of 61
Supporting Information
© Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2013
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
1
Supporting Information for
Palladium
-
Catalyzed Decarbonylative Dehydration of Fatty Acids
for the Production of Linear Alpha Olefins
Yiyang Liu, Kelly E. Kim, Myles B. Herbert, Alexey Fedorov, Robert H. Grubbs*, and
Brian M. Stoltz*
The Warren and Katharine Schlinger Laboratory of Chemistry and Chemical Engineering,
Division of Chemistry and Chemical Engineering, California Institute of Technology,
Pasadena, California 91125
, USA
stoltz@caltech.edu
,
rhg@caltech.edu
Table of Contents:
Materials and Methods
SI
2
General Procedure for Optimization Reactions (
Route
A)
SI
3
General Procedure for
Optimization R
eactions
(
Route
B)
SI
5
General Procedure for
Preparative
Pd
-
Catalyzed Decarbonylative Dehydration
SI
6
Spectroscopic Data for Acid Substrates
SI
8
Spectroscopic Data for Olefin Products
SI
10
General
Procedure for Pheromone Synthesis by
Ru
-
Catalyzed Cross Metathesis
SI
1
6
1
H NMR and
13
C NMR Spectra
SI
20
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
2
Materials and Methods
.
Unless
otherwise stated, re
actions were performed in flame
-
dried glassware under a
nitrogen atmosphere or under vacuum without the use of solvents.
Reaction progress was
monitored by
1
H NMR analysis
of the crude reaction mixture
.
Silicycle
Silia
Flash
®
P60
Acade
mic Silica
gel (particle size 40
63 nm)
was used for flash
c
hromatography.
1
H
NMR spectra were recorded on a Varian Inova 500 MHz spectrometer and are reported
relative to residual CHCl
3
(
δ
7.26 ppm)
or DMSO (
δ
2.50 ppm)
.
13
C NMR spectra were
recorded on
a Varian Inova 500 MHz spectrometer (125 MHz) and are reported relative to
CHCl
3
(
δ
77.16 ppm)
or DMSO (
δ
39.52 ppm)
.
Data for
1
H NMR are reported as follows:
chemical shift (
δ
ppm) (multiplicity, coupling constant (Hz), integration). Multiplicities
are
reported as follows: s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, sept =
septuplet, m = multiplet, br s = broad singlet, br d = broad doublet, app = apparent. Data
for
13
C NMR are reported in terms of chemical shifts (
δ
ppm). IR spect
ra were obtained by
use of a Perkin Elmer Spectrum BXII spectrometer using thin films deposited on NaCl
plates and reported in frequency of absorption (cm
-
1
).
High resolution mass spectra
(HRMS) were
provided by the California Institute of Technology Mass
Spectrometry
Facility using a JEOL JMS
-
600H High Resolution Mass Spectrometer by positive
-
ion
FAB, or
obtained
with an
Agilent 6200 Series TOF
using
Agilent G1978A Multimode
source in
negative
electrospray ionization (ESI
),
negative
atmospheric pressure
chemical
ionization (APCI
), or
negative
mixed ionization mode (
N
MM: ESI
-
APCI
).
Reagents were purchased from Sigma
-
Aldrich, Acros Organics, Strem, or Alfa Aesar
and used as received unless otherwise stated.
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
3
General Procedure for Optimization Reactions (
Route
A)
To a 20 x 150 mm Kimble glass tube equipped with a magnetic stir bar was added
PdCl
2
(nbd) (0.005 mmol, 0.1 mol
%), ligand (mo
nophosphine: 0.04 mmol, 0.8 mol
%;
diphosphine: 0.02 mmol, 0.4 mol
%), and stearic acid
1a
(5 mmol, 1 equiv). The tube was
sealed with a rubber septum, evacuated and refilled with N
2
(x 3), and acetic anhydride (10
mmol, 2 equiv) was added via syringe. The reaction tube placed in a preheated 132 °C oil
bath (glass thermometer reading = 132 °C
, IKA reading = 140 °C) and stirred for 2 h. The
oil bath was removed, and methyl benzoate (internal standard, 5 mmol, 1 equiv) was added
and the resulting mixtu
re stirred for 1 min. An aliquo
t of the crude mixture was taken by
pipette and analyzed by
1
H
NMR. The results of additional liga
nd screen are listed below
.
PdCl
2
(nbd)
(0.1
mol%)
ligand
neat,
132
°
C,
2
h
1
atm
N
2
CO,
AcOH
C
15
H
31
internal
olefins
C
15
H
31
OH
O
1a
+
Ac
2
O
+
2a
3a
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
4
Table S1.
