Iron-catalyzed, highly regioselective synthesis of α-aryl carboxylic acids from styrene derivatives and CO2

Article abstract of DOI:10.1021/ja3045053

The iron-catalyzed hydrocarboxylation of aryl alkenes has been developed using a highly active bench-stable iron(II) precatalyst to give α-aryl carboxylic acids in excellent yields and with near-perfect regioselectivity. Using just 1 mol % FeCl₂, bis(imino)pyridine 6 (1 mol %), CO ₂ (atmospheric pressure), and a hydride source (EtMgBr, 1.2 equiv), a range of sterically and electronically differentiated aryl alkenes were transformed to the corresponding α-aryl carboxylic acids (up to 96% isolated yield). The catalyst was found to be equally active with a loading of 0.1 mol %. Preliminary mechanistic investigations show that an iron-catalyzed hydrometalation is followed by transmetalation and reaction with the electrophile (CO₂).

Full text of DOI:10.1021/ja3045053

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
stephen.thomas@bristol.ac.uk
Supporting Information
Table of Contents
General Experimental
S2
S3
General Procedures
Ligand Preparation: Analytical Data for 5, 6
Synthesis of Styrene Derivatives: Analytical Data for 7e,f
Table S1. Catalyst Identification
S4
S5
S7
Table S2. Reaction Scope and Limitations: Analytical Data for 2, 8a-l
Mechanistic Investigations
S14
S23
S30
S32
S59
S67
ICP Analysis, and Investigation of Potential Catalytic Role of Trace Metals
NMR Traces: 5, 6, 7e-h, j, 2, 8a-o
GC-MS Traces: 2, 8a-o
References
S1

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
i
glassware was cleaned using base (KOH, PrOH) then acid (HCl ) baths.
aq
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
5
and Tokyo Chemical Industries, UK, or synthesised within the laboratory. All Grignard reagents, d -
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).
1
13
19
H, C and F 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)
1
13
were recorded in parts per million (ppm) and the coupling constants (J) in Hertz (Hz). H and C NMR
multiplicity and coupling constants are reported where applicable. H and C spectra were referenced
1
13
to the residual deuterated solvent peak (CHCl 7.27ppm, 77.00ppm).
3
Aqueous sulphate buffer was prepared by dissolving Na SO (1.5 mol) H SO (0.5 mol) and adding water
2
4
2
4
3
to give a total volume of 2000 cm . Flash chromatography was performed on silica gel (Merck Kielselgel
0). Analytical thin layer chromatography was performed on aluminium backed silica plates (60 F ).
6
254
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.
S2

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 (MgSO ) and concentrated in vacuo to give the styrene derivative.
4
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 H O and brine, dried (MgSO ) and concentrated in vacuo
2
4
to give the crude reaction products. Dimethoxybenzene (19.3 mg, 0.14 mmol) was added as an internal
1
standard, and a yield for the reaction determined for H NMR.
1
All products were known, identified by H 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 Et O, 0.9 mmol)
2
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
3
0 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 H O and brine, dried
2
(
MgSO ) and concentrated in vacuo to give the crude reaction products.
4
1
Known products were identified by H 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 H O and brine, dried (MgSO ) and concentrated in vacuo to give the purified
2
4
carboxylic acid product. If necessary, the product was further purified by flash silica chromatography.
S3

Ligand preparation
1
(
±)-(N,N’-bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine 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). δ (300 MHz, CDCl ) 8.56 (ddd, J= 4.8 Hz, 1.7 Hz, 1.0 Hz, 2H), 8.32 (s, 2H),
H
3
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). δ (100 MHz, CDCl ) 161.4, 154.6, 149.2,
C
3
-1
1
1
36.4, 124.5, 121.3, 73.5, 32.7, 24.3. IR (neat) max cm 3053, 3007, 2936, 2851, 1644, 1586, 1567, 1467,
436, 1370.
1
Data were in accordance with those previously reported in the literature.
2
2
,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 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 (CH Cl ). δ (400
2
2
H
MHz, CDCl ) 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,
3
J= 6.9 Hz, 4H), 2.29 (s, 6H), 1.18 (d, J= 6.9 Hz, 24H). δ (125 MHz, CDCl ) 166.9, 155.1, 146.5, 136.8, 135.8,
C
3
-
1
1
1
23.6, 123.0, 122.2, 28.3, 23.2, 22.9, 17.1. IR (neat) max cm 3060, 2959, 2925, 2867, 1643, 1570, 1455,
435, 1364.
2
Data were in accordance with those previously reported in the literature.
S4

