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S1 Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl Carboxylic Acids from Styrene Derivatives and CO 2 Mark D. Greenhalgh, and Stephen P. Thomas* School of Chemistry, University of Bristol, Cantocks Close, Bristol, BS8 1TS, United Kingdom [email protected] Supporting Information Table of Contents General Experimental S2 General Procedures S3 Ligand Preparation: Analytical Data for 5, 6 S4 Synthesis of Styrene Derivatives: Analytical Data for 7e,f S5 Table S1. Catalyst Identification S7 Table S2. Reaction Scope and Limitations: Analytical Data for 2, 8a-l S14 Mechanistic Investigations S23 ICP Analysis, and Investigation of Potential Catalytic Role of Trace Metals S30 NMR Traces: 5, 6, 7e-h, j, 2, 8a-o S32 GC-MS Traces: 2, 8a-o S59 References S67
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Page 1: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S1

Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl Carboxylic Acids from Styrene Derivatives and CO2

Mark D. Greenhalgh, and Stephen P. Thomas*

School of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, United Kingdom

[email protected]

Supporting Information

Table of Contents

General Experimental

S2

General Procedures

S3

Ligand Preparation: Analytical Data for 5, 6

S4

Synthesis of Styrene Derivatives: Analytical Data for 7e,f

S5

Table S1. Catalyst Identification

S7

Table S2. Reaction Scope and Limitations: Analytical Data for 2, 8a-l

S14

Mechanistic Investigations

S23

ICP Analysis, and Investigation of Potential Catalytic Role of Trace Metals

S30

NMR Traces: 5, 6, 7e-h, j, 2, 8a-o

S32

GC-MS Traces: 2, 8a-o

S59

References

S67

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General Experimental

All air and moisture sensitive manipulations were carried out using standard vacuum line and Schlenk

techniques, or in a drybox containing a purified argon atmosphere. Solvents for air and moisture

sensitive manipulations were obtained from an Anhydrous Engineering Solvent Purification System. All

glassware was cleaned using base (KOH, iPrOH) then acid (HClaq) baths.

Iron(II) chloride was purchased from Strem Chemicals Inc. (UK); anhydrous iron chloride, 98% (product

number 93-2631. Lot 19226800, 44.00000% Fe, expect 44.059%). Iron(II) chloride tetrahydrate was

purchased from Sigma Aldrich (UK); puriss. p.a., >99.0% (product number 44939. Lot BCBF5170V).

Iron(II) chloride 99.99% was purchased from Sigma Aldrich (UK); anhydrous beads, -10 mesh, 99.99%

(product number 450936). All styrene derivatives used were purchased from Sigma Aldrich, Alfa Aesar

and Tokyo Chemical Industries, UK, or synthesised within the laboratory. All Grignard reagents, d5-

Bromoethane, (1-bromoethyl)benzene and (2-bromoethyl)benzene were purchased from Sigma Aldrich

(UK). Carbon dioxide was purchased from BOC LTD (UK) (C40-VB – Carbon dioxide cylinder, vapour, B-

size 10).

1H, 13C and 19F NMR spectra were recorded on Varian VNMR 400 and 500MHz or Jeol Eclipse 300MHz

and 400MHz spectrometers. All spectra were obtained at ambient temperature. The chemical shifts (δ)

were recorded in parts per million (ppm) and the coupling constants (J) in Hertz (Hz). 1H and 13C NMR

multiplicity and coupling constants are reported where applicable. 1H and 13C spectra were referenced

to the residual deuterated solvent peak (CHCl3 7.27ppm, 77.00ppm).

Aqueous sulphate buffer was prepared by dissolving Na2SO4 (1.5 mol) H2SO4 (0.5 mol) and adding water

to give a total volume of 2000 cm3. Flash chromatography was performed on silica gel (Merck Kielselgel

60). Analytical thin layer chromatography was performed on aluminium backed silica plates (60 F254).

Gas chromatography was performed on an Agilent HP6890 gas chromatograph equipped with an Agilent

J&W DB-5ms capillary column (15 m × 0.25 mm × 0.25 µm). Several different methods were used:

[70-1]: Injector temp. 250 °C, 70 °C for 3 min, ramps 25 °C/min to 200 °C, ramps 45 °C/min to 250 °C,

holds for 3 min, ramps 45 °C/min to 300 °C, holds for 3 min.

[35-AJP]: Injector temp. 250 °C, 35 °C for 3 min, 45 °C/min to 250 °C, hold for 3 min, 45 °C/min to 300 °C,

hold for 3 min.

Infra-red spectra were recorded on a Perkin-Elmer Spectrum One FT-IR spectrometer. Melting points

were determined using a Stuart Scientific SMP10 and were uncorrected. High resolution mass spectra

were recorded on a VG autospec mass spectrometer.

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General Procedures

General procedure A: Synthesis of styrene derivatives

A benzaldehyde derivative (5 mmol) was added to potassium carbonate (1.1 g, 8 mmol) and

methyltriphenylphosphonium bromide (2.1 g, 6 mmol) in anhydrous 1,4-dioxane (5 mL), and heated at

reflux for 16 hours. The reaction mixture was cooled, filtered and concentrated in vacuo. The residue

was dissolved in hot n-pentane, cooled to 0 °C, filtered, and washed with cold n-pentane. The filtrate

was dried (MgSO4) and concentrated in vacuo to give the styrene derivative.

General procedure B: Catalyst optimisation

Styrene (80 µL, 0.7 mmol) was added to a solution of an iron salt and ligand in anhydrous

tetrahydrofuran (5 mL) at room temperature. The Grignard reagent (1.1 mmol) was added dropwise

over 10 minutes and the reaction stirred at room temperature under an atmosphere of nitrogen for 1

hour. Carbon dioxide was bubbled through the reaction via a needle for 30 minutes. Aqueous sulphate

buffer solution (10 mL) was added and the aqueous phase extracted with diethyl ether (3 x 20 mL). The

combined organic extracts were washed with H2O and brine, dried (MgSO4) and concentrated in vacuo

to give the crude reaction products. Dimethoxybenzene (19.3 mg, 0.14 mmol) was added as an internal

standard, and a yield for the reaction determined for 1H NMR.

All products were known, identified by 1H NMR, and characterised by comparison with authentic

samples of spectral data.

General procedure C: Hydrocarboxylation of styrene derivatives

A styrene derivative (0.7 mmol) was added to a solution of iron(II) chloride (0.9 mg, 0.007 mmol) and

2,6-bis-[1-(2,6-diisoprpylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol) in anhydrous

tetrahydrofuran (5 mL) at room temperature. Ethylmagnesium bromide (0.3 mL, 3M in Et2O, 0.9 mmol)

was added dropwise over 10 minutes and the reaction stirred at room temperature under an

atmosphere of nitrogen for 2 hours. Carbon dioxide was bubbled through the reaction via a needle for

30 minutes. Aqueous sulphate buffer solution (10 mL) was added and the aqueous phase extracted with

diethyl ether (3 x 20 mL). The combined organic extracts were washed with H2O and brine, dried

(MgSO4) and concentrated in vacuo to give the crude reaction products.

Known products were identified by 1H NMR, and characterised by comparison with authentic samples of

spectral data.

In order to determine isolated yields, sodium hydroxide (1M aqueous) was added to the crude reaction

products and extracted with diethyl ether (3 x 20 mL). The aqueous phase was acidified to pH 1 with

concentrated hydrochloric acid, and extracted with diethyl ether (3 x 20 mL). The combined organic

phases were washed with H2O and brine, dried (MgSO4) and concentrated in vacuo to give the purified

carboxylic acid product. If necessary, the product was further purified by flash silica chromatography.

