inter- and intramolecular hydroacylation of alkenes employing a

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Supporting Information for

Inter- and Intramolecular Hydroacylation of Alkenes employing a Novel Bifunctional Catalyst System

Nicolas R. Vautravers, Damien D. Regent, and Bernhard Breit*

Institute fűr Organische Chemie und Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21,

79104, Freiburg, Germany

Table of contents General considerations S-2 General procedure for hydroacylation reactions S-2 Characterization data

- Ligand L S-2 - Substrates S-5 - Products S-12

References S-17 1H NMR and 13C NMR spectra of isolated compounds S-18

Electronic Supplementary Material (ESI) for Chemical CommunicationsThis journal is © The Royal Society of Chemistry 2011

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General considerations All reactions were carried out in oven-dried glasswares under an argon atmosphere (Argon 5.0 from Sauerstoffwerke Friedrichshafen) using standard Schlenk techniques. All reagents were purchased from commercial sources and used as received. All solvents were dried and distilled by standard procedures. Chromatographic purification of products was accomplished using Machery-Nagel silica gel 60® (230-400 mesh). Nuclear magnetic resonance spectra were acquired on a Bruker Avance 400 spectrometer (400 MHz, 162.0 MHz and 100.6 MHz for 1H, 31P and 13C respectively) and on a Varian Mercury (300 MHz, 121.5 MHz and 75.5 MHz for 1H, 31P and 13C respectively). All 1H NMR spectra are reported in parts per million (ppm) downfield of TMS and were measured relative to the signals at 7.26 ppm (CHCl3) and 2.50 ppm (d6-DMSO). All 13C NMR spectra were reported in ppm relative to residual CHCl3 (77.16 ppm) and d6-DMSO (39.52 ppm) and were obtained with 1H decoupling. 31P NMR spectrum was referenced to external 85 % H3PO4. Data for 1H NMR are described as follow: chemical shift (δ in ppm), multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; quint, quintuplet; m, multiplet; br, broad signal), coupling constant (Hz), integration. Data for 13C NMR and 31P NMR spectra are described in terms of chemical shift (δ in ppm). High resolution mass spectra were obtained on a Finnigan MAT 8200 instrument (EI: 70 eV; CI/NH3: 110 eV). Elementary analysis were performed on an Elementar vario (Fa. Elementar Analysensysteme GmbH). 2-amino-6-picoline, 2-amino-3-picoline, N-bromosuccinimide (Fluorochem), 2,6-di-tert-butylcresol, allyl benzene, styrene, 4-vinyl-1-cyclohexene (Acros), o-bromostyrene, 3-bromo-4-methylaniline, 4-bromo-3-methylbenzoic acid methyl ester, 2-bromo-4-methylbenzaldehyde, 5-hexen-1-ol, 5-hexenoic acid (AlfaAesar), potassium vinyltrifluoroborate, 2-bromo-4-nitrotoluene, 2-bromopyridine, 2-bromo-5-fluorobenzaldehyde, 2-bromo-5-hydroxybenzaldehyde, benzaldehyde, p-chlorobenzaldehyde, p-methoxybenzaldehyde, biphenyl-4-carboxaldehyde, methyl acrylate, 1-octene, tributyl(vinyl)tin, [Rh(COD)Cl]2, [Rh(CO)2Cl]2, [Pd(PPh3)4], [CoCl2.6H2O] (Sigma Aldrich), [PdCl2] (Merck), 2-bromo-5-chlorotoluene, 1-bromo-2-methylnaphthalene (ABCR), 6-bromoveratraldehyde, ethyl 4-piperidinecarboxylate (ChemPur) were purchased commercially and used as received. [Rh(COD)2BF4] and [Rh(COD)acac] was generously given by Umicore. Diphenyl(2-pyridyl)phosphine (L´) was made according to literature procedure.1

General procedure for hydroacylation reactions GP1

R1 R1

O

R2R2

O

H+

[Rh(COD)Cl]2 (5 mol%)L (10 mol%)

Toluene (c = 1.1 M) 150 °C, 24 h.

A mixture of substituted benzaldehyde (0.22 mmol), ligand L (0.022 mmol, 6.8 mg) and [Rh(COD)Cl]2 (0.011 mmol, 5.4 mg) was dissolved in toluene (200 μL) in a 8 mL closed Schlenk tube and magnetically stirred for 24 hours at 150 °C. The solution was concentrated to give a residue that was purified by silica gel column chromatography (eluting with Petroleum Ether/ CH2Cl2 = 2/1).


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GP2 [Rh(COD)2]BF4 (5 mol%)

L (5 mol%)

Toluene (c = 1.1 M) 150 °C, 1h.

O O

RR

H

A mixture of substituted o-vinylbenzaldehyde (0.22 mmol), ligand L (0.011 mmol, 3.4 mg) and [Rh(COD)2]BF4 (0.011 mmol, 4.5 mg) was dissolved in toluene (200 μL) in a 8 mL closed Schlenk tube and magnetically stirred for 1 hour at 150 °C. The solution was concentrated to give a residue that was purified by silica gel column chromatography (eluting with CH2Cl2). Characterization data Ligand L 6-methyl-2-(pivaloylamino)-pyridine (1)2

A solution of trimethylacetylchloride (12.51 mL, 101.7 mmol) in DCM (15 mL) was slowly added to an ice-cooled solution of 2-amino-6-picoline (10 g, 92.5 mmol) and NEt3 (16.11 mL, 115.6 mmol) in DCM (200 mL). The reaction mixture was stirred at 0 °C for 15 minutes and

overnight at room temperature. It was then poured into water (150 mL) and extracted with DCM (3 x 60 mL). The organic phase was washed with dilute NaHCO3 (60 mL), dried over MgSO4 and concentrated in vacuo. The residue was recrystallized from pentane leaving 6-methyl-2-(pivaloylamino)-pyridine (1) as white crystals (17.7 g, 92.0 mmol, 99%). 1H NMR (400.13 MHz, CDCl3): δ = 1.33 (s, 9H), 2.45 (s, 3H), 6.88 (bd, J = 7.5 Hz, 1H), 7.58 (dd, J = 8.2 Hz, J = 7.5 Hz, 1H), 7.96 (bs, 1H), 8.05 (d, J = 8.2 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 24.1, 27.6, 39.9, 110.9, 119.2, 138.8, 151.1, 154.8, 177.2. LRMS (CI): Calcd. for C11H17N2O (M+H): 193.3; Found: 193.2. Elemental analysis for C11H16N2O: C, 68.72; H, 8.39; N, 14.57. Found: C, 68.76; H, 8.55; N, 14.44. 3,6-dimethyl-2-(pivaloylamino)-pyridine (2)

n-BuLi (2.5 M in hexanes, 34.4 mL, 85.9 mmol) was added dropwise at -78 °C to a solution of 6-methyl-2-(pivaloylamino)-pyridine (1) (7.5 g, 39 mmol) in 100 mL of THF. The resulting orange solution was stirred at this temperature for 30 minutes before being stirred at 0 °C for one

further hour. Methyl iodide (2.68 mL, 43 mmol) was then slowly added to the ice-cooled solution and the reaction mixture was allowed to warm to room temperature overnight. The mixture was then poured into water, and extracted three times with Et2O (3 x 30 mL). The combined organic layers were washed with brine, dried over MgSO4 and evaporated to dryness. The crude was purified by silica gel column chromatography (eluting with Cyclohexane/EtOAc, 70/30) yielding 3,6-dimethyl-2-(pivaloylamino)-pyridine (2) as white crystals (5.2 g, 28.9 mmol, 74%). 1H NMR (400.13 MHz, CDCl3): δ = 1.34 (s, 9H), 2.17 (s, 3H), 2.46 (s, 3H), 6.95 (d, J = 7.8 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.72 (bs, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 17.9, 23.7, 27.8, 39.5, 121.6, 126.1, 140.3, 148.7, 154.7, 176.9; HRMS (EI): Calcd. for C12H18N2O (M): 206.1419; Found: 206.1423. Elemental analysis for C12H18N2O: C, 69.87; H, 8.79; N, 13.58. Found: C, 69.57; H, 8.91; N, 13.35.

