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Org. Synth. 1997, 74, 187
DOI: 10.15227/orgsyn.074.0187
NICKEL-CATALYZED, GEMINAL DIMETHYLATION OF ALLYLIC DITHIOACETALS: (E)-1-PHENYL-3,3-DIMETHYL-1-BUTENE
[Benzene, (3,3-dimethyl-1-butenyl)- (E)-]
Submitted by Tien-Min Yuan and Tien-Yau Luh1.
Checked by Yugang Liu and Robert K. Boeckman, Jr..
1. Procedure
CAUTION! 1,2-Ethanedithiol has a powerful stench. Steps A and C should be performed in a well-ventilated hood.
A. (E)-2-Methyl-2-(2-phenylethenyl)-1,3-dithiolane. In a 500-mL, round-bottomed flask equipped with a magnetic stirring bar are placed 29.2 g (0.2 mol) of (E)-4-phenyl-3-buten-2-one (Note 1) and 20.7 g (0.22 mol) of 1,2-ethanedithiol in 200 mL of methanol. To the stirred solution is added 11 mL (12.4 g, 0.087 mol) of boron trifluoride etherate. The mixture is stirred at room temperature for 45 min. To the mixture is added 50 mL of aqueous 10% sodium hydroxide, and the methanol is removed under reduced pressure. Dichloromethane (300 mL) is introduced and the solution is washed with aqueous 10% sodium hydroxide solution (2 × 100 mL). The aqueous layer is extracted with dichloromethane (3 × 200 mL). The combined organic layers are washed with 200 mL of water, dried over anhydrous magnesium sulfate, and filtered. The solvent is removed under reduced pressure and the residue is fractionally distilled to give 24.9–27.1 g (56–61%) of (E)-2-methyl-2-(2-phenylethenyl)-1,3-dithiolane (Note 2) and (Note 3) as a yellowish liquid, bp 109–112°C (0.16 mm), that solidifies on standing, mp 52–53°C.
B. Methylmagnesium iodide. A 500-mL, three-necked, round-bottomed flask containing 9.7 g (0.4 g-atom) of magnesium turnings is equipped with a rubber septum, reflux condenser, an addition funnel, and a magnetic stirring bar. The system is flame-dried and flushed with nitrogen. Anhydrous ether (20 mL, (Note 4)) is introduced to cover the magnesium. As the contents of the flask are stirred, iodomethane (56.7 g, 0.4 mol) in 180 mL of anhydrous ether is added dropwise through the addition funnel. The addition requires about 2 hr; the mixture is then stirred for an additional 30 min.
C. (E)-1-Phenyl-3,3-dimethyl-1-butene. In a 1-L, two-necked, round-bottomed flask fitted with a reflux condenser, rubber septum, and a magnetic stirring bar are placed 17.8 g (0.08 mol) of 2-methyl-2-(2-phenylethenyl)-1,3-dithiolane and 2.17 g (0.004 mol) of [1,3-bis(diphenylphosphino)propane]nickel(II) chloride [NiCl2(dppp)] (Note 5). The flask is evacuated and flushed with nitrogen three times. To the above mixture is added 300 mL of anhydrous tetrahydrofuran (Note 6). The ether solution of methylmagnesium iodide prepared in Step B is introduced with a double-ended needle in one portion (Note 7). The mixture is heated under reflux for 24 hr, cooled to room temperature, and treated with 200 mL of saturated ammonium chloride solution. The organic layer is separated and the aqueous layer is extracted with ether (3 × 200-mL). The combined organic layers are washed twice with aqueous 10% sodium hydroxide solution (100 mL) and with brine (100 mL). The organic solution is dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure and the residue is filtered through a short column packed with 30 g of silica gel (Note 8) and flushed under a positive nitrogen pressure with 350 mL of hexane. After the solvent is evaporated under reduced pressure, the yellowish residue is distilled through a spinning band (Note 9) to give 10.4 g (81%) of (E)-1-phenyl-3,3-dimethyl-1-butene (Note 10) as a colorless liquid, bp 91–93°C/30 mm.
2. Notes
1. (E)-4-Phenyl-3-buten-2-one was purchased from Division of Janssen Pharmaceutica and used directly.
2. A 6-cm Vigreux column was employed for fractional distillation.
3. The spectral properties of the (E)-2-methyl-2-(2-phenylethenyl)-1,3-dithiolane are as follows: IR (neat) cm−1: 3025, 2922, 1637, 1600, 1494, 1446, 1275, 1065, 964, 754, 692; 1H NMR (300 MHz, CDCl3) δ: 2.01 (s, 3 H), 3.33–3.46 (m, 4 H), 6.47 (d, 1 H, J = 15.5), 6.63 (d, 1 H, J = 15.5), 7.21–7.43 (m, 5 H); 13C NMR (75 MHz, CDCl3) δ: 29.6, 40.1, 65.4, 126.6, 127.0, 127.5, 128.4, 135.0, 136.4; MS m/e (rel) 222 (M+, 100), 207 (17), 194 (59), 161 (44), 129 (45), 117 (39); HRMS calcd for C12H14S2: 222.0537. Found 222.0546.
4. Ethyl ether is distilled from sodium-benzophenone ketyl before use.
