Insights into the mechanism and selectivity of the Rh(I)-catalyzed cycloisomerization reaction of benzylallene-alkynes involving C–H bond activation

Abstract

A systematic theoretical study has been carried out with the aid of density functional theory (DFT) calculations on the mechanism of the Rh-catalyzed cycloisomerization of benzylallene-alkynes involving C_sp2–H bond activation on the benzyl phenyl ring. Experimentally, it was found that the substituent on the allene moiety has a drastic effect on the cycloisomerization selectivity and the terminal substituent on the alkyne moiety also shows an effect on the product selectivity. In this work, through our detailed mechanistic calculations, we found that when the terminal substituent on the alkyne moiety is a hydrogen, regardless of the substituent Y on the allene moiety is an EDG or EWG, the pathway involving β-elimination of this hydrogen in an intermediate (derived from an olefin insertion step following oxidative coupling and σ-bond metathesis) is always favorable. When the terminal substituent on the alkyne moiety is an alkyl, two scenarios were found depending on whether the substituent Y on the allene moiety is an EWG or EDG.

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Introduction

Transition metal-catalyzed cyclization of unsaturated systems involving the activation of C–H and/or C–C bonds has become one of the powerful and effective methods to construct complex cyclic frameworks in organic synthesis.¹ Allenes, which have a cumulated diene structure with an sp-hybridized central carbon, are widely used in the construction of cyclic compounds. Actually, allenes have been discovered in many natural products with biological activities.² They can react with various unsaturated hydrocarbons, such as alkenes and alkynes. With different substituents, allenes show different interesting reactivities and reaction modes.³ Rhodium-catalyzed cyclizations of allenes with other multiple bonds have attracted much attention over the last few decades for the construction of complex polycyclic skeletons.^4–6

Recently, Mukai and co-workers reported [RhCl(CO)₂]₂-catalyzed cycloisomerization of benzylallene-alkynes via C–H bond activation to form tricyclic compounds (Scheme 1).^7–9 The reactions shown in Scheme 1 indicate that the terminal substituent R¹ on the alkyne moiety and the internal substituent Y on the allene moiety play significant roles in the product selectivity. When the terminal substituent R¹ on the alkyne moiety is a hydrogen, product 2 is produced (Scheme 1a). When the terminal substituent R¹ on the alkyne moiety is non-hydrogen, product 3 (Scheme 1b) or 4 (Scheme 1c) was observed, depending on whether the substituent Y on the allene moiety is SO₂Ph/PO(OEt)₂ or Me.

Scheme 1 [RhCl(CO)₂]₂-catalyzed cycloisomerization of benzylallene-alkynes.

On the basis of their experimental findings, Mukai and co-workers proposed a plausible mechanism (Scheme 2) to describe the formation of the experimentally observed products shown in Scheme 1.^7–9 As shown in Scheme 2, the coordination complex A of [Rh(I)] with the substrate 1 undergoes oxidative coupling to give the rhodabicyclic intermediate B, which would form the arylrhodium intermediate C through σ-bond metathesis between an ortho C_sp2–H bond on the phenyl ring and the C_sp2–Rh bond. Then, insertion of the exocyclic double bond unit into the C_sp2–Rh(III) bond in C would produce the tricyclic intermediate D. When R¹ = H, D undergoes β-hydride (R¹) elimination to form the σ-allylrhodium intermediate E, which undergoes reductive elimination to give the six/seven/six tricyclic product 2. When R¹ = alkyl (using Me as the representative in Scheme 2), D undergoes an alternative β-hydride (H_A) elimination followed by reductive elimination to give a different six/seven/six tricyclic product 3. When Y = alkyl (instead of an electron-withdrawing group (EWG); again using Me as the representative in Scheme 2), the intermediate C should be in equilibrium via a 1,3-Rh shift with another σ-allylrhodium intermediate G, which undergoes reductive elimination to give the six/six/six tricyclic product 4.

Scheme 2 A plausible mechanism to account for the formation of the experimentally observed products shown in Scheme 1.

The proposed mechanism (Scheme 2) nicely links and describes the experimentally observed reaction products with different reaction pathways. However, the understanding of the substituent effect, which is crucially important in the rational design of new pharmaceutical compounds, is particularly lacking. In this work, by taking advantage of the insightful mechanism, we carried out DFT calculations to understand how the above-mentioned different substituents affect the preference of one reaction pathway over the other. We hope that the insights obtained through our DFT calculations will contribute to the development of new synthetic methods for building complex polycyclic frameworks.