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Ligand preparation

(±)-(N,N’-bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine1 5

2-Pyridinecarboxaldehyde (2.52 mL, 26.4 mmol) in anhydrous methanol (30 mL) was added to a solution

of (±)-trans-diaminocyclohexane (1.44 mL, 12 mmol) in anhydrous methanol (30 mL) and molecular

sieves (3 Å) at 0 °C under an atmosphere of nitrogen. The reaction mixture was shaken for 16 hours,

allowing the reaction to warm to room temperature over this time. The solution was filtered through

celite and the solvent removed in vacuo to give the crude product which was recrystallized from hot

ethanol to give (±)-(N,N’-bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine 5 (2.6 g, 74 %) as colourless

needles. m.p 139-141 °C (EtOH). δH (300 MHz, CDCl3) 8.56 (ddd, J= 4.8 Hz, 1.7 Hz, 1.0 Hz, 2H), 8.32 (s, 2H),

7.89 (dt, J= 7.9 Hz, 1.1 Hz, 2H), 7.65 (ddd, J= 7.7 Hz, 1.7 Hz, 0.6 Hz, 2H), 7.23 (ddd, J= 7.6 Hz, 4.8 Hz, 1.2

Hz, 2H), 3.60-3.49 (m, 2H), 1.95-1.78 (m, 6H), 1.58-1.46 (m, 2H). δC (100 MHz, CDCl3) 161.4, 154.6, 149.2,

136.4, 124.5, 121.3, 73.5, 32.7, 24.3. IR (neat) max cm-1 3053, 3007, 2936, 2851, 1644, 1586, 1567, 1467,

1436, 1370.

Data were in accordance with those previously reported in the literature.1

2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine2 6

2,6-Diisopropylaniline (10.9 mL, 58 mmol) was added to a stirred suspension of 2,6-diacetylpyridine (4.2

g, 26 mmol) and p-toluene sulfonic acid (0.3 g, 1.5 mmol) in anhydrous toluene (350 mL) and heated at

reflux under Dean-Stark conditions for 16 hours. The solvent was removed in vacuo and the yellow solid

recrystallized from dichloromethane by slow evaporation to give 2,6-bis-[1-(2,6-

diisopropylphenylimino)ethyl]pyridine 6 (9.1 g, 73%) as yellow needles. m.p 298-299 °C (CH2Cl2). δH (400

MHz, CDCl3) 8.50 (d, J= 7.8Hz, 2H), 7.95 (t, J= 7.8Hz, 1H), 7.21-7.17 (m, 4H), 7.15-7.09 (m, 2H), 2.79 (sept,

J= 6.9 Hz, 4H), 2.29 (s, 6H), 1.18 (d, J= 6.9 Hz, 24H). δC (125 MHz, CDCl3) 166.9, 155.1, 146.5, 136.8, 135.8,

123.6, 123.0, 122.2, 28.3, 23.2, 22.9, 17.1. IR (neat) max cm-1 3060, 2959, 2925, 2867, 1643, 1570, 1455,

1435, 1364.

Data were in accordance with those previously reported in the literature.2

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Synthesis of styrene derivatives

4-iso-Butylstyrene3 7e

According to general procedure A, 4-iso-butylbenzaldhyde (0.83 mL, 5 mmol), potassium carbonate (1.1

g, 8 mmol) and methyltriphenylphosphonium bromide (2.1 g, 6 mmol) in anhydrous 1,4-dioxane (5 mL)

were heated at reflux for 16 hours to give 4-iso-butylstyrene 7e as a colourless oil (666 mg, 84%). δH

(400 MHz, CDCl3) 7.37-7.32 (m, 2H), 7.15-7.10 (m, 2H), 6.72 (dd, J= 17.6 Hz, 10.9 Hz, 1H), 5.72 (dd, J=

17.6 Hz, 1.0 Hz, 1H), 5.21 (dd, J= 10.9 Hz, 1.0 Hz, 1H), 2.48 (d, J= 7.2 Hz, 2H), 1.88 (app. non, app J= 6.8

Hz, 1H), 0.92 (d, J= 6.6 Hz, 6H). δC (100 MHz, CDCl3) 141.5, 136.8, 135.1, 129.3, 125.9, 112.8, 45.2, 30.2,

22.3. IR (neat) max cm-1 3086, 3019, 2954, 2920, 2847, 1631, 1511, 1464, 1405, 1383, 1366.

Data were in accordance with those previously reported in the literature.3

3-(Benzyloxy)styrene4 7f

According to general procedure A, 3-benzyloxybenzaldhyde (1.06 g, 5 mmol), potassium carbonate (1.1

g, 8 mmol) and methyltriphenylphosphonium bromide (2.1 g, 6 mmol) in anhydrous 1,4-dioxane (5 mL)

were heated at reflux for 16 hours to give 3-benzyloxystyrene 7f as a colourless oil (934 mg, 89%). δH

(400 MHz, CDCl3) 7.49-7.45 (m, 2H), 7.44-7.39 (m, 2H), 7.38-7.32 (m, 2H), 7.30-7.24 (m, 1H), 7.09-7.03

(m, 2H), 6.93-6.89 (m, 1H), 6.71 (dd, J= 17.6 Hz, 10.9 Hz, 1H), 5.76 (dd, J= 17.6 Hz, 0.9 Hz, 1H), 5.27 (dd,

J= 10.9 Hz, 0.9 Hz, 1H), 5.10 (s, 2H) δC (100 MHz, CDCl3) 159.0, 139.1, 137.0, 136.7, 129.5, 128.6, 128.0,

127.5, 119.2, 114.21, 114.17, 112.6, 70.0. IR (neat) max cm-1 3032, 2867, 1597, 1575, 1487, 1441, 1258,

1241, 1155, 1025. HRMS (ESI+) calculated for C15H14ONa+ 233.0937. Found 233.0942.

Data were in accordance with those previously reported in the literature.4

2-Methoxystyrene5 7g

According to general procedure A, 2-methoxybenzaldhyde (670 mg, 5 mmol), potassium carbonate (1.1

g, 8 mmol) and methyltriphenylphosphonium bromide (2.1 g, 6 mmol) in anhydrous 1,4-dioxane (5 mL)

were heated at reflux for 16 hours to give 2-methoxystyrene 7g as a colourless oil (476 mg, 72%). δH

(400 MHz, CDCl3) 7.52-7.48 (m, 1H), 7.30-7.24 (m, 1H), 7.09 (dd, J= 17.7 Hz, 11.1 Hz, 1H), 6.99-6.94 (m,

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1H), 6.92-6.88 (m, 1H), 5.77 (dd, J= 17.7 Hz, 1.5 Hz, 1H), 5.30 (dd, J= 11.1 Hz, 1.5 Hz, 1H), 3.87 (s, 3H). δC

(100 MHz, CDCl3) 156.7, 131.8, 128.8, 126.7, 126.5, 120.6, 114.4, 110.8, 55.4.

Data were in accordance with those previously reported in the literature.5

3-Methoxystyrene5 7h

According to general procedure A, 3-methoxybenzaldhyde (670 mg, 5 mmol), potassium carbonate (1.1

g, 8 mmol) and methyltriphenylphosphonium bromide (2.1 g, 6 mmol) in anhydrous 1,4-dioxane (5 mL)

were heated at reflux for 16 hours to give 3-methoxystyrene 7h as a colourless oil (495 mg, 75%). δH

(400 MHz, CDCl3) 7.30-7.24 (m, 1H), 7.05-7.02 (m, 1H), 6.99-6.96 (m, 1H), 6.86-6.82 (m, 1H), 6.72 (dd, J=

17.5 Hz, 10.8 Hz, 1H), 5.77 (dd, J= 17.5 Hz, 1.0 Hz, 1H), 5.27 (dd, J= 10.8 Hz, 1.0 Hz, 1H), 3.84 (s, 3H). δC

(100 MHz, CDCl3) 159.8, 139.0, 136.8, 129.5, 118.9, 114.1, 113.4, 111.5, 55.2.

Data were in accordance with those previously reported in the literature.5

2,5-Dimethoxystyrene6 7j

According to general procedure A, 2,5-dimethoxybenzaldhyde (831 mg, 5 mmol), potassium carbonate

(1.1 g, 8 mmol) and methyltriphenylphosphonium bromide (2.1 g, 6 mmol) in anhydrous 1,4-dioxane (5

mL) were heated at reflux for 16 hours to give 2,5-dimethoxystyrene 7j as a colourless oil (623 mg, 76%).

δH (400 MHz, CDCl3) 7.07-7.05 (m, 1H), 7.05 (dd, J= 17.7 Hz, 11.1 Hz, 1H), 6.85-6.78 (m, 2H), 5.75 (dd, J=

17.7 Hz, 1.4 Hz, 1H), 5.29 (dd, J= 11.1 Hz, 1.4 Hz, 1H), 3.82 (s, 3H), 3.81 (s, 3H). δC (100 MHz, CDCl3) 153.7,

151.2, 131.5, 127.6, 114.9, 113.8, 112.2, 111.8, 56.2, 55.7. IR (neat) max cm-1 3085, 2997,2941, 2906,

2833, 1625, 1580, 1492, 1463, 1426, 1418, 1282, 1217, 1179, 1161, 1119, 1058, 1038, 1024.

