Tris-Annelated Benzenes Selectively Perfunctionalized on One Side Only: Hexachlorobenzotrinorbornadiene as a Versatile Scaffold for the Construction of Molecular Domes

Abstract

Well-defined, rigid molecular domes are obtained via substitution of the chlorine atoms of hexachlorobenzotrinorbornadiene syn-3, efficiently synthesized in 1:2 ratio along with its anti-isomer by CuTC-promoted cyclotrimerization of 3-bromo-2-tri­methylstannylnorbornadiene 8. The three dichlorovinyl functions at the edge of syn-3 are displaced by sulfur nucleophiles and Grignard reagents with Ni(II)Cl₂dppe as catalyst, gaining the persubstituted vinyl sulfides 9 and 10, and persubstituted methyl 12 and phenylethynyl 13.

cyclotrimerization - cross-coupling - nucleophilic substitution - copper(I) 2-thiophenecarboxylate - dendrimers

References

1 Borsato G. De Lucchi O. Fabris F. Groppo L. Lucchini V. Zambon A. J. Org. Chem.  2002,  67:  7894 

2 Borsato G. De Lucchi O. Fabris F. Lucchini V. Pasqualotti M. Zambon A. Tetrahedron Lett.  2003,  44:  561 

3a Allred GD. Liebeskind LS. Sanford S. J. Am. Chem. Soc.  1996,  118:  2748 

3b Zhang S. Zhang D. Liebeskind LS. J. Org. Chem.  1997,  62:  2312 

4 Herberich GE. Spaniol TP. Steffan U. Chem. Ber.  1994,  127:  1401 

5 Nagendrappa G. Tetrahedron  1989,  45:  6485 

6

Cyclotrimerization Reaction. CuTC (23.39 g, 123 mmol) was added portionwise to a solution of 8 (33 g, 82 mmol) in 420 mL dry NMP and stirred at -15 °C. After 3 h the mixture was quenched with 10% aq NH₃ and extracted with EtOAc (3 × 100 mL). The organic layers were dried over MgSO₄ and concentrated in vacuo. The syn- and anti-isomers (11.7 g, 24.6 mol, 90%) were separated by FC (eluant: hexane-CCl₄ 1:1). The syn/anti ratio was 1:2. Compound syn-3: mp 274 °C (dec). ¹H NMR (400 MHz, CDCl₃): δ = 3.86 (6 H, H₁ and H₄, t, J = 1.8 Hz), 2.66 (3 H, H_7s, dt, J = 7.6, 1.5 Hz), 2.24 (3 H, H_7a, dt, J = 7.6, 1.8 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 139.2 (6 C, C₅ and C₆), 136.9 (6 C, C₂ and C₃), 62.0 (3 C, C₇), 53.8 (6 C, C₁ and C₄).
Compound anti-3: mp 215 °C (dec). ¹H NMR (400 MHz, CDCl₃): δ = 3.89 (2 H, H_{1 ′} and H_{4 ′}, t, J = 1.8 Hz), 3.89 and 3.88 (4 H, H₁ and H₄, t, J = 1.8, Hz), 2.66 (2 H, H_7s, dt, J = 7.6, 1.8 Hz), 2.65 (1 H, H_{7s ′}, dt, J = 7.6, 1.8 Hz), 2.25 (1 H, H_{7a ′}, dt, J = 7.6, 1.9 Hz), 2.24 (2 H, H_7a, dt, J = 7.6, 1.9 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 139.0, 138.7 and 138.5 (12 C, C₅, C₆, C_{5 ′} and C_{6 ′}), 137.0, 136.7 and 136.5 (12 C, C₂, C₃, C_{2 ′} and C_{3 ′}), 62.5 and 62.3 (6 C, C₁, C₄, C_{1 ′} and C_{4 ′}), 58.9 (1 C, C_{7 ′}) 53.8 (2 C, C₇).

