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S1
Supplementary Information
for:
Catalyst-Controlled Reverse Selectivity in C-C Bond Formation:
NHC-Cu-Catalyzed α-Selective Allylic Alkylation with Organolithium Reagents
Stefano F. Pizzolato, Massimo Giannerini, Pieter H. Bos, Martín Fañanás-Mastral*
and Ben L. Feringa*
Stratingh Institute for Chemistry, University of Groningen,
Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
[email protected], [email protected]
Contents
General Methods S2
General Procedures for the Copper-Catalyzed Allylic Alkylation of S3
Allylic Halides with Organolithium Reagents
Optimization Study: Additional Data S5
Product Characterization S12
References S18
1H NMR and 13C NMR Spectra of New Compounds S19
Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2015
S2
General Methods
Chromatography: Merck silica gel type 9385 230-400 mesh, TLC: Merck silica gel 60, 0.25 mm.
Components were visualized by UV light (254 nm) and/or phosphomolybdic acid or potassium
permanganate staining. Progress and conversion of the reaction were determined by GC-MS (GC,
HP6890: MS HP5973) with an HP1 or HP5 column (Agilent Technologies 19091s-433, Palo Alto,
CA). Mass spectra were recorded on an AEI-MS-902 mass spectrometer (EI) or a LTQ Orbitrap
XL (APCI; ESI). 1H NMR and 13C NMR were recorded on a Varian AMX400 (400 and 100.59
MHz, respectively) or a Varian VXR200 (200 and 50 MHz, respectively) using CDCl3 as solvent.
Chemical shift values are reported in ppm with the solvent resonance as the internal standard
(CHCl3: δ = 7.26 ppm for 1H, δ = 77.0 ppm for 13C). Data are reported as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, quint = quintuplet, sept = septet, br =
broad, m = multiplet), coupling constants (Hz) and integration (nH). All reactions were carried out
under a nitrogen atmosphere using oven dried glassware or using standard Schlenk techniques.
CH2Cl2 was dried and distilled over calcium hydride; toluene was dried and distilled over sodium; nhexane was dried over molecular sieves. Cinnamyl bromide (1a), cinnamyl chloride (1j), NatOBu,
KtOBu and all copper-salts (CuCl CuSCN, CuTC [Copper(I)-thiophene-2-carboxylate] and
CuBr.SMe2) were purchased from Sigma-Aldrich and used without further purification. Allyl
bromides 1b-k were prepared following literature procedures (1b1, 1c2, 1d1, 1e1, 1f3, 1g4, 1h5, 1i6,
1k3). Organolithium reagents were purchased from Sigma-Aldrich (MeLi (1.6 M in diethyl ether),
EtLi (0.5 M in benzene/cyclohexane 9:1), nHexLi (2.3 M in nhexane), secBuLi (1.4 M in
cyclohexane), PhLi (1.8 M in dibutyl ether)) or from Acros (nBuLi (1.6 M in nhexane), isoBuLi (1.6
M in nheptane)). Ligands L1-2-3-6-8 were purchased from Sigma-Aldrich. Ligands L4,7 L5,8 L77
and L99 were prepared as reported in the literature.
S3
General Procedures for the Copper-Catalyzed Allylic Alkylation of Allylic Halides with
Organolithium Reagents
General Procedure (A) for Cu-NHC catalyzed allylic alkylation of allylic halides with
organolithium reagents (preformation of the catalyst by addition of NaOtBu or KOtBu).
A flame-dried Schlenk tube equipped with septum and stirring bar under nitrogen atmosphere is
charged with copper salt (0.015 mmol, 5 mol%), NHC ligand salt (0.0165 mmol, 5.5 mol%) (the
copper and ligand salts used in each experiment are reported in the optimization and scope tables)
and solid base (NaOtBu or KOtBu as reported) (0.0165 mmol, 5.5 mol%). The tube is evacuated and
backfilled with nitrogen three times, then dry CH2Cl2 (1 mL) is added and the solution is stirred
under nitrogen at r.t. for 30 min. The solution is cooled down (at the reported temperature) and
stirred over 10 min. The allylic halide (0.3 mmol) is dissolved in dry CH2Cl2 (1 mL), injected in the
mixture under stirring and stirred over 10 min. In a separate flame-dried Schlenk tube, the
organolithium reagent (reported equivalents) is diluted to a combined volume of 1 mL with dry
hexane (dry toluene was employed in the case of MeLi due to gelation) under nitrogen and slowly
injected dropwise in the reaction mixture (over the reported time) using a syringe pump. The flow of
inert gas was turned off during the addition to prevent the drops of organolithium reagent from
drying on the tip of the needle. Once the addition is complete, the mixture is stirred for 2 h. The
reaction is quenched with NH4Cl sat. (2 mL), the mixture is warmed up to r.t., diluted with CH2Cl2
(5 mL) and the layers are separated. The aqueous layer is extracted with CH2Cl2 (3 x 5 mL) and the
combined organic layers are dried over Na2SO4, filtered and the solvent is evaporated in vacuo.
Purification is performed by column chromatography on silica gel using different mixtures of
pentane:Et2O as eluent. Note: Gas chromatography analysis is carried out to determine the
SN2:SN2’:homocoupling ratio on a sample obtained after work up, which has been passed through a
short plug of silica gel to remove transition metal residues.