Data were in accordance with those previously reported in the literature.6

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Table S1. Catalyst identification for the hydrocarboxylation of styrenea

Yield (%)b

entry Iron salt Ligand RMgX 2 2

1 FeCl2 - EtMgClc <1 0

2 Fe(OTf)2 - EtMgClc 1 0

3 FeCl3 - EtMgClc 2 0

4 FeCl2d

- EtMgClc 2 <1

5 Fe(OTf)2d

- EtMgClc 59 2

6 FeCl2 NMP 3 EtMgClc 27 <1

7 FeCl2 TMEDA 4 EtMgClc 62 <1

8 FeCl2 PBu3 EtMgBrf 60 2

9 FeCl2 5 EtMgClc 66 0

10 FeCl2 6 EtMgClc 85 <1

11 FeCl2 6 i-PrMgCle

79 6 12 FeCl2 6 EtMgBr

f 98 (96)

g 1

13 FeCl2 6 Cyclopentyl-MgBrh

87 6 14

FeCl2 (1 mol%) 6 (1 mol%)

EtMgBr

f 97 <1

15i FeCl2 (0.1 mol%) 6 (0.1 mol%)

EtMgBr

f 97 1

16 FeCl2.4H2O (1 mol%) 6 (1 mol%)

EtMgBr

f 97 1

a Conditions: 0.7mmol 1, 5 mol% iron salt, 5 mol% ligand, THF (0.15M), rt, (i) 150 mol%

RMgX, 1h, (ii) CO2, 30 min. b Yield determined by

1H NMR using an internal standard.

c 2M

in THF. d Reaction heated at reflux.

e 1M in THF.

f 3M in Et2O.

g Isolated yield.

h 2M in Et2O.

i

3h reaction time.

According to general procedure B, styrene (80 µL, 0.7 mmol), an iron salt, ligand and Grignard reagent

were reacted in tetrahydrofuran for 1 hour, after which carbon dioxide was bubbled through the

reaction mixture. Dimethoxybenzene (19.3 mg, 0.14 mmol, 20 mol%) was added as an internal standard,

and a yield for the reaction determined for 1H NMR.

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Table S1, entry 1: FeCl2 (4.4 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (0.01/3) × 20 = 0.07% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); 0% Yield

Table S1, entry 2: Fe(OTf)2 (12.4 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (0.19/3) × 20 = 1.3% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); 0% Yield

Table S1, entry 3: FeCl3 (5.7 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (0.33/3) × 20 = 2.2% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); 0% Yield

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Table S1, entry 4: FeCl2 (4.4 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol), heated at reflux

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (0.36/3) × 20 = 2.4% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.03/2) × 20 = 0.3% Yield

Table S1, entry 5: Fe(OTf)2 (12.4 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol), heated at reflux

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (8.79/3) × 20 = 58.6% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.24/2) × 20 = 2.4% Yield

Table S1, entry 6: FeCl2 (4.4 mg, 5 mol%), N-methylpyrrolidone (20 µL, 30mol%), EtMgCl (2M in THF,

0.55 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (4.11/3) × 20 = 27.4% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.05/2) × 20 = 0.5% Yield

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Table S1, entry 7: FeCl2 (4.4 mg, 5 mol%), tetramethylethylenediamine (25 µL, 25mol%), EtMgCl (2M in

THF, 0.55 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (9.34/3) × 20 = 62.3% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.05/2) × 20 = 0.5% Yield

Table S1, entry 8: FeCl2 (4.4 mg, 5 mol%), tributylphosphine (35 µL, 20 mol%), EtMgBr (3M in Et2O,

0.35 mL, 1.1 mmol)

Trimethoxybenzene (20 mol%): 6.11ppm (s, 3H); 2-Phenylpropionic acid: 1.53 (d, 3H); (8.96/3) × 20 = 59.7% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.19/2) × 20 = 1.9% Yield

Table S1, entry 9: FeCl2 (4.4 mg, 5 mol%), (±)-(N,N’-bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine

5 (10.2 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (9.83/3) × 20 = 65.5% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); 0% Yield

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Table S1, entry 10: FeCl2 (4.4 mg, 5 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6

(16.9 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (12.79/3) × 20 = 85.3% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.01/2) × 20 = 0.1% Yield

Table S1, entry 11: FeCl2 (4.4 mg, 5 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6

(16.9 mg, 5 mol%), iPrMgCl (1M in THF, 1.1 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (11.91/3) × 20 = 79.4% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.55/2) × 20 = 5.5% Yield

Table S1, entry 12: FeCl2 (4.4 mg, 5 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6

(16.9 mg, 5 mol%), EtMgBr (3M in Et2O, 0.35 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (14.64/3) × 20 = 97.6% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.13/2) × 20 = 1.3% Yield

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Table S1, entry 13: FeCl2 (4.4 mg, 5 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6

(16.9 mg, 5 mol%), cyclopentylMgBr (2M in Et2O, 0.55 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (13.04/3) × 20 = 86.9% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.61/2) × 20 = 6.1% Yield

Table S1, entry 14: FeCl2 (0.9 mg, 1 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4

mg, 1 mol%), EtMgBr (3M in Et2O, 0.35 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (14.61/3) × 20 = 97.4% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.13/2) × 20 = 1.3% Yield

Table S1, entry 15: FeCl2 (0.9 mg, 1 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4

mg, 1 mol%) in THF (10 mL). 1 mL (0.1 mol% catalyst) sample taken for use in reaction. EtMgBr (3M in

Et2O, 0.35 mL, 1.1 mmol). Reaction left for 3 hours before CO2.

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (14.52/3) × 20 = 96.8% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.10/2) × 20 = 1.0% Yield

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Table S1, entry 16: FeCl2.4H2O (1.4 mg, 1 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine

6 (3.4 mg, 1 mol%), EtMgBr (3M in Et2O, 0.35 mL, 1.1 mmol)

Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (14.58/3) × 20 = 97.2% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.07/2) × 20 = 0.7% Yield

Variation in solvent and temperature

The reaction was attempted in diethyl ether, acetonitrile and toluene at room temperature under

otherwise optimised conditions, however in each case no conversion of styrene to 2-phenylpropanoic

acid was observed. The reaction at 0 °C in tetrahydrofuran resulted in <10% 2-phenylpropanoic acid. At -

20 °C and -40 °C no reaction was observed. Raising the temperature to 45 °C in tetrahydrofuran resulted

in slightly lower yields than that observed at room temperature.

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Table S2. Iron-catalyzed hydrocarboxylation of styrene derivatives: scope and limitationsa

a

Conditions: 0.7mmol 1, 7a-l, 1 mol% FeCl2, 1 mol% 6, THF (0.15M), rt, (i) 120 mol% EtMgBr (3M in Et2O), 2h (ii) CO2, 30 min.

b 120 mol% Cyclopentylmagnesium bromide used (2M in Et2O).

2-Phenylpropanoic acid7 2

According to general procedure C, styrene (80 µL, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007 mmol), 2,6-

bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium bromide (3M

in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran to give the

crude reaction product, which was purified by acid-base work-up to give 2-phenylpropanoic acid 2 as a

colourless oil (101 mg, 0.67 mmol, 96%). δH (400 MHz, CDCl3) 11.38 (s, br, 1H), 7.40-7.26 (m, 5H), 3.75 (q,

J= 7.2Hz, 1H), 1.53 (d, J= 7.2Hz, 3H). δC (100 MHz, CDCl3) 180.9, 139.7, 128.7, 127.6, 127.4, 45.3, 18.1. IR

(neat) max cm-1 3030, 2980, 2937, 1702, 1496, 1453, 1413, 1230. GC-MS [70-1] (M+, relative abundance):

5.75 min (150, 99%).