Computational methods

Molecular geometries of all the structures studied in this work were optimized without constraints via DFT calculations at the M06 level.¹⁰ Frequency analysis was performed at the same level of theory for all of the obtained stationary points to characterize them as transition states (one imaginary frequency) and minima (no imaginary frequency). The 6-31G(d,p) basis set¹¹ was chosen to describe C, H, and O atoms. The effective core potentials of Hay and Wadt with double-ζ valence basis sets (LANL2DZ)¹² were employed for Rh, Cl, and S atoms. Polarization functions were also added to Rh (ζ_f = 1.350), Cl (ζ_d = 0.640), and S (ζ_d = 0.503) atoms.¹³ The M06 method has been confirmed to be appropriate for Rh-catalyzed reactions in a number of recent theoretical studies.¹⁴ Intrinsic reaction coordinate (IRC) calculations¹⁵ were carried out on transition state structures to further verify that such structures connect two relevant minimum species. To match with the experimental conditions given in ref. 7–9, all the thermodynamic data reported in this work were calculated under an actual reaction temperature of 383.15 K. Natural bond orbital (NBO)¹⁶ analysis was performed on selected optimized structures. Single-point energy calculations with a better basis set at the level of M06/6-311+G(d,p)¹⁷ (using LANL2DZ+f for the Rh atom and LANL2DZ+d for Cl and S atoms) were conducted with the SMD solvation model (solvent = toluene)¹⁸ for all the structures optimized at the M06/6-31G(d,p) level. In all of the Gibbs energy profiles discussed, basis-set- and solvation-corrected relative Gibbs energies (kcal mol⁻¹) were employed. The selected key structures of the optimized intermediates were visualized using the XYZviewer software developed by de Marothy.¹⁹ All of the calculations were performed with the Gaussian 09 software package.²⁰

Results and discussion

Scheme 1 clearly shows that if the benzylallene-alkyne substrates contain a terminal alkyne moiety, no matter what the linker X and the internal substituent Y on the allene moiety are, product 2 was always produced. For non-terminal alkyne substrates, the internal substituent Y affects the reaction outcome depending on whether it is an electron-withdrawing group (EWG) such as SO₂Ph or PO(OEt)₂ or an electron-donating group (EDG) such as Me. Among the reactions shown in Scheme 1, the linker X clearly had no effect on the reaction outcome. In view of this, we considered models having X = C(CO₂Me)₂ for our calculations.

Reactions of benzylallene-alkyne substrates having an EWG internal substituent Y on the allene moiety

Terminal alkynes. To examine the reactions of benzylallene-alkyne substrates with a terminal alkyne moiety, we first calculated the cycloisomerization reaction of the model benzylallene-alkyne substrate shown in eqn (1), considering R¹ = H, X = C(CO₂Me)₂ and Y = SO₂Ph which are electron-withdrawing groups. For the convenience of discussion, we intentionally labeled three hydrogen atoms on the substrate as H_A, H_R, and H_B (see eqn (1)).
Oxidative coupling followed by σ-bond metathesis (A → B → C) in the central cycle of Scheme 2. According to Scheme 2, the first step of the reaction is oxidative coupling. A closely related oxidative coupling step has been theoretically thoroughly studied in our recent work on Rh-catalyzed cycloisomerization of homopropargylallene-alkynes,²¹ which was also developed by Mukai and co-workers.^4g Therefore, we will only give a brief account of this step calculated for substrate 1_H without a detailed discussion of other possible structural isomers involved. Furthermore, pathways related to other structural isomers show higher barriers (Fig. S1 and S2 in the ESI†). Fig. 1 shows the Gibbs energy profile calculated for the favorable oxidative coupling process (A → B). The oxidative coupling starts with a square planar complex containing metal fragment Rh(CO)₂Cl^6d,e and the substrate molecule as a ligand. The oxidative coupling initially gives a pseudo-octahedral complex (B1_H) containing a weakly coordinated alkene moiety in the newly-formed six-membered ring. Then, a series of structural re-organizations (isomerization) occurs to release the ring strain and achieve optimal coordination, giving the most stable oxidative coupling species B4_H that contains phenyl π coordination to the Rh(III) metal center.

