DFT Studies of Mechanism and Origin of Stereoselectivity of Palladium

Article pubs.acs.org/Organometallics

DFT Studies of Mechanism and Origin of Stereoselectivity of Palladium-Catalyzed Cyclotrimerization Reactions Affording synTris(norborneno)benzenes Masahiro Yamanaka,*,† Masumi Morishima,† Yukihiro Shibata,† Shuhei Higashibayashi,‡ and Hidehiro Sakurai‡ †

Department of Chemistry and Research Center for Smart Molecules, Faculty of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan ‡ Institute for Molecular Science, Myodaiji, Okazaki, Aichi 444-8787, Japan S Supporting Information *

ABSTRACT: Pd-catalyzed cyclotrimerization reactions of enantiopure halonorbornene derivatives furnished C3 or C3v symmetric syn-tris(norborneno)benzenes with high syn selectivity. To elucidate the reaction mechanism as well as the stereoselectivity of the present Pd-catalyzed cyclotrimerization, DFT calculations were carried out. The promising reaction pathway consists of (1) sequential olefin insertion followed by an HX elimination reaction of halonorbornene with the norbornenylpalladium intermediate, (2) electrocyclization of the trienylpalladium intermediate with a lower activation barrier than a triene compound, and (3) the β-elimination of HPdX of the cyclohexadienylpalladium intermediate. In addition, the stereoselectivity would be controlled by the regioselectivity in the olefin insertion process (homo and hetero positions) and the symmetry breaking in the palladacyclic intermediate.

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INTRODUCTION C3- or C3v-symmetric syn-tris(norborneno)benzenes with various substituents have been recently utilized as synthetic intermediates for the syntheses of C3- or C3v-symmetric buckybowls1 or as cup- or basket-shaped host molecules to encapsulate guest molecules.2 In the synthesis of syntris(norborneno)benzenes by the cyclotrimerization of norbornene derivatives, both syn and anti isomers are generally formed. As only the syn isomer is useful as the synthetic intermediate for buckybowls or as a host molecule, syn/anti selectivity is an important issue in synthetic organic chemistry. We have previously reported a Pd-catalyzed cyclotrimerization reaction of enantiopure iodonorbornene derivatives 1, which afforded C3- or C3v-symmetric syn-tris(norborneno)benzenes 2 with high syn selectivity (Scheme 1).3 Fabris and Scarso have recently reported a relevant modification of our method for the preparation of enantiopure 2 with good syn selectivity.4 In comparison with the Cu-mediated cyclotrimerization of halostannylnorbornene derivatives,5 our Pd-catalyzed cyclotrimerization reaction offers several advantages, including (1) the ease of preparation of iodonorbornene derivatives, (2) the use of nontoxic reagents and lower loading heavy metals, (3) high syn selectivity, (4) compatibility with various functional groups, (5) facile preparation of chiral syn-tris(norborneno)benzenes, etc. Then, we applied this reaction to the preparation of various syn-tris(norborneno)benzenes from the corresponding enantiopure iodonorbornenes.3 The syn/anti selectivity © 2014 American Chemical Society

Scheme 1. Pd-Catalyzed Cyclotrimerization of Enantiopure Iodonorbornenes

induced by the substituents of 1 ranged from 100/0 to 77/23.3c The cyclotrimerization of nonsubstituted iodonorbornene 1a afforded 2a with a syn/anti selectivity of 77/23. Similar syn/anti selectivity was obtained by using iodonorbornene 1b with an acetonide group (78/22). Iodonorbornene 1c with a TBS ether group (TBS = t-BuMe2Si) at the exo position afforded 2c with a syn/anti selectivity of 90/10. In the cyclotrimerization of 1d (PMB = p-methoxybenzyl), the syn isomer 2d was obtained exclusively without the formation of the anti isomer (Scheme Received: March 25, 2014 Published: June 11, 2014 3060

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Scheme 2. Three Reaction Pathways for the Pd-Catalyzed Cyclotrimerization of Enantiopure Halonorbornene

considered to be monomeric Pd atoms generated from the nanoclusters. Similar Pd-catalyzed C−C bond formation reactions have been achieved under nanocluster conditions.8 Therefore, the monomeric and naked Pd atom was employed in the present DFT calculations. The realistic chemical model, which is based on the ideal reaction mechanism, was also addressed to investigate the stereoselectivity (Figure 1b). In both models, a chlorine atom was used instead of an iodine atom. All calculations were performed with the Gaussian 03 package.9 Geometry optimization and frequency calculation of the neutral compounds were carried out with the B3LYP method10 using the 631LAN basis set consisting of LANL2DZ11 for Pd and 6-31G(d)12 for the rest of the atoms. The larger 6311+LAN basis set consisting of LANL2DZ for Pd and 6311+G(d,p)12 for the rest of the atoms was employed to assess the accuracy of the computational method for some stationary points. For the anionic compounds, 6-31+G(d) was employed except for Pd (631+LAN). Free energies were also computed for the gas phase.