Data were in accordance with those previously reported in the literature.7

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2-(4-Methylphenyl)propanoic acid7 8a

According to general procedure C, 4-methylstyrene (93 µL, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007

mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium

bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran

to give the crude reaction product, which was purified by acid-base work-up to give 2-(4-

methylphenyl)propanoic acid 8a as a colourless amorphous solid (107 mg, 0.63 mmol, 90%). m.p. 34-

35 °C (CH2Cl2). δH (300 MHz, CDCl3) 11.27 (s, br, 1H), 7.27-7.20 (m, 2H), 7.20-7.13 (m, 2H), 3.72 (q, J=

7.2Hz, 1H), 2.34 (s, 3H), 1.51 (d, J= 7.2Hz, 3H). δC (75 MHz, CDCl3) 181.0, 137.1, 136.8, 129.4, 127.4, 44.9,

21.0, 18.1. IR (neat) max/cm-1 2983, 2940, 2920, 2735, 2631, 2546, 1695, 1513, 1418, 1231. GC-MS [70-

1] (M+, relative abundance): 6.35 min (164, 96%).

Data were in accordance with those previously reported in the literature.7

2-(3-Methylphenyl)propanoic acid 8b

According to general procedure C, 3-methylstyrene (93 µL, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007

mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium

bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran

to give the crude reaction product, which was purified by acid-base work-up to give 2-(3-

methylphenyl)propanoic acid 8b as colourless needles (107 mg, 0.65 mmol, 93%). m.p. 62-63 °C (CH2Cl2).

δH (400 MHz, CDCl3) 11.03 (s, br, 1H), 7.26-7.21 (m, 1H), 7.16-7.08 (m, 3H), 3.72 (q, J= 7.2Hz, 1H), 2.36 (s,

3H), 1.52 (d, J= 7.2Hz, 3H). δC (100 MHz, CDCl3) 180.5, 139.7, 138.4, 128.6, 128.3, 128.2, 124.6, 45.2,

21.4, 18.1. IR (neat) max/cm-1 3023, 2980, 2935, 2722, 2619, 1695, 1454, 1321, 1244, 1221. GC-MS [70-

1] (M+, relative abundance): 6.28 min (164, 99%). HRMS (ESI-) calculated for C10H11O2- 163.0765. Found

163.0766.

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2-(2-Methylphenyl)propanoic acid7 8c

According to general procedure C, 2-methylstyrene (90 µL, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007

mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium

bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran

to give the crude reaction product, which was purified by flash silica chromatography (8:1 hexanes:ethyl

acetate) to give 2-(2-methylphenyl)propanoic acid 8c as a colourless amorphous solid (78 mg, 0.48 mmol,

68%). Rf = 0.22 (4:1 hexanes:ethyl acetate). δH (500 MHz, CDCl3) 7.32-7.29 (m, 1H), 7.23-7.16 (m, 3H),

4.00 (q, J= 7.2Hz, 1H), 2.39 (s, 3H), 1.50 (d, J= 7.2Hz, 3H). δC (125 MHz, CDCl3) 180.1, 138.3, 135.9, 130.5,

127.2, 126.6, 126.5, 41.0, 19.6, 17.5. GC-MS [70-1] (M+, relative abundance): 6.33 min (164, 93%).

Data were in accordance with those previously reported in the literature.7

2-(4-tert-Butylphenyl)propanoic acid 8d

According to general procedure C, 4-tert-butylstyrene (128 µL, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007

mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium

bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran

to give the crude reaction product, which was purified by acid-base work-up to give 2-(4-tert-

butylphenyl)propanoic acid 8d as colourless needles (112 mg, 0.54 mmol, 78%). m.p. 100-102 °C (CH2Cl2).

δH (400 MHz, CDCl3) 7.38-7.34 (m, 2H), 7.29-7.24 (m, 2H), 3.73 (q, J= 7.2Hz, 1H), 1.52 (d, J= 7.2Hz, 3H),

1.32 (s, 9H). δC (100 MHz, CDCl3) 181.0, 137.1, 136.8, 129.4, 127.4, 44.9, 21.0, 18.1. IR (neat) max/cm-1

2965, 2905, 2870, 1693, 1509, 1458, 1413, 1285, 1262, 1229. GC-MS [70-1] (M+, relative abundance):

7.33 min (206, 99%).

Data were in accordance with those previously reported in the literature.8

2-(4-iso-Butylphenyl)propanoic acid 8e

According to general procedure C, 4-iso-butylstyrene (112 mg, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007

mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium

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bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran

to give the crude reaction product, which was purified by acid-base work-up to give 2-(4-iso-

butylphenyl)propanoic acid 8e as colourless needles (120 mg, 0.58 mmol, 83%). m.p. 76-77 °C (CH2Cl2).

δH (500 MHz, CDCl3) 11.74 (s, br, 1H), 7.26-7.22 (m, 2H), 7.14-7.10 (m, 2H), 3.73 (q, J= 7.2Hz, 1H), 2.47 (d,

J= 7.2Hz, 2H), 1.87 (m, 1H), 1.52 (d, J= 7.2Hz, 3H), 0.92 (d, J= 6.6Hz, 6H). δC (125 MHz, CDCl3) 181.0, 137.1,

136.8, 129.4, 127.4, 44.9, 21.0, 18.1. IR (neat) max/cm-1 3047, 2955, 2924, 2869, 2727, 1708, 1507, 1462,

1418, 1379, 1321, 1230. GC-MS [70-1] (M+, relative abundance): 7.38 min (206, 97%).

Data were in accordance with those previously reported in the literature.9

2-(3-(Benzyloxy)phenyl)propanoic acid 8f

According to general procedure C, 3-(benzyloxy)styrene (147 mg, 0.7 mmol), iron(II) chloride (0.9 mg,

0.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),

ethylmagnesium bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous

tetrahydrofuran to give the crude reaction product, which was purified by acid-base work-up to give 2-

(3-(benzyloxy)phenyl)propanoic acid 8f a colourless amorphous solid (129 mg, 0.50 mmol, 72%). m.p.

121-123 °C (CH2Cl2). δH (400 MHz, CDCl3) 10.29 (s, br, 1H), 7.46-7.42 (m, 2H), 7.41-7.37 (m, 2H), 7.35-7.31

(m, 1H), 7.28-7.24 (m, 1H), 6.99-6.97 (m, 1H), 6.95-6.92 (m, 1H), 6.91-6.88 (m, 1H), 5.06 (s, 2H), 3.73 (q,

J= 7.2Hz, 1H), 1.52 (d, J= 7.2Hz, 3H). δC (125 MHz, CDCl3) 178.8, 159.0, 141.3, 136.9, 129.7, 128.6, 128.0,

127.6, 120.2, 114.4, 133.5, 70.0, 45.1, 18.1. IR(neat) max/cm-1 3032, 2972, 2915, 2725, 2621, 2541, 1704,

1595, 1495, 1447, 1385, 1268, 1250, 1225, 1164, 1021. HRMS (ESI-) calculated for C16H15O3- 255.1027.

Found 255.1031.

2-(2-Methoxyphenyl)propanoic acid 8g

According to general procedure C, 2-vinylanisole (94 mg, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007

mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium

bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran

to give the crude reaction product, which was purified by acid-base work-up to give 2-(2-

methoxyphenyl)propanoic acid 8g as a colourless amorphous solid (117 mg, 0.65 mmol, 93%). m.p. 101-

102 °C (CH2Cl2). δH (400 MHz, CDCl3) 11.45 (s, br, 1H), 7.33-7.22 (m, 2H), 7.01-6.93 (m, 1H), 6.92-6.87 (m,

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1H), 4.10 (q, J= 7.2Hz, 1H), 3.84 (s, 3H), 1.50 (d, J= 7.2Hz, 3H). δC (100 MHz, CDCl3) 180.7, 156.7, 128.7,

128.3, 128.0, 120.8, 110.7, 55.5. 39.1, 16.8. GC-MS [70-1] (M+, relative abundance): 6.75 min (180, 99%).

Data were in accordance with those previously reported in the literature.7

2-(3-Methoxyphenyl)propanoic acid 8h

According to general procedure C, 3-vinylanisole (94 mg, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007

mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium

bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran

to give the crude reaction product, which was purified by acid-base work-up to give 2-(3-

methoxyphenyl)propanoic acid 8h as a yellow oil (115 mg, 0.64 mmol, 91%). m.p. 53-54 °C (CH2Cl2). δH

(400 MHz, CDCl3) 11.34 (s, br, 1H), 7.32-7.28 (m, 1H), 6.97-6.93 (m, 1H), 6.92-6.90 (m, 1H), 6.88-6.84 (m,

1H), 3.84 (s, 3H), 3.76 (q, J= 7.2Hz, 1H), 1.55 (d, J= 7.2Hz, 3H). δC (100 MHz, CDCl3) 180.1, 159.8, 141.2,

129.6, 119.9, 113.4, 112.7, 55.2, 45.3, 18.1. GC-MS [70-1] (M+, relative abundance): 6.97 min (180, 98%).