Synthesis of styrene derivatives
3
4
-iso-Butylstyrene 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, CDCl ) 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=
3
1
7.6 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). δ (100 MHz, CDCl ) 141.5, 136.8, 135.1, 129.3, 125.9, 112.8, 45.2, 30.2,
C
3
-
1
2
2.3. IR (neat) max cm 3086, 3019, 2954, 2920, 2847, 1631, 1511, 1464, 1405, 1383, 1366.
3
Data were in accordance with those previously reported in the literature.
4
3
-(Benzyloxy)styrene 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, CDCl ) 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
3
(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) δ (100 MHz, CDCl ) 159.0, 139.1, 137.0, 136.7, 129.5, 128.6, 128.0,
C
3
-
1
1
1
27.5, 119.2, 114.21, 114.17, 112.6, 70.0. IR (neat)  cm 3032, 2867, 1597, 1575, 1487, 1441, 1258,
max
+
+
241, 1155, 1025. HRMS (ESI ) calculated for C H ONa 233.0937. Found 233.0942.
15 14
4
Data were in accordance with those previously reported in the literature.
5
2
-Methoxystyrene 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, CDCl ) 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,
3
S5

1
H), 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, CDCl ) 156.7, 131.8, 128.8, 126.7, 126.5, 120.6, 114.4, 110.8, 55.4.
3
5
Data were in accordance with those previously reported in the literature.
5
3
-Methoxystyrene 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, CDCl ) 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=
3
1
7.5 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, CDCl ) 159.8, 139.0, 136.8, 129.5, 118.9, 114.1, 113.4, 111.5, 55.2.
3
5
Data were in accordance with those previously reported in the literature.
6
2
,5-Dimethoxystyrene 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%).
δ (400 MHz, CDCl ) 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=
H
3
1
1
2
7.7 Hz, 1.4 Hz, 1H), 5.29 (dd, J= 11.1 Hz, 1.4 Hz, 1H), 3.82 (s, 3H), 3.81 (s, 3H). δ (100 MHz, CDCl ) 153.7,
51.2, 131.5, 127.6, 114.9, 113.8, 112.2, 111.8, 56.2, 55.7. IR (neat) max cm 3085, 2997,2941, 2906,
833, 1625, 1580, 1492, 1463, 1426, 1418, 1282, 1217, 1179, 1161, 1119, 1058, 1038, 1024.
C
1
3
-
6
Data were in accordance with those previously reported in the literature.
S6

a
Table S1. Catalyst identification for the hydrocarboxylation of styrene
b
Yield (%)
2 2
entry
Iron salt
FeCl2
Ligand
RMgXc
1
2
3
4
5
6
7
8
9
-
-
-
-
EtMgCl
<1
1
2
0
0
0
c
Fe(OTf)2
FeCl3d
EtMgClc
EtMgClc
EtMgClc
EtMgCl
FeCl2
2
<1
2
d
Fe(OTf)2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
-
59
27
62
60
66
85
79
98 (96)
87
97
97
97
c
NMP 3
TMEDA 4
PBu3
5
EtMgClc
<1
<1
2
0
<1
6
1
6
<1
EtMgCl
f
EtMgBrc
EtMgCl
EtMgCl
c
1
1
1
1
1
0
1
2
3
4
6
6
6
e
i-PrMgCl
EtMgBr
f
g
h
6
Cyclopentyl-MgBr
f
FeCl (1 mol%)
6 (1 mol%)
6 (0.1 mol%)
6 (1 mol%)
EtMgBr
EtMgBr
EtMgBr
2
i
f
15
FeCl (0.1 mol%)
1
1
2
f
16
FeCl .4H O (1 mol%)
2
2
a
Conditions: 0.7mmol 1, 5 mol% iron salt, 5 mol% ligand, THF (0.15M), rt, (i) 150 mol%
b
1
c
RMgX, 1h, (ii) CO , 30 min. Yield determined by H NMR using an internal standard. 2M
2
d
e
f
g
h
i
in THF. Reaction heated at reflux. 1M in THF. 3M in Et O. Isolated yield. 2M in Et O.
2
2
3
h 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,
1
and a yield for the reaction determined for H NMR.
S7