N NH

O

N NH

O


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3-methyl-2-(pivaloylamino)-6-(trimethylsilylmethyl)-pyridine (3) n-BuLi (2.5 M in hexanes, 9.4 mL, 23.5 mmol) wad slowly added at -78 °C to a mixture of KOtBu (2.6 g, 23.2 mmol), DIPA (3.19 mL, 22.6 mmol) and anhydrous THF (25 mL). It was stirred at this temperature for 30 minutes before a solution of 3,6-dimethyl-2-(pivaloylamino)-pyridine (2) (2.06 g, 10.0 mmol) in THF (170 mL)

being slowly canuled in and reacted for a further hour at -78 °C. The red mixture was subsequently quenched with a solution of TMSCl (16 mmol, 2.1 mL) in THF (5 mL) and stirred overnight at room temperature. After hydrolysis (30 mL H2O), DCM extraction (3 x 30 mL) and drying (MgSO4), the solvent was removed in vacuo and the crude was purified by column chromatography on silica gel (eluting with Cyclohexane/EtOAc, 70/30) affording 3-methyl-2-(pivaloylamino)-6-(trimethylsilylmethyl)-pyridine (3) as white crystals (2.00 g, 7.22 mmol, 72%). 1H NMR (400.13 MHz, CDCl3): δ = 0.01 (s, 9H), 1.34 (s, 9H), 2.14 (s, 3H), 2.24 (s, 2H), 6.78 (d, J = 7.8 Hz, 1H), 7.36 (d, J = 7.8 Hz, 1H), 7.55 (bs, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = -1.5, 17.9, 27.8, 29.3, 39.5, 120.5, 124.1, 140.1, 148.5, 157.7, 176.7. HRMS (EI): Calcd. for C15H26ON2Si (M): 278.1814; Found: 278.1814. Elemental analysis for C15H26N2OSi: C, 64.70; H, 9.41; N, 10.06. Found: C, 64.50; H, 9.57; N, 9.85. 6-chloromethyl-3-methyl-2-(pivaloylamino)-pyridine (4)

Dry CsF (1.1 g, 7.2 mmol) was added at 25 °C to a solution of 3-methyl-2-(pivaloylamino)-6-(trimethylsilylmethyl)-pyridine (3) (0.5 g, 1.8 mmol) and C2Cl6 (1.7 g, 7.2 mmol) in CH3CN (30 mL). The heterogeneous solution was stirred at 60 °C for 5 hours. After cooling to

25 °C, the mixture was poured into a separatory funnel containing EtOAc (45 mL) and H2O (45 mL) and was extracted with EtOAc (3 x 45 mL). The combined organic fractions were washed with brine (70 mL) and dried over MgSO4 and concentrated in vacuo to give pure 6-chloromethyl-3-methyl-2-(pivaloylamino)-pyridine (4) as a yellowish solid (0.38 g, 88%). 1H NMR (400.13 MHz, CDCl3): δ = 1.35 (s, 9H), 2.22 (s, 3H), 4.57 (s, 2H), 7.26 (d, J = 7.7 Hz, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.70 (bs, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 18.2, 27.7, 39.6, 46.3, 121.1, 129.1, 141.0, 149.2, 152.9, 177.0. HRMS (EI): Calcd. for C12H17ON2Cl (M): 240.1029; Found: 240.1031. 6-chloromethyl-3-methyl-2-aminopyridine (5)

A solution of 6-chloromethyl-3-methyl-2-(pivaloylamino)-pyridine (4) (0.38 g, 1.58 mmol) was dissolved in a concentrated HCl solution (5 mL) and refluxed overnight. After cooling to room temperature, the mixture was neutralized with K2CO3 and extracted with DCM (3 x 20 mL). The combined

organic fractions were dried over MgSO4, filtered and concentrated in vacuo. The crude was purified by flash chromatography on silica gel (Cyclohexane/EtOAc, 70/30) affording 6-chloromethyl-3-methyl-2-aminopyridine (5) as white crystals (0.18 g, 1.15 mmol, 72%). The product has to be stored at -20 °C to avoid any polymerisation. 1H NMR (400.13 MHz, CDCl3): δ = 2.12 (s, 3H), 4.47 (s, 2H), 4.50 (br s, 2H), 6.73 (d, J = 7.4 Hz, 1H), 7.27 (br d, J = 7.4 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 17.0, 47.0, 113.5, 116.5, 138.6, 152.5, 157.0. LRMS (EI): Calcd. for C7H9N2Cl (M): 156.6; Found: 157.0. Elemental analysis for C7H9ClN2: C, 53.68; H, 5.79; N, 17.89. Found: C, 53.69; H, 5.95; N, 17.72.

N NH

O

Si

N NH

O

Cl

N NH2

Cl


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6-diphenylphosphinomethyl-3-methyl-2-aminopyridine L Na (236.2 mg, 9.84 mmol) was added over 10 min to liquid ammonia (30 mL) at -78 °C. The dark blue solution was stirred at this temperature for 20 minutes and then treated portionwise with PPh3 (1.29 g, 4.92 mmol) over 5 minutes. The dark red-orange solution was stirred for a further 2 hours at -78

°C before the addition of 6-chloromethyl-3-methyl-2-aminopyridine (5) (770 mg, 4.78 mmol). THF (30 mL) was then added after 40 minutes and the cooling bath removed. Ammonia was allowed to evaporate overnight and the residue was quenched with H2O (10 mL), extracted with Et2O (3 x 8 mL) and dried over Na2SO4. The solvent was evaporated in vacuo, and subsequent flash column chromatography on silica gel (DCM, then DCM/EtOAc, 10/3) afforded ligand L, 6-diphenylphosphinomethyl-3-methyl-2-aminopyridine, as a white solid (1.2 g, 3.9 mmol, 80%). 1H NMR (400.13 MHz, CDCl3): δ = 2.05 (s, 3H), 3.44 (s, 2H), 4.38 (br s, 2H), 6.29 (dd, J = 7.4 Hz, J = 1.5 Hz, 1H), 7.06 (d, J = 7.4 Hz, 1H), 7.31 (m, 6H), 7.44 (m, 4H); 13C{1H} NMR (100.6 MHz, CDCl3): 16.8, 38.1 (d, J = 14.9 Hz), 113.8 (d, J = 2.7 Hz), 114.3 (d, J = 6.7 Hz), 128.4 (d, J = 6.7 Hz), 128.7, 133.1 (d, J = 18.7 Hz), 138.3, 138.8 (d, J = 15.3 Hz), 153.7 (d, J = 8.0 Hz), 156.6; 31P{1H} NMR (101.3 MHz, CDCl3) δ = -12.1; HRMS (EI): Calcd. for C19H19N2P (M): 306.1286; Found: 306.1286. Elemental analysis for C19H19N2P: C, 74.49; H, 6.25; N, 9.14. Found: C, 74.39; H, 6.15; N, 9.21. Substrates o-vinylbenzaldehyde3

n-BuLi (2.5 M solution in hexanes, 4.82 mL, 12.03 mmol) was slowly added to a solution of o-bromostyrene (2 g, 1.37 mL, 10.93 mmol) in THF (40 mL) at -78 °C and stirred for 1 hour at this temperature. DMF (1.02 mL, 13.12 mmol) was then added dropwise to the suspension and the mixture stirred for a further 20

min. Saturated aqueous NH4Cl (40 mL) was added and the mixture was extracted with Et2O (3 x 30 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluting with a gradient of Cyclohexane/EtOAc, 50:1 to 20:1) to afford o-vinylbenzaldehyde as a colorless oil (1.08 g, 8.17 mmol, 75%). 1H NMR (300.07 MHz, CDCl3) δ = 5.48 (d, J = 11.0 Hz, 1H), 5.70 (d, J = 17.3 Hz, 1H), 7.43 (m, 1H), 7.52 (dd, J = 17.3 Hz, J = 11.0 Hz, 1H), 7.52 (m, 2H), 7.82 (d, J = 7.7 Hz, 1H), 10.29 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 119.5, 127.6, 128.0, 131.3, 133.0, 133.5, 133.9, 140.6, 192.5. HRMS (EI): Calcd. for C9H8O (M): 132.0575; Found: 132.0576. 2-methyl-5-phthalimido-bromobenzene