Data were in accordance with those previously reported in the literature.10

2-(4-Methoxyphenyl)propanoic acid 8i

According to general procedure C, 4-vinylanisole (93 µL, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007

mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium

bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran

to give the crude reaction product, which was purified by acid-base work-up to give 2-(4-

methoxyphenyl)propanoic acid 8i as a yellow amorphous solid (69 mg, 0.39 mmol, 55%). m.p. 53-54 °C

(CH2Cl2). δH (300 MHz, CDCl3) 10.17 (s, br, 1H), 7.29-7.22 (m, 2H), 6.91-6.83 (m, 2H), 3.80 (s, 3H), 3.70 (q,

J= 7.2Hz, 1H), 1.50 (d, J= 7.2Hz, 3H). δC (75 MHz, CDCl3) 180.7, 158.9, 131.8, 128.6, 114.1, 55.3, 44.4, 18.1.

IR(neat) max/cm-1 3035, 2836, 1704, 1512, 1302, 1248, 1180. GC-MS [70-1] (M+, relative abundance):

7.03 min (180, 92%).

Data were in accordance with those previously reported in the literature.7

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2-(2,5-Dimethoxyphenyl)propanoic acid 8j

According to general procedure C, 2,5-dimethoxystyrene (115 mg, 0.7 mmol), iron(II) chloride (0.9 mg,

0.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),

ethylmagnesium bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous

tetrahydrofuran to give the crude reaction product, which was purified by acid-base work-up to give 2-

(2,5-dimethoxyphenyl)propanoic acid 8j as a colourless amorphous solid (137 mg, 0.65 mmol, 93%). m.p.

102-104 °C (Ethyl acetate/hexane). δH (400 MHz, CDCl3) 11.46 (br, 1H), 6.86-6.81 (m, 2H), 6.80-6.76 (m,

1H), 4.07 (q, J= 7.2Hz, 1H), 3.80 (s, 3H), 3.78 (s, 3H), 1.48 (d, J= 7.2Hz, 3H). δC (125 MHz, CDCl3) 180.3,

153.7, 150.9, 129.8, 114.6, 112.3, 111.9, 56.2, 55.7, 39.1, 16.8. IR(neat) max/cm-1 2984, 2938, 2837, 2719,

2623, 1703, 1611, 1589, 1497, 1455, 1406, 1239, 1219, 1180, 1159, 1044, 1023. GC-MS [70-1] (M+,

relative abundance): 7.77 min (210, 99%).

Data were in accordance with those previously reported in the literature.7

2-(3,4-Dimethoxyphenyl)propanoic acid 8k

According to general procedure C, 3,4-dimethoxystyrene (104 µL, 0.7 mmol), iron(II) chloride (0.9 mg,

0.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),

ethylmagnesium bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous

tetrahydrofuran to give the crude reaction product, which was purified by flash silica chromatography

(7:1 hexanes:ethyl acetate) to give 2-(3,4-dimethoxyphenyl)propanoic acid 8k as a yellow amorphous

solid (38 mg, 0.18 mmol, 26%). δH (500 MHz, CDCl3) 6.90-6.80 (m, 3H), 3.89 (s, 3H), 3.87 (s, 3H), 3.70 (q,

J= 7.2Hz, 1H), 1.52 (d, J= 7.2Hz, 3H). δC (125 MHz, CDCl3) 179.8, 149.0, 148.4, 132.3, 119.7, 111.2, 110.8,

55.9, 55.9, 44.8, 18.2. GC-MS [70-1] (M+, relative abundance): 7.85 min (210, 92%). HRMS (ESI-)

calculated for C11H13O4- 209.0819. Found 209.0826.

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2-(2-Biphenyl)propanoic acid 8l

According to general procedure C, 4-vinylbiphenyl (126 mg, 0.7 mmol, added as a tetrahydrofuran

solution (1mL)), iron(II) chloride (0.9 mg, 0.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)

ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and

carbon dioxide were reacted in anhydrous tetrahydrofuran to give the crude reaction product, which

was purified by acid-base work-up to give 2-(2-biphenyl)propanoic acid 8l as a yellow amorphous solid

(63 mg, 0.28 mmol, 40%). m.p. 142-144 °C (CH2Cl2). δH (400 MHz, CDCl3) 10.17 (s, br, 1H), 7.60-7.55 (m,

4H), 7.47-7.39 (m, 4H), 7.38-7.33 (m, 1H), 3.81 (q, J= 7.2Hz, 1H), 1.57 (d, J= 7.2Hz, 3H). δC (100 MHz,

CDCl3) 180.2, 140.7, 140.4, 138.8, 128.7, 128.0, 127.4, 127.3, 127.1, 45.0, 18.1. IR(neat) max/cm-1 3032,

2982, 2919, 2849, 2622, 1693, 1486, 1409. GC-MS [70-1] (M+, relative abundance): 9.04 min (226,

99%).HRMS (ESI-) calculated for C15H13O2- 225.0921. Found 225.0920.

Data were in accordance with those previously reported in the literature.11

2-(4-Fluorophenyl)propanoic acid 8m

According to general procedure C, 4-fluorostyrene (83 µL, 0.7 mmol), iron(II) chloride (0.9 mg, 0.007

mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol), ethylmagnesium

bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran

to give the crude reaction product, which was purified by flash silica chromatography (8:1 hexanes:ethyl

acetate) to give 2-(4-fluorophenyl)propanoic acid 8m as a colourless oil (44 mg, 0.26 mmol, 37%). δH

(500 MHz, CDCl3) 7.32-7.27 (m, 2H), 7.05-6.99 (m, 2H), 3.74 (q, J= 7.2Hz, 1H), 1.51 (d, J= 7.2Hz, 3H). δC

(125 MHz, CDCl3) 180.1, 162.1 (d, J= 246Hz), 135.4 (d, J= 3Hz), 129.2 (d, J= 8Hz), 115.5 (d, J= 21Hz),

44.5, 18.2. δF (470 MHz, CDCl3) -115.3. GC-MS [70-1] (M+, relative abundance): 5.78 min (168, 97%).

HRMS (ESI-) calculated for C9H8FO2- 167.0514. Found 167.0520.

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2-(2,4-Dimethylphenyl)propanoic acid and 3-(2,4-dimethylphenyl)propanoic acid 8n

According to general procedure C, 2,4-dimethylstyrene (102 µL, 0.7 mmol), iron(II) chloride (0.9 mg,

0.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),

ethylmagnesium bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous

tetrahydrofuran to give the crude reaction product, which was purified by acid-base work-up to give 2-

(2,4-dimethylphenyl)propanoic acid and 3-(2,4-dimethylphenyl)propanoic acid as a colourless

amorphous solid (56 mg, 0.32 mmol, 45%, : 20:25). The isomers were separated by flash silica

chromatography (0.01:8:1 acetic acid:hexanes:ethyl acetate).

When ethylmagnesium bromide was replaced with cyclopentylmagnesium bromide (2M in Et2O, 0.45 mL,

0.9 mmol), 2-(2,4-dimethylphenyl)propanoic acid and 3-(2,4-dimethylphenyl)propanoic acid were

produced as a colourless amorphous solid (92 mg, 0.52 mmol, 74%, : 13:61).

2-(2,4-Dimethylphenyl)propanoic acid: m.p. 106-108 °C (CH2Cl2). δH (400 MHz, CDCl3) 7.21-7.17 (m, 1H),

7.05-6.99 (m, 2H), 3.96 (q, J= 7.2Hz, 1H), 3.35 (s, 3H), 3.30 (s, 3H), 1.49 (d, J= 7.2Hz, 3H). δC (100 MHz,

CDCl3) 180.5, 136.8, 135.7, 135.4, 131.3, 127.1, 126.5, 40.7, 20.9, 19.5, 17.6. GC-MS [70-1] (M+, relative

abundance): 6.75 min (178, 96%). HRMS (ESI-) calculated for C11H13O2- 177.0921. Found 177.0927.