General Procedure (B) for Cu-NHC catalyzed allylic alkylation of allylic halides with
organolithium reagents (preformation of the catalyst by addition of nBuLi).
A flame-dried Schlenk tube equipped with septum and stirring bar under nitrogen atmosphere is
charged with CuBr.SMe2 (0.015 mmol, 5 mol%) and NHC ligand salt (0.0165 mmol, 5.5 mol%) (the
ligand salt used in each experiment are reported in the optimization and scope tables). The tube is
evacuated and backfilled with nitrogen three times, then dry CH2Cl2 (1 mL) is added and the
solution is stirred under nitrogen at r.t. for 10 min. The solution is cooled down to -80 °C, then 2
drops of nBuLi (0.0165 mmol, 5.5 mol%, 1.6 M) are injected in the mixture and stirred over 15 min.
The addition of allylic halide and organolithium reagent, work up of the reaction and analysis are
performed as previously described in Procedure (A).
S4
General Procedure (C) for Cu-NHC catalyzed allylic alkylation of allylic halides with
organolithium reagents (without preformation of the catalyst).
A flame-dried Schlenk tube equipped with septum and stirring bar under nitrogen atmosphere is
charged with CuBr.SMe2 (0.015 mmol, 5 mol%) and NHC ligand salt (0.0165 mmol, 5.5 mol%) (the
ligand salt used in each experiment are reported in the optimization and scope tables). The tube is
evacuated and backfilled with nitrogen three times, then dry CH2Cl2 (1 mL) is added and the
solution is stirred under nitrogen at r.t. for 10 min. The solution is cooled down to -80 °C and stirred
over 10 min. The addition of allylic halide and organolithium reagent, work up of the reaction and
analysis are performed as previously described in Procedure (A).
S5
Optimization Study: Additional Data
A. Blank reactions in different solvents
Ph Br + nBuLiSolvent , T
Ph Ph+nBu
nBu
α−product γ−product
Ph+
Ph
1a
2a 3a Ph
Ph
homocoupling products
Allylic substitutionproducts
4
Table S1
Entrya Solvent Addition time Temperature Conversion (%)b 2a:3a:4 (%)b
1 CH2Cl2 3 h -80 °C 83 48:16:36
2 CH2Cl2 3 h r.t. full 47:19:34
3 CH2Cl2 direct r.t. full 48:21:31
4 toluene 3 h -80 °C 50 57:15:28
5 toluene 3 h 0 °C full 50:21:29
6 toluene 3 h r.t. full 49:25:26
7 toluene direct r.t. full 54:23:23
8 THF 3 h -80 °C full 21:5:74
9 MTBE 3 h -80 °C full 53:17:30
a Reaction conditions: 0.3 mmol of 1a in 2 mL of dry solvent. nBuLi (0.45 mmol, 1.6 M in hexane) diluted with dry hexane (final
conc. 0.45 M) added over 3h. Reaction mixture was further stirred for 2 h at -80 oC. b Determined by GC and 1H NMR.
Preliminary results obtained by addition of to a solution of cinnamyl bromide in CH2Cl2 at -80 °C
over 3 hours showed incomplete conversion, low selectivity and large amount of homocoupling
products (Table S1, entry 1). Performing the reaction at room temperature with long or short time of
addition of nBuLi afforded full conversion without any improvement in regioselectivity (entries 2-3).
The use of toluene afforded similar results in all the previous conditions (entries 4-7). The use of a
coordinating solvent as THF afforded full conversion unfortunately with large quantities of
homocoupling products (entry 8). The use of MTBE yielded result comparable to CH2Cl2 (entry 9).
S6
B. Catalyzed reactions in different solvents
Ph Br + nBuLi Ph Ph+nBu
nBu
α−product γ−product
Ph+
Ph
1a
2a 3a Ph
Ph
homocoupling products
Allylic substitutionproducts
4
CuBr.SMe2
5 mol%
solvent, -80 °C
L1 5.5 mol%
NaOtBu 5.5 mol%
Table S2
Entrya Solvent Copper Ligand Conversion (%)b 2a:3a:4 (%)b
1 CH2Cl2 full 95:5:-
2 CH2Cl2 full 73:17:10
3 CH2Cl2 80 49:18:33
4 CH2Cl2 83 48:16:36
5 toluene full 94:4:2
6 toluene 50 53:20:27
7 THF full 21:5:74
8 THF full 21:5:74
9 MTBE full 53:17:30
10 MTBE full 53:17:30
a Reaction conditions: General Procedure (A). 0.015 mmol of CuBr·SMe2, 0.0165 mmol of L1 and 0.0165 mmol of NaOtBu in 1 mL
of dry solvent cooled at -80 C̊. 0.3 mmol of 1a in 1 mL of dry solvent added to the cooled mixture. nBuLi (0.45 mmol, 1.6 M in
hexane) diluted with dry hexane (final conc. 0.45 M) added over 3h. Reaction mixture further stirred for 2 h at -80 oC. b Determined
by GC and 1H NMR.