7

CCDC 261321 contains the crystallographic data for syn-3. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

8 Bürgi H. Baldridge KK. Hardcastle K. Frank NL. Gantzel P. Sigel JS. Ziller J. Angew. Chem., Int. Ed. Engl.  1995,  34:  1454 

9 Balci M. Cossu S. Dastan A. De Lucchi O. Demirci B. Lucchini V. Valle G. Tetrahedron Lett.  1997,  38:  5319 

10 Rathore R. Lindeman SV. Kumar AS. Kochi JK. J. Am. Chem. Soc.  1998,  120:  6012 

11

Reaction of syn -3 with 1-Dodecanthiol.
A solution of dodecanthiol (260 µL, 1.07 mmol) in 5 mL of dry DMF was added portionwise to a solution of syn-3 (50 mg, 0.1 mmol) and NaH 60% (143 mg, 3.59 mmol) in 5 mL DMF. The mixture was stirred under argon 3 d at 110 °C, and then quenched with diluted HCl and extracted with Et₂O (3 × 10 mL). The ethereal extracts were washed with 10% NaOH solution, dried over MgSO₄ and concentrated in vacuo. The reaction crude was purified by FC (eluant: CH₂Cl₂-hexane, 1:9), giving 9 (60%) as brown oil. ¹H NMR (400 MHz, CDCl₃): δ = 3.95 (6 H, H₁ and H₄, t, J = 1.7 Hz), 2.90 and 2.72 (12 H, H₈, t split in an AB system, J = 12.6, 7.6 Hz), 2.22 (3 H, H_7s, dt, J = 7.5, 1.7 Hz), 2.10 (3 H, H_7a, dt, J = 7.5, 1.7 Hz), 1.56 (12 H, H₉, m), 1.43-1.34 (12 H, H₁₀, m), 1.29-1.20 (96 H, CH₂, m), 0.87 (18 H, CH₃, t, J = 7.1 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 144.2 (6 C, C₂ and C₃), 136.8 (6 C, C₅ and C₆), 61.6 (3 C, C₇), 52.1 (6 C, C₁ and C₄), 32.5 (6 C, C₈), 30.3 (6 C, C₉), 29.8-29.5 (6 C, C₁₀), 29.8-29.7 (48 C, CH₂), 14.2 (6 C, CH₃).

12

Reaction of syn -3 with Thiophenol. MeONa was generated in situ by reaction of 5 mL dry MeOH and Na (27.5 mg, 1.2 mmol). The solvent was removed, thiophenol (0.125 mL, 1.2 mmol) and a solution of syn -3 (50 mg, 0.1 mmol) in NMP (5 mL) were added. The mixture was stirred 3 d at 150 °C and then the solvent removed at reduced pressure. The residue was diluted with EtOAc and washed 3 times with 10% NaOH solution. The organic layers were dried over MgSO₄ and concentrated in vacuo. The reaction crude was purified by FC (eluant: EtOAc-hexane, 3:7); giving 10 (90%) as white solid and traces of 11 as a brown oil. Compound 10: ¹H NMR (400 MHz, CDCl₃): δ = 7.33 (12 H, H₉, m), 7.21 (18 H, H₁₀ and H₁₁, m), 3.76 (6 H, H₁ and H₄, t, J = 1.6 Hz), 2.36 (3 H, H_7s, dt, J = 7.7, 1.6 Hz), 2.09 (3 H, H_7a, dt, J = 7.7, 1.6 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 148.7 (6 C, C₂ and C₃), 137.6 (6 C, C₅ and C₆), 135.7 (6 C, C₈), 129.8 (12 C, C₉), 128.8 (12 C, C₁₀), 126.3 (6 C, C₁₁), 60.4 (3 C, C₇), 53.0 (6 C, C₁ and C₄).
Compound 11: ¹H NMR (400 MHz, CDCl₃): δ = 7.42 (4 H, H_{9 ′}, m), 7.37-7.35 (6 H, H_{10 ′} and H_{11 ′}, m), 7.26 (6 H, H₁₀ and H₁₁, m), 7.21 (4 H, H₉, m), 3.80 (2 H, H₁, m), 3.79 (2 H, H₄, m), 3.67 (2 H, H_{1 ′} and H_{4 ′}, t, J = 1.9 Hz), 2.53 (1 H, H_{7s ′}, dt, J = 7.5, 1.8 Hz), 2.36 (2 H, H_7s, dt, J = 7.7, 1.6 Hz), 2.15 (2 H, H_7a, dt, J = 7.7, 1.6 Hz), 2.08 (1 H, H_{7a ′}, J = 7.5, 1.8 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 150.2 (2 C, C₂), 146.0 (2 C, C₃), 139.6 (2 C, C_{2 ′} and C_{3 ′}), 138.2 (2 C, C₅), 137.9 (2 C, C₆), 135.9 (2 C, C_{5 ′} and C_{6 ′}), 135.8 (2 C, C₈), 134.0 (2 C, C_{8 ′}), 130.9 (4 C, C_{9 ′}), 129.4 (6 C, C₁₀ and C₁₁), 129.0 (4 C, C₉), 126.9 (6 C, C_{10 ′} and C_{11 ′}), 53.7 (2 C, C_{1 ′} and C_{4 ′}), 53.4 (2 C, C₁), 53.7 (2 C, C₄), 62.4 (1 C, C_{7 ¢}), 59.6 (2 C, C₇).