Additional ligand screen
.
[a]
[a]
1a
(5 mmol, 1 equiv), Ac
2
O (2 equiv).
[b]
Determined by
1
H NMR with methyl benzoate as internal
standard.
[c]
Y x A = Yield x Alpha.
PdCl
2
(nbd)
(0.1
mol%)
ligand
neat,
132
°
C,
2
h
1
atm
N
2
CO,
AcOH
C
15
H
31
internal
olefins
C
15
H
31
OH
O
1a
+
Ac
2
O
+
2a
3a
Entry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
PPh
3
(0.8)
P(4-MeOC
6
H
4
)
3
(0.8)
P(4-CF
3
C
6
H
4
)
3
(0.8)
P(2-furyl)
3
(0.8)
P(
o
-tolyl)
3
(0.8)
PCy
3
(0.8)
RuPhos
(0.8)
dppe
(0.4)
dppp
(0.4)
dppb
(0.4)
dppf
(0.4)
rac
-BINAP
(0.4)
DPEphos
(0.4)
Xantphos
(0.4)
0
0
0
0
0
0
0
0
0
0
0
0
43
60
59
55
25
33
0
0
0
0
0
0
0
0
0
0
0
0
--
--
--
--
--
--
--
--
--
--
--
--
Ligand
(mol%)
Yield
(%)
[b]
Alpha
(%)
[b]
Y
x
A
(%)
[c]
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
5
General Procedure for
O
ptimization
R
eactions
(
Route
B)
The procedure for the
representative
reaction
(
Table 1, entry 12
)
is shown as follows.
To a 20
x
150 mm Kimble glass tube equipped with a magnetic stir bar was added
PdCl
2
(PPh
3
)
2
(0.005 mmol, 0.1 mol
%),
Xantphos (0.006 mmol, 0.12 mol
%), (
t
-
Bu)
4
biphenol (0.05 mmol, 1 mol
%), and stearic anhydride
1a’
(5 mmol, 1 equiv). The
tube was sealed with a rubber septum, evacuated and refilled with N
2
(
x 3
)
, and placed in a
preheated
132 °C o
il bath
and stirred for 2 h. The oil bath was removed, and methyl
benzoate (internal standard, 5 mmol, 1 equiv) was added and the resulting mixtu
re stirred
for 1 min. An aliquo
t of the crude mixture was taken by pipette and analyzed by
1
H NMR.
PdCl
2
(PPh
3
)
2
(0.1
mol%)
Xantphos
(0.12
mol%)
(
t
-Bu)
4
biphenol
(1
mol%)
neat,
132
°
C,
2
h
1
atm
N
2
CO
C
15
H
31
O
O
O
C
15
H
31
C
15
H
31
internal
olefins
1a'
+
2a
3a
OH
OH
t
-Bu
t
-Bu
t
-Bu
t
-Bu
(
t
-Bu)
4
biphenol
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
6
Genera
l Procedure for
Preparative
Pd
-
Catalyzed Decarbonylative
Dehydration
A 15 mL round
-
bottom flask was charged with PdCl
2
(PPh
3
)
2
(0.01 mmol, 0.05 mol
%),
Xantphos (0.012 mmol, 0.06 mol%), (
t
-
Bu)
4
biphenol (0.1 mmol, 0.5 mol
%
), and fatty acid
substrate (20 mmol, 1 equiv). The flask was equipped with a distillation head and a 25 mL
round
-
bottom receiving flask. The
closed
system was connected to a
vacuum manifold,
equipped with a needle valve and a digital vacuum gauge
.
The
system was evacuated and
refilled with N
2
(
x 3
)
,
and
the first
portion
of acetic anhydride (20 mmol, 1 equiv) was
added
via
syringe through the septum
that seals the top of the distillation head
. The flask
was lowered into a 20 °C oil bath and gradually h
eated to 132 °C in 23 min.
When oil
bath temperature rose to 122 °C, the needle valve was closed, switched to vacuum, and the
needle
valve carefully and slowly opened to allow distillation of acetic acid
into a
receiving flask
, which
was cooled to
78 °C.
