Archive for the 'Bergman cyclization' Category

Bergman Cyclization on a Gold Surface

The Bergman cyclization and some competitive reactions are discussed in detail in Chapter 4 of by book. The Bergman cyclization makes the C1-C6 bond from an enediyne. Another, but rarer, option is to make the C1-C5 bond, the Schreiner-Pascal cyclization pathway. de Oteyza and coworkers have examined the competition between these two pathways for 1 on a gold surface, and used STM and computations to identify the reaction pathway.1

The two pathways are shown below. The STM images identify 1 as the reactant on the gold surface and the product is 6. No other product is observed.

Projector augmented wave (PAW) pseudo-potential computations using the PBE functional were performed for the reaction on a Au (111) surface was modeled by a 7 x 7 x 3 supercell. The optimized geometries of the critical points are show in Figure 1.










Figure 1. Optimized geometries of the critical points on the two reaction pathways.

Explicit values of the relative energies are not given in either the paper or the supporting information, but rather a plot shows the relative positions of the critical points. The important points are the following: (a) the barrier for the C1-C5 cyclization is lower than the barrier for the C1-C6 cyclization and 3 is lower in energy than 2; (b) 5 is lower in energy than 6; and (c) the barrier for taking 2 to 6 is significantly below the barrier taking 3 into 5. The barrier for the phenyl migration taking 3 into 5 is so high because of a strong interaction between the carbon radical and a gold atom of the surface. The authors suggest that the two initial cyclizations are reversible, but the very high barrier for forming 5 precludes it from taking place, leaving only the route to 6 as a viable pathway.


(1) de Oteyza, D. G.; Paz, A. P.; Chen, Y.-C.; Pedramrazi, Z.; Riss, A.; Wickenburg, S.; Tsai, H.-Z.; Fischer, F. R.; Crommei, M. F.; Rubio, A. “Enediyne Cyclization on Au(111),” J. Amer. Chem. Soc. 2016, 138, 10963–10967, DOI: 10.1021/jacs.6b05203.


1: InChI=1S/C22H14/c1-3-9-19(10-4-1)15-17-21-13-7-8-14-22(21)18-16-20-11-5-2-6-12-20/h1-14H

2: InChI=1S/C22H14/c1-3-9-17(10-4-1)21-15-19-13-7-8-14-20(19)16-22(21)18-11-5-2-6-12-18/h1-14H

3: InChI=1S/C22H14/c1-3-9-17(10-4-1)15-22-20-14-8-7-13-19(20)16-21(22)18-11-5-2-6-12-18/h1-14H

4: InChI=1S/C22H14/c1-3-9-17(10-4-1)20-15-19-13-7-8-14-21(19)22(16-20)18-11-5-2-6-12-18/h1-14H

5: InChI=1S/C22H14/c1-3-9-17(10-4-1)15-19-16-22(18-11-5-2-6-12-18)21-14-8-7-13-20(19)21/h1-14H

6: InChI=1S/C22H14/c1-3-9-15(10-4-1)19-17-13-7-8-14-18(17)21-20(22(19)21)16-11-5-2-6-12-16/h1-14H

Bergman cyclization Steven Bachrach 19 Sep 2016 No Comments

Synthetic application of the Bergman cyclization

Synthetic application of the Bergman cyclization is rare. Basak reports a real interesting use of this reaction to create polycyclic aromatics.1 So, for example, heating up 1 in DMSO leads to the 4helicene 2. The proposed mechanism is shown in Figure 1. The Bergman cyclization leads to the biradical 3, which adds to the pendant phenyl group to give 4. Hydrogen abstraction then gives 5, which abstracts hydrogens from the solvent to produce 6. (Use of DMSO-d 6 provides deuterium incorporated products consistent with the diradical shown in 4.) Oxidation then gives the final product 2.

Figure 1. Proposed mechanism for the conversion of 1 to 2.

B3LYP computations were performed to examine the relative rates with substituents on the phenyl ring. The structure of 1’ (with a methyl group replacing the Ns group – 4-nitrobenzenesulfonyl) and the transition state for the Bergman cyclization are shown in Figure 2. Unfortunately, computations were not used to analyze the complete proposed mechanism – a project that awaits the eager student perhaps?



Figure 2. B3LYP/def2-TZVP//BP86/def2-TZVP optimized structures of 1’ and transition state for the Bergman cyclization of 1’.