5. [1,3-Bis(diphenylphosphino)propane]nickel(II) chloride was purchased from Aldrich Chemical Company, Inc., and used without further purification. The catalyst can also be prepared according to literature procedures.2
6. Tetrahydrofuran is distilled from sodium-benzophenone ketyl before use.
7. An excess of the Grignard reagent is required to maximize the yield; otherwise the reaction is incomplete.
8. Silica gel (230–400 mesh) was purchased from E. Merck Co.
9. A spinning band distillation setup is employed (800 Mirco Still, B/R Instrument Corporation, 3000 rpm, theoretical plates 23–26). The mixture was heated under reflux for 3 hr to reach equilibrium before distillation (reflux/distillation ratio = 5–10/1).
10. The spectral properties of the product are as follows: IR (neat) cm−1: 3027, 2960, 1648, 1598, 1493, 1362, 1266, 968, 746, 693; 1H NMR (300 MHz, CDCl3) δ: 1.16 (s, 9 H), 6.30 (d, 1 H, J = 16.2), 6.34 (d, 1 H, J = 16.2), 7.18–7.41 (m, 5 H); 13C NMR (75 MHz, CDCl3) δ: 29.6, 33.3, 124.6, 126.0, 126.7, 128.4, 138.1, 141.8; MS m/e (rel) 160 (M+, 35), 145 (100), 117 (21), 105 (11), 103 (11), 91 (25), 77 (12); HRMS calcd for C12H16: 160.1252, Found 160.1250.
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
Geminal dimethylation at a carbon center is useful in organic synthesis. Much effort has been devoted to the attachment of a tert-butyl group or a quarternary carbon center to olefinic carbon atom(s) in order to synthesize crowded olefins.3 4 5 6 7 Although Tebbe-like reagents are effective for converting a carbonyl group into a gem-dimethyl substituent, their application to an allylic carbonyl substrate is limited by poor regioselectivity.8,9,10,11,12,13 The present procedure is based on a series of reports on the nickel-catalyzed cross coupling reactions of dithioacetals with Grignard reagents.14,15,16,17,18,19,20 α,β-Unsaturated aldehydes or ketones react as the dithioacetal in a polar solvent (such as tetrahydrofuran) or non-polar aromatic solvent (such as benzene or toluene) with methylmagnesium iodide in the presence of a catalytic amount NiCl2 (dppp) or [1,2-bis(diphenylphosphino)ethane]nickel(II) chloride [NiCl2 (dppe)], under a nitrogen atmosphere to give the corresponding geminal dimethylation products.15,16,17 Substrates with structural variety react smoothly.15,16,17 Allylic orthothioesters, on the other hand, give the corresponding trimethylation products with different regioselectivity.16
References and Notes
  1. Department of Chemistry, National Taiwan University, Taipei, Taiwan 106, Republic of China.
  2. Van Hecke, G. R.; Horrocks, W. DeW., Jr. Inorg. Chem. 1966, 5, 1960.
  3. For examples: (a) Mulzer, J.; Lammer, O. Angew. Chem., Int. Ed. Engl. 1983, 22, 628;
  4. Russell, G. A.; Tashtoush, H.; Ngoviwatchai, P. J. Am. Chem. Soc. 1984, 106, 4622;
  5. Ager, D. J. J. Chem. Soc., Perkin Trans. I 1986, 183;
  6. Smegal, J. A.; Meier, I. K.; Schwartz, J. J. Am. Chem. Soc. 1986, 108, 1322;
  7. Palomo, C.; Aizpurua, J. M.; Garcia, J. M.; Ganboa, I.; Cossio, F. P.; Lecea, B.; López, C. J. Org. Chem. 1990, 55, 2498.
  8. Posner, G. H.; Brunelle, D. J. Tetrahedron Lett. 1972, 293.
  9. Meisters, A.; Mole, T. J. Chem. Soc., Chem. Commun. 1972, 595.
  10. Reetz, M. T.; Westermann, J.; Steinbach, R. Angew. Chem., Int. Ed. Engl. 1980, 19, 900.
  11. Brown-Wensley, K. A.; Buchwald, S. L.; Cannizzo, L.; Clawson, L.; Ho, C. S.; Meinhardt, D.; Stille, J. R.; Straus, D.; Grubbs, R. H. Pure Appl. Chem. 1983, 55, 1733.
  12. Pine, S. H.; Pettit, R. J.; Geib, G. D.; Cruz, S. G.; Gallego, C. H.; Tijerina, T.; Pine, R. D. J. Org. Chem. 1985, 50, 1212.
  13. Reetz, M. T.; Westermann, J.; Kyung, S.-H. Chem. Ber. 1985, 118, 1150.
  14. Luh, T.-Y. Acc. Chem. Res. 1991, 24, 257.
  15. Yang, P.-F.; Ni, Z.-J.; Luh, T.-Y. J. Org. Chem. 1989, 54, 2261.
  16. Tzeng, Y.-L.; Yang, P.-F.; Mei, N.-W.; Yuan, T.-M.; Yu, C.-C.; Luh, T.-Y. J. Org. Chem. 1991, 56, 5289.
  17. Yuan, T.-M.; Luh, T.-Y. J. Org. Chem. 1992, 57, 4550.
  18. Ni, Z.-J.; Mei, N.-W.; Shi, X.; Tzeng, Y.-L.; Wang, M. C.; Luh, T.-Y. J. Org. Chem. 1991, 56, 4035 and references therein.
  19. Ni, Z.-J.; Yang, P.-F.; Ng, D. K. P.; Tzeng, Y.-L.; Luh, T.-Y. J. Am. Chem. Soc. 1990, 112, 9356.
  20. Yu, C.-C.; Ng, D. K. P.; Chen, B.-L.; Luh, T.-Y. Organometallics 1994, 1487 and references therein.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