Table S1, entry 1: FeCl (4.4 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol)
2
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) (12.4 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol)
2
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: FeCl (5.7 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol)
3
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
S8

Table S1, entry 4: FeCl (4.4 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol), heated at reflux
2
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) (12.4 mg, 5 mol%), EtMgCl (2M in THF, 0.55 mL, 1.1 mmol), heated at reflux
2
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: FeCl (4.4 mg, 5 mol%), N-methylpyrrolidone (20 µL, 30mol%), EtMgCl (2M in THF,
2
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
S9

Table S1, entry 7: FeCl (4.4 mg, 5 mol%), tetramethylethylenediamine (25 µL, 25mol%), EtMgCl (2M in
2
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: FeCl (4.4 mg, 5 mol%), tributylphosphine (35 µL, 20 mol%), EtMgBr (3M in Et O,
2
2
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;
-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.19/2) × 20 = 1.9% Yield
3
Table S1, entry 9: FeCl (4.4 mg, 5 mol%), (±)-(N,N’-bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine
2
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;
-Phenylpropionic acid: 3.02-2.95 (m, 2H); 0% Yield
3
S10

Table S1, entry 10: FeCl (4.4 mg, 5 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6
2
(
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;
-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.01/2) × 20 = 0.1% Yield
3
Table S1, entry 11: FeCl (4.4 mg, 5 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6
2
(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;
-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.55/2) × 20 = 5.5% Yield
3
Table S1, entry 12: FeCl (4.4 mg, 5 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6
2
(
16.9 mg, 5 mol%), EtMgBr (3M in Et O, 0.35 mL, 1.1 mmol)
2
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
S11

Table S1, entry 13: FeCl (4.4 mg, 5 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6
2
(
16.9 mg, 5 mol%), cyclopentylMgBr (2M in Et O, 0.55 mL, 1.1 mmol)
2
Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (13.04/3) × 20 = 86.9% Yield;
-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.61/2) × 20 = 6.1% Yield
3
Table S1, entry 14: FeCl (0.9 mg, 1 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4
2
mg, 1 mol%), EtMgBr (3M in Et O, 0.35 mL, 1.1 mmol)
2
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: FeCl (0.9 mg, 1 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4
2
mg, 1 mol%) in THF (10 mL). 1 mL (0.1 mol% catalyst) sample taken for use in reaction. EtMgBr (3M in
Et O, 0.35 mL, 1.1 mmol). Reaction left for 3 hours before CO .
2
2
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
S12

Table S1, entry 16: FeCl .4H O (1.4 mg, 1 mol%), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine
2
2
6
(3.4 mg, 1 mol%), EtMgBr (3M in Et O, 0.35 mL, 1.1 mmol)
2
Dimethoxybenzene (20 mol%): 6.85ppm (s, 4H); 2-Phenylpropionic acid: 1.53 (d, 3H); (14.58/3) × 20 = 97.2% Yield;
-Phenylpropionic acid: 3.02-2.95 (m, 2H); (0.07/2) × 20 = 0.7% Yield
3
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 -
2
0 °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.
S13