When CuBr.SMe2 and IAd.HBF4 (L1) were used in CH2Cl2, good regioselectivity was observed as
well as full conversion and complete suppression of the side-reactions leading to homocoupling
products (Table S2, entry 1). When the ligand was removed, the selectivity of the reaction dropped,
yielding significant amount of branched and homocoupling products (entry 2). When only the
copper salt was removed (entry 3) the selectivity of the reaction was completely compromised,
affording results not significantly different from the blank reaction (entry 4). The use of toluene as
solvent led to comparable results obtained with CH2Cl2, affording good (entry 5) or bad selectivity
(entry 6) depending on the presence of the catalyst. When THF or MTBE were used, the catalytic
system resulted to be ineffective due to the high reactivity of the organolithium specie (entries 7-10).
S7
C. Screening of copper salts
Ph Br + nBuLi Ph Ph+nBu
nBu
α−product γ−product
Ph+
Ph
1a
2a 3a Ph
Ph
homocoupling products
Allylic substitutionproducts
4
CuX 5 mol%
CH2Cl2, -80 °C
L1 5.5 mol%
NaOtBu 5.5 mol%
Table S3
Entrya CuX Conversion (%)b 2a:3a:4 (%)b
1 CuBr.SMe2 full 95:5:-
2 CuTCc 55 83:9:8
3 CuCl 96 72:10:18
4 CuSCN full 92:8:-
a Reaction conditions: General Procedure (A). 0.015 mmol of copper salt (CuX), 0.0165 mmol of L1 and 0.0165 mmol of NaOtBu in 1
mL of dry CH2Cl2 cooled at -80 C̊. 0.3 mmol of 1a in 1 mL of dry CH2Cl2 added to the cooled mixture. nBuLi (0.45 mmol, 1.6 M in
hexane) diluted with dry hexane (final conc. 0.45 M) added over 3h. Reaction mixture further stirred for 2 h at -80 oC. b Determined
by GC and 1H NMR. c CuTC = (Copper(I)-thiophene-2-carboxylate)
The conditions which afforded the best result by employing CuBr.SMe2 (Table S3, entry 1) were
also applied to other commercially available copper precursors. The use of copper(I)-thiophene-2-
carboxylate (CuTC) caused a dramatic decrease in conversion (entry 2). The use of CuCl caused a
significant decrease in selectivity (entry 3). When CuSCN was used, only the regioselectivity was
affected by a slight decrease (entry 4).
S8
D. Effects of base
Ph Br + nBuLi Ph Ph+nBu
nBu
α−product γ−product
Ph+
Ph
1a
2a 3a Ph
Ph
homocoupling products
Allylic substitutionproducts
4
CuBr.SMe2
5 mol%
CH2Cl2, -80 °C
L1 5.5 mol%
Base 5.5 mol%
Table S4
Entry Base Conversion (%)a 2a:3a:4 (%)b
1b NaOtBu full 95:5:-
2b KOtBu full 95:5:-
3c nBuLi full 93:7:-
4d - full 95:5:-
a Determined by GC and 1H NMR. b Reaction conditions: General Procedure (A). 0.015 mmol of CuBr·SMe2, 0.0165 mmol of L1 and
0.0165 mmol of base (NaOtBu or KOtBu) in 1 mL of dry CH2Cl2 cooled at -80 C̊. 0.3 mmol of 1a in 1 mL of dry CH2Cl2 added to the
cooled mixture. nBuLi (0.45 mmol, 1.6 M in hexane) diluted with dry hexane (final conc. 0.45 M) added over 3h. Reaction mixture
further stirred for 2 h at -80 oC. c Reaction conditions: General Procedure (B). 0.015 mmol of CuBr·SMe2 and 0.0165 mmol of L1 in 1
mL of dry CH2Cl2 cooled at -80 C̊. nBuLi (0.0165 mmol, 1.6 M in hexane) injected in the mixture and stirred over 15 min. 0.3 mmol
of 1a in 1 mL of dry CH2Cl2 added to the cooled mixture. nBuLi (0.45 mmol, 1.6 M in hexane) diluted with dry hexane (final conc.
0.45 M) added over 3h. Reaction mixture stirred for 2 h at -80 oC. d Reaction conditions: General Procedure (C). 0.015 mmol of
CuBr·SMe2 and 0.0165 mmol of L1 in 1 mL of dry CH2Cl2 cooled at -80 C̊. 0.3 mmol of 1a in 1 mL of dry CH2Cl2 added to the
cooled mixture. nBuLi (0.45 mmol, 1.6 M in hexane) diluted with dry hexane (final conc. 0.45 M) and added via syringe pump over 3
h. Reaction mixture stirred for 2 h at -80 oC.
Different common bases, used to generate in situ the carbene specie starting from the corresponding
NHC ligand salt, were screened. NaOtBu and KOtBu, charged as solids in the reaction flask together
with CuBr.SMe2 and L1 (General Procedure A), gave comparable results in term of good conversion
and selectivity (Table S4, entries1-2). nBuLi (1.6 M in hexane) could also be used, by injection in the
reaction mixture prior the addition of the substrate (General Procedure B), with similar results
(entries 3). Eventually, the addition of an external base could be avoided (General Procedure C), by
harnessing the basicity of the organolithium compound and the slow addition. The formation of the
carbene occurs before any other chemical process, forming in situ the catalyst and affording the
product without any erosion of the selectivity (entry 4).