1). With regard to its reaction mechanism, the present Pdcatalyzed cyclotrimerization possesses several interesting aspects in contrast to the Pd-catalyzed Heck-type reaction that generally does not proceed in norbornene (vide infra). To elucidate the reaction mechanism and the stereoselectivity of the present Pd-catalyzed cyclotrimerization, DFT calculations were carried out.

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CHEMICAL MODELS AND COMPUTATIONAL METHODS

There are three possible reaction pathways (paths A−C), as shown in Scheme 2. In path A, as was proposed previously,3a,b the sequential olefin insertion and HX elimination reactions of halonorbornene with the norbornenylpalladium(II) intermediate derived from Pd and halonorbornene would yield the trimer intermediate. The trimer intermediate would undergo electrocyclization followed by βelimination of HPdX and aromatization to afford the tris(norborneno)benzene product with syn selectivity. In addition to our proposed mechanism, related reaction mechanisms (e.g., paths B and C) through the formation of a palladacycle should be investigated according to the Catellani reaction.6 Paths B and C would both involve the formation of the five-membered palladacycle species from the dimer intermediate. In path B, the Pd(IV) intermediate generated by the oxidative addition of halonorbornene to the palladacycle species would undergo reductive elimination to afford the trimer intermediate. In path C, the direct insertion of halonorbornene into the fivemembered palladacycle species and the subsequent HX elimination would yield the seven-membered palladacycle species, leading to the product by reductive elimination. To identify the ideal reaction mechanism, those reaction pathways were compared by using the simplified chemical model (Figure 1a). As we previously reported,3 Pd nanoclusters were generated through the reduction of Pd(II) to Pd(0) by phosphine under our conditions.7 The actual catalytic species were

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RESULTS AND DISCUSSION Simplified Model Study. The three reaction pathways (paths A−C) in the simplified chemical model were explored first. In path A, the insertion of vinyl chloride into the Pd(II) intermediate (TS4‑5, TS7‑8) and the subsequent HCl elimination (TS5‑6, TS8‑9) yielded trimer intermediate 9. The relative trans configuration of PdCl and H in the realistic halonorbornene system allowed us to ignore the β-elimination of HPdCl in Pd(II) intermediates 5 and 8. Instead, the elimination of HCl to furnish the dienylpalladium or trienylpalladium intermediate (6 or 9) was investigated. After electrocyclization (TS9‑10) and the subsequent β-elimination of HPdCl (TS10‑11), product 11 is formed. The energy profile is exothermic, consistent with the experimental conditions (Figure 2). The insertion steps (TS4‑5, TS7‑8) require an energy barrier of ca. 15 kcal/mol. This value seems appropriate as the activation energy for olefin insertion into the Pd−C bond.13 In spite of the structural difference between CH2CH and CH2CHCHCH groups, the cyclic transition structures are similar. This is consistent with the almost identical activation energies (TS4‑5 and TS7‑8 in Figure 3). The energy barriers of the subsequent HCl elimination step (TS5‑6, TS8‑9) are much larger but are obviously overestimated. Both transition structures would be highly polarized and destabilized by the large structural deformation in which chloride ion is almost eliminated (TS5‑6 and TS8‑9 in Figure 3). Therefore, a polar solvent (e.g., 1,4-dioxane) and/or an anion species

Figure 1. Chemical models. 3061

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Figure 2. Energy profile of path A in the simplified chemical model at the B3LYP/631LAN level. Calculations at the B3LYP/6311+LAN level are shown in parentheses.