A mixture of 3-bromo-4-methylaniline (3.0 g, 16.1 mmol) and phthalic anhydride (2.38 g, 16.1 mmol) were stirred and held at 190 °C for 1 hour. After cooling to room temperature, the residue was purified by silica gel chromatography (eluting with EtOAc) to yield 2-methyl-5-phthalimido-bromobenzene as a white crystalline solid (5

g, 15.8 mmol, 98%). 1H NMR (400.13 MHz, CDCl3) δ = 2.45 (s, 3H), 7.31 (dd, J = 8.1 Hz, J = 2.1 Hz, 1H), 7.37 (br d, J = 8.1 Hz, 1H), 7.65 (d, J = 2.1 Hz, 1H), 7.80 (m, 2H), 7.95 (m, 2H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 22.8, 124.0, 124.9, 125.5, 130.4, 130.5, 131.1, 131.8, 134.7, 138.2, 167.1. HRMS (EI): Calcd. for C15H10O2NBr (M): 314.9895; Found: 314.9888.

N NH2

PPh2

O

Br

N

O

O


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2-dibromomethyl-5-phthalimido-bromobenzene A mixture of 2-methyl-5-phthalimido-bromobenzene (2.75 g, 8.7 mmol), N-bromosuccinimide (4.64 g, 26.1 mmol) and AIBN (50 mg) in anhydrous benzene (30 mL) was stirred and held at reflux for 16 hours. (AIBN (50 mg) was added every 3 hours) After cooling to room temperature, the solvent was removed in vacuo

and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 2-dibromomethyl-5-phthalimido-bromobenzene as a white solid (2.79 g, 5.89 mmol, 68%). 1H NMR (400.13 MHz, CDCl3) δ = 7.10 (s, 1H), 7.60 (dd, J = 2.1 Hz, J = 8.6 Hz, 1H), 7.70 (d, J = 2.1 Hz, 1H), 7.83 (m, 2H), 7.98 (m, 2H), 8.15 (d, J = 8.6 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 38.9, 119.8, 124.2, 126.2, 129.7, 131.5, 131.6, 133.8, 134.9, 139.8, 166.7. HRMS (EI): Calcd. for C15H8O2NBr2 (M-Br): 391.8922; Found: 391.8914. 2-bromo-4-phthalimidobenzaldehyde

2-dibromomethyl-5-phthalimido-bromobenzene (2.2 g, 4.64 mmol) in H2SO4 (20 mL) was stirred for 1 hour at room temperature. EtOAc (20 mL) was added and the aqueous phase was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL) and dried over

MgSO4. After evaporation of the solvent, the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 2-bromo-4-phthalimidobenzaldehyde as a white solid (1.2 g, 3.63 mmol, 78%). 1H NMR (400.13 MHz, CDCl3) δ = 7.67 (ddd, J = 8.4 Hz, J = 1.9 Hz, J = 0.8 Hz, 1H), 7.84 (m, 2H), 7.92 (d, J = 1.9 Hz, 1H), 7.99 (m, 2H), 8.05 (d, J = 8.4 Hz, 1H), 10.40 (d, J = 0.8 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 124.3, 125.2, 127.1, 130.3, 130.8, 131.5, 132.4, 135.2, 137.8, 166.5, 191.2. HRMS (EI): Calcd. for C15H8O3NBr (M): 328.9688; Found: 328.9687. 4-phthalimido-2-vinylbenzaldehyde

A solution of 2-bromo-4-phthalimidobenzaldehyde (0.492 g, 1.5 mmol), potassium vinyltrifluoroborate (0.20 g, 1.5 mmol), PdCl2 (5.3 mg, 0.03 mmol), PPh3 (23.5 mg, 0.09 mmol) and Cs2CO3 (1.5 g, 4.5 mmol) in THF/H2O (9/1) (3 mL) was heated at 85 °C for 22 hours under an argon atmosphere in a sealed tube. After cooling to

room temperature, H2O (3 mL) was added, followed by extraction with CH2Cl2 (3 x 10 mL). The solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 4-phthalimido-2-vinylbenzaldehyde as a pale yellow solid (0.334 g, 1.2 mmol, 81%). 1H NMR (400.13 MHz, CDCl3) δ = 5.58 (dd, J = 11.1 Hz, J = 1.0 Hz, 1H), 5.77 (dd, J = 17.4 Hz, J = 1.0 Hz; 1H), 7.57 (dd, J = 17.4 Hz, J = 11.1 Hz, 1H), 7.61 (dd, J = 8.1 Hz, J = 1.8 Hz, 1H), 7.74 (d, J = 1.8 Hz, 1H), 7.84 (m, 2H), 7.98 (m, 3H), 10.32 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 120.7, 124.2, 125.0, 125.4, 131.7, 131.9, 132.1, 132.8, 134.9, 136.7, 141.7, 166.8, 191.4. HRMS (EI): Calcd. for C17H11O3N (M): 277.0739; Found: 277.0737.

Br

N

O

O

Br

Br

Br

N

O

O

O

N

O

O

O


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2-bromo-1-dibromomethyl-4-nitrobenzene A mixture of 2-bromo-4-nitrotoluene (15.0 g, 69.4 mmol), N-bromosuccinimide (37.0 g, 208.3 mmol) and AIBN (50 mg) in anhydrous benzene (200 mL) was stirred and held at reflux for 16 hours. (AIBN (50 mg) was added every 3 hours) After cooling to room temperature, the

solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 2-bromo-1-dibromomethyl-4-nitrobenzene as a pale yellow solid (7.1 g, 19.0 mmol, 27%). 1H NMR (400.13 MHz, CDCl3) δ = 7.05 (s, 1H), 8.20 (d, J = 8.6 Hz, 1H), 8.31 (dd, J = 8.6 Hz, J = 2.2 Hz, 1H), 8.40 (d, J = 2.2 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 37.4, 120.1, 123.4, 128.0, 132.2, 146.7, 148.2. HRMS (EI): Calcd. for C7H4O3NBr2 (M-Br): 291.8609; Found: 291.8608. 2-bromo-4-nitrobenzaldehyde4

2-bromo-1-dibromomethyl-4-nitrobenzene (7.1 g, 19.0 mmol) in H2SO4 (70 mL) was heated for 3 hours at 60 °C. EtOAc (70 mL) was added and the aqueous phase was extracted with EtOAc (3 x 70 mL). The combined organic layers were washed with water (70 mL) and brine (70 mL) and dried

over MgSO4. After evaporation of the solvent, the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 2-bromo-4-nitrobenzaldehyde as a white solid (4.2 g, 18.2 mmol, 96%). 1H NMR (400.13 MHz, CDCl3) δ = 8.08 (d, J = 8.6 Hz, 1H), 8.27 (ddd, J = 8.6 Hz, J = 2.1 Hz, J = 0.8 Hz, 1H), 8.53 (d, J = 2.1 Hz, J = 2.2 Hz, 1H), 10.40 (d, J = 0.8 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 122.9, 126.9, 129.2, 130.9, 137.5, 151.1, 190.1. HRMS (EI): Calcd. for C7H4O3NBr (M): 228.9375; Found: 228.9374. 4-nitro-2-vinylbenzaldehyde