S9
E. Effects of temperature
Ph Br + nBuLi Ph Ph+nBu
nBu
α−product γ−product
Ph+
Ph
1a
2a 3a Ph
Ph
homocoupling products
Allylic substitutionproducts
4
CuBr.SMe2
5 mol%
L1 5.5 mol%
CH2Cl2, T
Table S5
Entrya Temperature (oC) Conversion (%)b 2a:3a:4 (%)b
1 -50 full 76:19:5
2 -74 full 88:10:2
3 -80 full 95:5:-
4 -82 full 94:5:1
a Reaction conditions: General Procedure (C). 0.015 mmol of CuBr·SMe2 and 0.0165 mmol of L1 in 1 mL of dry CH2Cl2. 0.3 mmol
of 1a in 1 mL of dry CH2Cl2 added to the cooled mixture (reported temperature). nBuLi (0.45 mmol, 1.6 M in hexane) diluted with
dry hexane (final conc. 0.45 M) and added via syringe pump over 3 h. Reaction mixture stirred for 2 h at -80 oC. b Determined by GC
and 1H NMR.
The test reaction was performed at different temperatures to highlight its effect on the selectivity.
When the reaction was performed at temperatures higher than -80 oC, the selectivity was
significantly affected (Table S5, entries 1-2). Performing the reaction of -80 oC afforded the best
results (entry 3). When the temperature was further decrease, no improvement was observed (entry
4).
S10
F. Effects of addition time
Ph Br + nBuLi Ph Ph+nBu
nBu
α−product γ−product
Ph+
Ph
1a
2a 3a Ph
Ph
homocoupling products
Allylic substitutionproducts
4
CuBr.SMe2
5 mol%
CH2Cl2, -80 °C
L1 5.5 mol%
Table S6
Entrya Addition time Conversion (%)b 2a:3a:4 (%)b
1 3 hr full 95:5:-
2 1 hr full 84:6:10
3 90 sec full 66:10:24
a Reaction conditions: General Procedure (C). 0.015 mmol of CuBr·SMe2 and 0.0165 mmol of L1 in 1 mL of dry CH2Cl2 cooled at -
80 C̊. 0.3 mmol of 1a in 1 mL of dry CH2Cl2 added to the cooled mixture. nBuLi (0.45 mmol, 1.6 M in hexane) diluted with dry
hexane (final conc. 0.45 M) added over reported time. Reaction mixture stirred for 2 h at -80 oC. b Determined by GC and 1H NMR.
The test reaction was performed with different time of addition of nBuLi to the reaction mixture to
investigate its effect on the selectivity. While a slow addition in 3 hours ensures good selectivity
(Table S6, entry 1), shortening to 1 hour mainly caused a significant production of homocoupling
products (entry 2). Worse results were obtained when fast addition in 90 seconds was performed
(entry 3), showing the slow addition to be a key parameter in order to guide the reaction through the
catalytic cycle.
G. Large scale test
The optimized condition were also applied to a 3.0 mmol scale (10 times larger than previously
described) with a reduced catalyst loading (2 mol%), while the concentration of the substrate and
organolithium were not modified (respectively 0.15 M in CH2Cl2 and 0.36 M in hexane). The
selectivity of the reaction was not affected by the larger scale and reduced catalyst content.
α:γ =
97:3 a
Ph Br nBuLi Ph nBu + Ph
nBuCuBr.SMe2
2 mol%
(12.33
mg)
CH2Cl2 (20
mL), -80
oC SN2-product SN2'-product3.0 mmol
(0.591
g)
1.2 eq., 3.6
mmol (2
.25 mL)
(1.6
M
in
hexane)
diluted to
10
mL with
hexane,
injected over 3
h
L2 2.2
mol%
(21.13 mg)
0.15 M
in
CH2Cl2
+
yield 86
%
(0
.449 g)
Reaction conditions: General Procedure (C). 0.06 mmol of CuBr·SMe2 and 0.066 mmol of L2 in 10 mL of dry CH2Cl2 cooled at -
80 C̊. 3.0 mmol of 1a dissolved in 10 mL of dry CH2Cl2 and added to the cooled mixture. nBuLi (3.6 mmol, 1.6 M in hexane) diluted
with dry hexane (final conc. 0.36 M) added over 3 h. Reaction mixture stirred for 2 h at -80 oC. a Determined by GC and 1H NMR.
S11
H. Preliminary studies on olefin geometry retention
In preliminary studies, a Z:E = 70:30 mixture of o-methoxycinnamyl bromide was converted into a
Z:E = 68:32 mixture of the corresponding alkylated linear product, with a regioselectivity of α:γ =
95:5, (yield not determined).