Table S2. Iron-catalyzed hydrocarboxylation of styrene derivatives: scope and
a
limitations
a
Conditions: 0.7mmol 1, 7a-l, 1 mol% FeCl , 1 mol% 6, THF (0.15M), rt, (i) 120 mol% EtMgBr (3M in Et O), 2h (ii)
2
2
b
CO , 30 min. 120 mol% Cyclopentylmagnesium bromide used (2M in Et O).
2
2
7
2
-Phenylpropanoic acid 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 Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran to give the
2
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%). δ (400 MHz, CDCl ) 11.38 (s, br, 1H), 7.40-7.26 (m, 5H), 3.75 (q,
H
3
J= 7.2Hz, 1H), 1.53 (d, J= 7.2Hz, 3H). δ (100 MHz, CDCl ) 180.9, 139.7, 128.7, 127.6, 127.4, 45.3, 18.1. IR
C
3
-
1
+
(
neat) max cm 3030, 2980, 2937, 1702, 1496, 1453, 1413, 1230. GC-MS [70-1] (M , relative abundance):
5
.75 min (150, 99%).
7
Data were in accordance with those previously reported in the literature.
S14

7
2
-(4-Methylphenyl)propanoic acid 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 Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran
2
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-
3
7
2
1
5 °C (CH Cl ). δ (300 MHz, CDCl ) 11.27 (s, br, 1H), 7.27-7.20 (m, 2H), 7.20-7.13 (m, 2H), 3.72 (q, J=
2
2
H
3
.2Hz, 1H), 2.34 (s, 3H), 1.51 (d, J= 7.2Hz, 3H). δ (75 MHz, CDCl ) 181.0, 137.1, 136.8, 129.4, 127.4, 44.9,
C
3
-
1
1.0, 18.1. IR (neat)  /cm 2983, 2940, 2920, 2735, 2631, 2546, 1695, 1513, 1418, 1231. GC-MS [70-
max
+
] (M , relative abundance): 6.35 min (164, 96%).
7
Data were in accordance with those previously reported in the literature.
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 Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran
2
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 (CH Cl ).
2
2
δ (400 MHz, CDCl ) 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,
H
3
3
2
1
1
H), 1.52 (d, J= 7.2Hz, 3H). δ (100 MHz, CDCl ) 180.5, 139.7, 138.4, 128.6, 128.3, 128.2, 124.6, 45.2,
C
3
-
1
1.4, 18.1. IR (neat)  /cm 3023, 2980, 2935, 2722, 2619, 1695, 1454, 1321, 1244, 1221. GC-MS [70-
max
+
-
-
] (M , relative abundance): 6.28 min (164, 99%). HRMS (ESI ) calculated for C H O 163.0765. Found
10
11
2
63.0766.
S15

7
2
-(2-Methylphenyl)propanoic acid 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 Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran
2
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,
6
4
1
8%). R = 0.22 (4:1 hexanes:ethyl acetate). δ (500 MHz, CDCl ) 7.32-7.29 (m, 1H), 7.23-7.16 (m, 3H),
f
H
3
.00 (q, J= 7.2Hz, 1H), 2.39 (s, 3H), 1.50 (d, J= 7.2Hz, 3H). δ (125 MHz, CDCl ) 180.1, 138.3, 135.9, 130.5,
C
3
+
27.2, 126.6, 126.5, 41.0, 19.6, 17.5. GC-MS [70-1] (M , relative abundance): 6.33 min (164, 93%).
7
Data were in accordance with those previously reported in the literature.
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 Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran
2
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 (CH Cl ).
2
2
δ (400 MHz, CDCl ) 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),
H
3
-
1
1
2
7
.32 (s, 9H). δ (100 MHz, CDCl ) 181.0, 137.1, 136.8, 129.4, 127.4, 44.9, 21.0, 18.1. IR (neat) max/cm
C
3
+
965, 2905, 2870, 1693, 1509, 1458, 1413, 1285, 1262, 1229. GC-MS [70-1] (M , relative abundance):
.33 min (206, 99%).
8
Data were in accordance with those previously reported in the literature.
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
S16