energy barrier (see Figures S2 and S3 in the Supporting Information). The electrocyclization of 9 with an energy barrier of 18.3 kcal/mol is an exothermic and irreversible step (TS9‑10). The electrocyclization of hexatriene proceeds through a disrotatory ring-closing mechanism with an energy barrier of 20.3 kcal/mol (CPtriene and TStriene in Figure 3). The energy barrier of TS9‑10 is 2.0 kcal/mol smaller than that of TStriene. On the other hand, the electrocyclization of trienyl metal compounds also occurs in a disrotatory fashion to afford cyclohexadienyl metal compounds.14 The difference in the electrocyclization between the triene and the trienyl metal compounds is still unclear. Our DFT calculations revealed the structural feature of a TS generated by the disrotatory electrocyclization of the trienylpalladium intermediate (TS9‑10). In contrast to TStriene having a highly symmetric and resonance-stabilized structure (C−C bond lengths 1.40− 1.41 Å), TS9‑10 has a nonsymmetric and less resonancestabilized structure due to the PdCl substituent (C−C bond lengths 1.36−1.45 Å). However, the intramolecular coordination of the central alkene moiety on Pd stabilizes TS9‑10 (Figure 3). This indicates that the electrocyclization of the trienyl metal compounds would readily proceed. The following β-elimination step occurs easily with an energy barrier of 12.5 kcal/mol (TS10‑11). This is due to the small difference in gross structure between 10 and TS10‑11 other than the distance of Pd−H. The Pd−H interaction is enhanced when the C−H bond is weakened in TS10‑11 (Figure 3). To investigate the alternative pathways (paths B and C) via palladacycle formation, we attempted to confirm the possibility of palladacyclization (Figures 4 and 5). In comparison to dimer intermediate 6, five-membered palladacycle 12 would be labile and 32.4 kcal/mol less stable in energy (Figure 5a). Because of this, we failed to identify a TS that would directly form 12 from 6. In a manner similar to the HCl elimination step, anion species, such as hydroxide ion, would accelerate sp2 C−H bond cleavage and nucleophilic addition on Pd to form 12 under basic conditions. Then, the simplified chemical model with hydroxide ion (basic conditions model) was employed at the B3LYP/631+LAN level. The palladacyclization of 6-OH (TS6‑12-OH) requires an energy barrier of 20.7 kcal/mol to form 12-OH that is 7.5 kcal/mol less stable than 6-OH. The

Figure 3. 3D structures in (a) path A (Pd, sky blue; Cl, green; C, gray; H, white) and (b) the electrocyclization of hexatriene. Bond lengths are shown in Å.

generated under basic conditions (e.g., hydroxide ion) would stabilize the polarized transition state (TS) in the HCl elimination step to decrease the activation energy. The hydroxide anion, in particular, accelerates deprotonation followed by elimination of chloride anion with the lower 3062

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OH, 7-OH, TS7‑8-OH, and 8-OH in the basic conditions model would remain almost unchanged from those in the simplified chemical model (Figure 5c). Then, the two reaction pathways (paths B and C) via palladacycle formation in the simplified chemical model were explored (Figures 6 and 7). The alternative pathway is shown in

Figure 4. Energy profiles of palladacyclization (left) and olefin insertion (right) in the basic conditions model.

Figure 6. Energy profile of path B in the simplified chemical model.

Figure 5. 3D structures of palladacyclization (a, b) and olefin insertion (c) in the simplified chemical model (a) and the basic conditions model (b, c) (Pd, sky blue; Cl, green; O, red; C, gray; H, white). Bond lengths are shown in Å.

Figure 7. Energy profile of path C in the simplified chemical model.

blue in path B (Figure 6). The reaction of 12 with vinyl chloride affords the labile Pd carbenoid intermediate 14 through TS13‑14 with an energy barrier of ca. 30 kcal/mol. After Pd−C bond cleavage and decomposition of 14, the sevenmembered palladacycle 15 is formed as a palladacycle intermediate more stable than 12. The σ-bond metathesis of 15 occurs through TS15‑10. In TS15‑10, Pd−C and C−Cl bonds are cleaved and Pd−Cl and C−C bonds are formed simultaneously to afford 10 and connect path A. Another possible pathway is shown in green in path C (Figure 7). Trimer intermediate 17 connecting path A was directly obtained by the oxidative addition of vinyl chloride to 12 (TS13‑17).15 Reductive elimination would occur through Pd(IV) intermediate 16, which was independently optimized and would be the inflection point of the potential energy surface between TS13‑17 and 17. As TS13‑14 in path B and TS13‑17 in path C are located at a higher energy level than the TSs in path A, both paths B and C should be negligible.