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500GMG112cr_cdcl3_Proton_20120521153323GMG112cr
5.19
2.19
2.39
1.00
2.24
4.10
4.11
4.15
4.15
4.16
4.17
4.17
4.21
4.21
5.94
5.98
5.99
6.02
6.03
6.04
6.08
6.36
6.40
6.44
6.47
6.47
6.51
6.67
6.73
1
2
3
4
5
6
O7
CH38
9
10
11
Br12
13
14
15
16
17
18
O19
CH320
21
22
23
Br24
starting bromide, Z:E = 70:30
Et2O1H 9
Et2O
1H 22
1H 22
2H 23
1H 11
Z-bromide E-bromide
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500
550
600
650
700
750
800
GMG114cr
0.32
2.20
0.17
1.02
2.00
0.52
0.44
4.98
4.98
4.98
4.99
5.00
5.00
5.03
5.07
5.70
5.72
5.73
5.74
5.75
5.77
5.94
5.96
5.97
5.99
6.00
6.01
6.18
6.20
6.21
6.22
6.22
6.24
6.26
6.49
6.49
6.50
6.52
6.52
6.53
6.68
6.68
6.69
6.72
6.73
1
2
3
4
5
6
O7
CH38
9
10
11
12
13
14
CH315
16
17
18
19
20
21
O22
CH323
24
25
26
27
28
29
CH330
31
32
33
34
35
36
O37
CH338
39
40
CH241
42
43
44
CH345
Z-linear
1H 9
E-linear
1H 25 1H10
branched
1H 40
1H 24
1H 41
product distribution:Z:E = 68:32
alpha:gamma = 95:5
starting from linear bromide:Z:E = 70:30
CH2Cl2
Reaction conditions: General Procedure (C). 0.015 mmol (5.0 mol%) of CuBr·SMe2 and 0.0165 mmol (5.0 mol%) of L2 in 1 mL of dry CH2Cl2 cooled at -80 C̊. 0.3 mmol of substrate dissolved in 1 mL of dry CH2Cl2 and added to the cooled mixture. nBuLi (0.36 mmol, 1.6 M in hexane) diluted with dry hexane (final conc. 0.36 M) added over 3 h. Reaction mixture stirred for 2 h at -80 oC. Ratios determined by GC and 1H NMR.
S12
Product Characterization
(E)-Hept-1-enylbenzene (2a)
Synthesized according to General Procedure C. Colorless oil obtained
as a 98:2 mixture of 2a and 3a after column chromatography (SiO2,
pentane), [78% yield] from 1a as starting material and nBuLi. A 94:6
mixture of 2a and 3a was obtained after column chromatography (SiO2, pentane), [85% yield] from
1j as starting material and nBuLi. The physical data were identical in all respects to those previously
reported.10 2a: 1H NMR (400 MHz, CDCl3, 25 °C) δ 7.36 (d, J = 7.7 Hz, 2H), 7.29 (t, J = 7.5 Hz,
2H), 7.20 (t, J = 7.1 Hz, 1H), 6.39 (d, J = 15.9 Hz, 1H), 6.24 (dt, J = 15.9, 7.1 Hz, 1H), 2.21 (q, J =
7.1 Hz, 2H), 1.54-1.44 (m, 2H), 1.40-1.31 (m, 4H), 0.89 (t, J = 5.7 Hz, 3H). 13C NMR (100.59 MHz,
CDCl3, 25 °C) δ 137.9, 131.2, 129.7, 128.4, 126.7, 125.9, 33.0, 31.4, 29.1, 22.6, 14.1. HRMS (ESI)
m/z [M+] calcd for C13H18: 174.1403; found: 174.0923.
(E)-Pent-1-enylbenzene (2b)
Synthesized according to General Procedure C from 1a as starting material
and EtLi. Colorless oil obtained as a 96:4 mixture of 2b and 3b after column
chromatography (SiO2, pentane), [60% yield]. The physical data were
identical in all respects to those previously reported.11 2b: 1H NMR (400 MHz, CDCl3, 25 °C) δ 7.35
(d, J = 7.9 Hz, 2H), 7.30 (t, J = 7.7 Hz, 2H), 7.19 (t, J = 6.7 Hz, 1H), 6.39 (d, J = 15.9 Hz, 1H),
6.28–6.18 (m, 1H), 2.20 (q, J = 7.1 Hz, 2H), 1.56–1.45 (m, 2H), 0.97 (t, J = 7.3 Hz, 3H). 13C NMR
(100.59 MHz, CDCl3, 25 °C) δ 137.9, 131.0, 129.9, 128.4, 126.7, 125.9, 35.1, 22.5, 13.7. HRMS
(APCI) m/z [M+H]+ calcd for C11H15: 147.1168; found: 147.1155.
(E)-(5-Methyl)-hex-1-enylbenzene (2c)
Synthesized according to General Procedure C from 1a as starting material
and isoBuLi. Colorless oil obtained as a 97:3 mixture of 2c and 3c after
column chromatography (SiO2, pentane), [76% yield]. The physical data
were identical in all respects to those previously reported.11 2c: 1H NMR (400 MHz, CDCl3, 25 °C)
δ 7.35 (d, J = 7.3 Hz, 2H), 7.29 (t, J = 7.3 Hz, 2H), 7.19 (t, J = 7.1 Hz, 1H), 6.38 (d, J = 15.8 Hz,
1H), 6.22 (dt, J = 15.6, 6.8 Hz, 1H), 2.25 (dt, J = 7.8, 7.2 Hz, 2H), 1.62 (sept, J = 6.6 Hz, 1H), 1.36
S13
(q, J = 7.3 Hz, 2H), 0.93 (d, J = 6.6 Hz, 6H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 138.0, 131.3,
129.5, 128.4, 126.7, 125.8, 38.5, 30.9, 27.5, 22.5. HRMS (ESI) m/z [M+] calcd for C13H18: 174.1403;
found: 174.0923.
(E)-Non-1-enylbenzene (2d)
Synthesized according to General Procedure C from 1a as starting
material and nHexLi. Colorless oil obtained as a 98:2 mixture of 2d
and 3d after column chromatography (SiO2, pentane), [70% yield].
