Synthesis of the αβ-unsaturated · PDF fileSynthesis of the...

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# Supplementary Material (ESI) for New Journal of Chemistry # This journal is ' The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004 Synthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph 3 PCH 2 OMeCl THF R O MeOH MCPBA R O O O CH 2 Cl 2 pyridine CrO 3 Celite R O O THF KOtBu Ph 3 PCH 3 Cl R O CHCl 3 silica gel oxal acid 90% 90% 90% 93% 95% The synthesis of the α,β-unsaturated aldehyde shown in the scheme above is described in F. Huet, M. Pellet, A. Lechevalier, J.-M. Conia, J. Chem. Res. Miniprint, 1982, 9, 2528 - 2551. Synthesis of 1,1,6,7-Tetrafluoroindanes O C 3 H 7 F F Br O F Br F C 3 H 7 LDA 1. 2. 1 2 Under nitrogen 60.4 g (313 mmol) 1-bromo-3,4-difluorobenzene dissolved in 60 ml THF was slowly added to a solution of 167 ml (324 mmol) 2M LDA in cyclohexane/ethylbenzene/ THF diluted with 580 ml THF at 70C. After 1h 49.9 g (277 mmol) of the α,β-unsaturated aldehyde 1 dissolved in 60 ml THF were added. After additional 2h the reaction mixture was allowed to warm to room temperature and was stirred over night. After acidification with 1N HCl the aqueous layer was extracted three times with mtb-ether. The organic layer was washed with brine, dried (Na 2 SO 4 ) and evaporated. The residue was purified by column

Transcript of Synthesis of the αβ-unsaturated · PDF fileSynthesis of the...

Page 1: Synthesis of the αβ-unsaturated  · PDF fileSynthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph3PCH2OMeCl THF R O MeOH MCPBA R O O O CH2Cl2 pyridine CrO3 Celite R O

# Supplementary Material (ESI) for New Journal of Chemistry # This journal is © The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004

Synthesis of the α,β-unsaturated Aldehyde

R H

O

KOtBuPh3PCH2OMeCl

THF RO

MeOHMCPBA

RO

O

OCH2Cl2

pyridineCrO3

Celite

RO

OTHF

KOtBuPh3PCH3Cl

RO

CHCl3silica geloxal acid

90%90%

90%

93%

95% The synthesis of the α,β-unsaturated aldehyde shown in the scheme above is described in F. Huet, M. Pellet, A. Lechevalier, J.-M. Conia, J. Chem. Res. Miniprint, 1982, 9, 2528 - 2551.

Synthesis of 1,1,6,7-Tetrafluoroindanes

O

C3H7

F

F

BrO

F

Br

F

C3H7LDA1.

2.

1 2

Under nitrogen 60.4 g (313 mmol) 1-bromo-3,4-difluorobenzene dissolved in 60 ml THF was slowly added to a solution of 167 ml (324 mmol) 2M LDA in cyclohexane/ethylbenzene/ THF diluted with 580 ml THF at �70°C. After 1h 49.9 g (277 mmol) of the α,β-unsaturated aldehyde 1 dissolved in 60 ml THF were added. After additional 2h the reaction mixture was allowed to warm to room temperature and was stirred over night. After acidification with 1N HCl the aqueous layer was extracted three times with mtb-ether. The organic layer was washed with brine, dried (Na2SO4) and evaporated. The residue was purified by column

Page 2: Synthesis of the αβ-unsaturated  · PDF fileSynthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph3PCH2OMeCl THF R O MeOH MCPBA R O O O CH2Cl2 pyridine CrO3 Celite R O

# Supplementary Material (ESI) for New Journal of Chemistry # This journal is © The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004 chromatography (mtb-ether/n-heptane 1:10, rf = 0.3) to obtain 85.7g of the allylic alcohol 2 as a yellow oil (92% GC, 84%). The substance was identified via GC-MS (M = 373.28).

OH

F

Br

F

C3H7

OF

F

C3H7NEt3

[(o-tolyl)3P]2Pd(II)Cl2

2 3

Under nitrogen 85.7g (92%) (211 mmol) of the allylic alcohol 2 was dissolved in 800 ml acetonitrile. 122 ml triethylamine and 12.25g Pd-catalyst were added, and the mixture was warmed to 87°C until the starting material was no longer detectable (2 nights, additional 10.0g catalyst was added after 24 h), (HPLC, RP-18 Superspher 250-4, UV (210 nm). The solution was diluted with 300 ml mtb-ether and poured into brine. The aqueous layer was extracted with mtb-ether three times, the organic layer was dried (Na2SO4) and evaporated. After column chromatography (mtb-enter/n-heptane 1:10, rf = 0.3) 40.1g (87% GC, (57%)) indanone 3 was obtained as yellow oil. The substance was identified via GC-MS (M = 292.37).

Page 3: Synthesis of the αβ-unsaturated  · PDF fileSynthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph3PCH2OMeCl THF R O MeOH MCPBA R O O O CH2Cl2 pyridine CrO3 Celite R O

# Supplementary Material (ESI) for New Journal of Chemistry # This journal is © The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004

O

F

F

C3H7

SH

SH SSF

F

C3H7

BF3*Et2O+

3 4

Under nitrogen 40.0g (87%) (119 mmol) indanone 3 and 24.0 ml (285 mmol) 1,2-ethanedithiol were dissolved in 260 ml dichloromethane and cooled to �15°C. 82.6 ml boron trifluoride-diethyl ether complex was added at this temperature. The mixture was stirred for an additional 3h at �15°C - -10°C and at room temperature over night. The solution was poured carefully into saturated NaHCO3-solution. Stirring was continued until CO2 evolution subsided. Ph 8 was adjusted using 2N NaOH. The aqueous layer was extracted three times with dichloromethane. The organic layer was washed with brine, dried (Na2SO4) and evaporated. The residue was purified by column chromatography (mtb-ether/n-hexane 1:30, rf = 0.6) and recrystallization from boiling methanol (36.6g colourless crystals (83%)).