hydroxide anion coordinating on Pd abstracts a proton from the terminal alkene moiety to promote nucleophilic addition on Pd and palladacycle formation (left in Figure 4). Then, the hydroxide anion constructs a stable planar four-coordinated Pd(II) structure in 6-OH and TS6‑12-OH (Figure 5b). In 12OH, H2O generated by the abstraction of proton and chloride ion weakly coordinates on Pd. To confirm whether palladacyclization is a bifurcated pathway in path A, palladacyclization was compared with olefin insertion in the basic conditions model (right-hand side in Figure 4). The energy barrier of the second olefin insertion of 6-OH (20.4 kcal/mol) is almost the same as that of palladacyclization (20.7 kcal/mol). This indicates that palladacyclization would occur competitively during the course of path A. As the stable planar four-coordinated Pd(II) structure is maintained through the second olefin insertion, the relative energy differences among 63063

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to 10 is energetically less stable than TS9‑10 due to the deformed four-membered cyclic structure (TS15‑10 in Figure 8). In path C, TS13‑17 has a deformed tetrahedral coordination on the Pd(II) center, which is electronically deficient to yield a large activation energy for the oxidative addition (TS13‑17 in Figure 8). Pd(IV) intermediate 16, as a potential intermediate between TS13‑17 and 17, has a completely Cs symmetric structure (16 in Figure 8). Symmetry breaking of 16 would induce reductive elimination to afford trimer intermediate 17. On the basis of computational studies on the simplified chemical model, the sequential insertion and elimination reactions followed by the electrocyclization (path A) would be the most ideal reaction pathway for the present Pd-catalyzed cyclotrimerization. As was reported experimentally, enantiopure syn-tris(norborneno)benzenes syn-2 were stereoselectively synthesized from enantiopure iodonorbornenes 1 (syn/anti selectivity ranging from 77/23 to 100/0). To elucidate the major factor contributing to the stereochemical induction in the formation of 2, possible reaction pathways leading to the stereoisomers were addressed by using the realistic chemical model (Figure 1) based on path A. Realistic Chemical Model Study. According to the ideal path A, the syn/anti selectivity would be controlled by the olefin insertion process. In this process, there are two possible TSs corresponding to the regioselective C−C bond formation: hetero position a and homo position b (red dotted box in Scheme 3). There are four possible reaction pathways, depending on the combination of the two olefin insertion processes (aa, ab, ba, bb in Scheme 3). In addition, after the

Instead of the direct formation of 15 via the olefin insertion of 12, the unusual Pd carbenoid intermediate 14 is formed in path B. The shorter Pd−C bond of 14 (1.96 Å) in comparison to that of 12 (2.00 Å) indicates that 14 is a Pd carbenoid intermediate (14 in Figure 8). The relatively small activation

Figure 8. 3D structures in paths B and C (Pd, sky blue; Cl, green; C, gray; H, white). Bond lengths are shown in Å.

energy of TS14‑15 (ca. 4 kcal/mol) is attributed to the small structural difference between 14 and TS14‑15. TS15‑10 connecting

Scheme 3. Six Diastereomeric Reaction Pathways in the Realistic Chemical Model

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Figure 9. Energy profile of the most energetically favored pathway based on path A in the realistic chemical model.

Figure 10. 3D structures in the realistic chemical model (Pd, sky blue; Cl, green; C, gray; H, white). Bond lengths are shown in Å.

formation of the dimer intermediate, two diastereomeric reaction pathways from the enantiomer of the dimer

intermediate via palladacycle formation and decomposition (the position of Pd is transferred from the blue carbon to the 3065