When
the
oil bath temperature reached 130
°C, time was recorded as t = 0. After distillation ceased (about t = 3 min), the needle valve
was opened
fully and
a vacuum of 1
5 mmHg
was drawn
. At t = 30 min, the system was
refilled with N
2
, and the second
portion
of acetic anhydride (2.8 mmol, 0.14 equiv) was
When the reaction was performed at 100 mmol scale with high
-
melting substrates such as stearic acid,
the
reaction flask was first heated to 85
°
C until all solid melted, and then to 132
°
C. Overall heating time from
20 to 132
°
C
was approximately 40 min.
R
OH
O
+
Ac
2
O
(6
portions)
PdCl
2
(PPh
3
)
2
(0.05
mol%)
Xantphos
(0.06
mol%)
(
t
-Bu)
4
biphenol
(0.5
mol%)
neat,
132
°
C,
3
h
1
5
mmHg
distillation
CO,
AcOH
R
internal
olefins
1
+
2
3
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
7
added
via
syringe.
T
he system was
then gradually (
t = 35 min
) resubjected to a vacuum of
1
5 mmHg
.
A
cetic anhydride
was
added
as follows
(0.12, 0.10, 0.09. 0.08 equiv)
in the
same manner every 30
min. The reaction was stopped at t = 3 h and allowed to cool to
ambient temperature. The residual reaction mixture was purified by flash chromatography
.
I
f it contained solids, it was suction
-
filtered first and the solids washed with he
xanes, and
the fi
ltrate
was c
oncentrated and purified by chromatography
. In cases where the product
was distilled together with acetic acid, the distillate was added dropwise to a saturated
NaHCO
3
solution,
stirred for 30
min
, and the resulting mixture was extracted with
dichloromethane (30 mL x 3). The combined extracts were dried over Na
2
SO
4
, filtered and
concentrated. The crude product was then subjected to flash chromatography or
distillation to afford the olefin in pure form.
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
8
Spectroscopic Data for Acid
Substrates
Saturated fatty acids
1a
1d
and
1m
are commercially available. Carboxylic acids
1e
,
[
1
]
1f
,
[
2
]
1g
,
[
3
]
1i
,
[
4
]
1j
,
[
5
]
1k
,
[
6
]
1l
,
[
7
]
and
1n
[
8
]
are known compounds and prepared according to
literature
methods.
15
-
Chloropentadecanoic acid (1h)
1
H NMR (500 MHz,
CDCl
3
)
δ
3.52 (t,
J
= 6.8 Hz,
2
H), 2.34 (t,
J
= 7.5 Hz,
2
H), 1.79
1.73
(m,
2
H), 1.62 (p,
J
= 7.5 Hz,
2
H), 1.46
1.20 (m,
20
H);
13
C NMR (126 MHz,
CDCl
3
)
δ
180.6
, 45.3, 34.2, 32.
8
,
29.7,
29.7, 29.7, 29.7, 29.6, 29.6, 29.
4
, 29.
2
, 29.0,
27.0,
24.8
;
IR
(Neat Film) 2916, 2848, 1701, 1462, 1410, 1302, 943, 721 cm
-
1
; HRMS
(NMM: ESI
-
APCI
)
m/z
calc’d for C
15
H
28
O
2
Cl [M
H]
: 275.1783, found 275.1794.
3
-
Methylpentadecanoic acid (1o)
1
H NMR (500 MHz,
CDCl
3
)
δ
2.35 (dd,
J
= 15.0, 5.9 Hz, 1H), 2.14 (dd,
J
= 15.0, 8.2 Hz,
1H), 2.01
1.90 (m, 1H), 1.38
1.15 (m, 22
H), 0.96 (d,
J
= 6.7 Hz, 3H), 0.88 (t,
J
= 6.9 Hz,
3H
);
13
C NMR (126 MHz,
CDCl
3
)
δ
180.1, 41.8, 36.8, 32.
1
, 30.3, 29.
9
, 29.8, 29.8, 29.8,
29.8, 29.
8
, 29.5, 27.0, 22.
9
, 19.8, 14.
3
; IR (Neat Film) 2914, 2852, 1701, 1473, 1410,
Cl
1h
OH
O
1o
OH
O
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
9
1300, 1151, 1123, 954, 715; HRMS (NMM: ESI
-
APCI
)
m/z
calc’d for C
16
H
31
O
2
[M
H]
:
255.2330, found 255.2328.
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
10
Spectroscopic Data for Olefin Products
1
-
Heptadecene (2a)
[
9
]
1
H NMR (500 MHz, CDCl
3
)
δ
5.82 (ddt,
J
= 16.9, 10.2, 6.7 Hz, 1H), 5.07
4.86 (m, 2H),
2.11
1.98 (m, 2H), 1.49
1.08 (m, 26H), 0.88 (t,
J
= 6.9 Hz, 3H);
13
C NMR (126 MHz,
CDCl
3
)
δ
139.4, 114.2, 34.0, 32.1, 29.