Fig. 1 Gibbs energy profile calculated for the oxidative coupling process (A → B) (oxidative coupling followed by structural rearrangement in the organic ligand (isomerization)) and the followed σ-bond metathesis process (B → C) shown in Scheme 2. Relative Gibbs energies and electronic energies (in parentheses) are given in kcal mol⁻¹.

As also shown in Fig. 1, from B4_H, σ-bond metathesis takes place involving a C_sp2–H bond activation giving the alkene-coordinated intermediate C1_H. The corresponding transition state TSB4-C1_H is a four-center species, with a moderate Gibbs energy barrier of 17.2 kcal mol⁻¹.

C → D insertion process in the central cycle of Scheme 2. C is a bifurcation point in the reaction mechanism proposed in Scheme 2. Let us discuss the C → D insertion process in the central cycle first. Fig. 2(a) shows the Gibbs energy profile calculated for the C → D insertion process. The insertion of the alkene unit into the C_sp2–Rh^III bond in C1_H occurs via the transition state TSC1-D1_H to produce intermediate D1_H. Intermediate D1_H then undergoes a very facile stepwise structural re-arrangement, which turns off the weaker Rh–arene interaction and switches to the stronger Rh–alkene interaction to generate a much more stable species D3_H containing allyl coordination. D3_H is an η⁴-coordinated species in which the Rh metal center coordinates with four carbon atoms of the organic ligand in an η⁴ mode.

Fig. 2 Gibbs energy profiles calculated for (a) C → D (insertion), (b) D → E (β-hydride elimination) followed by E → A (reductive elimination) to give product 2_H, (c) D → F (β-hydride elimination) followed by F → A (reductive elimination) to give product 3_H, and (d) C → G (bond rotation) followed by G → A (reductive elimination) to give product 4_H. Relative Gibbs energies and electronic energies (in parentheses) are given in kcal mol⁻¹.

D → E β-hydride elimination process in the central cycle of Scheme 2. Here, we discuss D → E β-hydride elimination proposed in the central cycle of Scheme 2. Our calculation results indicate that D → E starts with D1_H (Fig. 2(b)), instead of the more stable η⁴-coordinated species D3_H, although D3_H should be considered as a resting state for this pathway. Then, a simple configurational change in the organic ligand of D1_H easily leads to an agostic interaction between C–H_R and the metal center (E1_H in Fig. 2(b)), a species ready for the desired β-hydride (H_R) elimination. From E1_H, β-hydride elimination forms σ-allylrhodium intermediate E3_H. In E2_H, a double bond moiety and a carbon atom of the seven-membered ring both coordinate with the rhodium metal center. The ring strain results in the instability of E2_H, which easily dissociates the olefinic unit from the metal center to form the more stable intermediate E3_H. Finally, reductive elimination followed by a ligand exchange of substrate 1_H takes place to produce product 2_H and regenerates A1_H to complete the catalytic cycle. It can be seen that the process (D → E) requires a Gibbs energy barrier of 29.1 kcal mol⁻¹ relative to intermediate D3_H.
D → F β-hydride elimination process in the left cycle of Scheme 2. Next, we discuss the D → F process shown in the left cycle of Scheme 2, leading to the six/seven/six tricyclic product 3_H. Fig. 2(c) shows that the η⁴-coordinated species D3_H undergoes a stepwise structural rearrangement, leading to intermediate F2_H with an agostic interaction between C–H_A and the Rh center. The barrier calculated for this rearrangement is significantly high (35.0 kcal mol⁻¹). From F2_H, β-hydride elimination followed by the first reductive elimination and then a ligand exchange produces product 3_H and regenerates the initial species A1_H.
C → G 1,3-Rh shift process in the right cycle of Scheme 2. Finally, we discuss the C → G process proposed in the right cycle of Scheme 2, leading to the six/six/six tricyclic product 4_H. According to Scheme 2, C → G involves the 1,3-Rh shift. However, we found that the bond rotation in C easily leads to a species ready for reductive elimination to give the product. Fig. 2(d) shows the calculated Gibbs energy profile. From intermediate C1_H, a rotation of approximately 180 degrees of the heterocyclic ring along the C_sp2–C_sp3 bond affords intermediate G1_H, which undergoes reductive elimination followed by a ligand exchange to give the final product 4_H and regenerates the initial species A1_H. The reductive elimination transition state TSG1-product 4_H is rate-determining for this pathway. The barrier from C1_H to TSG1-product 4_H was only 24.1 kcal mol⁻¹, which is considered easily accessible. However, since the Gibbs energy of insertion transition state TSC1-D1_H (from C1_H) is much lower (by 12.8 kcal mol⁻¹) than that of TSG1-product 4_H, D3_H becomes a thermodynamic sink for this pathway. Thus, we saw a prohibitively high overall Gibbs energy barrier of 52.4 kcal mol⁻¹ (with respect to the η⁴-coordinated species D3_H) for the pathway leading to product 4_H.
Brief summary. Combining all the calculated Gibbs energy profiles shown in Fig. 1 and 2, we have the following findings: (1) the oxidative coupling A → B is an irreversible process; (2) the η⁴-coordinated species D3_H, derived from the insertion process C → D, is the resting state for all of the three catalytic cycles; (3) TSD1-E1_H or TSE2-E3_H (Fig. 2(b)), TSD3-F1_H (Fig. 2(c)) and TSG1-product 4_H (Fig. 2(d)) are the rate-determining transition states, respectively, for the formation of products 2_H, 3_H and 4_H.