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red carbon) would also affect the stereoselectivity. In a total of six diastereomeric reaction pathways, the two olefin insertion processes would occur at the hetero position (involving only the cross-coupling between blue and red carbons: aa) to afford only syn-2. On the other hand, the C−C bond formation at the homo position in one of the two olefin insertion processes (involving cross-coupling between same-colored carbons: ab, ba, bb) would yield anti-2. To elucidate the syn/anti selectivity, the two olefin insertion processes were explored in detail. In addition, the substituent effect of iodonorbornene derivatives on the stereoselectivity was addressed. The energy profile of the most energetically favored pathway based on path A is shown in Figure 9. The energy profile of the realistic chemical model was found to be very similar to that of the small model. Whereas the two olefin insertion steps (TS19‑20-a1 and TS23‑24-a1) have almost the same activation energies (ca. 13 kcal/mol), the activation energies for the two HCl elimination steps (TS21‑22 and TS24‑25) are also overestimated (Figure 9 and Figure S2 (Supporting Information)). The gross structures of the reaction centers in the realistic chemical model are similar to those in the simplified chemical model through the sequential olefin insertion and HCl elimination reactions (19 to 25 in Figure 10). Instead of the sterically hindered norbornene component, the 16.7 kcal/mol energy barrier for the electrocyclization of 25 in the realistic chemical model (TS25‑26 in Figure 10) becomes smaller than that of 9 in the simplified chemical model (TS9‑10 in Figure 3). A structural difference in the reaction center is noted between TS9‑10 and TS25‑26. The former would be stabilized by the coordination of the central alkene moiety on Pd (vide supra). In contrast, the latter has an agostic interaction between Pd and the CH bond and remains as a relatively symmetric conjugated structure that would induce resonance stabilization (C−C bond lengths around the reaction center 1.38−1.44 Å, TS25‑26 in Figure 10). Pd is located in the concave face of the norbornene moiety to promote the inward rotation of the methylene bridge due to π-orbital overlap. Although the diastereomeric TS (Pd, convex face; methylene bridge, outward rotation) should exist in the realistic chemical model, the inward rotation of the more hindered ethylene bridge would induce a larger steric repulsion to destabilize the diastereomeric TS. The β-elimination step, furthermore, has a very small activation energy (1.4 kcal/mol). The norbornene component would structurally confine the CH group at the β-position to induce a strong agostic interaction even in 26. Therefore, TS26‑2(syn) requires very minimal structural deformation for the β-elimination step (TS26‑2(syn) in Figure 10). The bifurcation point of the syn/anti selectivity is the olefin insertion process (red dotted box in Scheme 3). In the first olefin insertion process, we compared TSs of the C−C bond formation at the hetero position (TS19‑20-a) leading to syn-2 and the homo position (TS19‑20-b) leading to anti-2. According to the norbornene structure, enantiopure chloronorbornene and 18 would approach each other from either the convex or concave face. There are four possible TSs that correspond to the facial selectivity of the substrates (convex or concave face) in the C−C bond formation at both hetero and homo positions (Table 1). The C−C bond formation at the hetero position (TS19‑20-a) is energetically more favored than that at the homo position (TS19‑20-b). Whereas TS19‑20-a1 (chloronorbornene, convex; 18, convex) is the most stable TS, TS19‑20-a2 is slightly less stable than TS19‑20-a1 within 1 kcal/mol. Chloronorbornene readily approaches 18 from the convex face because of the

Table 1. Relative Energies of Diastereomeric TSs for the First Olefin Insertion Process (TS19‑20)a

(18, chloronorbornene) (convex, convex) (concave, convex) (convex, concave) (concave, concave) a

hetero TS19‑20-a1 TS19‑20-a2 TS19‑20-a3 TS19‑20-a4

(0.0) (0.8) (9.2) (7.1)

homo TS19‑20-b1 TS19‑20-b2 TS19‑20-b3 TS19‑20-b4

(3.9) (4.2) (12.6) (13.8)

Relative energies are shown in kcal/mol.

smaller steric repulsion by the less hindered methylene group of the norbornene structure (Figure 11). On the other hand, the

Figure 11. 3D structures of diastereomeric TSs for the first olefin insertion process (TS19‑20,; Pd, sky blue; Cl, green; C, gray; H, white). Bond lengths are shown in Å. Relative energies (kcal/mol) are shown in parentheses.

