Checked by Yugang Liu and Robert K. Boeckman, Jr..
1. Procedure
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.
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
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, CDCl
3) 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, CDCl
3) 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 C
12H
14S
2: 222.0537. Found 222.0546.
4.
Ethyl ether 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, CDCl
3) 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, CDCl
3) 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 C
12H
16: 160.1252, Found 160.1250.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
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 [NiCl
2 (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
Appendix
Compounds Referenced (Chemical Abstracts 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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