A solution of 2-bromo-4-nitrobenzaldehyde (0.343 g, 1.5 mmol), potassium vinyltrifluoroborate (0.20 g, 1.5 mmol), PdCl2 (5.3 mg, 0.03 mmol), PPh3 (23.5 mg, 0.09 mmol) and Cs2CO3 (1.5 g, 4.5 mmol) in THF/H2O (9/1) (3 mL) was heated at 85 °C for 22 hours under an argon

atmosphere in a sealed tube. After cooling to room temperature, H2O (3 mL) was added, followed by extraction with CH2Cl2 (3 x 10 mL). The solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 4-nitro-2-vinylbenzaldehyde as a pale yellow solid (0.193 g, 1.1 mmol, 73%). 1H NMR (400.13 MHz, CDCl3) δ = 5.71 (d, J = 11.1 Hz, 1H), 5.88 (d, J = 17.7 Hz, 1H), 7.51 (dd, J = 17.7 Hz, J = 11.1 Hz, 1H), 8.01 (d, J = 8.5 Hz, 1H), 8.23 (dd, J = 8.5 Hz, J = 2.2 Hz, 1H), 8.41 (d, J = 2.2 Hz, 1H), 10.40 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 122.4, 122.5, 122.7, 131.4, 132.0, 136.5, 142.0, 150.8, 190.5. HRMS (EI): Calcd. for C9H7O3N (M): 177.0426; Found: 177.0428. 4-bromo-3-diacetoxymethylbenzoic acid methyl ester5

CrO3 (6.0 g, 60 mmol) was added in portions over 30 minutes to an ice-cooled solution of 4-bromo-3-methylbenzoic acid methyl ester (4.60 g, 20.1 mmol) in AcOH (33 mL) and Ac2O (34 mL) containing H2SO4 (5 mL). The mixture was stirred for another hour as the ice-

bath expired and then poured onto chilled water (300 mL). After 40 minutes of vigorous

Br

Br

Br

O2N

Br

O

O2N

O

O2N

O

O OAc

OAc

Br


S8

stirring, the white precipitate was filtrated and washed with water (3 x 20 mL) yielding 4-bromo-3-diacetoxymethylbenzoic acid methyl ester as a white precipitate (5.7 g, 16.5 mmol, 82%). 1H NMR (400.13 MHz, CDCl3) δ = 2.16 (s, 6H), 3.94 (s, 3H), 7.68 (d, J = 8.3 Hz, 1H), 7.90 (dd, J = 8.3 Hz, J = 2.1 Hz, 1H), 7.92 (s, 1H), 8.2 (d, J = 2.1 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 20.7, 52.4, 88.6, 127.8, 129.1, 129.8, 131.7, 133.5, 135.5, 165.8, 168.3. 4-bromo-3-formylbenzoic acid methyl ester5

4-bromo-3-diacetoxymethylbenzoic acid methyl ester (5.7 g, 16.5 mmol) was heated at reflux in a solution of MeOH/H2O (1/1, 50 mL) containing H2SO4 for 1 hour. After cooling to room temperature, the solution was diluted with H2O (120 mL) and extracted with EtOAc (3 x 30 mL). The

combined extracts were washed with H2O (30 mL) and brine (30 mL), then dried over MgSO4. The solvent was removed in vacuo giving a pale yellow oil, which was refluxed for 3 hours in a solution of THF (40 mL) and 1N HCl (10 mL). THF was removed in vacuo and 4-bromo-3-formylbenzoic acid methyl ester isolated as above as a pale yellow solid (3.1 g, 12.8 mmol, 77%). 1H NMR (300.07 MHz, CDCl3) δ = 3.94 (s, 3H), 7.75 (d, J = 8.3 Hz, 1H), 8.09 (dd, J = 8.3 Hz, J = 2.2 Hz, 1H), 8.53 (d, J = 2.2 Hz, 1H), 10.38 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 52.7, 130.4, 131.1, 131.7, 133.7, 134.4, 135.6, 165.5, 190.9. HRMS (EI): Calcd. for C9H7O3Br (M): 241.9579; Found: 241.9574. 3-formyl-4-vinylbenzoic acid methyl ester

A solution of 4-bromo-3-formylbenzoic acid methyl ester (0.542 g, 2.24 mmol), potassium vinyltrifluoroborate (0.30 g, 2.24 mmol), PdCl2 (8.0 mg, 0.045 mmol), PPh3 (35.0 mg, 0.135 mmol) and Cs2CO3 (2.19 g, 6.72 mmol) in THF/H2O (9/1) (5 mL) was heated at 85 °C for 22 hours under an argon atmosphere in a sealed tube. After cooling to room temperature, H2O (5 mL)

was added, followed by extraction with CH2Cl2 (3 x 10 mL). The solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 3-formyl-4-vinylbenzoic acid methyl ester as a pale yellow solid (0.332 g, 1.75 mmol, 78%). 1H NMR (400.13 MHz, CDCl3) δ = 3.96 (s, 3H), 5.62 (dd, J = 11.2 Hz, J = 1.0 Hz, 1H), 5.82 (dd, J = 17.5 Hz, J = 1.0 Hz, 1H), 7.60 (dd, J = 17.5 Hz, J = 11.2 Hz, 1H), 7.66 (br d, J = 8.2 Hz, 1H), 8.20 (ddd, J = 8.2 Hz, J = 1.9 Hz, J = 0.6 Hz, 1H), 8.48 (d, J = 1.9 Hz, 1H), 10.29 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 52.6, 121.4, 127.8, 130.0, 132.9, 133.0, 133.3, 134.4, 144.3, 166.0, 191.8. HRMS (EI): Calcd. for C11H10O3 (M): 190.0630; Found: 190.0630. 2-bromopyridine-3-carbaldehyde6

Freshly distilled 2-bromopyridine (16.5 g, 104 mmol) was added dropwise to a solution of LDA at -78 °C (prepared by the dropwise addition of n-BuLi (2.5 M in hexanes, 115 mmol, 46 mL) to a solution of i-Pr2NH (135 mmol, 19.1 mL) in THF (250 mL) at -78 °C and stirred for 20 minutes). After 4 hours at this

temperature, freshly distilled DMF (16 mL) was added dropwise and the reaction mixture was left to stir for further 30 minutes at -78 °C before being warmed to room temperature over 2 hours. Saturated aqueous NH4Cl (100 mL) was added to the reaction mixture, followed by extraction with Et2O (3 x 50 mL). The combined organic extracts were washed with brine (2 x

O

O

O

Br

O

O O

N

O

Br


S9

50 mL), dried over MgSO4 and concentrated in vacuo to yield a red oil, which was purified by silica gel chromatography (eluting with n-Hexane/EtOAc, 9/1) to yield 2-bromopyridine-3-carbaldehyde as a white crystalline solid (14.6 g, 78.3 mmol, 75%). 1H NMR (400.13 MHz, CDCl3) δ = 7.43 (ddd, J = 7.9 Hz, J = 4.7 Hz, J = 0.9 Hz, 1H), 8.17 (dd, J = 7.9 Hz, J = 2.2 Hz, 1H), 8.56 (dd, J = 2.2 Hz, J = 4.7 Hz, 1H), 10.33 (d, J = 0.9 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 123.6, 130.7, 138.1, 145.5, 154.6, 191.2. HRMS (EI): Calcd. for C6H4ONBr (M): 184.9476; Found: 184.9472. 2-vinylpyridine-3-carbaldehyde