bromide (3M in Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran
2
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 (CH Cl ).
2
2
δ (500 MHz, CDCl ) 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,
H
3
J= 7.2Hz, 2H), 1.87 (m, 1H), 1.52 (d, J= 7.2Hz, 3H), 0.92 (d, J= 6.6Hz, 6H). δ (125 MHz, CDCl ) 181.0, 137.1,
C
3
-
1
1
1
36.8, 129.4, 127.4, 44.9, 21.0, 18.1. IR (neat)  /cm 3047, 2955, 2924, 2869, 2727, 1708, 1507, 1462,
max
+
418, 1379, 1321, 1230. GC-MS [70-1] (M , relative abundance): 7.38 min (206, 97%).
9
Data were in accordance with those previously reported in the literature.
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,
.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),
0
ethylmagnesium bromide (3M in Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous
2
tetrahydrofuran to give the crude reaction product, which was purified by acid-base work-up to give 2-
(
1
3-(benzyloxy)phenyl)propanoic acid 8f a colourless amorphous solid (129 mg, 0.50 mmol, 72%). m.p.
21-123 °C (CH Cl ). δ (400 MHz, CDCl ) 10.29 (s, br, 1H), 7.46-7.42 (m, 2H), 7.41-7.37 (m, 2H), 7.35-7.31
2
2
H
3
(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). δ (125 MHz, CDCl ) 178.8, 159.0, 141.3, 136.9, 129.7, 128.6, 128.0,
C
3
-
1
1
1
27.6, 120.2, 114.4, 133.5, 70.0, 45.1, 18.1. IR(neat) max/cm 3032, 2972, 2915, 2725, 2621, 2541, 1704,
-
-
595, 1495, 1447, 1385, 1268, 1250, 1225, 1164, 1021. HRMS (ESI ) calculated for C H O 255.1027.
16
15
3
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 Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran
2
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-
1
02 °C (CH Cl ). δ (400 MHz, CDCl ) 11.45 (s, br, 1H), 7.33-7.22 (m, 2H), 7.01-6.93 (m, 1H), 6.92-6.87 (m,
2
2
H
3
S17

1
1
H), 4.10 (q, J= 7.2Hz, 1H), 3.84 (s, 3H), 1.50 (d, J= 7.2Hz, 3H). δ (100 MHz, CDCl ) 180.7, 156.7, 128.7,
28.3, 128.0, 120.8, 110.7, 55.5. 39.1, 16.8. GC-MS [70-1] (M , relative abundance): 6.75 min (180, 99%).
C
3
+
7
Data were in accordance with those previously reported in the literature.
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 Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran
2
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 (CH Cl ). δ
2
2
H
(
400 MHz, CDCl ) 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,
3
1
1
H), 3.84 (s, 3H), 3.76 (q, J= 7.2Hz, 1H), 1.55 (d, J= 7.2Hz, 3H). δ (100 MHz, CDCl ) 180.1, 159.8, 141.2,
29.6, 119.9, 113.4, 112.7, 55.2, 45.3, 18.1. GC-MS [70-1] (M , relative abundance): 6.97 min (180, 98%).
C
3
+
10
Data were in accordance with those previously reported in the literature.
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 Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran
2
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
(
CH Cl ). δ (300 MHz, CDCl ) 10.17 (s, br, 1H), 7.29-7.22 (m, 2H), 6.91-6.83 (m, 2H), 3.80 (s, 3H), 3.70 (q,
2
2
H
3
J= 7.2Hz, 1H), 1.50 (d, J= 7.2Hz, 3H). δ (75 MHz, CDCl ) 180.7, 158.9, 131.8, 128.6, 114.1, 55.3, 44.4, 18.1.
C
3
-
1
+
IR(neat) max/cm 3035, 2836, 1704, 1512, 1302, 1248, 1180. GC-MS [70-1] (M , relative abundance):
.03 min (180, 92%).
7
7
Data were in accordance with those previously reported in the literature.
S18