On the basis of the findings given above, the overall barriers for the formation of products 2_H, 3_H and 4_H were calculated to be 29.1, 35.0 and 52.4 kcal mol⁻¹, respectively, corresponding to the energy differences between the rate-determining transition states and the η⁴-coordinated resting state D3_H. These results suggest that only product 2 is kinetically possible when R¹ = H, completely in agreement with the experimental observation shown in Scheme 1a.

Internal alkynes. When R¹ = alkyl (Scheme 1b), we conveniently assumed that among the three reaction pathways discussed, the pathway leading to product 2 is expected to be turned off. This is easily understood. The pathway leading to product 2 requires β-R¹ elimination. If R¹ is an alkyl substituent, β-alkyl elimination is well known to be energetically very costly. Thus, on the basis of the results given above, among the two remaining possible pathways, the pathway leading to product 3, which is kinetically much more favorable should be expected, as experimentally confirmed in Scheme 1b.
DFT results. Our calculations using the model benzylallene-alkyne substrate with R¹ = Me, X = C(CO₂Me)₂ and Y = SO₂Ph confirm that the Gibbs energy profiles (Fig. 3) for the two possible pathways resemble in general what we have obtained for the model reaction with R¹ = H, in which the corresponding η⁴-coordinated species D3_Me is also the resting state, and the overall barrier with respect to D3_Me for the formation of product 3_Me was calculated to be 32.5 kcal mol⁻¹ (versus 35.0 kcal mol⁻¹ when R¹ = H). Although this barrier is relatively high, this pathway should be feasible in view of the experimental conditions with an actual reaction temperature of 110 °C. D3_Me is also a thermodynamic sink for the pathway leading to product 4_Me whose overall barrier (with respect to D3_Me) was 42.7 kcal mol⁻¹ (versus 52.4 kcal mol⁻¹ when R¹ = H). These results are consistent with the experimental observation showing that only product 3 was produced (Scheme 1b).

Fig. 3 Gibbs energy profiles calculated for (a) C → D (insertion), (b) D → F (β-hydride elimination) followed by F → A (reductive elimination) to give product 3_Me, and (c) C → G (bond rotation) followed by G → A (reductive elimination) to give product 4_Me, according to Scheme 2. Relative Gibbs energies and electronic energies (in parentheses) are given in kcal mol⁻¹.

Brief comments on the subtle differences between the Gibbs energy profiles calculated for the reactions of terminal and internal alkynes. Despite the resemblance found between the energy profiles calculated for the two substrates having R¹ = H and R¹ = Me when X = C(CO₂Me)/Y = SO₂Ph, some subtle differences are discussed here.

Comparing Fig. 2(a) and 3(a), we found that changing from R¹ = H to R¹ = Me, the C1 → D3 transformation becomes less exergonic (−28.3 versus −16.3 kcal mol⁻¹, a noticeable, significant difference of 12.0 kcal mol⁻¹). Clearly, the introduction of a methyl group significantly destabilizes the insertion “products” D1, D2 and D3 relatively much more than C1, and at the same time hinders the structural re-arrangement from D1 to D3. Examining the structures of the insertion “products”, we found that the C–C(Ar) bond formation as a result of the insertion makes the methyl group to repulsively interact with the nearest H on the aryl ring (having a very close contact of 2.121 Å in D1_Me). In other words, an alkyl substituent on the terminal alkynyl moiety of the substrate molecule significantly reduces the exergonicity of the insertion process leading to the above-mentioned C–C(Ar) bond formation.