A solution of 2-bromopyridine-3-carbaldehyde (0.278 g, 1.5 mmol), potassium vinyltrifluoroborate (0.20 g, 1.5 mmol), PdCl2 (5.3 mg, 0.03 mmol), PPh3 (23.5 mg, 0.09 mmol) and Cs2CO3 (1.5 g, 4.5 mmol) in THF/H2O (9/1) (3 mL) was heated at 85 °C for 22 hours under an argon atmosphere in a sealed tube. After

cooling to room temperature, H2O (3 mL) was added, followed by extraction with CH2Cl2 (3 x 10 mL). The solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 2-vinylpyridine-3-carbaldehyde as a pale yellow solid (0.143 g, 1.1 mmol, 71%). 1H NMR (400.13 MHz, CDCl3) δ = 5.74 (dd, J = 10.8 Hz, J = 1.8 Hz, 1H), 6.47 (dd, J = 17.0 Hz, J = 1.8 Hz, 1H), 7.35 (dd, J = 7.8 Hz, J = 4.8 Hz, 1H), 7.58 (dd, J = 17.0 Hz, J = 10.8 Hz, 1H), 8.11 (dd, J = 7.8 Hz, J = 1.9 Hz, 1H), 8.75 (dd, J = 4.8 Hz, J = 1.9 Hz, 1H), 10.36 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 122.9, 124.1, 128.2, 131.7, 138.2, 153.6, 156.5, 191.0. HRMS (EI): Calcd. for C8H7ON (M): 133.0528; Found: 133.0528. 1-bromo-4-chloro-2-dibromomethylbenzene

A mixture of 2-bromo-5-chlorotoluene (12.5 g, 60.8 mmol), N-bromosuccinimide (32.5 g, 182.5 mmol) and AIBN (40 mg) in anhydrous benzene (150 mL) was stirred and held at reflux for 16 hours. (AIBN (40 mg) was added every 3 hours) After cooling to room temperature, the solvent was removed in vacuo and the crude product was purified by silica gel

chromatography (eluting with CH2Cl2) to yield 1-bromo-4-chloro-2-dibromomethylbenzene as a pale yellow solid (15.9 g, 43.8 mmol, 72%). 1H NMR (400.13 MHz, CDCl3) δ = 6.98 (s, 1H), 7.15 (dd, J = 8.6 Hz, J = 2.5 Hz, 1H), 7.43 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 2.5 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 38.5, 117.7, 131.3, 131.4, 133.8, 134.7, 142.1. HRMS (EI): Calcd. for C7H4Br2Cl (M-Br): 280.8368; Found: 280.8365. 2-bromo-5-chlorobenzaldehyde7

1-bromo-4-chloro-2-dibromomethylbenzene (2.8 g, 7.7 mmol) in H2SO4 (30 mL) was heated for 3 hours at 60 °C. EtOAc (30 mL) was added and the aqueous phase was extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with water (30 mL) and brine (30 mL) and dried over MgSO4. After evaporation of the solvent, the crude product was purified by

silica gel chromatography (eluting with CH2Cl2) to yield 2-bromo-5-chlorobenzaldehyde as a white solid (1.61 g, 7.3 mmol, 95%). 1H NMR (400.13 MHz, CDCl3) δ = 7.41 (dd, J = 8.5 Hz, J = 2.7 Hz, 1H), 7.59 (d, J = 8.5 Hz, 1H), 7.86 (d, J = 2.7 Hz, 1H), 10.29 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 124.7, 129.8, 134.6, 134.8, 135.2, 135.3, 190.6. HRMS (EI): Calcd. for C7H3O3BrCl (M-H): 216.9056; Found: 216.9051.

N

O

Cl

BrBr

Br

Cl

BrO


S10

5-chloro-2-vinylbenzaldehyde A solution of 2-bromo-5-chlorobenzaldehyde (0.42 g, 1.9 mmol), potassium vinyltrifluoroborate (0.26 g, 1.9 mmol), PdCl2 (6.9 mg, 0.04 mmol), PPh3 (30.5 mg, 0.12 mmol) and Cs2CO3 (1.9 g, 5.7 mmol) in THF/H2O (9/1) (3

mL) was heated at 85 °C for 22 hours under an argon atmosphere in a sealed tube. After cooling to room temperature, H2O (3 mL) was added, followed by extraction with CH2Cl2 (3 x 10 mL). The solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 5-chloro-2-vinylbenzaldehyde as a pale yellow solid (0.256 g, 1.54 mmol, 81%). 1H NMR (400.13 MHz, CDCl3) δ = 5.55 (dd, J = 11.0 Hz, J = 1.1 Hz, 1H), 5.70 (dd, J = 17.4 Hz, J = 1.1 Hz, 1H), 7.44 (dd, J = 17.4 Hz, J = 11.0 Hz, 1H), 7.51 (s, 1H), 7.52 (br s, 1H), 7.80 (t, J = 1.4 Hz, 1H), 10.26 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 120.4, 129.1, 130.4, 132.2, 133.9, 134.1, 134.3, 139.0, 190.9. HRMS (EI): Calcd. for C9H7OCl (M): 166.0185; Found: 166.0185. 5-fluoro-2-vinylbenzaldehyde8

A solution of 2-bromo-5-fluorobenzaldehyde (0.39 g, 1.9 mmol), potassium vinyltrifluoroborate (0.26 g, 1.9 mmol), PdCl2 (6.9 mg, 0.04 mmol), PPh3 (30.5 mg, 0.12 mmol) and Cs2CO3 (1.9 g, 5.7 mmol) in THF/H2O (9/1) (3

mL) was heated at 85 °C for 22 hours under an argon atmosphere in a sealed tube. After cooling to room temperature, H2O (3 mL) was added, followed by extraction with CH2Cl2 (3 x 10 mL). The solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 5-fluoro-2-vinylbenzaldehyde as a yellow oil (0.231 g, 1.54 mmol, 81%). 1H NMR (300.07 MHz, CDCl3) δ = 5.53 (d, J = 11.0 Hz, 1H), 5.64 (d, J = 17.4 Hz, 1H), 7.25 (td, J = 8.6 Hz, J = 3.0 Hz, 1H), 7.42 (dd, J = 17.4 Hz, J = 11.0 Hz, 1H), 7.52 (dd, J = 8.6 Hz, J = 3.0 Hz, 1H), 7.54 (dd, J = 8.6 Hz, J = 5.3 Hz, 1H), 10.31 (d, J = 2.1 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 116.2 (d, J = 22.2 Hz), 120.0 (br s), 121.3 (d, J = 22.2 Hz), 129.8 (d, J = 7.3 Hz), 132.1, 134.5 (d, J = 5.9 Hz), 137.1 (d, J = 3.5 Hz), 162.5 (d, J = 249.8 Hz), 190.7 (d, J = 1.8 Hz). HRMS (EI): Calcd. for C9H7OF (M): 150.0481; Found: 150.0478. 4-methyl-2-vinylbenzaldehyde

A solution of 2-bromo-4-methylbenzaldehyde (0.39 g, 1.9 mmol), potassium vinyltrifluoroborate (0.26 g, 1.9 mmol), PdCl2 (6.9 mg, 0.04 mmol), PPh3 (30.5 mg, 0.12 mmol) and Cs2CO3 (1.9 g, 5.7 mmol) in THF/H2O (9/1) (3 mL) was heated at 85 °C for 22 hours under an argon atmosphere in a sealed tube. After cooling to room temperature, H2O (3 mL) was added, followed by extraction

with CH2Cl2 (3 x 10 mL). The solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 4-methyl-2-vinylbenzaldehyde as a pale yellow solid (0.218 g, 1.5 mmol, 77%). 1H NMR (400.13 MHz, CDCl3) δ = 2.42 (s, 3H), 5.48 (dd, J = 11.0 Hz, J = 1.3 Hz, 1H), 5.68 (dd, J = 17.4 Hz, J = 1.3 Hz, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.36 (s, 1H) 7.52 (dd, J = 17.4 Hz, J = 11.0 Hz, 1H), 7.72 (d, J = 8.1 Hz, 1H), 10.22 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 21.9, 119.1, 128.1, 128.9, 130.8, 131.7, 133.7, 140.6, 144.8, 192.1. HRMS (EI): Calcd. for C10H10O (M): 146.0732; Found: 146.0731.