(1) Roy, S.; Anoop, A.; Biradha, K.; Basak, A., "Synthesis of Angularly Fused Aromatic Compounds from Alkenyl Enediynes by a Tandem Radical Cyclization Process," Angew. Chem. Int. Ed., 2011, 50, 8316-8319, DOI: 10.1002/anie.201103318


1’: InChI=1/C21H17N/c1-22-15-7-12-20-10-5-6-11-21(20)14-13-19(17-22)16-18-8-3-2-4-9-18/h2-6,8-11,16H,15,17H2,1H3/b19-16+

2’: InChI=1/C21H17N/c1-22-12-16-10-14-6-2-4-8-18(14)21-19-9-5-3-7-15(19)11-17(13-22)20(16)21/h2-11H,12-13H2,1H3

Bergman cyclization Steven Bachrach 07 Feb 2012 No Comments

Garrat-Braverman vs Myers-Saito Cyclization

The competition between Bergman cyclization and Myers-Saito cyclization of ene-ynes and related species is discussed in Chapter 3.3 of my book and also in these posts. Yet another variation, the Garratt-Braverman cyclization1-3 has now been examined in terms of competition with the Myers-Saito cyclization for 1 using both experiments and computations.4 Subjecting 1 to base should cause the rearrangement to either GB1 or MS2. These can undergo either the Garratt-Braverman cyclization to give GB2 or the Myers-Saito cyclization to MS2.

B3LYP/6-31G(d) predicts that GB1 is only slightly higher in energy than MS1 (by 0.7 kcal mol-1). The transition states (GB1toGB2 or MS1toMS2 – see Figure 1) each lie 24.4 kcal mol-1 above their respective reactants. However, the diradical GB2 is 7.2 kcal mol-1 below GB1 but MS2 is only 0.3 kcal mol-1 below MS1. So while the two reactions are of similar kinetic probability, having identical activation barriers, the GB route leads to the more thermodynamically stable intermediate. Furthermore, the GB route ultimately results in GBP, via an intramolecular cyclization of the diradical, while the MS route, which ends with MSP, requires intermolecular abstraction of 4 hydrogens. Thus, the unimolecularity of the GB path further favors the GB route over the MS pathway. In fact, experimental studies of 1 and related compounds all give rise to the GB product only.







Figure 1. B3LYP/6-31G(d) optimized structures.4


(1) Braverman, S.; Segev, D., "Novel cyclization of diallenic sulfones," J. Am. Chem. Soc. 2002, 96, 1245-1247, DOI: 10.1021/ja00811a060

(2) Garratt, P. J.; Neoh, S. B., "Strained heterocycles. Properties of five-membered heterocycles fused to four-, six-, and eight-membered rings prepared by base-catalyzed rearrangement of 4-heterohepta-1,6-diynes," J. Org. Chem. 2002, 44, 2667-2674, DOI: 10.1021/jo01329a016

(3) Zafrani, Y.; Gottlieb, H. E.; Sprecher, M.; Braverman, S., "Sequential Intermediates in the Base-Catalyzed Conversion of Bis(π-conjugated propargyl) Sulfones to 1,3-Dihydrobenzo- and Naphtho[c]thiophene-2,2-dioxides," J. Org. Chem. 2005, 70, 10166-10168, DOI: 10.1021/jo051692i

(4) Basak, A.; Das, S.; Mallick, D.; Jemmis, E. D., "Which One Is Preferred: Myers-Saito Cyclization of Ene-Yne-Allene or Garratt-Braverman Cyclization of Conjugated Bisallenic Sulfone? A Theoretical and Experimental Study," J. Am. Chem. Soc. 2009, 131, 15695-15704, DOI: 10.1021/ja9023644

Bergman cyclization Steven Bachrach 14 Dec 2009 No Comments

C1-C5 cyclization of enediynes – Alternative to the Bergman reaction

Cyclization of enediynes is thoroughly discussed in Chapter 3.3 of my book. The reaction that started all the excitement is the C1-C6 cyclization (the Bergman cyclization, Reaction 1). Meyers and Saito then proposed the alternative C2-C7 cyclization (Reaction 2), and a variant on this, the Schmittel cyclization (Reaction 3) followed soon thereafter. Now, Pascal completes the theme with a report on the C1-C5 cyclization (Reaction 4).1