Comparing Fig. 2(c) and 3(b) (pathway leading to product 3), we found that the two Gibbs energy profiles look very similar to each other, where the only difference between them is that the profile calculated for R¹ = Me is energetically relatively higher than that calculated for R¹ = H by approximately 10 ± 3 kcal mol⁻¹. Clearly, this levelling up is a result of destabilization related to the insertion “product” D3 discussed in the last paragraph.

Comparing Fig. 2(d) and 3(c) (pathway leading to product 4), we found that the two profiles also look very similar to each other where the profile calculated for R¹ = Me is energetically relatively higher than that calculated for R¹ = H in a range of only 1–4 kcal mol⁻¹. We assume that this levelling up is a result of relatively less stable C1_Me when compared with C1_H.

Combining all the subtle changes from R¹ = H to Me discussed here, we can understand the changes related to the overall barriers leading to products 3 and 4 mentioned above.

Reactions of benzylallene-alkyne substrates having an EDG internal substituent Y on the allene moiety

Scheme 1c indicates that when the substituent Y is an electron-donating alkyl group (EDG) (instead of an electron-withdrawing group (EWG)), the six/six/six tricyclic product 4 instead of the six/seven/six tricyclic product 3 becomes favorable. In Scheme 1c, R¹ is also an alkyl substituent. Thus, it is expected that the pathway leading to product 2 is also turned off. To understand the origin behind the interesting selectivity of products 3versus4, we examined the two possible pathways leading to products 3 and 4, considering two other substrates having Y = Me (EDG) and R¹ = Me, and Y = Me (EDG) and R¹ = tBu.

Reactions of the benzylallene-alkyne substrate having Y = Me (EDG) and R¹ = Me. Fig. 4 shows the Gibbs energy profiles calculated for the reaction of the substrate having Y = Me (EDG) and R¹ = Me on the basis of the two possible reaction pathways discussed above. At the first glance, the Gibbs energy profiles shown in Fig. 4 also closely resemble those shown in Fig. 3. Comparison between Fig. 3 and 4 allows us to meaningfully observe the changes of the Gibbs energy profiles upon a change of the substituent Y from SOPh₂ (EWG) to Me (EDG). The exergonicity for the insertion process C1 → D3 was further narrowed (−16.3 kcal mol⁻¹ in Fig. 3(a)versus −11.7 kcal mol⁻¹ in Fig. 4(a)). Both C1 and D3 were stabilized when Y changed from the EWG to the EDG, but C1 was relatively stabilized much more, which is understandable because an EDG Y makes the coordinated olefinic moiety more π-electron-rich and strengthens the coordination bonding interaction in C1. For the pathway leading to Me-product 3_Me from Me-D3_Me (Fig. 4(b)), the species involved are all relatively stabilized by 2–8 kcal mol⁻¹ when compared to those shown in Fig. 3(b).

Fig. 4 Gibbs energy profiles calculated for (a) C → D (insertion), (b) D → F (β-hydride elimination) followed by F → A (reductive elimination) to give Me-product 3_Me, and (c) C → G (bond rotation) followed by G → A (reductive elimination) to give Me-product 4_Me, according to Scheme 2. Relative Gibbs energies and electronic energies (in parentheses) are given in kcal mol⁻¹.