3-(2,4-Dimethylphenyl)propanoic acid: δH (400 MHz, CDCl3) 10.97 (s, br, 1H), 7.08-7.03 (m, 2H), 7.01-

6.94 (m, 2H), 2.97-2.90 (m, 2H), 2.67-2.60 (m, 2H), 2.30 (s, 6H). δC (125 MHz, CDCl3) 178.4, 136.0, 135.8,

135.2, 131.2, 128.4, 126.8, 34.4, 27.6, 20.9, 19.1. IR(neat) max/cm-1 2977, 2917, 2714, 2622, 1699, 1431,

1406, 1313, 1279, 1216. GC-MS [70-1] (M+, relative abundance): 7.02 min (178, 96%). HRMS (ESI-)

calculated for C11H13O2- 177.0921. Found 177.0926.

2-(2,5-Dimethylphenyl)propanoic acid and 3-(2,5-dimethylphenyl)propanoic acid 8o

According to general procedure C, 2,5-dimethylstyrene (102 µL, 0.7 mmol), iron(II) chloride (0.9 mg,

0.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),

ethylmagnesium bromide (3M in Et2O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous

tetrahydrofuran to give the crude reaction product, which was purified by acid-base work-up to give 2-

(2,5-dimethylphenyl)propanoic acid and 3-(2,5-dimethylphenyl)propanoic acid as a colourless

amorphous solid (58 mg, 0.33 mmol, 47%, : 27:20). The isomers were separated by flash silica

chromatography (0.01:8:1 acetic acid:hexanes:ethyl acetate).

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When ethylmagnesium bromide was replaced with cyclopentylmagnesium bromide (2M in Et2O, 0.45 mL,

0.9 mmol), 2-(2,5-dimethylphenyl)propanoic acid and 3-(2,5-dimethylphenyl)propanoic acid were

produced as a colourless amorphous solid (97 mg, 0.55 mmol, 78%, : 14:64).

2-(2,5-Dimethylphenyl)propanoic acid: δH (400 MHz, CDCl3) 7.13-7.05 (m, 2H), 7.02-6.96 (m, 1H), 3.97 (q,

J= 7.2Hz, 1H), 2.35 (s, 3H), 2.32 (s, 3H), 1.49 (d, J= 7.2Hz, 3H). δC (100 MHz, CDCl3) 180.4, 138.1, 135.9,

132.7, 130.4, 127.9, 127.2, 41.0, 21.1, 19.1, 17.5. GC-MS [70-1] (M+, relative abundance): 6.73 min (178,

99%).

Data were in accordance with those previously reported in the literature.7

3-(2,5-Dimethylphenyl)propanoic acid: δH (400 MHz, CDCl3) 7.09-7.03 (m, 1H), 7.01-6.93 (m, 2H), 2.97-

2.90 (m, 2H), 2.69-2.61 (m, 2H), 2.31 (s, 3H), 2.30 (s, 3H). δC (100 MHz, CDCl3) 178178.9, 138.1, 135.6,

132.7, 130.3, 129.3, 127.2, 34.4, 28.0, 20.9, 18.7. GC-MS [70-1] (M+, relative abundance): 7.01 min (178,

96%). HRMS (ESI-) calculated for C11H13O2- 177.0921. Found 177.0927.

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Mechanistic investigations into the iron-catalyzed hydrometallation of alkenes

and isomerization of Grignard reagents

i) Deuterium quench

Styrene (80 L, 0.7 mmol) was added to a solution of iron(II) chloride (0.9 mg, 0.007 mmol) and 2,6-bis-

[1-(2,6-diisoprpylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol) in anhydrous tetrahydrofuran (5

mL) at room temperature. Ethylmagnesium bromide (0.3 mL, 3M in Et2O, 0.9 mmol) was added

dropwise over 10 minutes and the reaction stirred at room temperature under an atmosphere of

nitrogen for 1 hour. d4-Methanol was added and the reaction stirred for 30 minutes. Aqueous sulphate

buffer solution (10 mL) was added and the aqueous phase extracted with diethyl ether (3 x 20 mL). The

combined organic extracts were washed with H2O and brine, dried (MgSO4) and concentrated in vacuo

to give ethyl-1-d1-benzene. δH (400 MHz, CDCl3) 7.37-7.15 (m, 5H), 2.65 (qt, JHH = 7.6 Hz, JHD = 2.1Hz, 1H),

1.25 (dt, JHH = 7.6 Hz, JHD = 1.1 Hz, 3H). GC-MS [35-AJP] (M+, relative abundance): 3.11 min (107, 98%).

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ii) Experiment using d5-ethylmagnesium bromide

d5-Bromoethane (0.2 mL, 3 mmol) was added to magnesium turnings (650 mg, 27 mmol) in hot diethyl

ether (10 mL). A single iodine crystal was added to initiate the reaction, and the remaining d5-

bromoethane (1.8 mL, 24 mmol) was added dropwise at a rate to maintain reflux. The reaction was

stirred for a further 2 hours, allowed to settle, and the Grignard reagent siphoned off and stored in a

Young’s flask under an atmosphere of nitrogen. The concentration of the Grignard reagent was

determined to be 1.5M after titration against 2-hydroxybenzaldehyde phenylhydrazone.

Styrene (80 L, 0.7 mmol) was added to a solution of iron(II) chloride (0.9 mg, 0.007 mmol) and 2,6-bis-

[1-(2,6-diisoprpylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol) in anhydrous tetrahydrofuran (5

mL) at room temperature. d5-Ethylmagnesium bromide (0.6 mL, 1.5M in Et2O, 0.9 mmol) was added

dropwise over 10 minutes and the reaction stirred at room temperature under an atmosphere of

nitrogen for 1 hour. Carbon dioxide was bubbled through the reaction via a needle for 30 minutes.

Aqueous sulphate buffer solution (10 mL) was added and the aqueous phase extracted with diethyl

ether (3 x 20 mL). The combined organic extracts were washed with H2O and brine, dried (MgSO4) and

concentrated in vacuo to give a mixture of 4 products.

δH (400 MHz, CDCl3) 7.38-7.26 (m, 5H), 3.79-3.72 (m, 1H), 1.56-1.47 (m, 1.07H). GC-MS [70-1] (M+,

relative abundance): 5.75 min (153, 152, 151, 150, 92%).

2-Phenylpropanoic acid

δC (125 MHz, CDCl3) 181.1, 139.7, 128.6, 127.6, 127.3, 45.37, 18.03.

2-Phenyl-3-d1-propanoic acid

δC (125 MHz, CDCl3) 181.1, 139.7, 128.6, 127.6, 127.3, 45.30, 17.75 (t, JCD = 19.9 Hz)

2-Phenyl-3,3-d2-propanoic acid

δC (125 MHz, CDCl3) 181.1, 139.7, 128.6, 127.6, 127.3, 45.23, 17.48 (quintet, JCD = 19.8 Hz)

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2-Phenyl-3,3,3-d3-propanoic acid

δC (125 MHz, CDCl3) 181.1, 139.7, 128.6, 127.6, 127.3, 45.16, 17.36 (septet, JCD = 19.8 Hz)

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GC-MS [70-1] (M+, relative abundance): 5.75 min (153, 152, 151, 150, 92%)

iii) Preparation of phenethylmagnesium bromide and isomerization under reaction

conditions

(2-Bromoethyl)benzene (0.15 mL, 1 mmol) was added to magnesium turnings (300 mg, 12 mmol) in hot

diethyl ether (5 mL). A single iodine crystal was added to initiate the reaction, and the remaining (2-

bromoethyl)benzene (1.2 mL, 9 mmol) was added dropwise at a rate to maintain reflux. The reaction

was stirred for a further 2 hours, allowed to settle, and the Grignard reagent siphoned off and stored in

a Young’s flask under an atmosphere of nitrogen. The concentration of the Grignard reagent was

determined to be 1.4M after titration against 2-hydroxybenzaldehyde phenylhydrazone.

Control:

Phenethylmagnesium bromide 10 (0.7 mL, 1 mmol) was added to anhydrous tetrahydrofuran and

carbon dioxide was bubbled through the reaction for 30 minutes to give 3-phenylpropanoic acid 2 as

colourless needles (140 mg, 93%). δH (400 MHz, CDCl3) 7.35-7.28 (m, 2H), 7.26-7.20 (m, 2H), 3.01-2.95

(m, 2H), 3.74-3.68 (m, 2H). δC (100 MHz, CDCl3) 178.8, 140.1, 128.54, 128.3, 126.4, 35.5, 30.6.