most stable TS19‑20-b1 in the TS-b series is less stable than TS19‑20-a1 by 3.9 kcal/mol, in agreement with the syn-selective formation of 2. In TS19‑20-b1, the two norbornene moieties are located very closely to induce large steric repulsion (purple curves in Figure 11). Olefin insertion product 20 would directly connect to the second olefin insertion (TS23‑24-a1) through the isomerization to 21 (TS20‑21) and HCl elimination (TS21‑22). Isomerized product 21 would be directly formed via TS19‑20-a2. In the second olefin insertion process, a similar structural tendency is predicted for the C−C bond formation at the hetero and homo positions. Therefore, only TSs corresponding to the convex face approach were explored. According to the simplified chemical model study in relation to the possibility of palladacycle formation, the diastereomeric reaction pathway from the enantiomer of dimer intermediate ent-22 should be compared (red dotted box in Scheme 3). In a manner similar to the first olefin insertion process, the C−C bond formation at the hetero position is energetically favorable for 22 (Table 2). TS23‑24-a1 (hetero position) is more stable than TS23‑24-b1 (homo position) by 5.0 kcal/mol. On the other hand, the reverse tendency was observed for ent-22, in which the position of Pd is transferred from a blue carbon to a red carbon (Table 2). TS23‑24-d1 (homo position) is 6.9 kcal/mol more stable than TS23‑24-c1 (hetero position). In both TS23‑24-a1 and TS23‑24-d1, there is hardly any steric hindrance between the two norbornene moieties (Figure 12). These structural properties are consistent with the small energy difference between TS23‑24a1 and TS23‑24-d1. In contrast, the terminal and Pd-connected norbornene moieties induce large steric repulsion with chloronorbornene in TS23‑24-b1 and TS23‑24-c1, respectively 3066

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introduction of a substituent into 1a breaks the Cs symmetry of the palladacycle intermediate to energetically differentiate the two diastereomeric dimer intermediates (e.g., 22 and ent-22) and preferentially promote the main reaction pathway rather than the diastereomeric pathway. To estimate the stability of the diastereomeric dimer intermediates, four palladacycle intermediates 27−30 derived from 1a−d were structurally investigated (Figure 13). In a manner similar to that for 27, 28

Table 2. Relative Energies of Diastereomeric TSs for the Second Olefin Insertion Process (TS23‑24)a

a

(X, chloronorbornene)

hetero

homo

X = 22 (convex, convex) X = ent-22 (convex, convex)

TS23‑24-a1 (+0.9) TS23‑24-c1 (+6.9)

TS23‑24-b1 (+5.0) TS23‑24-d1 (0.0)

Relative energies are shown in kcal/mol.

Figure 13. 3D structures of palladacycles 27−30 derived from 1a−d (Pd, sky blue; Cl, green; O, red; N, blue; C, gray; H, white). Bond lengths are shown in Å.

has a Cs-symmetric structure to afford moderate syn/anti selectivity for 1b. On the other hand, the Cs-symmetric structure of the palladacycle intermediate is slightly broken in 29. The shorter and stronger Pd−C (red carbon) bond in comparison to the Pd−C (blue carbon) bond would prevent the diastereomeric pathway affording anti-2. In 30 as the most crucial case leading to complete syn selectivity, coordination of the p-MeOC 6 H 4 group with Pd much enhances the desymmetrization of the palladacycle structure. The intramolecular coordination of the Ar group would stabilize the dimer intermediate with the Pd−C (red carbon) bond to promote the main reaction pathway affording syn-2. These computational predictions of syn/anti selectivity are consistent with the experimental results (syn selectivity: 1a ≈ 1b < 1c < 1d). In conclusion, we carried out detailed DFT calculations to elucidate the reaction mechanism as well as the stereoselectivity of the present Pd-catalyzed cyclotrimerization. The reaction would proceed through the sequential olefin insertion followed by the HX elimination reaction of halonorbornene with the norbornenylpalladium intermediate. The trienylpalladium intermediate would undergo disrotatory electrocyclization with an activation barrier lower than that for a triene compound. This process yields the cyclohexadienylpalladium intermediate leading to the tris(norborneno)benzene via the β-elimination of HPdX. In this promising reaction pathway, the stereoselectivity is controlled by two major factors: regioselectivity in the olefin

Figure 12. 3D structures of diastereomeric TSs for the first olefin insertion process (TS23‑24; Pd, sky blue; Cl, green; C, gray; H, white). Bond lengths are shown in Å. Relative energies (kcal/mol) are shown in parentheses.

(purple curves in Figure 12). TS23‑24-a1 would yield syn-2, whereas TS23‑24-d1 would be involved in the diastereomeric pathway to afford anti-2. The reaction proceeding via the palladacycle formation would furnish 2 with 1/1 syn/anti selectivity because of the small energy difference between TS23‑24-a1 and TS23‑24-d1. As described in the simplified chemical model study, palladacyclization would proceed competitively during the course of the main reaction pathway (path A). The experimentally observed moderate syn/anti selectivity (77/23) for 1a would be eventually caused by the nearly zero energy difference between the main reaction pathway affording syn-2 and the alternative reaction pathways via palladacycle formation affording 2 with 1/1 syn/anti selectivity. Two diastereomeric dienylpalladium intermediates actually exist in equilibrium through palladacycle formation and decomposition. Therefore, the key point for enhancing syn selectivity is the equilibrium control of the palladacyclization to suppress the diastereomeric reaction. The 3067