For the pathway leading to Me-product 4_Me from Me-C1_Me (Fig. 4(c)), we see the most significant effect as a result of the change from Y = SOPh₂ (EWG) to Y = Me (EDG). The barrier from Me-C1_Me to Me-TSG1-product 4_Me was reduced to 15.7 kcal mol⁻¹ (versus 26.4 kcal mol⁻¹ in Fig. 3(c) for Y = SO₂Ph). Furthermore, the relative Gibbs energy of Me-TSG1-product 4_Me (Fig. 4(c)) is now lower than that of Me-TSC1-D1_Me. This switch in the stability order of the two competing transition states has far-reaching impact on the reaction mechanism, indicating that the reaction will favorably proceed directly through G and then produce Me-product 4_MeviaMe-TSG1-product 4_Me once the metathesis (B → C) step is completed, without falling into the corresponding thermodynamic sink Me-D3_MeviaMe-TSC1-D1_Me (Fig. 4(a)) and then producing Me-product 3_Me (Fig. 4(b)). In other words, for the reaction of a benzylallene-alkyne substrate having Y = Me (EDG) and R¹ = Me, the pathway leading to Me-product 4_Me from Me-C1_Me (Fig. 4(c)) is the most favorable. Indeed, as indicated in Scheme 1, when Y = Me, product 4 was experimentally produced. The bond rotation step from Me-C1_Me to Me-G1_Me involves a series of conformational changes with accessible barriers as shown in the ESI (Fig. S3†).

Reactions of the benzylallene-alkyne substrate having Y = Me (EDG) and R¹ = tBu. One may question that the energy difference between the two competing transition states discussed above is not large enough to make a valid claim. Nevertheless, the trend is very clear and readers will be convinced by our results for the case when Y = Me and R¹ = tBu in the ESI (see Fig. S4† for the corresponding Gibbs energy profiles). When R¹ = tBu instead of Me, the energy difference between the two corresponding competing transition states Me-TSC1-D1_tBu and Me-TSG1-product 4_tBu was as large as 8.9 kcal mol⁻¹ in favor of the latter. As discussed above, a sterically bulky substituent R¹ actually impedes the insertion process C → D. Indeed, we found that the barrier from Me-C1_R1 to Me-TSC1-D1_R1 increased from 17.3 kcal mol⁻¹ for R¹ = Me (Fig. 4(a)) to 24.6 kcal mol⁻¹ for R¹ = tBu (Fig. S4(a)†). However, the barriers from Me-C1_R1 to Me-TSG1-product 4_R1 were 15.7 kcal mol⁻¹ for both R¹ = Me (Fig. 4(c)) and R¹ = tBu (Fig. S4(c)†).

Reactions of the benzylallene-alkyne substrate having Y = Me (EDG) and R¹ = H. When R¹ = H, the impeding effect on the C → D insertion was absent. Therefore, the C → D insertion is very facile and irreversible (Fig. 2(a)), preventing the process involving C → G, followed by reductive elimination. In other words, although the process involving C → G and the following reductive elimination was promoted using an EDG Y, the very facile C → D insertion when R¹ = H still made the β-H (R¹ = H) elimination process D → E favorable and produced product 2 experimentally as observed in Scheme 1a.

Understanding how an EDG Y promotes the pathway leading to product 4viaG

In order to understand how an EDG Y promotes the pathway leading to product 4viaG, we show the two competing transition states starting from C, which is a bifurcation point for the two pathways, for both Y = SO₂Ph (EWG) and Y = Me (EDG) cases. Comparing the structures of Me-C1_Me and C1_Me, we found that the olefinic moiety in the former is more strongly bonded to the Rh(III) metal center than that in the latter (2.495 versus 2.545 Å in their average bond distances (Fig. 5)). We clearly see from Fig. 6 that from Y = SO₂Ph (EWG) to Y = Me (EDG), the olefin insertion in the pathway for product 3 becomes less favored. An EDG Y makes the olefinic moiety π-electron richer, leading to a stronger metal–olefin bonding interaction. It is understandable that stronger metal–olefin bonding interactions impede the insertion process.

Fig. 5 Structures calculated for C1_Me, G1_Me, Me-C1_Me and Me-G1_Me. Bond lengths are given in angstroms (Å).

Fig. 6 A brief version of the two competing pathways leading to products 3 (leftward) and 4 (rightward) starting from the σ-bond metathesis “product” C for the substrates when (a) Y = SO₂Ph (EWG); and (b) Y = Me (EDG). Relative Gibbs energies and electronic energies (in parentheses) are given in kcal mol⁻¹.

