is opposite to that of III. A more negative charge found for the C4 atom makes the 5-exodig cyclization more feasible than that for 2TSb in comparison to that for 2TSa (Figure S1). 3.3. Effect of Changing the Substrate’s Acetyl Group by Pivaloyl Group. In the original experiment, Hashmi and co-workers also reported that the change of the acetyl group by the pivaloyl group in the substrate suppresses the side product formation and increases the yield of 3b (Scheme 1).17 Energy profiles for reaction pathways a and b using pivaloyl group containing substrate 3a are shown in Figure 5. The optimized geometries for the reactants, intermediates, transition states, and products are given in Figure S3 along with selected bond lengths. Starting gold intermediate 3I follows a similar mechanism as that described above for I, involving four main steps, namely, (i) 1,3-acyl-shift, (ii) 6-endo-dig or 5-exo-dig cyclization, (iii) Friedel−Crafts-type, and (iv) proton transfer. As mentioned above, the activation barrier of the nucleophilic attack of the C1 atom onto the C4 or C5 atom determines which product is preferentially formed. Transition state 3TSb lies 3.4 kcal/mol above 3TSa (Figure 5), suggesting G

DOI: 10.1021/acs.organomet.7b00042 Organometallics XXXX, XXX, XXX−XXX

Organometallics



strain. Therefore, the torsional strain is a significant factor that influences product selectivity. In addition, compared with the energy profile of unsubstituted substrate 1a (Figure 1), both the activation free energies of the rate-limiting steps (6-endo-dig and 5-exo-dig) increase by 1.4 and 2.4 kcal/mol in the substituted energy profile when using 3a. The calculation results for the NBO charge of the C1, C4, and C5 atoms in 3III are 0.0049, − 0.09, and −0.137 au, respectively (in III, these values are 0.006, − 0.067, and −0.124 au, respectively). Compared with III, changing the acetyl group by the pivaloyl group reduces a positive charge of the C1 atom and increases a negative charge of the C4 and C5 atoms, which causes the activation free energy of the rate-limiting step (6-endo-dig or 5exo-dig) to increase by 1.4 and 2.4 kcal/mol in the substituted energy profile. Moreover, the presence of pivaloyl group enhances the steric hindrance of the reaction.

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Ran Fang: 0000-0001-6804-6572 Notes

The authors declare no competing financial interest.



ACKNOWLEDGMENTS This research has been supported by the National Natural Science Foundation of China (Nos. 21203080, 21301080, and 21672090), and the Fundamental Research Funds for the Central Universities (Grant No. lzujbky-2016-44).



4. CONCLUSIONS In summary, the detailed mechanism and the chemoselectivity of the gold(I)-catalyzed rearrangement (tandem cyclization) of propargyl esters with different substituents were investigated by the DFT method. The calculations provided important mechanistic insights into the electronic influence on the product distribution, namely, showing that the reaction involves four main steps: (i) 1,3-acyl-shift, (ii) 6-endo-dig or 5-exo-dig cyclization, (iii) Friedel−Crafts-type, and (iv) proton transfer. Furthermore, the cyclization is the rate-determining step in all pathways. The calculated activation energy for transition states indicates that the 6-endo-dig cyclization is the preferable pathway when using unsubstituted substrate 1a (R2 = R3 = H, Scheme 1). Hence, the calculation results support an experimental fact wherein products represent a 80:20 mixture of the 6-endo-dig and 5-exo-dig cyclization compounds. If a very strong electron-donating substituent introduced at the backbone (substrate 2a, R2 = OMe, R3 = H, Scheme 1), then the calculated activation energy of the 6-endo-dig cyclization is slightly higher than that of the 5-exo-dig cyclization, thus supporting an experimentally observed isomeric ratio of products (12:88). However, the activation barrier difference between the 6-endo-dig and 5-exo-dig cyclizations increases and suppresses the formation of benzofulvenes on changing the acetyl group (1a, R1 = CH3, Scheme 1) by a pivaloyl group (3a, R1 = C(CH3)3) in the substrate. Accordingly, we can conclude that a catalytic reaction may proceed via different cyclization pathways when the substrate is simply modified by tuning the polarization of the remaining alkyne. This study thus has a considerable potential to contribute toward better understanding of the substituent-guided control of cyclization pathways in the yne-allene substrates and provide significant hints for estimating the substrate scope.