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Scheme 4. Substituent Control of syn/anti Selectivity

2010; Vol. 292, pp 1−34. (b) Maestri, G.; Motti, E.; Della Ca’, N.; Malacria, M.; Derat, E.; Catellani, M. J. Am. Chem. Soc. 2011, 133, 8574−8585. (7) Instead of Pd(OAc)2 and triphenylphosphine, allylpalladium chloride dimer without phosphine ligand can be used under the same conditions in Scheme 1. Heating allylpalladium chloride dimer generates Pd(0), forming Pd nanoclusters. The role of the phosphine ligand is not important in the subsequent catalytic process. (8) (a) Thathagar, M. B.; ten Elshof, J. E.; Rothenberg, G. Angew. Chem., Int. Ed. 2006, 45, 2886−2890. (b) Gaikwad, A. V.; Holuigue, A.; Thathagar, M. B.; ten Elshof, J. E.; Rothenberg, G. Chem. Eur. J. 2007, 13, 6908−6913. (c) Reimann, S.; Stötzel, J.; Frahm, R.; Kleist, W.; Grunwaldt, J.-D.; Baiker, A. J. Am. Chem. Soc. 2011, 133, 3821− 3930. (9) Frisch, M. J., et al. Gaussian 03, Revision E.01; Gaussian, Inc., Wallingford, CT, 2004. (10) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648−5652. (b) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785−789. (11) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 299−310. (12) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab initio Molecular Orbital Theory; Wiley: New York, 1986, and references cited therein. (13) For selected references: (a) Michalak, A.; Ziegler, T. J. Am. Chem. Soc. 2001, 123, 12266−12278. (b) Lin, B.-L.; Liu, L.; Fu, Y.; Luo, S.-W.; Chen, Q.; Guo, Q.-X. Organometallics 2004, 23, 2114− 2123. (c) García-Iglesias, M.; Bunñuel, E.; Cárdenas, D. J. Organometallics 2006, 25, 3620−3627. (d) Lan, Y.; Deng, L.; Liu, J.; Wang, C.; Wiest, O.; Yang, Z.; Wu, Y.-D. J. Org. Chem. 2009, 74, 5049−5058. (e) Kilyanek, S. M.; Stoebenau, E. J., III; Vinayavekhin, N.; Jordan, R. F. Organometallics 2010, 29, 1750−1760. (14) For related references of the electrocyclization of trienyl metal compounds: (a) Lee, G. C. M.; Tobias, B.; Holmes, J. M.; Harcourt, D. A.; Garst, M. E. J. Am. Chem. Soc. 1990, 112, 9330−9336. (b) Meyer, F. E.; de Meijere, A. Synlett 1991, 777−778. (c) Rathore, R.; Linderman, S. V.; Kumar, A. S.; Kochi, J. K. J. Am. Chem. Soc. 1998, 120, 6012−6018. (d) Kinoshita, H.; Takahashi, H.; Miura, K. Org. Lett. 2013, 15, 2962−2965. (15) Although the possibility of transmetalation between 12 and vinylpalladium chloride through the bimetallic pathway could not be excluded, the TS of this process would be located at a higher energy level than the TSs in path A (see also ref 6b).

insertion process (homo and hetero positions) and symmetry breaking in the palladacycle intermediate. The C−C bond formation in the olefin insertion process preferentially proceeds at the hetero position to yield a syn product. The palladacycle formation and decomposition provides an opportunity to switch to the C−C bond formation at the homo position to generate the anti product. As the palladacyclization competes with the main reaction pathway (Figure 4), the equilibrium control between two diastereomeric dienylpalladium intermediates is the key for enhancing syn selectivity (Scheme 4).

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ASSOCIATED CONTENT

S Supporting Information *

Text, figures, and xyz files giving computational details (Cartesian coordinates and absolute energies for stationary points). This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Notes

The authors declare no competing financial interest.

ACKNOWLEDGMENTS This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Advanced Molecular Transformations by Organocatalysts” from the MEXT of Japan and MEXT-Supported Program for the Strategic Research Foundation at Private Universities.

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REFERENCES

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dx.doi.org/10.1021/om500322b | Organometallics 2014, 33, 3060−3068