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,
.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),
0
ethylmagnesium bromide (3M in Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous
2
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.
1
1
1
2
02-104 °C (Ethyl acetate/hexane). δ (400 MHz, CDCl ) 11.46 (br, 1H), 6.86-6.81 (m, 2H), 6.80-6.76 (m,
H
3
H), 4.07 (q, J= 7.2Hz, 1H), 3.80 (s, 3H), 3.78 (s, 3H), 1.48 (d, J= 7.2Hz, 3H). δ (125 MHz, CDCl ) 180.3,
C
3
-
1
53.7, 150.9, 129.8, 114.6, 112.3, 111.9, 56.2, 55.7, 39.1, 16.8. IR(neat) max/cm 2984, 2938, 2837, 2719,
+
623, 1703, 1611, 1589, 1497, 1455, 1406, 1239, 1219, 1180, 1159, 1044, 1023. GC-MS [70-1] (M ,
relative abundance): 7.77 min (210, 99%).
7
Data were in accordance with those previously reported in the literature.
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,
.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),
0
ethylmagnesium bromide (3M in Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous
2
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%). δ (500 MHz, CDCl ) 6.90-6.80 (m, 3H), 3.89 (s, 3H), 3.87 (s, 3H), 3.70 (q,
H
3
J= 7.2Hz, 1H), 1.52 (d, J= 7.2Hz, 3H). δ (125 MHz, CDCl ) 179.8, 149.0, 148.4, 132.3, 119.7, 111.2, 110.8,
C
3
+
-
5
5.9, 55.9, 44.8, 18.2. GC-MS [70-1] (M , relative abundance): 7.85 min (210, 92%). HRMS (ESI )
-
calculated for C H O 209.0819. Found 209.0826.
11
13
4
S19

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 Et O, 0.3 mL, 0.9 mmol) and
2
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 (CH Cl ). δ (400 MHz, CDCl ) 10.17 (s, br, 1H), 7.60-7.55 (m,
2
2
H
3
4
H), 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). δ (100 MHz,
C
-
1
CDCl ) 180.2, 140.7, 140.4, 138.8, 128.7, 128.0, 127.4, 127.3, 127.1, 45.0, 18.1. IR(neat)  /cm 3032,
2
9
3
max
+
982, 2919, 2849, 2622, 1693, 1486, 1409. GC-MS [70-1] (M , relative abundance): 9.04 min (226,
-
-
9%).HRMS (ESI ) calculated for C H O 225.0921. Found 225.0920.
15
13
2
11
Data were in accordance with those previously reported in the literature.
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 Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous tetrahydrofuran
2
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
(
(
4
500 MHz, CDCl ) 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). δ
3
C
125 MHz, CDCl ) 180.1, 162.1 (d, J= 246Hz), 135.4 (d, J= 3Hz), 129.2 (d, J= 8Hz), 115.5 (d, J= 21Hz),
3
+
4.5, 18.2. δ (470 MHz, CDCl ) -115.3. GC-MS [70-1] (M , relative abundance): 5.78 min (168, 97%).
F
3
-
-
HRMS (ESI ) calculated for C H FO 167.0514. Found 167.0520.
9
8
2
S20