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Isomerization experiment in the absence of tert-butylstyrene:

Phenethylmagnesium bromide 10 (0.7 mL, 1 mmol) was added to a solution of iron(II) chloride (0.9 mg,

0.007 mmol) and 2,6-bis-[1-(2,6-diisoprpylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol) in

anhydrous tetrahydrofuran (5 mL) at room temperature, and the reaction mixture stirred for 2 hours.

Carbon dioxide was bubbled through the reaction via a needle for 30 minutes. Aqueous sulphate buffer

solution (10 mL) was added and the aqueous phase extracted with diethyl ether (3 x 20 mL). The

combined organic extracts were washed with H2O and brine, dried (MgSO4) and concentrated in vacuo

to give a mixture of the crude products of the reaction. Trimethoxybenzene (33.6 mg, 0.2 mmol) was

added as an internal standard, and a yield for the reaction determined by 1H NMR.

Trimethoxybenzene (20 mol%): 6.85ppm (s, 3H); 2-Phenylpropionic acid: 1.53 (d, 3H); (1.26/3) × 20 = 8% Yield;

3-Phenylpropionic acid: 3.02-2.95 (m, 2H); (7.91/2) × 20 = 79% Yield

3% styrene and a similar quantity of ethylbenzene were also observed.

Addition of tert-butylstyrene:

Phenethylmagnesium bromide 10 (0.7 mL, 1 mmol) was added to a solution of iron(II) chloride (0.9 mg,

0.007 mmol) tert-butylstyrene (180 µL, 1 mmol) and 2,6-bis-[1-(2,6-diisoprpylphenylimino)ethyl]pyridine

6 (3.4 mg, 0.007 mmol) in anhydrous tetrahydrofuran (5 mL) at room temperature, and the reaction

mixture stirred for 2 hours. Carbon dioxide was bubbled through the reaction via a needle for 30

minutes. Aqueous sulphate buffer solution (10 mL) was added and the aqueous phase extracted with

diethyl ether (3 x 20 mL). The combined organic extracts were washed with H2O and brine, dried

(MgSO4) and concentrated in vacuo to give a mixture of the crude products of the reaction.

Trimethoxybenzene (33.6 mg, 0.2 mmol) was added as an internal standard, and a yield for the reaction

determined by 1H NMR.

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Trimethoxybenzene (20 mol%): 6.85ppm (s, 3H);

2-Phenylpropionic acid: 1.53 (d, 3H); (4.23/1.5) × 20 = 56% Yield; 3-Phenylpropionic acid: 3.02-2.95 (m, 2H);

((0.38+1.12-0.45+0.38)/2) × 20 = 14% Yield; Styrene: 5.26 (dd, 2H); (1.15/1) × 20 = 23% Yield.

2-(4-tert-Butylphenyl)propanoic acid: 1.52 (d, 3H); (1.68/1.5) × 20 = 22% Yield; 3-(4-tert-Butylphenyl)propionic

acid: 2.98-2.90 (m, 2H); ((0.45+1.16-0.38+0.45)/2) × 20 = 17% Yield; tert-Butylstyrene: 5.21 (dd, 2H); (2.63/1) × 20

= 53% Yield.

iv) Attempted preparation of (1-phenylethyl)magnesium bromide from (1-

bromoethyl)benzene

(1-Bromoethyl)benzene 11 (0.14 mL, 1 mmol) was added to magnesium turnings (150 mg, 6 mmol) in

hot tetrahydrofuran (5 mL). A single iodine crystal was added to initiate the reaction, and the remaining

(1-bromoethyl)benzene (0.54 mL, 4 mmol) was added dropwise at a rate to maintain reflux. The reaction

was allowed to settle, and a 1 mL (1 mmol) sample removed and added to a Schlenk tube containing

tetrahydrofuran (5 mL). Carbon dioxide was bubbled through the reaction for 30 minutes. Aqueous

sulphate buffer solution (10 mL) was added and the aqueous phase extracted with diethyl ether (3 x 20

mL). The combined organic extracts were washed with H2O and brine, dried (MgSO4) and concentrated

in vacuo to give a mixture of the crude products, which were analysed 1H NMR and by GC-MS.

Dimethoxybenzene (27.6 mg, 0.2 mmol) was added as an internal standard, and a yield for the reaction

determined for 1H NMR. A near quantitative conversion to 2,3-diphenylbutane 12 was observed, with no

formation of 2-phenylpropanoic acid 2.

Page 29: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

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Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); (RR,SS)-2,3-diphenylbutane: 3.01-2.87 (m, 2H), 1.33-1.22 (m, 6H);

(2.39/2) × 20 = 24% Yield; (RS,RS)-2,3-diphenylbutane: 2.86-2.74 (m, 2H), 1.07-0.98 (m, 6H); (2.41/2) × 20 = 24%

Yield, therefore overall yield of 48% (of a possible 50% due to dimerization).

GC-MS [70-1] (M+, identity, rel. intensity): 4.35 min (138, dimethoxybenzene, n/a), 7.13 min (210, 2,3-

diphenylbutane, 50%), 7.24 min (210, 2,3-diphenylbutane, 50%).

v) Preliminary investigation of reaction rate with respect to reaction concentration

According to general procedure C, nine (three sets of three) parallel reactions were undertaken in 5, 10

and 20 mL of tetrahydrofuran. Within each set of 3 reactions, carbon dioxide was bubbled through the

reaction mixture after either 10, 20 or 30 minutes, and the yield of 2-phenylpropanoic acid determined

by 1H NMR (using dimethoxybenzene as an internal standard). The rate of reaction in 5 mL of THF was

found to be higher than in 10 mL, which was in turn higher than the rate of reaction in 20 mL. Although

the rates of reaction were not accurately measured, the initial rates appeared to be approximately first

order with respect to concentration, implying a homogeneous reaction mixture. Further, more detailed

investigations are currently being pursued.

% Yield after

THF volume/mL 10 min 20 min 30 min

5 33 45 57 10 26 34 41 20 19 26 30

Page 30: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

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ICP Analysis

ICP-MS (Inductively Coupled Plasma-Mass Spectrometry) of the reaction mixture: A standard reaction mixture (FeCl2 (Strem Chemicals Inc. (UK); anhydrous iron chloride, 98% (product number 93-2631. Lot 19226800, 44.00000% Fe), bis(imino)pyridine ligand 6, ethylmagnesium bromide (3M in Et2O, Sigma Aldrich), THF) was evaporated to dryness, redissolved in 6 mL of HNO3 and diluted by a factor of 50 with Milli-Q water. Analysis was conducted on a Thermo-Finnigan Neptune multiple-collector inductively coupled plasma mass spectrometer (MC-ICP-MS) (Bristol Neptune 1, Serial No. 1002), using an SLSRS5 standard for calibration. The abundance of each metal in the sample was recorded relative to the abundance of iron.

Table S3. ICP-MS Analysis on the abundance (ppm) of elements in reaction mixture, relative to Fe

Ti Co Ni Cu Zr Ru Rh Pd Ag Ir Pt Au 560 570 60 130 210 <1 30 1060 <1 60 <1 10

Investigation of potential catalytic role of trace metal impurities

Fifteen parallel reactions (A-G) were undertaken to investigate if trace metal impurities present in the

iron salt used could have a role in the observed catalysis.13 Copper(II) chloride, nickel(II) acetylacetonate,

cobalt(II) chloride, bis(1,5-cyclooctadiene)diiridium(I) dichloride, bis(1,5-cyclooctadiene)rhodium(I)

tetrafluoroborate, tetrakis(triphenylphosphine)palladium(0) and ruthenium(III) chloride were used. The

metal complexes were added at a 1000 ppm concentration relative to iron, and reactions were

conducted in the presence and absence of iron to ascertain any beneficial effect of the trace metal salt

in isolation or in conjunction with iron.

