Bastien Doumèche et al.
FULL PAPERS
due was purified by bulb-to-bulb distillation (1308C,
0.1mbar) to give rac-1 as a translucent colourless liquid.
1H NMR: d=1.22 (6H, m), 2.78 (m, 2H), 3.10 (m, 1H),
3.60, (4H, m), 4.34 (1H, d, J=4.4 Hz);13C NMR: d=15.4
(2CH3); 44.0 (CH2); 52.0 (CH); 62.5 (CH2); 63 (CH2); 101.6
(CH).
2-(Diisopropoxymethyl)oxirane (2): para-Toluenesulfonic
acid (250mg) was dissolved in triisopropyl orthoformate
(50mL, 224mmol) under a nitrogen atmosphere and the so-
lution was refluxed at 408C. Distilled acrolein was added
dropwise until total conversion of triisopropyl orthoformate.
The reaction mixture was neutralised with solid NaHCO3,
filtered over celite and then diluted with pentane. The or-
ganic phase was dried over MgSO4 and solvent was removed
under atmospheric pressure. 3,3-Diisopropoxyprop-1-ene
was recovered as a translucent colourless liquid after distil-
lation (808C, 10mbar); yield: 38–42%. 1H NMR: d=1.18
(12H, m), 3.89 (2H, septet J=6.1 Hz), 4.93 (1H, d, J=
5.4 Hz), 5.30 (2H, m), 5.86 (1H, m).
(À208C) and solvent was eliminated by evaporation at at-
mospheric pressure. The obtained 5,5-dimethyl-2-(oxiran-2-
yl)-1,3-dioxane (3) was further purified by flash chromatog-
raphy (pentane/ether gradient) then distilled (908C, 5 mbar)
1
to provide a colourless oil; yield: 57.4 g (72%). H NMR:
d=0.70 (3H, s), 1.18 (3H, s), 2.77 (2H, m), 3.07 (1H, m),
3.42 (2H, m) 3.62 (2H, m), 4.31 (1H, d, J=4.1 Hz);
13C NMR: d=21.7 (CH3); 22.8 (CH3); 30.3 (C); 43.5 (CH2);
51.5 (CH); 76.9 (2CH2); 100.3 (CH).
2-(Diethoxymethyl)-2-methyloxirane (4): 2-Methyl-2-pro-
penal (10mL, 121mmol) was distilled prior use and added
dropwise to a stirred solution of triethyl orthoformate
(18mL, 108mmol) and pTSA (70mg) at 08C under a nitro-
gen atmosphere. After 4h, consumption of triethyl orthofor-
mate was total. The reaction media was washed with satu-
rated NaHCO3 solution, and extracted three times with
CH2Cl2. The organic phase was dried over MgSO4 and the
solvent removed under normal pressure before distillation.
3,3-Diethoxy-2-methylprop-1-ene was recovered as a translu-
1
3,3-Diisopropoxyprop-1-ene (31 g, 196 mmol), NaHCO3
(7 g), benzonitrile (27 g, 262 mmol) and methanol (150 mL)
were mixed at 358C. H2O2 (35%, 25 mL) was added drop-
wise until total conversion of benzonitrile. The reaction mix-
ture was extracted with CH2Cl2 and dried over MgSO4. The
solvent was distilled and the formed benzamide was precipi-
tated in cold pentane. The solvent was distilled under atmos-
pheric pressure, then 2 was isolated by distillation (708C,
7 mbar) and further purified by flash chromatography (pen-
tane/ether gradient). The solvent was evaporated at atmos-
pheric pressure and rac-2 was recovered as a translucent col-
ourless liquid after distillation under reduced pressure;
cent liquid (618C, 100mbar); yield: 7.47g (43%). H NMR:
d=1.22 (6H, m), 1.74 (3H, s), 3.53 (4H, m), 4.69 (1H, s),
4.98 (1H, m), 5.10 (1H, m).
To a solution of 3,3-diethoxy-2-methylprop-1-ene (7.4 g,
51 mmol) dissolved in dichloromethane were added
mCPBA (9 g, 52 mmol) and NaF (2.2 g, 52 mmol) and this
solution was stirred at room temperature. After 24 h,
mCPBA (4.5 g, 26 mmol) and NaF (1.1 g, 26 mmol) were
added to the reaction mixture to complete the reaction.
After total conversion of 3,3-diethoxy-2-methylprop-1-ene,
the reaction mixture was filtered over celite and mCPBA
was destroyed by addition of an aqueous solution of Na2SO3
(10%). The organic phase was isolated and the aqueous
phase was saturated with NaHCO3 and extracted by CH2Cl2.