OCl

FO

O


S11

6-vinylveratraldehyde9 A solution of 6-bromoveratraldehyde (0.4 g, 1.63 mmol), tributyl(vinyl)tin (475 µL, 1.63 mmol), [Pd(PPh3)4] (38 mg, 0.03 mmol) and 2,6-di-tert-butyl-p-cresol (56 mg, 0.25 mmol) in toluene (3 mL) was heated at 110 °C for 16 hours under an argon atmosphere in a sealed tube. After cooling to room temperature, H2O (3 mL) was added, followed by extraction with CH2Cl2 (3 x

10 mL). The solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 6-vinylveratraldehyde as a pale yellow solid (0.285 g, 1.49 mmol, 91%). 1H NMR (400.13 MHz, CDCl3) δ = 3.92 (s, 3H), 3.97 (s, 3H), 5.48 (dd, J = 11.0 Hz, J = 1.1 Hz, 1H), 5.62 (dd, J = 17.3 Hz, J = 1.1 Hz, 1H), 6.96 (s, 1H), 7.35 (s, 1H), 7.42 (dd, J = 17.3 Hz, J = 11.0 Hz, 1H), 10.24 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 56.1, 56.2, 109.1, 110.4, 118.9, 126.5, 132.3, 136.3, 149.1, 153.9, 190.0. HRMS (EI): Calcd. for C11H12O3 (M): 192.0786; Found: 192.0784. 1-bromo-2-dibromomethylnaphthalene10

A mixture of 1-bromo-2-methylnaphthalene (9.4 g, 42.5 mmol), N-bromosuccinimide (22.7 g, 127.5 mmol) and AIBN (30 mg) in anhydrous benzene (100 mL) was stirred and held at reflux for 16 hours. (AIBN (30 mg) was added every 3 hours) After cooling to room temperature, the

solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with CH2Cl2) to yield 1-bromo-2-dibromomethylnaphthalene as a pale yellow solid (15.6 g, 41.2 mmol, 97%). 1H NMR (400.13 MHz, CDCl3) δ = 7.49 (s, 1H), 7.62 (m, 2H), 7.84 (d, J = 8.3 Hz, 1H), 7.90 (d, J = 8.9 Hz, 1H), 8.07 (d, J = 8.9 Hz, 1H), 8.31 (d, J = 8.3 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 41.4, 119.7, 126.9, 128.1, 128.4, 128.5, 128.6, 129.2, 131.4, 134.8, 138.1. HRMS (EI): Calcd. for C11H7Br3 (M): 375.8098; Found: 375.8099. 1-bromonaphtalene-2-carbaldehyde11

A mixture of 1-bromo-2-dibromomethylnaphthalene (15.6 g, 41.2 mmol) and CaCO3 (9.1 g, 90.6 mmol) in H2O (350 mL) was heated at reflux for 8 hours. It was then cooled to room temperature and extracted with EtOAc (2 x 150 mL). The organic layer was washed with water (100 m L), brine (100

mL) and dried over MgSO4. The solvent was removed in vacuo and the crude compopund was purified by crystallisation from Petroleum Ether/EtOAc (95/5) giving 1-bromonaphtalene-2-carbaldehyde as a white solid (9.31 g, 39.6 mmol, 95%). 1H NMR (400.13 MHz, CDCl3) δ = 7.68 (m, 2H), 7.85 (d, J = 8.7 Hz, 1H), 7.88 (m, 1H), 7.93 (d, J = 8.7 Hz, 1H), 8.50 (m, 1H), 10.67 (d, J = 0.9 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 124.2, 128.3, 128.4, 128.5, 128.6, 129.9, 131.3, 131.5, 132.3, 137.4, 193.0. HRMS (EI): Calcd. for C11H7OBr (M): 233.9680; Found: 233.9677. 1-vinylnaphtalene-2-carbaldehyde12

A solution of 1-bromonaphtalene-2-carbaldehyde (2 g, 8.51 mmol), tributyl(vinyl)tin (2.7 mL, 9.36 mmol) and [Pd(PPh3)4] (203 mg, 0.18 mmol) in toluene (12 mL) was heated at 110 °C for 16 hours under an argon atmosphere in a sealed tube. After cooling to room temperature, H2O

(12 mL) was added, followed by extraction with CH2Cl2 (3 x 20 mL). The solvent was

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O

O

BrBr

Br

Br

O

O


S12

removed in vacuo and the crude product was purified by silica gel chromatography (eluting with Petroleum Ether/DCM, 1/1) to yield 1-vinylnaphtalene-2-carbaldehyde as a pale yellow solid (1.43 g, 7.83 mmol, 92%). 1H NMR (400.13 MHz, CDCl3) δ = 5.50 (dd, J = 17.6 Hz, J = 1.6 Hz, 1H), 6.02 (dd, J = 11.3 Hz, J = 1.6 Hz, 1H), 7.39 (dd, J = 17.6 Hz, J = 11.3 Hz, 1H), 7.61 (m, 2H), 7.84 (d, J = 8.5 Hz, 1H), 7.88 (br d, J = 8.3 Hz, 1H), 8.00 (d, J = 8.5 Hz, 1H), 8.20 (br d, J = 8.3 Hz, 1H), 10.46 (d, J = 0.9 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 123.0, 126.0, 126.2, 127.0, 128.2, 128.6, 128.9, 130.7, 131.5, 131.7, 135.9, 143.4, 192.8. HRMS (EI): Calcd. for C13H10O (M): 182.0732; Found: 182.0732. 5-hydroxy-2-vinylbenzaldehyde

A solution of 2-bromo-5-hydroxybenzaldehyde (0.2 g, 1.0 mmol), tributyl(vinyl)tin (324 µL, 1.1 mmol) and [Pd(PPh3)4] (26 mg, 0.02 mmol) in toluene (6 mL) was heated at 110 °C for 16 hours under an argon atmosphere in a sealed tube. After cooling to room temperature, H2O (5

mL) was added, followed by extraction with CH2Cl2 (3 x 15 mL). The solvent was removed in vacuo and the crude product was purified by silica gel chromatography (eluting with EtOAc/CH2Cl2, 1/50) to yield 5-hydroxy-2-vinylbenzaldehyde as a pale yellow solid (0.12 g, 0.81 mmol, 81%). 1H NMR (300.07 MHz, CDCl3) δ = 5.44 (dd, J = 11.0 Hz, J = 1.1 Hz, 1H), 5.55 (br s, 1H), 5.60 (dd, J = 17.3 Hz, J = 1.1 Hz, 1H), 7.08 (dd, J = 8.5 Hz, J = 2.9 Hz, 1H), 7.31 (d, J = 2.9 Hz, 1H), 7.39 (dd, J = 17.3 Hz, J = 11.0 Hz, 1H), 7.48 (d, J = 8.5 Hz, 1H), 10.28 (s, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 115.8, 118.5, 121.8, 129.4, 132.3, 134.0, 134.1, 155.8, 192.0. HRMS (EI): Calcd. for C9H8O2 (M): 148.0524; Found: 148.0526. Products (from Intermolecular Reactions) 1-(4-Methoxy-phenyl)-nonan-1-one13