Article

REFERENCES

(1) (a) Asiri, A. M.; Hashmi, A. S. K. Chem. Soc. Rev. 2016, 45, 4471− 4503. (b) Corma, A.; Leyva-Perez, A.; Sabater, M. J. Chem. Rev. 2011, 111, 1657−1712. (c) Schmidbaur, H.; Raubenheimer, H. G.; Dobrzanska, L. Chem. Soc. Rev. 2014, 43, 345−380. (d) Ibrahim, N.; Vilhelmsen, M. H.; Pernpointner, M.; Rominger, F.; Hashmi, A. S. K. Organometallics 2013, 32, 2576−2583. (e) Sun, Y.-M.; Gu, P.; Gao, Y.N.; Xu, Q.; Shi, M. Chem. Commun. 2016, 52, 6942−6945. (f) Wei, Y.; Shi, M. ACS Catal. 2016, 6, 2515−2524. (g) Krause, N.; Winter, C. Chem. Rev. 2011, 111, 1994−2009. (2) (a) Xie, J.; Pan, C.; Abdukader, A.; Zhu, C. Chem. Soc. Rev. 2014, 43, 5245−5256. (b) Ye, L.; Wang, Y.; Aue, D. H.; Zhang, L. J. Am. Chem. Soc. 2012, 134, 31−34. (c) Hashmi, A. S. K.; Braun, I.; Rudolph, M.; Rominger, F. Organometallics 2012, 31, 644−661. (d) Rao, W.; Koh, M. J.; Kothandaraman, P.; Chan, P. W. H. J. Am. Chem. Soc. 2012, 134, 10811−10814. (e) Lian, J.-J.; Chen, P.-C.; Lin, Y.-P.; Ting, H.-C.; Liu, R.-S. J. Am. Chem. Soc. 2006, 128, 11372−11373. (f) Tomás-Mendivil, E.; Toullec, P. Y.; Borge, J.; Conejero, S.; Michelet, V.; Cadierno, V. ACS Catal. 2013, 3, 3086−3098. (3) (a) Samanta, D.; Rana, A.; Schmittel, M. J. Org. Chem. 2015, 80, 2174−2181. (b) Lauterbach, T.; Higuchi, T.; Hussong, M. W.; Rudolph, M.; Rominger, F.; Mashima, K.; Hashmi, A. S. K. Adv. Synth. Catal. 2015, 357, 775−781. (c) Wirtanen, T.; Muuronen, M.; Melchionna, M.; Patzschke, M.; Helaja, J. J. Org. Chem. 2014, 79, 10269−10283. (d) Blanco Jaimes, M. C.; Rominger, F.; Pereira, M. M.; Carrilho, R. M. B.; Carabineiro, S. A. C.; Hashmi, A. S. K. Chem. Commun. 2014, 50, 4937−4940. (e) Hashmi, A. S. K.; Wieteck, M.; Braun, I.; Rudolph, M.; Rominger, F. Angew. Chem., Int. Ed. 2012, 51, 10633−10637. (4) (a) Rao, W.; Susanti, D.; Chan, P. W. H. J. Am. Chem. Soc. 2011, 133, 15248−15251. (b) Nösel, P.; dos Santos Comprido, L. N.; Lauterbach, T.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. J. Am. Chem. Soc. 2013, 135, 15662−15666. (c) Lauterbach, T.; Gatzweiler, S.; Nosel, P.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. Adv. Synth. Catal. 2013, 355, 2481−2487. (5) (a) Shiroodi, R. K.; Gevorgyan, V. Chem. Soc. Rev. 2013, 42, 4991−5001. (b) Yang, C.-Y.; Lin, G.-Y.; Liao, H.-Y.; Datta, S.; Liu, R.S. J. Org. Chem. 2008, 73, 4907−4914. (c) Li, D.-Y.; Wei, Y.; Shi, M. Chem. - Eur. J. 2013, 19, 15682−15688. (d) Hansmann, M. M.; Rominger, F.; Hashmi, A. S. K. Chem. Sci. 2013, 4, 1552−1559. (6) (a) Mohamed, R. K.; Peterson, P. W.; Alabugin, I. V. Chem. Rev. 2013, 113, 7089−7129. (b) Mirabdolbaghi, R.; Dudding, T. Org. Lett. 2015, 17, 1930−1933. (c) Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.; McKervey, M. A. Chem. Rev. 2015, 115, 9981−10080. (d) López, X.; Carbó, J. J.; Bo, C.; Poblet, J. M. Chem. Soc. Rev. 2012, 41, 7537−7571. (7) (a) Peng, Q.; Paton, R. S. Acc. Chem. Res. 2016, 49, 1042−1051. (b) Huple, D. B.; Ghorpade, S.; Liu, R.-S. Adv. Synth. Catal. 2016, 358, 1348−1367. For our recent theoretical studies of gold catalyzedcatalyzed reactions, see (c) Fang, R.; Su, C.-Y.; Zhao, C.; Phillips, D. L. Organometallics 2009, 28, 741−748. (d) Fang, R.; Yang, L.; Wang, Y.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.7b00042. Additional calculated energy parameters, optimized structures, and thermodynamic properties of structures (PDF) Optimized Cartesian coordinates with the self-consistent field (SCF) energies and the imaginary frequencies of transition states (XYZ) H