The physical data were identical in all respects to those previously reported.12 2d: 1H NMR (400
MHz, CDCl3, 25 °C) δ 7.34 (d, J = 7.2 Hz, 2H), 7.29 (t, J = 7.3 Hz, 2H), 7.19 (t, J = 7.2 Hz, 1H),
6.38 (d, J = 15.8 Hz, 1H), 6.23 (dt, J = 15.8, 6.8 Hz, 1H), 2.21 (dt, J = 6.8, 1.1 Hz, 2H), 1.47 (quint,
J = 6.8 Hz, 2H), 1.40-1.20 (m, 8H), 0.89 (t, J = 6.9 Hz, 3H). 13C NMR (100.59 MHz, CDCl3, 25 °C)
δ 137.9, 131.2, 129.6, 128.4, 126.7, 125.9, 33.0, 31.8, 29.4, 29.2, 22.6, 14.1. HRMS (APCI) m/z
[M+H]+ calcd for C15H23: 203.1799; found: 203.1775.
(E)-But-1-enylbenzene (2e)
Synthesized according to General Procedure C from 1a as starting material and
MeLi. Colorless oil obtained as a 91:9 mixture of 2e and 3e, [full conversion,
yield not determined]. The product was not purified due to the high volatility
and Rf similar to toluene, used for diluting the MeLi. Analysis was performed by comparing the
physical data with precedent literature.13 2e: 1H NMR (400 MHz, CDCl3, 25 °C) δ 7.40-7.19 (m,
5H), 6.46 (d, J = 15.9 Hz, 1H), 6.33 (dt, J = 15.9, 6.0 Hz, 1H), 2.30 (dq, J = 7.3, 5.8 Hz, 2H), 1.17 (t,
J = 7.4 Hz, 3H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 137.9, 132.6, 128.7, 128.4, 126.7, 125.8,
26.05, 13.6. LRMS (ESI) m/z (abundance%, ion label): 51(6), 63(4), 65(6), 77(7), 78(6), 89(4),
91(24), 102(4), 103(4), 104(4), 115(45), 116(12), 117(100), 118(11), 128(5), 131(11, M+-H),
132(44, M+), 210(5, M++H).
(E)-(2-Methyl)-hex-1-enylbenzene (2f)
Synthesized according to General Procedure C from 1a as starting material
and secBuLi. Colorless oil obtained as a 90:10 mixture of 2f and 3f after
S14
column chromatography (SiO2, pentane) [50% yield]. The physical data were identical in all respects
to those previously reported.14 2f: 1H NMR (400 MHz, CDCl3, 25 °C) δ 7.35 (d, J = 7.2 Hz, 2H),
7.29 (t, J = 7.6 Hz, 2H), 7.19 (t, J = 7.2 Hz, 1H), 6.38 (d, J = 15.8 Hz, 1H), 6.22 (dt, J = 15.8, 7.2
Hz, 1H), 2.22 (ddd, J = 13.8, 6.4, 1.1 Hz, 1H), 2.05 (ddd, J = 13.8, 7.4, 3.7 Hz, 1H), 1.57–1.47 (m,
1H), 1.46–1.36 (m, 1H), 1.27–1.14 (m, 1H), 0.92 (t, J = 6.7 Hz, 3H), 0.90 (t, J = 7.3 Hz, 3H). 13C
NMR (100.59 MHz, CDCl3, 25 °C) δ 138.3, 131.1, 130.20, 128.8, 127.1 126.3, 40.5, 35.3, 29.5,
19.5, 11.9. HRMS (APCI) m/z [M+H]+ calcd for C13H19: 175.1481, found: 175.0954.
(E)-4-(Hept-1-enyl)-1-chlorobenzene (2g)
Synthesized according to General Procedure C from 1b as starting
material and nBuLi. Colorless oil obtained as a 98:2 mixture of 2g
and 3g after column chromatography (SiO2, pentane), [86% yield].
The physical data were identical in all respects to those previously reported.15 2g: 1H NMR (400
MHz, CDCl3, 25 °C) δ 7.30–7.22 (m, 4H), 6.33 (d, J = 15.8 Hz, 1H), 6.20 (dt, J = 15.7, 6.7 Hz, 1H),
2.20 (dt, J = 7.8, 6.7 Hz, 2H), 1.47 (quint, J = 7.2 Hz, 2H), 1.40–1.28 (m, 4H), 0.91 (t, J = 6.9 Hz,
3H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 136.4, 132.2, 132.0, 128.5, 128.5, 127.1, 33.0, 31.4,
29.0, 22.5, 14.0. HRMS (EI) m/z [M+] calcd for C13H17Cl: 208.1019, found: 208.1018.
(E)-4-(Hept-1-enyl)-1-bromobenzene (2h):
Synthesized according to General Procedure C from 1c as starting
material and nBuLi. Colorless oil obtained as a 98:2 mixture of 2h
and 3h after column chromatography (SiO2, pentane), [86% yield].
The physical data were identical in all respects to those previously reported.16 2h: 1H NMR (400
MHz, CDCl3, 25 °C) δ 7.40 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 6.31 (d, J = 15.9 Hz, 1H),
6.22 (dt, J = 15.9, 6.6 Hz, 1H), 2.19 (dt, J = 7.2, 6.7 Hz, 2H), 1.47 (quint, J = 7.3 Hz, 2H), 1.39–1.27
(m, 4H), 0.90 (t, J = 7.1 Hz, 3H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 136.9, 132.1, 131.5,
128.5, 127.4, 120.3, 33.0, 31.4, 28.9, 22.5, 14.0. HRMS (APCI) m/z [M+H]+ calcd for C13H1881Br:
255.0571, found: 255.0933.