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,
.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),
0
ethylmagnesium bromide (3M in Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous
2
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 Et O, 0.45 mL,
2
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
7
-(2,4-Dimethylphenyl)propanoic acid: m.p. 106-108 °C (CH Cl ). δ (400 MHz, CDCl ) 7.21-7.17 (m, 1H),
2
2
H
3
.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). δ (100 MHz,
C
+
CDCl ) 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 C H O 177.0921. Found 177.0927.
3
-
-
11
13
2
3
6
1
1
-(2,4-Dimethylphenyl)propanoic acid: δ (400 MHz, CDCl ) 10.97 (s, br, 1H), 7.08-7.03 (m, 2H), 7.01-
H
3
.94 (m, 2H), 2.97-2.90 (m, 2H), 2.67-2.60 (m, 2H), 2.30 (s, 6H). δ (125 MHz, CDCl ) 178.4, 136.0, 135.8,
C
3
-
1
35.2, 131.2, 128.4, 126.8, 34.4, 27.6, 20.9, 19.1. IR(neat) max/cm 2977, 2917, 2714, 2622, 1699, 1431,
+
-
406, 1313, 1279, 1216. GC-MS [70-1] (M , relative abundance): 7.02 min (178, 96%). HRMS (ESI )
-
calculated for C H O 177.0921. Found 177.0926.
11
13
2
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,
.007 mmol), 2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine 6 (3.4 mg, 0.007 mmol),
0
ethylmagnesium bromide (3M in Et O, 0.3 mL, 0.9 mmol) and carbon dioxide were reacted in anhydrous
2
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).
S21

When ethylmagnesium bromide was replaced with cyclopentylmagnesium bromide (2M in Et O, 0.45 mL,
2
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: δ (400 MHz, CDCl ) 7.13-7.05 (m, 2H), 7.02-6.96 (m, 1H), 3.97 (q,
H
3
J= 7.2Hz, 1H), 2.35 (s, 3H), 2.32 (s, 3H), 1.49 (d, J= 7.2Hz, 3H). δ (100 MHz, CDCl ) 180.4, 138.1, 135.9,
C
3
+
1
9
32.7, 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,
9%).
7
Data were in accordance with those previously reported in the literature.
3
2
1
9
-(2,5-Dimethylphenyl)propanoic acid: δ (400 MHz, CDCl ) 7.09-7.03 (m, 1H), 7.01-6.93 (m, 2H), 2.97-
H
3
.90 (m, 2H), 2.69-2.61 (m, 2H), 2.31 (s, 3H), 2.30 (s, 3H). δ (100 MHz, CDCl ) 178178.9, 138.1, 135.6,
C
3
+
32.7, 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,
-
-
6%). HRMS (ESI ) calculated for C H O 177.0921. Found 177.0927.
11
13
2
S22

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 Et O, 0.9 mmol) was added
2
dropwise over 10 minutes and the reaction stirred at room temperature under an atmosphere of
4
nitrogen for 1 hour. d -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 H O and brine, dried (MgSO ) and concentrated in vacuo
2
4
1
to give ethyl-1-d -benzene. δ (400 MHz, CDCl ) 7.37-7.15 (m, 5H), 2.65 (qt, J = 7.6 Hz, J = 2.1Hz, 1H),
H
3
HH
HD
+
1
.25 (dt, J = 7.6 Hz, J = 1.1 Hz, 3H). GC-MS [35-AJP] (M , relative abundance): 3.11 min (107, 98%).
HH
HD
S23

5
ii)
Experiment using d -ethylmagnesium bromide
5
d -Bromoethane (0.2 mL, 3 mmol) was added to magnesium turnings (650 mg, 27 mmol) in hot diethyl
5
ether (10 mL). A single iodine crystal was added to initiate the reaction, and the remaining d -
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
5
mL) at room temperature. d -Ethylmagnesium bromide (0.6 mL, 1.5M in Et O, 0.9 mmol) was added
2
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 H O and brine, dried (MgSO ) and
2
4
concentrated in vacuo to give a mixture of 4 products.
+
δ (400 MHz, CDCl ) 7.38-7.26 (m, 5H), 3.79-3.72 (m, 1H), 1.56-1.47 (m, 1.07H). GC-MS [70-1] (M ,
H
3
relative abundance): 5.75 min (153, 152, 151, 150, 92%).
2
2
2
-Phenylpropanoic acid
δ (125 MHz, CDCl ) 181.1, 139.7, 128.6, 127.6, 127.3, 45.37, 18.03.
C
3
1
-Phenyl-3-d -propanoic acid
δ (125 MHz, CDCl ) 181.1, 139.7, 128.6, 127.6, 127.3, 45.30, 17.75 (t, J = 19.9 Hz)
C
3
CD
2
-Phenyl-3,3-d -propanoic acid
δ (125 MHz, CDCl ) 181.1, 139.7, 128.6, 127.6, 127.3, 45.23, 17.48 (quintet, J = 19.8 Hz)
C
3
CD
S24