13 Durr R. Cossu S. De Lucchi O. Synth. Commun.  1997,  27:  1369 

14 Grube GH. Elliot EL. Steffens RJ. Jones CS. Baldridge KK. Siegel JS. Org. Lett.  2003,  5:  713 

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16

Reaction of syn -3 with MeMgBr.
A 3 M solution of MeMgBr in Et₂O (1 mL, 3 mmol), was added dropwise to a solution of syn-3 (100 mg, 0.22 mmol) in 5 mL dry THF at r.t. under argon, and then a catalytic amount of Ni(II)Cl₂(dppe) was added portionwise. The brown solution was quenched after 1 d with sat. NH₄Cl solution, extracted with Et₂O (3 × 20 mL), the organic layers dried over MgSO₄ and concentrated in vacuo, giving 12 (90%) as brown oil. ¹H NMR (400 MHz, CDCl₃): δ = 3.49 (6 H, H₁ and H₄, t, J = 1.7 Hz), 2.13 (3 H, H_7s, dt, J = 6.9, 1.7 Hz), 1.93 (3 H, H_7a, dt, J = 6.9, 1.7 Hz), 1.65 (18 H, CH₃, s). ¹³C NMR (100 MHz, CDCl₃): δ = 142.0 (6 C, C₅ and C₆), 137.2 (6 C, C₂ and C₃), 62.6 (3 C, C₇), 52.6 (6 C, C₁ and C₄), 14.2 (6 C, CH₃).

17

Reaction of syn -3 with PhC≡CH.
A 1.15 M solution of MeMgBr in Et₂O (4 mL, 4.6 mmol) was added dropwise to a solution of PhC≡CH (0.54 mL, 4.8 mmol) in 5 mL dry THF at -78 °C under argon. The thick white suspension was then allowed to warm to r.t., and then a solution of syn-3 (100 mg, 0.22 mmol) in 5 mL dry THF was added, followed by a catalytic amount of Ni(II)Cl₂(dppe). The dark solution was refluxed for 3 d. Then other 40 equiv of the Grignard reagent were added. The mixture was warmed for 2 d, quenched with sat. NH₄Cl and extracted with Et₂O (3 × 20 mL). The organic layers were dried over MgSO₄ and concentrated in vacuo. The reaction crude was purified by FC (eluant: toluene-hexane, 1:1), giving 13 (20%) as brown solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.20 (12 H, H₁₁, dd, J = 7.7, 1.3 Hz), 7.11 (6 H, H₁₃, dt, J = 7.6, 1.6 Hz), 6.9 (12 H, H₁₂, t, J = 7.8 Hz), 4.18 (6 H, H₁ and H₄, t, J = 1.7 Hz), 2.63 (3 H, H_7a or H_7s, dt, J = 7.7, 1.3 Hz), 2.31 (3 H, H_7s or H_7a, dt, J = 7.7, 1.2 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 140.3 (6 C, C₅ and C₆ or C₂ and C₃), 137.1 (6 C, C₅ and C₆ or C₂ and C₃), 131.3 (12 C, C₁₁), 128.0 (12 C, C₁₂), 127.0 (6 C, C₁₃), 123.3 (6 C, C₁₀), 102.8 (6 C, C₉), 85.1 (6 C, C₈), 65.6 (3 C, C₇), 53.0 (6 C, C₁ and C₄).

18 Dardel B. Guillon D. Heinrich B. Deschenaux R. J. Mater. Chem.  2001,  11:  2814 

19 Polydiacetylenes   Bloor D. Chance RR. Martinus Nijhoff Publishers; Boston, MA: 1985.