(E)-4-(Hept-1-enyl)-1-trifluoromethylbenzene (2i)
Cl
Br
S15
Synthesized according to General Procedure C from 1d as starting
material and nBuLi. Colorless oil obtained as a 98:2 mixture of 2i
and 3i after column chromatography (SiO2, pentane), [75% yield].
The physical data were identical in all respects to those previously reported.14 2i: 1H NMR (400
MHz, CDCl3, 25 °C) δ 7.54 (d, J = 8.2 Hz, 2H), 7.42 (d, J = 8.2 Hz, 2H), 6.41 (d, J = 15.8 Hz, 1H),
6.34 (dt, J = 15.8, 6.1 Hz, 1H), 2.24 (dt, J = 7.1, 6.9 Hz, 2H), 1.49 (quint, J = 7.2 Hz, 2H), 1.40–1.29
(m, 4H), 0.91 (t, J = 6.9 Hz, 3H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 141.4, 134.1, 128.5,
126.0, 125.6, 125.4, 123.0, 33.0, 31.4, 28.8, 22.5, 14.0. HRMS (APCI) m/z [M-CF3]+ calcd for
C13H17 [M-CF3]+: 173.1325, found: 173.1312.
(E)-Methyl-4-(hept-1-enyl)benzoate (2j)
Synthesized according to General Procedure C from 1e as starting
material and nBuLi. Colorless oil obtained as a 99:1 mixture of 2j
and 3j after column chromatography (SiO2, pentane:Et2O = 94:6),
[72% yield]. The physical data were identical in all respects to
those previously reported.17 2j: 1H NMR (400 MHz, CDCl3, 25 °C) δ 7.96 (dt, J = 8.4, 1.8 Hz, 2H),
7.38 (d, J = 8.4 Hz, 2H), 6.41 (d, J = 15.9 Hz, 1H), 6.35 (dt, J = 15.9, 6.10 Hz, 1H), 3.90 (s, 3H),
2.23 (dt, J = 7.2, 5.7 Hz, 2H), 1.48 (quint, J = 7.1 Hz, 2H), 1.39–1.28 (m, 4H), 0.91 (t, J = 6.9 Hz,
3H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 167.0, 142.5, 134.2, 129.8, 129.0, 128.2, 125.7, 51.9,
33.1, 31.4, 28.8, 22.5, 14.0. HRMS (APCI) m/z [M+H]+ calcd for C15H21O2: 233.1536, found:
233.1476.
(E)-2-(Hept-1-enyl)-1-methoxybenzene (2k)
Synthesized according to General Procedure C from 1f as starting
material and nBuLi. Colorless oil obtained as a 96:4 mixture of 2k and
3k after column chromatography (SiO2, pentane:Et2O = 98:2), [83%
yield]. The physical data were identical in all respects to those previously reported.18 2k: 1H NMR
(400 MHz, CDCl3, 25 °C) δ 7.42 (dd, J = 7.6, 1.5 Hz, 1H), 7.18 (dt, J = 6.4, 1.6 Hz, 1H), 6.91 (t, J =
7.5 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 6.71 (d, J = 15.9 Hz, 1H), 6.22 (dt, J = 15.9, 6.9 Hz, 1H), 3.85
(s, 3H), 2.23 (dt, J = 7.0, 6.6 Hz, 2H), 1.48 (quint, J = 7.2 Hz, 2H), 1.39–1.29 (m, 4H), 0.91 (t, J =
6.9 Hz, 3H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 156.2, 132.0, 127.7, 127.0, 126.3, 124.1,
120.6, 110.8, 55.4, 33.4, 31.5, 29.2, 22.6, 14.1. LRMS (ESI) m/z (abundance%, ion label): 51(3),
F3C
O
O
O
S16
77(6), 91(36), 103(5), 108(7), 115(19), 117(8), 119(17), 121(26), 131(16), 134(20), 147(100),
161(4), 204(40, M+).
(E)-(Oct-2-enyloxy)methylbenzene (2l)
Synthesized according to General Procedure C from 1g as starting
material and nBuLi. Colorless oil obtained as a 85:15 mixture of 2l
and 3l after column chromatography (SiO2, pentane:Et2O = 98:2),
[90% yield]. The spectra were compared with precedent literature.19 2l: 1H NMR (400 MHz, CDCl3,
25 °C) δ 7.38–7.32 (m, 4H), 7.31–7.26 (m, 1H), 5.78–5.66 (m, 1H), 5.66–5.55 (m, 1H), 4.51 (s, 2H),
3.98 (dt, J = 6.1, 0.8 Hz, 2H), 2.06 (dt, J = 7.1, 6.8 Hz, 2H), 1.45–1.20 (m, 6H), 0.90 (t, J = 6.6 Hz,
3H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 135.1, 128.3, 127.8, 127.5, 127.4, 126.1, 71.8, 71.0,
32.3, 31.4, 28.7, 22.5, 14.0. HRMS (APCI) m/z [M+H]+ calcd for C15H23O: 219.1743, found:
219.1720.