9
, 29.8, 29.8, 29.
8
, 29.7, 29.
7
, 29.5, 29.
5
, 29.
4
, 29.3,
29.1, 22.
9
, 14.
3
.
1
-
Pentadecene (2b)
[
10
]
1
H NMR (500 MHz, CDCl
3
)
δ
5.82 (ddt,
J
= 16.9, 10.2, 6.7 Hz, 1H), 5.07
4.85 (m, 2H),
2.11
1.97 (m, 2H), 1.46
1.08 (m, 22H), 0.88 (t,
J
= 6.9 Hz, 3H);
13
C NMR (126 MHz,
CDCl
3
)
δ
139.4, 114.2, 34.0, 32.1, 29.
9
, 29.
9
, 29.8, 29.8,
29.8, 29.7, 29.
6
, 29.3, 29.1, 22.
9
,
14.
3
.
1
-
Tridecene (2c)
[
11
]
1
H NMR (500 MHz, CDCl
3
)
δ
5.82 (ddt,
J
= 17.0, 10.1, 6.7 Hz, 1H), 5.09
4.83 (m, 2H),
2.11
1.97 (m, 2H), 1.48
1.11 (m, 18H), 0.88 (t,
J
= 6.9 Hz,
3
H);
13
C NMR (126 MHz,
CDCl
3
)
δ
139.4, 114.2, 34.0, 32.1, 29.8, 29.8, 29.8, 29.
7
, 29.5, 29.3, 29.1, 22.
9
, 14.
3
.
2a
2b
2c
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
11
1
-
Undecene (2d)
[
12
]
1
H NMR (500 MHz, CDCl
3
)
δ
5.82 (ddt,
J
= 16.9, 10.2, 6.7 Hz, 1H), 5.08
4.84 (m, 2H),
2.11
1.98 (m, 2H), 1.47
1.09 (m, 14H), 0.88 (t,
J
= 6.9 Hz,
3
H);
13
C
NMR (126 MHz,
CDCl
3
)
δ
139.4, 114.2, 34.0, 32.
1
, 29.
8
, 29.
7
, 29.5, 29.3, 29.1, 22.8, 14.
3
.
Ethyl non
-
8
-
enoate (2e)
[
13
]
1
H NMR (500 MHz, CDCl
3
)
δ
5.80 (ddt,
J
= 16.6, 9.9, 6.8 Hz, 1H), 5.07
4.87 (m, 2H),
4.12 (q,
J
= 7.2 Hz, 2H), 2.28 (t,
J
= 7.5 Hz, 2H)
, 2.10
1.98 (m, 2H), 1.69
1.54 (m, 2H),
1.46
1.28 (m, 6H), 1.25 (t,
J
= 7.1 Hz, 3H);
13
C NMR (126 MHz,
CDCl
3
)
δ
17
4
.
0
, 139.1,
114.
4
, 60.
3
, 34.
5
, 33.8, 29.
1
, 28.8, 28.8, 25.0, 14.
4
.
Non
-
8
-
en
-
1
-
yl acetate (2
f
)
[
14
]
1
H NMR (500 MHz,
CDCl
3
)
δ
5.80 (ddt,
J
= 16.9, 10.2, 6.7 Hz, 1H), 5.07
4.87 (m, 2H),
4.05 (t,
J
= 6.8 Hz, 2H), 2.14
1.94 (m, 5H), 1.70
1.52 (m, 2H), 1.47
1.18 (m, 8H);
13
C
NMR (126 MHz,
CDCl
3
)
δ
171.4, 139.2, 114.
4
, 64.
8
, 33.
9
, 29.2, 29.1, 2
9
.
0
, 28.7, 26.0,
21.
2
.
Tetradec
-
13
-
en
-
1
-
yl acetate (
2
g
)
[
15
]
2d
EtO
2e
O
AcO
2f
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
12
1
H NMR (500 MHz,
CDCl
3
)
δ
5.81 (ddt,
J
= 16.8, 10.1, 6.8 Hz, 1H), 5.08
4.86 (m, 2H),
4.05 (t,
J
= 6.8 Hz, 2H), 2.11
1.98 (m, 5H), 1.69
1.53 (m, 2H), 1.45
1.09 (m, 18H);
13
C
NMR (126 MHz,
CDCl
3
)
δ
171.