For the pathway leading to product 4viaG, we found that from Y = SO₂Ph (EWG) to Y = Me (EDG), the overall barrier decreases significantly (from 26.4 to 19.5 kcal mol⁻¹, Fig. 6). However, the decrease in the overall barrier does not come from the reductive elimination step starting from G, as we can clearly see that the two reductive elimination barriers (18.7 and 19.5 kcal mol⁻¹, Fig. 6) for both cases were almost the same. Clearly, the reductive elimination barrier is not sensitive to the substituent effect. This is true in the first case when Y = SO₂Ph and R¹ = H discussed above and the case when Y = Me and R¹ = tBu where the corresponding reductive elimination barriers were 19.2 kcal mol⁻¹ (Fig. 2(d)) and 19.6 kcal mol⁻¹ (Fig. S4(c)†), respectively. Instead, a decrease in the overall barrier is due to the bond rotation step. In the case when Y = SO₂Ph (EWG), the bond rotation leads to a much less stable isomer G1_Me (Fig. 6(a)), while in the case when Y = Me (EDG), it leads to a more stable isomer Me-G1_Me (Fig. 6(b)). The bond rotation isomer G1 contains an allyl ligand. In the early studies²² on how different substituents X affect the relative stability of the trans and cis isomers in the square planar palladium(II) complexes Pd(I)(PPh₃)(η³-XCHC(Ph)CH₂), it was demonstrated that an EWG X results in a strong trans-influence Pd–C(X) bond. Thus, we see a scenario that in G1_Me, two strong trans-influence ligands, Rh–C(SO₂Ph) (2.256 Å) and CO, are arranged in trans to each other, significantly destabilizing the structure. In Me-G1_Me, Rh–C(Me) (2.571 Å) is not strong trans-influencing, and therefore the destabilizing scenario is absent. Examining the calculated structures involved, we found that the Rh–CO (trans) bond distance changed from 1.862 (C1_Me) to 1.939 Å (G1_Me) and from 1.872 (Me-C1_Me) to 1.886 Å (Me-G1_Me) (Fig. 5). The NBO analysis shows that the C atom of Rh–C(Me) in Me-G1_Me reveals a much more positive charge than that the C atom of Rh–C(SO₂Ph) in G1_Me (+0.130e vs. −0.307e). The calculated results support the trans-influence argument above.

Conclusions

The cycloisomerization of benzylallene-terminal alkynes involving C_sp2–H bond activation on the benzyl phenyl ring catalyzed by [RhCl(CO)₂]₂ has been theoretically investigated with the aid of DFT calculations. Scheme 3 summarizes the mechanisms we have found on the basis of our DFT calculations.

Scheme 3 Mechanisms of [RhCl(CO)₂]₂-catalyzed cycloisomerization of benzylallene-alkynes through DFT calculations.

The reaction is initiated by oxidative coupling to form a rhodacyclopentane intermediate B, which undergoes σ-bond metathesis involving C_sp2–H bond activation to form arylrhodium intermediate C.

When the terminal substituent R¹ on the alkyne moiety is a hydrogen, regardless of the substituent Y on the allene moiety is an EDG or EWG, the exocyclic olefin in C inserts into the C_sp2–Rh^III bond producing the tricyclic intermediate D, which undergoes β-hydride (R¹) elimination to form the metal hydride intermediate E, reductive elimination of which gives the six/seven/six tricyclic product 2.

When the terminal substituent R¹ on the alkyne moiety is non-hydrogen, there are two scenarios depending on whether the substituent Y on the allene moiety is an EDG or EWG. We found that an electron-donating alkyl group Y significantly promotes a C_sp2–C_sp3(Rh) bond rotation step transforming C to G, which undergoes reductive elimination to give the six/six/six tricyclic product 4. G contains an allyl ligand, where the Rh–C(Y) σ bond is significantly weak due to the EDG substituent Y on the allyl ligand. A significantly weak Rh–C(Y) σ bond benefits the structure G in terms of its stability considering that the ligand trans to Rh–C(Y) is a very strong trans-influencing carbonyl CO ligand. When Y is an electron-withdrawing group, the C_sp2–C_sp3(Rh) bond rotation is significantly less favored because the Rh–C(Y) σ bond here is significantly strengthened, significantly destabilizing the bonding interaction between the metal center and the carbonyl CO which is trans to it. Thus, the reaction also proceeds to form D, followed by β-hydride elimination to produce F, which undergoes reductive elimination to give the six/seven/six product 3.

Conflicts of interest

The authors declare no competing financial interest.

Acknowledgements

This work is supported by the National Natural Science Foundation of China (21501115), the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province (20210044) and the Research Grants Council of Hong Kong (HKUST 16300620).

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Footnote

† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2qo01503j

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