The title product was obtained in 93% isolated yield as a white powder from 1-octene and p-methoxybenzaldehyde by using the general procedure (GP1). 1H NMR (400.13 MHz, CDCl3) δ = 0.87 (t, J = 6.8 Hz, 3H), 1.31 (m, 10H), 1.71 (quint, J = 7.5 Hz, 2H), 2.90 (t, J = 7.5 Hz, 2H), 3.86 (s, 3H), 6.91 (d, J = 8.5 Hz, 2H), 7.92 (d, J = 8.5 Hz, 2H);

13C{1H} NMR (100.6 MHz, CDCl3) δ = 14.2, 22.8, 24.8, 29.3, 29.6, 31.9, 38.4, 55.5, 113.7, 130.3, 130.4, 163.4, 199.3. HRMS (EI): Calcd. for C16H25O2 (M+H): 249.1855; Found: 249.1852. 1-Biphenyl-4-yl-nonan-1-one

The title product was obtained in 68% isolated yield as a white powder from 1-octene and biphenyl-4-carboxaldehyde by using the general procedure (GP1). 1H NMR (400.13 MHz, CDCl3) δ = 0.89 (t, J = 6.8 Hz, 3H), 1.34 (m, 10H), 1.76 (quint, J = 7.5 Hz, 2H), 2.99 (t, J = 7.5 Hz, 2H), 7.41 (m, 1H), 7.47 (m, 2H), 7.63

(m, 2H), 7.68 (m, 2H), 8.03 (m, 2H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 14.2, 22.8, 24.6, 29.3, 29.5, 29.6, 32.0, 38.8, 127.3 (2C), 127.4 (2C), 128.3, 128.8 (2C), 129.0 (2C), 135.9, 140.1, 145.6, 200.3. HRMS (EI): Calcd. for C21H26O (M): 294.1984; Found: 294.1987.

HO

O

O

O

O


S13

1-(4-Chloro-phenyl)-nonan-1-one

The title product was obtained in 70% isolated yield as a white powder from 1-octene and p-chlorobenzaldehyde by using the general procedure (GP1). 1H NMR (400.13 MHz, CDCl3) δ = 0.88 (t, J = 6.8 Hz,

3H), 1.32 (m, 10H), 1.72 (quint, J = 7.5 Hz, 2H), 2.92 (t, J = 7.5 Hz, 2H), 7.42 (d, J = 8.6 Hz, 2H), 7.89 (d, J = 8.6 Hz, 2H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 14.2, 22.8, 24.5, 29.3, 29.5, 29.6, 31.9, 38.7, 129.0, 129.6, 135.6, 139.4, 199.4. HRMS (CI): Calcd. for C15H22OCl (M+H): 253.1359; Found: 253.1363. 1,4-diphenyl-butan-1-one14

The title product was obtained in 72% isolated yield as a white powder from allylbenzene and benzaldehyde by using the general procedure (GP1). 1H NMR (400.13 MHz, CDCl3) δ = 2.09 (quint, J = 7.6 Hz, 2H),

2.73 (t, J = 7.6 Hz, 2H) , 2.98 (t, J = 7.6 Hz, 2H), 7.21 (m, 3H), 7.29 (tt, J = 7.4 Hz, J = 1.8 Hz, 2H), 7.44 (tt, J = 8.0 Hz, J = 1.8 Hz, 2H), 7.55 (tt, J = 7.4 Hz, J = 1.2 Hz, 1H), 7.92 (dd, J = 8.0 Hz, J = 1.2 Hz, 1H), 7.92 (q, J = 4.0 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 25.8, 35.4, 37.9, 126.1, 128.2, 128.5, 128.6, 128.7, 133.1, 137.2, 141.8, 200.3. HRMS (EI): Calcd. for C16H16O (M): 224.1201; Found: 224.1204. 7-oxo-7-phenyl heptanoic acid15

The title product was obtained in 51% isolated yield as a white powder from 5-hexenoic acid and benzaldehyde by using the general procedure (GP1). 1H NMR (400.13 MHz, CDCl3) δ = 1.46 (m, 2H), 1.74 (m, 4H), 2.39 (t, J = 7.4 Hz, 2H), 2.99 (t, J = 7.4 Hz, 2H), 7.46 (m,

2H), 7.56 (m, 1H), 7.96 (m, 2H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 24.0, 24.7, 28.9, 33.6, 38.4, 128.2, 128.7, 133.1, 137.1, 177.9, 200.3. HRMS (EI): Calcd. for C13H17O3 (M+H): 221.1178; Found: 221.1175. 7-Hydroxy-1-phenyl-heptan-1-one16

The title product was obtained in 75% isolated yield as a yellowish solid from 5-hexen-1-ol and benzaldehyde by using the general procedure (GP1). 1H NMR (400.13 MHz, CDCl3) δ = 1.42 (m, 4H), 1.59 (m,

2H), 1.76 (m, 2H), 2.98 (t, J = 7.6 Hz, 2H), 3.65 (t, J = 6.4 Hz, 2H), 7.46 (m, 2H), 7.56 (m, 1H), 7.96 (m, 2H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 24.4, 25.7, 29.2, 32.7, 38.6, 63.1, 128.2, 128.7, 133.1, 137.2, 200.6. HRMS (EI): Calcd. for C13H19O2 (M+H): 207.1385; Found: 207.1382. 3-Cyclohex-3-enyl-1-phenyl-propan-1-one17

The title product was obtained in 57% isolated yield as a colorless oil from 4-vinyl-1-cyclohexene and benzaldehyde by using the general procedure (GP1). 1H NMR (400.13 MHz, CDCl3) δ = 1.29 (m, 1H), 1.72 (m, 5H), 2.07

O

Cl

O

OH

O

O

OH

O

O


S14

(m, 2H), 2.16 (m, 1H), 3.02 (t, J = 7.4 Hz, 2H), 5.67 (m, 2H), 7.46 (m, 2H), 7.56 (m, 1H), 7.96 (m, 2H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 25.3, 29.0, 31.1, 31.9, 33.5, 36.3, 126.4, 127.2, 128.2, 128.7, 133.1, 137.3, 200.8. HRMS (EI): Calcd. for C15H18O (M): 214.1358; Found: 214.1359. 1-Phenylnonan-1-one18

The title product was obtained in 83% isolated yield as a colorless oil from 1-octene and benzaldehyde by using the general procedure (GP1). 1H NMR (400.13 MHz, CDCl3) δ = 0.88 (t, J = 7.2 Hz, 3H), 1.32 (m, 10H), 1.74 (quint, J = 7.3 Hz, 2H), 2.96 (t, J = 7.3 Hz,

2H), 7.46 (m, 2H), 7.56 (m, 1H), 7.96 (m, 2H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 14.3, 22.8, 24.6, 29.3, 29.5, 29.6, 32.0, 38.8, 128.2, 128.7, 133.0, 137.3, 200.8. HRMS (EI): Calcd. for C15H22O (M): 218.1671; Found: 218.1671. 4-Oxo-4-phenyl-butyric acid methyl ester19 The title product was obtained in 73% isolated yield as a white powder from methyl acrylate

and benzaldehyde by using the general procedure (GP1). 1H NMR (400.13 MHz, CDCl3) δ = 2.78 (t, J = 6.6 Hz, 2H), 3.32 (t, J = 6.6 Hz, 2H) , 3.71 (s, 3H), 7.47 (m, 2H), 7.58 (m, 1H), 7.99 (m, 2H); 13C{1H} NMR (100.6 MHz, CDCl3) δ = 28.2, 33.6, 52.0, 128.2, 128.8,

133.4, 136.7, 173.5, 198.2. HRMS (EI): Calcd. for C11H13O3 (M+H): 193.0865; Found: 193.0866. Products (from Intramolecular Reactions) 1-indanone20