(E)-Hept-1-enylbenzoate (2m)
Synthesized according to General Procedure C from 1h as starting
material and nBuLi. Colorless oil obtained as pure 2m from a 90:10
mixture of 2m and 3m after column chromatography (SiO2,
pentane:Et2O = 80:1), [72% yield]. The physical data were
identical in all respects to those previously reported.20 2m: 1H NMR (400 MHz, CDCl3, 25 °C) δ
8.09 (d, J = 8.2 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.31 (dt, J = 12.4, 1.4 Hz,
1H), 5.61 (dt, J = 12.4, 7.5 Hz, 1H), 2.07 (dq, J = 7.4, 6.3 Hz, 2H), 1.43 (quint, J = 7.1 Hz, 2H),
1.38–1.28 (m, 4H), 0.89 (t, J = 6.9 Hz, 3H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 163.9, 135.5,
133.3, 129.8, 129.3, 128.4, 115.7, 31.2, 29.2, 27.3, 22.4, HRMS (APCI) m/z [M+H]+ calcd for
C15H21O2: 233.1536, found: 233.1515.
6-Pentadecene (2n)
Synthesized according to General Procedure C from 1i as
starting material and nBuLi. Colorless oil obtained as a 75:25
mixture of 2n and 3n after column chromatography (SiO2, pentane), [95% yield]. The physical data
O
O
O
S17
were identical in all respects to those previously reported.21 2n: 1H NMR (400 MHz, CDCl3, 25 °C)
δ 5.41–5.36 (m, 2H), 2.05–1.86 (m, 4H), 1.43–1.16 (m, 18H), 0.97–0.79 (m, 6H). 13C NMR (100.59
MHz, CDCl3, 25 °C) δ 130.7, 33.0, 32.9, 32.3, 31.8, 30.0, 29.9, 29.7, 29.7, 29.5, 23.1, 22.9, 14.5,
14.4. One 13C signal is missing or overlapping (C=C double bond). LRMS (ESI) m/z (abundance%,
ion label): 55(99), 69(100), 83(76), 97(66), 111(26), 125(8), 210(20, M+).
(Z)-Hept-1-enylbenzene (2o)
Synthesized according to General Procedure C from 1k (Z:E ratio = 94:6)
as starting material and nBuLi. Colorless oil obtained as a 94:6 mixture of
2o (Z:E ratio = 94:6) and 3o after column chromatography (SiO2, pentane),
[77% yield]. The physical data were identical in all respects to those previously reported.15 (Z)-2o: 1H NMR (400 MHz, CDCl3, 25 °C) δ 7.38-7.28 (m, 4H), 7.25-7.23 (m, 1H), 6.43 (d, J = 11.7 Hz,
1H), 5.69 (dt, J = 11.7, 7.3 Hz, 1H), 2.35 (qt, J = 7.3, 1.7 Hz, 2H), 1.48 (quint, J = 7.3 Hz, 2H), 1.39-
1.28 (m, 4H), 0.91 (t, J = 7.1 Hz, 3H). 13C NMR (100.59 MHz, CDCl3, 25 °C) δ 133.4, 128.8, 128.5,
128.2, 126.8, 126.5, 31.7, 29.8, 28.7, 22.6, 14.1. HRMS (APCI) m/z [M+H]+ calcd for C13H19:
175.1481, found: 175.1479.
(Z)-Non-1-enylbenzene (2p)
Synthesized according to General Procedure C from 1k (Z:E ratio =
86:14) as starting material and nHexLi. Colorless oil obtained as a
93:7 mixture of 2p (Z:E ratio = 86:14) and 3p after column
chromatography (SiO2, pentane), [63% yield]. The physical data were identical in all respects to
those previously reported.22 (Z)-2p: 1H NMR (400 MHz, CDCl3, 25 °C) δ 7.41–7.31 (m, 4H), 7.23
(t, J = 6.9 Hz, 1H), 6.45 (d, J = 11.6 Hz, 1H), 5.72 (dt, J = 11.7, 7.3 Hz, 1H), 2.38 (qd, J = 7.5, 1.7
Hz, 2H), 1.47 (quint, J = 7.3 Hz, 2H), 1.39-1.24 (m, 8H), 0.93 (dd, J = 8.2, 4.5 Hz, 3H). 13C NMR
(100.59 MHz, CDCl3, 25 °C) δ 138.2, 133.6, 129.1, 129.0, 128.4, 126.7, 32.2, 30.3, 29.7, 29.5, 29.0,
23.0, 14.4. HRMS (APCI) m/z [M+H]+ calcd for C15H22: 202.1722, found: 202.1733.
S18
References
(1) A. W. van Zijl, L. A. Arnold, A. J. Minnaard, and B. L. Feringa, Adv. Synth. Catal., 2004, 346,
413-420.
(2) M. L. Hammond, R. A. Zambias, M. A. Chang, N. P. Jensen, J. McDonald, K. Thompson, D. A.
Boulton, I. E. Kopka, K. M. Hand, E. E. Opas, T. Bach, P. Davies, D. E. Macintyre, R. J. Bonney
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S19
1H NMR and 13C NMR Spectra of New Compounds
mixture
2f 3f
2f : 3f = 90 : 10
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
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0102030405060708090100110120130140150160170180190f1 (ppm)
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25000
30000
35000
40000
45000
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55000
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65000
70000
75000
S20
O O2l :
3l = 85 : 15
mixture
2l 3l
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
-200
0
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400
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0102030405060708090100110120130140150160170180f1 (ppm)
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32000