The organic phases were pooled, dried over MgSO4 and the
solvent was removed under atmospheric pressure. 2-(Dieth-
oxymethyl)-2-methyloxirane (4) was isolated by distillation
(908C, 6 mbar) as a translucent colourless liquid; yield:
1
yield: 50%. H NMR: d=1.18 (12H, m), 2.75 (2H, m), 3.05
(1H, m), 3.92 (2H, septet, J=6.1 Hz), 4.38 (1H, d, J=
4.5 Hz); 13C NMR: d=22.4 (CH3); 22.5 (CH3); 23.1 (CH3);
23.2 (CH3); 44.0 (CH2); 52.7 (CH); 68.8 (CH); 68.9 (CH);
99.0 (CH).
5,5-Dimethyl-2-(oxiran-2-yl)-1,3-dioxane (3): Acrolein
(200mL) was added dropwise to a stirred mixture of anhy-
drous copper sulfate (100g, 629mmol), 2,2-dimethylpro-
pane-1,3-diol (200g, 1.92 mol) and pTSA (500mg) in anhy-
drous CH2Cl2 (600mL) under a nitrogen atmosphere. After
total conversion of 2,2-dimethylene-1,3-propanediol, the re-
action medium was filtered over celite and washed with
CH2Cl2. Organic phases were dried over MgSO4, solvent
was removed under atmospheric pressure and the olefin was
purified by distillation (978C, 150mbar) to furnish 5,5-di-
methyl-2-vinyl-1,3-dioxane as a translucent liquid; yield:
1
19%. H NMR: d=1.24 (6H, m), 1.37 (3H, s), 2.60 (1H, d,
J=5.0 Hz), 2.82 (1H, d, J=5.0 Hz), 3.67 (4H, m), 4.18 (1H,
s); 13C NMR: d=15.21 (CH3); 15.26 (CH3); 16.01 (CH3);
50.43 (CH2); 57.1 (C); 63.54 (2CH2); 104.0 (CH).
5,5-Dimethyl-2-(2-methyloxiran-2-yl)-1,3-dioxane (5):
2-Methyl-2-propenal (20mL, 242mmol) was distilled prior
use and added dropwise to a stirred mixture of anhydrous
copper sulfate (10g), 2,2-dimethylpropane-1,3-diol (20g,
192mmol) and pTSA (50mg) in anhydrous CH2Cl2 (100mL)
under a nitrogen atmosphere. After 24h, conversion of the
diol was complete. The reaction media was filtered over
celite, washed with CH2Cl2 and dried over MgSO4. The sol-
vent was removed under normal pressure before isolation of
5,5-dimethyl-2-(prop-1-en-2-yl)-1,3-dioxane by distillation
(908C, 100mbar) as a translucent liquid; yield: 22g (58%).
1H NMR: d=0.74 (3H, s), 1.21 (3H, s), 1.82 (3H, s), 3.50
(2H, d, J=11 Hz), 3.66 (2H, d, J=11 Hz), 4.76 (1H, s), 4.98
(1H, m), 5.15 (1H, m).
To a solution of 5,5-dimethyl-2-(prop-1-en-2-yl)-1,3-diox-
ane (10 g, 64 mmol) in dichloromethane, were added
mCPBA (22.3 g, 128 mmol) and NaF (5.5 g, 131 mmol).
After stirring for 24 h at room temperature more mCPBA
(11 g, 63 mmol) and NaF (2.7 g, 64 mmol) were added and
the crude reaction mixture was stirred for 1 h. The reaction
media was filtered over celite and remaining mCPBA was
1
84%. H NMR: d=0.73 (3H, s), 1.20 (3H, s), 3.43 (2H, d,
J=11 Hz), 3.70 (2H, d, J=11 Hz), 4.87 (1H, d, J=4.5 Hz),
5.50 (1H, ddd, J=10.5 Hz, J=1.5 Hz, J=1.5 Hz), 5.50 (1H,
ddd, J=17.2 Hz, J=1.5 Hz, J=1.5 Hz), 5.88 (1H, ddd, J=
17 Hz, J=10.5 Hz, J=4.7 Hz).
To a stirred solution of 5,5-dimethyl-2-vinyl-1,3-dioxane
(71.5 g, 503 mmol), NaHCO3 (17 g) and benzonitrile (67 g,
650 mmol) in methanol (300 mL), 25 mL of H2O2 (35%)
were added dropwise at 408C until total conversion of 5,5-
dimethyl-2-vinyl-1,3-dioxane and of benzonitrile. The reac-
tion mixture was filtered over celite and Na2SO3 was added
to destroy the remaining H2O2. The reaction mixture was
extracted two times by CH2Cl2 and the organic phase dried
over MgSO4. Solvent was evaporated under atmospheric
pressure. Benzamide was precipitated in cold pentane
1954
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 1948 – 1957