Pascal begins with the assumption that terminal aryl substitution on the enediyne will both (a) inhibit the C1-C6 cyclization due to steric interactions and (b) the C1-C5 cyclization should be enhanced due to stabilization of the radical by the neighboring aryl group. He computed the activation energies of a series of analogues, some of which are listed in Table 1. The transition state structures are shown in Figure 1 for 1b and 1c. Phenyl substitution does accomplish both suggestions: the activation barrier for the Bergman cyclization increases by 4 kcal mol-1, while the barrier for the C1-C5 cyclization is lowered by nearly 6 kcal mol-1. Further substitution of the phenyl ring by either chloro or methyl groups brings the barriers into near degeneracy.

Table 1. RBLYP/6-31G(d) Activation energies (kcal mol-1) for
competing cyclization reactions of substituted enediynes.1





H (1a)




Phenyl (1b)




2,6-dichlorophenyl (1c)




2,6-dimethylphenyl (1d)




Phenyl (2a)




2,4,6-trichlorophenyl (2b)




aComputed at BCCD(T)/cc-pVDZ//-BLYP/6-31G(d).

C1-C5 TS of 1b

C1-C6 TS of 1b

C1-C5 TS of 1c

C1-C6 TS of 1c

Figure 1. RBLYP/6-31G(d) optimized geometries of the C1-C5 and C1-C6 transition states for 1b and 1c.1

The di-substituted enediynes were examined next. The C1-C5 and C1-C6 transition states for the phenyl (2a) analogue are shown in Figure 2, and the activation energies for it and the 2,4,6-trichlorophenyl (2b) analogue are listed in Table 1. With BLYP, the C1-C5 cyclization is favored by a significant amount over the Bergman cyclization. This may be an overestimation as the BCCD(T)/cc-pVDZ//-BLYP/6-31G(d) computations predict the opposite energy ordering.

C1-C5 TS of 2a

C1-C2 TS of 2a

Figure 1. RBLYP/6-31G(d) optimized geometries of the C1-C5 and C1-C6 transition states for 2a.1

Pascal synthesized 2b and subjected it to thermolysis. Only indenes were obtained, indicative of the C1-C5 cyclization occurring in total preference over the C1-C6 pathway. The presence of 1,4-cyclohexadiene does improve the yields, suggestive that the transfer hydrogenation mechanism may be operative. However, when the reaction is done in the absence of 1,4-cyclohexadiene and at lower temperature (180 °C), the C1-C5 cyclization is still observed and no Bergman cyclization is seen. It appears that C1-C5 cyclization of enediynes is a viable reaction.


(1) Vavilala, C.; Byrne, N.; Kraml, C. M.; Ho, D. M.; Pascal, R. A., "Thermal C1-C5 Diradical Cyclization of Enediynes," J. Am. Chem. Soc. 2008, 130, 13549-13551, DOI: 10.1021/ja803413f.


1a: InChI=1/C10H6/c1-3-9-7-5-6-8-10(9)4-2/h1-2,5-8H

1b: InChI=1/C16H10/c1-2-15-10-6-7-11-16(15)13-12-14-8-4-3-5-9-14/h1,3-11H

1c: InChI=1/C16H8Cl2/c1-2-12-6-3-4-7-13(12)10-11-14-15(17)8-5-9-16(14)18/h1,3-9H

1d: InChI=1/C18H14/c1-4-16-10-5-6-11-17(16)12-13-18-14(2)8-7-9-15(18)3/h1,5-11H,2-3H3

2a: InChI=1/C22H14/c1-3-9-19(10-4-1)15-17-21-13-7-8-14-22(21)18-16-20-11-5-2-6-12-20/h1-14H

2b: InChI=1/C22H8Cl6/c23-15-9-19(25)17(20(26)10-15)7-5-13-3-1-2-4-14(13)6-8-18-21(27)11-16(24)12-22(18)28/h1-4,9-12H

Bergman cyclization Steven Bachrach 24 Nov 2008 1 Comment

Cyclization of enyne allenes

In Chapter I discuss the computational and experimental results of Singleton1 regarding C2-C6 enyne allene cyclization. The reaction is shown below, and though Singleton could locate no transition state that connects the reactant to the diradical, molecular dynamics trajectory calculations show that the diradical is sampled, though the dominant pathway is the concerted route.