3
2
-Phenyl-3,3,3-d -propanoic acid
δ (125 MHz, CDCl ) 181.1, 139.7, 128.6, 127.6, 127.3, 45.16, 17.36 (septet, J = 19.8 Hz)
C
3
CD
S25

+
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%). δ (400 MHz, CDCl ) 7.35-7.28 (m, 2H), 7.26-7.20 (m, 2H), 3.01-2.95
H
3
(
m, 2H), 3.74-3.68 (m, 2H). δ (100 MHz, CDCl ) 178.8, 140.1, 128.54, 128.3, 126.4, 35.5, 30.6.
C
3
S26

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 H O and brine, dried (MgSO ) and concentrated in vacuo
2
4
to give a mixture of the crude products of the reaction. Trimethoxybenzene (33.6 mg, 0.2 mmol) was
1
added as an internal standard, and a yield for the reaction determined by H 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 H O and brine, dried
2
(
MgSO ) and concentrated in vacuo to give a mixture of the crude products of the reaction.
4
Trimethoxybenzene (33.6 mg, 0.2 mmol) was added as an internal standard, and a yield for the reaction
1
determined by H NMR.
S27

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 H O and brine, dried (MgSO ) and concentrated
2
4
1
in vacuo to give a mixture of the crude products, which were analysed H NMR and by GC-MS.
Dimethoxybenzene (27.6 mg, 0.2 mmol) was added as an internal standard, and a yield for the reaction
1
determined for H NMR. A near quantitative conversion to 2,3-diphenylbutane 12 was observed, with no
formation of 2-phenylpropanoic acid 2.
S28

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
1
by H 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
5
10 min
33
20 min
45
30 min
57
1
2
0
0
26
19
34
26
41
30
S29

ICP Analysis
ICP-MS (Inductively Coupled Plasma-Mass Spectrometry) of the reaction mixture: A standard reaction
mixture (FeCl (Strem Chemicals Inc. (UK); anhydrous iron chloride, 98% (product number 93-2631. Lot
2
1
9226800, 44.00000% Fe), bis(imino)pyridine ligand 6, ethylmagnesium bromide (3M in Et O, Sigma
2
Aldrich), THF) was evaporated to dryness, redissolved in 6 mL of HNO and diluted by a factor of 50 with
3
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
60
Co
570
Ni
60
Cu
130
Zr
210
Ru
<1
Rh
30
Pd
1060
Ag
<1
Ir
60
Pt
<1
Au
10
5
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
13
iron salt used could have a role in the observed catalysis. 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) (+/- FeCl (0.9 mg,
2
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
Et O, 0.9 mmol) was added dropwise over 10 minutes and the reaction stirred at room temperature
2
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 H O and brine, dried
2
(
0
MgSO ) and concentrated in vacuo to give the crude reaction products. Dimethoxybenzene (19.3 mg,
.14 mmol) was added as an internal standard, and a yield for the reaction determined for H NMR.
4
1
Table S4. Addition of trace metal quantities to standard reaction
Reaction FeCl /mol% Ligand 5/mol%
Metal salt (1000ppm) %Yield of 2-Phenylpropanoic acid
2
Control
1
1
-
1
-
1
-
1
1
1
1
1
1
1
1
1
-
80
79
0
74
0
80
0
78
A
A’
B
B’
C
C’
D
CuCl2
CuCl2
Ni(acac)2
Ni(acac)2
CoCl2
CoCl2
Ir Cl (COD)
2
2
2
S30