4
, 139.
4
, 114.2, 64.8, 3
4
.
0
, 29.
8
, 29.7, 29.
7
,
29.6, 29.6,
29.
4
, 29.
3
, 29.
1
, 28.7, 26.0, 21.
2
.
14
-
Chlorotetradec
-
1
-
ene (2h)
1
H NMR (500 MHz,
CDCl
3
)
δ
5.81 (ddt,
J
= 17.0, 10.2, 6.7 Hz, 1H), 5.07
4.86 (m, 2H),
3.53 (t,
J
= 6.8 Hz, 2H), 2.11
1.98 (m, 2H), 1.77 (dt,
J
= 14.
5, 6.9 Hz, 2H), 1.50
1.10 (m,
18
H);
13
C NMR (126 MHz,
CDCl
3
)
δ
139.
4
, 114.2, 45.3, 3
4
.
0
, 32.8, 29.
8
, 29.7, 29.
7
, 29.6,
29.6, 29.3, 29.
1
, 29.0, 27.0; IR (Neat Film, NaCl) 3076, 2925, 2854, 1641, 1465, 1309,
993, 966, 909, 723 cm
-
1
; HRMS (FAB+)
m/z
calc’d for C
14
H
2
7
35
Cl [M
]
+
: 230.1801,
found
230.1808
.
2
-
(Pent
-
4
-
en
-
1
-
yl)isoindoline
-
1,3
-
dione (2i)
[
16
]
1
H NMR (500 MHz,
CDCl
3
)
δ
7.89
7.73 (m, 2H), 7.73
7.58 (m, 2H), 5.77 (ddt,
J
= 16.9,
10.2, 6.6 Hz, 1H), 5.10
4.87 (m, 2H),
3.74
3.57 (m, 2H)
,
2.17
2.00 (m, 2H), 1.74 (p,
J
=
AcO
2g
Cl
2h
N
O
O
2i
Supporting Information for Liu, Kim, Herbert, Fedorov, Grubbs, and Stoltz
SI
13
7.5 Hz, 2H);
13
C NMR (126 MHz,
CDCl
3
)
δ
168.
4
, 137.3, 133.9, 132.
2
, 123.
2
, 115.3, 37.
6
,
31.0, 27.7.
tert
-
Butyl(pent
-
4
-
en
-
1
-
yloxy)diphenylsilane (2j)
[
17
]
1
H NMR (500 MHz,
CDCl
3
)
δ
7.67 (dt,
J
= 6.5, 1.5 Hz, 4H), 7.39 (dddd,
J
= 14.4, 8.3, 6.0,
2.1 Hz, 6H), 5.80 (ddt,
J
= 16.9, 10.2, 6.6 Hz, 1H), 5.09
4.87 (m, 2H), 3.68 (t,
J
= 6.5 Hz,
2H),
2.15 (tdd,
J
= 8.1, 6.8, 1.4 Hz, 2H)
, 1.73
1.60 (m, 2H), 1.05 (s, 9H);
13
C NMR (126
MHz,
CDCl
3
)
δ
138.
7
, 135.7, 134.
2
, 129.
7
, 127.7, 114.
7
, 63.4, 3
2
.
0
, 30.2, 27.0, 19.
4
.
1
-
Allyl
-
4
-
methoxybenzene (2k)
[
18
]
1
H NMR (500 MHz,
CDCl
3
)
δ
7.17
7.06 (m, 2H), 6.91
6.78 (m, 2H), 5.96 (ddt,
J
= 16.8,
10.1, 6.7 Hz, 1H), 5.13
4.99 (m, 2H), 3.79 (s, 3H), 3.34 (d,
J
= 6.7 Hz, 2H);
13
C NMR
(126 MHz, CDCl
3
)
δ
158.
1
, 138.0, 132.2, 129.6,
115.5, 113.9, 55.
4
, 39.
5
.
Tridec
-
12
-
en
-
2
-
one (2l)
[
19
]
1
H NMR (500 MHz,
CDCl
3
)
δ
5.81 (ddt,
J
= 16.9, 10.1, 6.7 Hz, 1H), 5.06
4.87 (m, 2H),
2.41 (t,
J
= 7.5 Hz, 2H), 2.13 (s, 3H), 2.09
1.97 (m, 2H), 1.62
1.49 (m, 2H), 1.46
1.11 (m,
TBDPSO
2j
2k
MeO
2l
O