Schmittel has expanded on this work by determining the kinetic isotope effects for four more analogues.2 The results are summarized in Table 1. Depending on the substituent, the predominant pathway can be concerted or stepwise or even a mixture of these two (termed “boundary”). Schmittel argues that the region about the single transition state, the one that directly connect reactant to product through a concerted path, is actually quite flat. This is a “broad transition state zone”. Trajectories can traverse through various regions of the zone, some that go on to diradical, some that go on to product. Substituents can alter the shape of the TS zone and thereby shift the set of trajectories in one direction or the other. The upshot is further support for the importance on non-statistical dynamics in dictating the course of reactions.

Table 1. Kinetic isotope effects for C2-C6 enyne allene cyclizations




R=TMS, R’=H, R”=TMS, Y=OAc



R=TMS, R’=iPr, R”=TMS, Y=H



R=tBu, R’=iPr, R”=TMS, Y=H



R=TIPS, R’=iPr, R”=p-An, Y=H



R=TMS, R’=iPr, R”=p-An, Y=H




(1) Bekele, T.; Christian, C. F.; Lipton, M. A.; Singleton, D. A., ""Concerted" Transition State, Stepwise Mechanism. Dynamics Effects in C2-C6 Enyne Allene Cyclizations," J. Am. Chem. Soc. 2005, 127, 9216-9223, DOI: 10.1021/ja0508673.

(2) Schmittel, M.; Vavilala, C.; Jaquet, R., "Elucidation of Nonstatistical Dynamic Effects
in the Cyclization of Enyne Allenes by Means of Kinetic Isotope Effects," Angew. Chem. Int. Ed. 2007, 46, 6911-6914, DOI: 10.1002/anie.200700709

Bergman cyclization &Dynamics Steven Bachrach 03 Dec 2007 No Comments

Bergman cyclization and [10]annulenes

In their continuing efforts to build novel aromatic systems, Siegel and Baldridge report the preparation of the decapropyl analogue of the per-ethynylated corrannulene 1.1 They were hoping that this might cyclize to the bowl 2. It is however stable up to 100 °C, however, the analogue 3 was obtained in the initial preparation of decapropyl-1.

The B3LYP/cc-pVDZ optimized structures of 1 and 3 are shown in Figure 1. 1 is bowl-shaped, reflecting the property of corranulene, but interestingly 3 is planar. The geometry of the {10]annulene is interesting as it is more consistent with the alkynyl resonance form B.



Figure 1. B3LYP/cc-pVDZ optimized structures of 1 and 3.1

Siegel and Baldridge speculate that the conversion of 1 → 3 occurs by first undergoing the Bergman cyclization to give 4, which then opens to give 3. Unfortunately, they did not compute the activation barrier for this process. They do suggest that further cyclization to give the hoped for 2 might be precluded by the long distances between radical center and neighboring alkynes in 4, but the radicals are too protected to allowing trapping by the solvent, allowing for the formation of 3.


(1) Hayama, T.; Wu, Y. T.; Linden, A.; Baldridge, K. K.; Siegel, J. S., "Synthesis, Structure, and Isomerization of Decapentynylcorannulene: Enediyne Cyclization/Interconversion of C40R10 Isomers," J. Am. Chem. Soc., 2007, 129, 12612-12613 DOI: 10.1021/ja074403b.


1: InChI=1/C40H10/c1-11-21-22(12-2)32-25(15-5)26(16-6)34-29(19-9)30(20-10)35-28(18-8)27(17-7)33-24(14-4)23(13-3)31(21)36-37(32)39(34)40(35)38(33)36/h1-10H

2: InChI=1/C40H10/c1-2-12-14-5-6-16-18-9-10-20-19-8-7-17-15-4-3-13-11(1)21-22(12)32-24(14)26(16)34-29(18)30(20)35-28(19)27(17)33-25(15)23(13)31(21)36-37(32)39(34)40(35)38(33)36/h1-10H

3: InChI=1/C40H12/c1-9-23-25(11-3)33-27(13-5)29(15-7)35-30(16-8)28(14-6)34-26(12-4)24(10-2)32-22-20-18-17-19-21-31(23)36-37(32)39(34)40(35)38(33)36/h1-8,17-18,31-32H/b18-17-

annulenes &Bergman cyclization &DFT &polycyclic aromatics Steven Bachrach 05 Nov 2007 No Comments