DOI: 10.1021/acs.organomet.7b00042 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Org. Biomol. Chem. 2011, 9, 2760−2770. (e) Yang, L.; Fang, R. J. Mol. Catal. A: Chem. 2013, 379, 197−205. (f) Fang, R.; Yang, L. Organometallics 2012, 31, 3043−3055. (g) Fang, R.; Yang, L.; Wang, Q. Organometallics 2012, 31, 4020−4030. (h) Fang, R.; Wei, X.; Yang, L. Org. Biomol. Chem. 2014, 12, 8433−8441. (8) (a) Rao, W.; Susanti, D.; Ayers, B. J.; Chan, P. W. H. J. Am. Chem. Soc. 2015, 137, 6350−6355. (b) Li, D.; Rao, W. D.; Tay, G. L.; Ayers, B. J.; Chan, P. W. H. J. Org. Chem. 2014, 79, 11301−11315. (c) Rao, W.; Koh, M. J.; Li, D.; Hirao, H.; Chan, P. W. H. J. Am. Chem. Soc. 2013, 135, 7926−7932. (d) Rao, W.; Chan, P. W. H. Chem. - Eur. J. 2014, 20, 713−718. (e) Bin, H.-Y.; Wei, X.; Zi, J.; Zuo, Y.-J.; Wang, T.C.; Zhong, C.-M. ACS Catal. 2015, 5, 6670−6679. (f) Jia, M.; Bandini, M. ACS Catal. 2015, 5, 1638−1652. (g) Joost, M.; Estevez, L.; MalletLadeira, S.; Miqueu, K.; Amgoune, A.; Bourissou, D. J. Am. Chem. Soc. 2014, 136, 10373−10382. (h) Finke, A. D.; Dumele, O.; Zalibera, M.; Confortin, D.; Cias, P.; Jayamurugan, G.; Gisselbrecht, J.-P.; Boudon, C.; Schweizer, W. B.; Gescheidt, G.; Diederich, F. J. Am. Chem. Soc. 2012, 134, 18139−18146. (9) (a) Hansmann, M. M.; Tšupova, S.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. Chem. - Eur. J. 2014, 20, 2215−2223. (b) Larsen, M. H.; Houk, K. N.; Hashmi, A. S. K. J. Am. Chem. Soc. 2015, 137, 10668−10676. (c) Hansmann, M. M.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. Angew. Chem., Int. Ed. 2013, 52, 2593−2598. (10) (a) Shin, S.; Son, J.-Y.; Choi, C.; Kim, S.; Lee, P. H. J. Org. Chem. 2016, 81, 11706−11715. (b) Mohamed, R. K.; Mondal, S.; Jorner, K.; Delgado, T. F.; Lobodin, V. V.; Ottosson, H.; Alabugin, I. V. J. Am. Chem. Soc. 2015, 137, 15441−15450. (c) Jin, S.; Jiang, C.; Peng, X.; Shan, C.; Cui, S.; Niu, Y.; Liu, Y.; Lan, Y.; Liu, Y.; Cheng, M. Org. Lett. 2016, 18, 680−683. (11) Shen, J.-J.; Shao, J.-Y.; Zhu, X.; Zhong, Y.-W. Org. Lett. 2016, 18, 256−259. (12) Das, J.; Bag, S. S.; Basak, A. J. Org. Chem. 2016, 81, 4623−4632. (13) Pati, K.; Gomes, G. P.; Harris, T.; Alabugin, I. V. Org. Lett. 2016, 18, 928−931. (14) Milián-Medina, B.; Gierschner, J. WIREs Comput. Mol. Sci. 2012, 2, 513−524. (15) Peterson, P. W.; Shevchenko, N.; Breiner, B.; Manoharan, M.; Lufti, F.; Delaune, J.; Kingsley, M.; Kovnir, K.; Alabugin, I. V. J. Am. Chem. Soc. 2016, 138, 15617−15628. (16) Wurm, T.; Bucher, J.; Duckworth, S. B.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. Angew. Chem., Int. Ed. 2017, 56, 3364. (17) Rettenmeier, E.; Hansmann, M. M.; Ahrens, A.; Rubenacker, K.; Saboo, T.; Massholder, J.; Meier, C.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. Chem. - Eur. J. 2015, 21, 14401−14409. (18) (a) Zhang, D.-H.; Zhang, Z.; Shi, M. Chem. Commun. 2012, 48, 10271−10279. (b) Shiroodi, R. K.; Gevorgyan, V. Chem. Soc. Rev. 2013, 42, 4991−5001. (c) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 8414−8415. (d) Soriano, E.; Fernandez, I. Chem. Soc. Rev. 2014, 43, 3041−3105. (e) Ghosh, A.; Basak, A.; Chakrabarty, K.; Ghosh, B.; Das, G. K. J. Org. Chem. 2014, 79, 5652−5663. (f) Á lvarez, E.; GarcíaGarcía, P.; Fernández-Rodríguez, M. A.; Sanz, R. J. Org. Chem. 2013, 78, 9758−9771. (g) Yang, W.; Hashmi, A. S. K. Chem. Soc. Rev. 2014, 43, 2941−2955. (19) (a) Lian, J.-J.; Liu, R.-S. Chem. Commun. 2007, 1337−1339. (b) Oh, C. H.; Kim, A. New J. Chem. 2007, 31, 1719−1721. (c) Vachhani, D. D.; Galli, M.; Jacobs, J.; Van Meervelt, L.; Van der Eycken, E. V. Chem. Commun. 2013, 49, 7171−7173. (d) Zhao, J.; Hughes, C. O.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 7436−7437. (20) (a) Campolo, D.; Arif, T.; Borie, C.; Mouysset, D.; Vanthuyne, N.; Naubron, J.-V.; Bertrand, M. P.; Nechab, M. Angew. Chem., Int. Ed. 2014, 53, 3227−3231. (b) Pradal, A.; Nasr, A.; Toullec, P. Y.; Michelet, V. Org. Lett. 2010, 12, 5222−5225. (c) Xia, Y.; Dudnik, A. S.; Gevorgyan, V.; Li, Y. J. Am. Chem. Soc. 2008, 130, 6940−6941. (21) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.;

Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision D.01; Gaussian, Inc.: Wallingford, CT, 2009. (22) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 1372−1377. (b) Lee, C. T.; Yang, W. T.; Parr, R. G. Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785−789. (c) Miehlich, B.; Savin, A.; Stoll, H.; Preuss, H. Chem. Phys. Lett. 1989, 157, 200−206. (23) (a) Zhao, Y.; Schultz, N. E.; Truhlar, D. G. J. Chem. Theory Comput. 2006, 2, 364−382. (b) Zhao, Y.; Truhlar, D. G. J. Phys. Chem. A 2006, 110, 13126−13130. (24) (a) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270−283. (b) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 284−298. (25) (a) Fukui, K. J. Phys. Chem. 1970, 74, 4161−4163. (26) (a) Fukui, K. Acc. Chem. Res. 1981, 14, 363−368. (b) Gonzalez, C.; Schlegel, H. B. J. Chem. Phys. 1989, 90, 2154−2161. (c) Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523−5527. (27) (a) Schuchardt, K. L.; Didier, B. T.; Elsethagen, T.; Sun, L.; Gurumoorthi, V.; Chase, J.; Li, J.; Windus, T. L. J. Chem. Inf. Model. 2007, 47, 1045−1052. (b) Feller, D. J. Comput. Chem. 1996, 17, 1571−1586. (28) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2009, 113, 6378−6396. (29) For a detailed, fully relativistic handling of such pi-alkyne gold complexes, see Pernpointner, M.; Hashmi, A. S. K. J. Chem. Theory Comput. 2009, 5, 2717−2725. (30) For a detailed discussion of the coordination bond between alkynes and gold catalysts, see Bistoni, G.; Belanzoni, P.; Belpassi, L.; Tarantelli, F. J. Phys. Chem. A 2016, 120, 5239−5247. (31) For an important effect of proton shuttles in gold catalysis, see Krauter, C. M.; Hashmi, A. S. K.; Pernpointner, M. ChemCatChem 2010, 2, 1226−1230.

I

DOI: 10.1021/acs.organomet.7b00042 Organometallics XXXX, XXX, XXX−XXX