brine

sodium-benzophenone ketyl

NiCl2 (dppp)

Benzene (71-43-2)

methanol (67-56-1)

ether,
ethyl ether (60-29-7)

ammonium chloride (12125-02-9)

sodium hydroxide (1310-73-2)

magnesium,
magnesium turnings (7439-95-4)

nitrogen (7727-37-9)

toluene (108-88-3)

iodomethane (74-88-4)

methylmagnesium iodide (917-64-6)

dichloromethane (75-09-2)

magnesium sulfate (7487-88-9)

Tetrahydrofuran (109-99-9)

hexane (110-54-3)

boron trifluoride etherate (109-63-7)

1,2-ethanedithiol (540-63-6)

(E)-4-phenyl-3-buten-2-one

(E)-1-Phenyl-3,3-dimethyl-1-butene,
Benzene, (3,3-dimethyl-1-butenyl)- (E)- (3846-66-0)

(E)-2-Methyl-2-(2-phenylethenyl)-1,3-dithiolane (107389-59-3)

2-methyl-2-(2-phenylethenyl)-1,3-dithiolane

[1,3-Bis(diphenylphosphino)propane]nickel(II) chloride (15629-92-2)

[1,2-bis(diphenylphosphino)ethane]nickel(II) chloride (15793-01-8)

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