Page 4: Synthesis of the αβ-unsaturated  · PDF fileSynthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph3PCH2OMeCl THF R O MeOH MCPBA R O O O CH2Cl2 pyridine CrO3 Celite R O

# Supplementary Material (ESI) for New Journal of Chemistry # This journal is © The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004

S

S

FF

C3H7

F

F

F

Br

F

F

F

FF

C3H7

Py*HFDBH +

4 5 6

Under nitrogen 118.2 ml (4.38 mmol) of a 65% solution of HF in pyridin was added to a suspension of 115.9 g (405 mmol) 1,3-dibromo-dimethylhydantoin and 330 ml dichloro-methane. The mixture was cooled to �74°C and a solution of 36.5g (99.0 mmol) thioketal 4 in 100 ml CH2Cl2 was added at a temperature below �65°C. After 4h the cooling bath was removed. The reaction mixture was stirred over night and was poured into 2.5 l 2N NaOH containing 140 ml 39% NaHSO3 solution. pH 8 was adjusted. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were washed with 1n HCl and brine, dried (Na2SO4) and evaporated. The residue was filtered through silica gel (n-hexane). After removal of the solvent the solid was recrystallized from boiling methanol to obtain 28.2g (88%) of a 1:3-mixture of the indanes (identified via GC-MS) 5 (M = 393.27) and 6 (M = 314.37).

FF

FF

Br

FF

FF

FF

FFF

F

FF

DBU

+ +

6 6

57

Under nitrogen 28.2g of the mixture of indanes 5 and 6 was dissolved in 90 ml dichloro-methane. 22 ml DBU diluted with 20 ml CH2Cl2 was added to the solution. After stirring over night the reaction mixture was acidified with 150 ml 1N HCl. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were washed with

Page 5: Synthesis of the αβ-unsaturated  · PDF fileSynthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph3PCH2OMeCl THF R O MeOH MCPBA R O O O CH2Cl2 pyridine CrO3 Celite R O

# Supplementary Material (ESI) for New Journal of Chemistry # This journal is © The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004 brine, dried (Na2SO4) and evaporated. The residue was filtered through silica gel (n-hexane). After removal of the solvent 23.2g of a mixture of the indanes (identified via GC-MS) 7 (M = 312.25) and 6 (M = 314.37) was obtained.

F

F

FF

C3H7

F

F

FF

C3H7

F

F

FF

C3H7

+Pd/C

H2

6 7 6

25.0g of the indane/indene mixture was dissolved in THF and was hydrogenated till the end of hydrogen uptake at ambient pressure. The solution was evaporated. The residue was filtered through silica gel (n-hexane). After removal of the solvent the solid was recrystallized from boiling methanol to obtain 19.3g of the indane 6 as colourless crystals.

Page 6: Synthesis of the αβ-unsaturated  · PDF fileSynthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph3PCH2OMeCl THF R O MeOH MCPBA R O O O CH2Cl2 pyridine CrO3 Celite R O

# Supplementary Material (ESI) for New Journal of Chemistry # This journal is © The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004

Page 7: Synthesis of the αβ-unsaturated  · PDF fileSynthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph3PCH2OMeCl THF R O MeOH MCPBA R O O O CH2Cl2 pyridine CrO3 Celite R O

# Supplementary Material (ESI) for New Journal of Chemistry # This journal is © The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004

Li

FF

FF

C3H7

FF

FF

C3H7

1.

2. MeI

6 8

Under nitrogen 11.3 ml (18.0 mmol) 15% nBuLi in hexane was slowly added to a solution of 4.8g (15.3 mmol) indane 6 in 150 ml THF. After 1h 5.0 ml (80 mmol) methyl iodide were injected into the reaction mixture. The reaction was quenched with 2.3 ml trimethyl borate for additional 4h. The mixture was allowed to warm to 5°C and was acidified with 2N HCl. The aqueous layer was extracted three times with mtb-ether. The combined organic layers were washed with brine, dried (Na2SO4) and evaporated. The residue was filtered through silica gel (n-hexane). After removal of the solvent the solid was recrystallized from boiling methanol to obtain 3.0g (60%) indane 8 as colourless crystals.

Page 8: Synthesis of the αβ-unsaturated  · PDF fileSynthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph3PCH2OMeCl THF R O MeOH MCPBA R O O O CH2Cl2 pyridine CrO3 Celite R O

# Supplementary Material (ESI) for New Journal of Chemistry # This journal is © The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004

Page 9: Synthesis of the αβ-unsaturated  · PDF fileSynthesis of the α,β-unsaturated Aldehyde R H O KOtBu Ph3PCH2OMeCl THF R O MeOH MCPBA R O O O CH2Cl2 pyridine CrO3 Celite R O

# Supplementary Material (ESI) for New Journal of Chemistry # This journal is © The Royal Society of Chemistry and # The Centre National de la Recherche Scientifique, 2004