The title product was obtained in 97% isolated yield as a white powder from o-vinylbenzaldehyde by using the general procedure (GP2). 1H NMR (300.07 MHz, CDCl3): δ = 2.68 (m, 2H), 3.14 (m, 2H), 7.36 (br t, J =

7.5 Hz, 1H), 7.47 (br d, J = 7.7 Hz, 1H), 7.57 (td, J = 7.5 Hz, J = 1.3 Hz, 1H), 7.75 (d, J = 7.7 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 25.9, 36.3, 123.8, 126.8, 127.4, 134.7, 137.2, 155.2, 207.1. HRMS (EI): Calcd. for C9H8O (M): 132.0575; Found: 132.0577. 5.6-dimethoxy-1-indanone21

The title product was obtained in 98% isolated yield as a white powder from 6-vinylveratraldehyde by using the general procedure (GP2). 1H NMR (400.13 MHz, CDCl3): δ = 2.63 (m, 2H), 3.01 (m, 2H), 3.87 (s, 3H), 3.93 (s, 3H), 6.86 (s, 1H), 7.14 (s, 1H); 13C{1H} NMR (100.6 MHz,

CDCl3): δ = 25.6, 36.5, 56.1, 56.3, 104.2, 107.6, 130.0, 149.5, 150.4, 155.5, 205.7. HRMS (EI): Calcd. for C11H12O3 (M): 192.0786; Found: 192.0789. 1-oxo-indan-5-carboxylic acid methyl ester22

The title product was obtained in 96% isolated yield as a white powder from 3-formyl-4-vinylbenzoic acid methyl ester by using the general procedure (GP2).

O

O

O

O

O

O

O

O

O

O

O


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1H NMR (400.13 MHz, CDCl3) δ = 2.76 (m, 2H), 3.21 (m, 2H), 3.94 (s, 3H), 7.55 (dq, J = 8.0 Hz, J = 0.8 Hz, 1H), 8.27 (dd, J = 8.0 Hz, J = 1.7 Hz, 1H), 8.42 (dq, J = 1.7 Hz, J = 0.8 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 26.2, 36.6, 52.5, 125.4, 127.0, 130.0, 135.5, 137.5, 159.6, 166.4, 206.0. HRMS (EI): Calcd. for C11H10O3 (M): 190.0630; Found: 190.0628. 5-methyl-1-indanone23

The title product was obtained in 97% isolated yield as a white powder from 4-methyl-2-vinylbenzaldehyde by using the general procedure (GP2). 1H NMR (400.13 MHz, CDCl3) δ = 2.44 (s, 3H), 2.67 (m, 2H), 3.09 (m,

2H), 7.18 (br d, J = 7.8 Hz, 1H), 7.27 (m, 1H), 7.65 (d, J = 7.8 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 22.2, 25.8, 36.5, 123.7, 127.2, 128.7, 135.0, 145.9, 155.8, 206.7. HRMS (EI): Calcd. for C10H10O (M): 146.0732; Found: 146.0730. 5-phthalimido-1-indanone

The title product was obtained in 95% isolated yield as a white powder from 4-phthalimido-2-vinylbenzaldehyde by using the general procedure (GP2). 1H NMR (300.07 MHz, CDCl3): δ = 2.76 (m, 2H), 3.23 (m, 2H), 7.52 (br d, J = 8.3 Hz, 1H), 7.63 (m, 1H), 7.83 (m, 2H), 7.89 (br d,

J = 8.3 Hz, 1H), 7.99 (m, 2H); 13C{1H} NMR (100.6 MHz, CDCl3) : δ = 26.0, 36.6, 124.2, 124.5, 124.6, 125.7, 131.7, 134.9, 136.4, 137.4, 156.0, 167.0, 206.0. HRMS (EI): Calcd. for C17H11O3N (M): 277.0739; Found: 277.0738. 5-nitro-1-indanone24

The title product was obtained in 93% isolated yield as a white powder from 4-nitro-2-vinylbenzaldehyde by using the general procedure (GP2). 1H NMR (400.13 MHz, CDCl3) δ = 2.83 (m, 2H), 3.28 (m, 2H), 7.90 (br d, J = 8.4 Hz, 1H), 8.23 (br d, J = 8.4 Hz, 1H), 8.35 (m, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 26.0, 36.8, 122.2, 123.0, 124.9, 141.4, 152.0, 155.8, 205.0. HRMS (EI): Calcd. for C9H7O3N (M): 177.0426; Found: 177.0427.

1,2-dihydro-cyclopenta[α]naphthalene-3-one25

The title product was obtained in 97% isolated yield as a white powder from 1-vinylnaphtalene-2-carbaldehyde by using the general procedure (GP2). 1H NMR (400.13 MHz, CDCl3): δ = 2.84 (m, 2H), 3.45 (m, 2H), 7.66 (m,

2H), 7.75 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.95 (br d, J = 7.9 Hz, 1H), 8.06 (br d, J = 7.9 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 24.5, 36.3, 119.6, 124.5, 127.2, 128.6, 129.0, 129.3, 130.7, 134.8, 136.7, 156.5, 206.9. HRMS (EI): Calcd. for C13H10O (M): 182.0732; Found: 182.0731. 6-chloro-1-indanone25

The title product was obtained in 91% isolated yield as a white powder from 5-chloro-2-vinylbenzaldehyde by using the general procedure (GP2).

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O

O

O

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OCl


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1H NMR (400.13 MHz, CDCl3) δ = 2.73 (m, 2H), 3.12 (m, 2H), 7.42 (dq, J = 8.2 Hz, J = 0.7 Hz, 1H), 7.54 (dd, J = 8.2 Hz, J = 2.1 Hz, 1H), 7.71 (dq, J = 2.1 Hz, J = 0.7 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 25.6, 36.8, 123.8, 128.0, 133.9, 134.7, 138.8, 153.2, 205.6. HRMS (EI): Calcd. for C9H7OCl (M): 166.0185; Found: 166.0181. 6-fluoro-1-indanone26

The title product was obtained in 92% isolated yield as a white powder from 5-fluoro-2-vinylbenzaldehyde by using the general procedure (GP2). 1H NMR (400.13 MHz, CDCl3) δ = 2.73 (m, 2H), 3.12 (m, 2H), 7.29 (dt, J = 8.6 Hz, J = 2.6 Hz, 1H), 7.38 (br d, J = 7.6 Hz, 1H), 7.44 (dd, J = 8.6 Hz, J =

4.6 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 25.4, 37.1, 109.7 (d, J = 22.1 Hz), 122.4 (d, J = 23.8 Hz), 128.2 (d, J = 8.1 Hz), 138.9 (d, J = 7.2 Hz), 150.6 (d, J = 2.2 Hz), 162.5 (d, J = 248.1 Hz), 206.0 (d, J = 3.1 Hz). HRMS (EI): Calcd. for C9H7OF (M): 150.0481; Found: 150.0480. 6-hydroxy-1-indanone27

The title product was obtained in 95% isolated yield as a white powder from 5-hydroxy-2-vinylbenzaldehyde by using the general procedure (GP2). 1H NMR (300.07 MHz, CDCl3) δ = 2.71 (m, 2H), 3.07 (m, 2H), 5.13 (br s, 1H), 7.14 (dd, J = 8.1 Hz, J = 2.5 Hz, 1H), 7.16 (br d, J = 2.5 Hz, 1H), 7.36

(dq, J = 8.1 Hz, J = 0.9 Hz, 1H); 13C{1H} NMR (100.6 MHz, CDCl3): δ = 25.4, 37.1, 108.8, 123.6, 127.8, 138.4, 147.9, 155.7, 207.6. HRMS (EI): Calcd. for C9H8O2 (M): 148.0524; Found: 148.0522.

OF

OHO


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1 1984, 687-695.


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1H NMR and 13C NMR spectra of isolated compounds Substrates


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inter- and intramolecular hydroacylation of alkenes employing a

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