Styrene (80µL, 0.7 mmol) was added to a solution of a metal complex (0.01 µmol) (+/- FeCl2 (0.9 mg,

0.007 mmol)) and (±)-(N,N’-bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine 5 (2.1 mg, 0.007 mmol)

in anhydrous tetrahydrofuran (5 mL) at room temperature. Ethylmagnesium bromide (0.3 mL, 3M in

Et2O, 0.9 mmol) was added dropwise over 10 minutes and the reaction stirred at room temperature

under an atmosphere of nitrogen for 1 hour. Carbon dioxide was bubbled through the reaction via a

needle for 30 minutes. Sulphate buffer solution (10 mL) was added and the aqueous phase extracted

with diethyl ether (3 x 20 mL). The combined organic extracts were washed with H2O and brine, dried

(MgSO4) and concentrated in vacuo to give the crude reaction products. Dimethoxybenzene (19.3 mg,

0.14 mmol) was added as an internal standard, and a yield for the reaction determined for 1H NMR.

Table S4. Addition of trace metal quantities to standard reaction

Reaction FeCl2 /mol% Ligand 5/mol% Metal salt (1000ppm) %Yield of 2-Phenylpropanoic acid

Control 1 1 - 80

A 1 1 CuCl2 79

A’ - 1 CuCl2 0

B 1 1 Ni(acac)2 74

B’ - 1 Ni(acac)2 0

C 1 1 CoCl2 80

C’ - 1 CoCl2 0

D 1 1 Ir2Cl2(COD)2 78

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D’ - 1 Ir2Cl2(COD)2 0

E 1 1 Rh(COD)2.BF4 76

E’ - 1 Rh(COD)2.BF4 0

F 1 1 Pd(Ph3)4 78

F’ - 1 Pd(Ph3)4 0

G 1 1 RuCl3 75

G’ - 1 RuCl3 0

The addition of metal salts of Cu, Ni, Co, Ir, Rh, Pd, and Ru to the reaction did not increase the yield of 2-

phenylpropanoic acid, and in the absence of iron, no catalytic activity was observed for any of the metal

salts added.

Page 32: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

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NMR traces of compounds 5, 6, 7e-f, 2, 8a-l

(±)-(N,N’-Bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine 5

300 MHz

100 MHz

Page 33: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S33

2,6-Bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6

400 MHz

125 MHz

Page 34: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S34

4-iso-Butylstyrene 7e

400 MHz

100 MHz

Page 35: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S35

3-Benzyloxystyrene 7f

400 MHz

100 MHz

Page 36: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S36

2-Methoxystyrene 8g

400 MHz

100 MHZ

Page 37: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S37

3-Methoxystyrene 8h

400 MHz

100 MHz

Page 38: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S38

2,5-Dimethoxystyrene 8j

400 MHz

100 MHz

Page 39: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S39

2-Phenylpropanoic acid 2

400 MHz

100 MHz

Page 40: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S40

3-Phenylpropanoic acid 2

400 MHz

100 MHz

Page 41: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S41

2-(4-Methylphenyl)propanoic acid 8a

300 MHz

75 MHz

Page 42: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S42

2-(3-Methylphenyl)propanoic acid 8b

400 MHz

100 MHz

Page 43: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S43

2-(2-Methylphenyl)propanoic acid 8c

500 MHz

125 MHz

Page 44: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S44

2-(4-tert-Butylphenyl)propanoic acid 8d

400 MHz

100 MHz

Page 45: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S45

2-(4-iso-Butylphenyl)propanoic acid 8e

500 MHz

125 MHz

Page 46: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S46

2-(3-(Benzyloxy)phenyl)propanoic acid 8f

500 MHz

125 MHz

Page 47: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S47

2-(2-Methoxyphenyl)propanoic acid 8g

400 MHz

100 MHz

Page 48: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S48

2-(3-Methoxyphenyl)propanoic acid 8h

400 MHz

100 MHz

Page 49: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S49

2-(4-Methoxyphenyl)propanoic acid 8i

300 MHz

75 MHz

Page 50: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S50

2-(2,5-Dimethoxyphenyl)propanoic acid 8j

400 MHz

100 MHz

Page 51: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S51

2-(3,4-Dimethoxyphenyl)propanoic acid 8k

500 MHz

125 MHz

Page 52: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S52

2-(2-biphenyl)propanoic acid 8l

500 MHz

125 MHz

Page 53: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S53

2-(4-Fluorophenyl)propanoic acid 8m

500 MHz

125 MHz

Page 54: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S54

470 MHz

Page 55: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S55

2-(2,4-Dimethylphenyl)propanoic acid 8n

400 MHz

100 MHz

Page 56: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S56

3-(2,4-Dimethylphenyl)propanoic acid 8n

400 MHz

100 MHz

Page 57: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S57

2-(2,5-Dimethylphenyl)propanoic acid 8o

400 MHz

100 MHz

Page 58: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S58

3-(2,5-Dimethylphenyl)propanoic acid 8o

400 MHz

100 MHz

Page 59: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S59

GC-MS traces of compounds 2, 8a-l

2-Phenylpropanoic acid 2

2-(4-Methylphenyl)propanoic acid 8a

Page 60: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S60

2-(3-Methylphenyl)propanoic acid 8b

2-(2-Methylphenyl)propanoic acid 8c

Page 61: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S61

2-(4-tert-Butylphenyl)propanoic acid 8d

2-(4-iso-Butylphenyl)propanoic acid 8e

Page 62: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S62

2-(2-Methoxyphenyl)propanoic acid 8g

2-(3-Methoxyphenyl)propanoic acid 8h

Page 63: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S63

2-(4-Methoxyphenyl)propanoic acid 8i

2-(2,5-Dimethoxyphenyl)propanoic acid 8j

Page 64: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S64

2-(3,4-Dimethoxyphenyl)propanoic acid 8k

2-(2-biphenyl)propanoic acid 8l

Page 65: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S65

2-(4-Fluorophenyl)propanoic acid 8m

2-(2,4-Dimethylphenyl)propanoic acid 8n

Page 66: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S66

3-(2,4-Dimethylphenyl)propanoic acid 8n

2-(2,5-Dimethylphenyl)propanoic acid 8o

Page 67: Iron-catalyzed, Highly Regioselective, Synthesis of -Aryl ...

S67

3-(2,5-Dimethylphenyl)propanoic acid 8o

References

1. Cristau, H.-J.; Ouali, A.; Spindler, J.-F.; Taillefer, M. Chem. Eur. J. 2005, 11, 2483-2492.

2. Small, B. L.; Brookhart, M.; Bennett, A. M. A. J. Am. Chem. Soc. 1998, 120, 4049-4050.

3. Smith, C. R.; RajunBabu, T. V. Tetrahedron. 2010, 66, 1102-1110.

4. Shen, R.; Chen, T.; Zhao, Y.; Qiu, R.; Zhou, Y.; Yin, S.; Wang, X.; Goto, M.; Han, L.-B. J. Am. Chem.

Soc. 2011, 133, 17037-17044.

5. Molander, G. A.; Brown, A. R. J. Org. Chem., 2006, 71, 9681-9686.

6. Sun, B.; Hoshino, J.; Jermihov, K.; Marler, L.; Pezzuto, J. M.; Mesecar, A. D.; Cushman, M. Bioorg.

Med. Chem. 2010, 18, 5352-5366.

7. Shiina, I.; Nakata, K.; Ono, K.; Onda, Y. And Itagaki, M. J. Am. Chem. Soc. 2010, 132, 11629-11641.

8. Konrad, T. M.; Fuentes, J. A.; Slawin, A. M. Z.; Clarke, M. L. Angew. Chem., Int. Ed. 2010, 49,

9197-9200.

9. Nugent, W. A.; McKinney, R. J. J. Org. Chem. 1985, 50, 5370-5372.

10. Kubler, W.; Petrov, O.; Winterfeldt, E. Tetrahedron, 1988, 44, 4371-4388.

11. Damodar, J.; Mohan, S. R. K.; Reddy, S. R. J. Electrochemistry Communications. 2001, 3, 762-766.

12. Shirakawa, E.; Ikeda, D.; Masui, S.; Yoshida, M.; Hayashi, T. J. Am. Chem. Soc. 2012, 134, 272-279.

13. (a) Buchwald, S. L; Bolm, C. Angew, Chem., Int, Ed. 2009, 48, 5586-5587. (b) Bedford, R. B.; Hall,

M. A.; Hodges, G. R.; Huwe, M.; Wilkinson, M. C. Chem. Commun. 2009, 42, 6430-6432.


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