Ligand Control of E/Z Selectivity in Nickel-Catalyzed Transfer Hydrogenative Alkyne Semireduction

Article abstract of DOI:10.1021/acs.joc.5b01047

A nickel-catalyzed transfer hydrogenative alkyne semireduction protocol that can be applied to both internal and terminal alkynes using formic acid and Zn as the terminal reductants has been developed. In the case of internal alkynes, the (E)- or (Z)-olefin isomer can be accessed selectively under the same reaction conditions by judicious inclusion of a triphos ligand.

Full text of DOI:10.1021/acs.joc.5b01047

Subscriber access provided by UNIV OF CALIFORNIA SAN DIEGO LIBRARIES
Note
Ligand Control of E/Z Selectivity in Nickel Catalyzed
Transfer Hydrogenative Alkyne Semi-Reduction
Edward Richmond, and Joseph Moran
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 01 Jun 2015
Downloaded from http://pubs.acs.org on June 4, 2015
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 18
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Ligand Control of E/Z Selectivity in Nickel Catalyzed Transfer
Hydrogenative Alkyne Semi-Reduction
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Edward Richmond and Joseph Moran*
ISIS & icFRC, Université de Strasbourg & CNRS, 8 allée Gaspard Monge, 67000, Strasbourg, France.
ABSTRACT: A nickel catalyzed transfer hydrogenative alkyne semi-reduction protocol has been developed
applicable to both internal and terminal alkynes using formic acid as the terminal reductant. In the case of in-
ternal alkynes, the (E)- or (Z)-olefin isomer can be accessed selectively under the same reaction conditions by
judicious inclusion of a triphos ligand.
The Lindlar semiꢀreduction of alkynes1 is a longstanding synthetic transformation that has found widespread applicaꢀ
tion in the preparation of pharmaceuticals, agrochemicals, natural products and fine fragrance components.2 It remains,
more than 60 years after its inception, the de rigueur method for alkyne reduction, typically affording the (Z)ꢀolefinic
product. Nevertheless, this classic reduction method is not without its limitations; commercial samples of Lindlar’s cataꢀ
lyst are notorious for their betweenꢀbatch variability, and (E/Z)ꢀselectivities can often be modest owing to isomerization
of products under the reaction conditions.3 Overꢀreduction of the alkenes to the fully saturated alkane is perhaps the
most common drawback, particularly with terminal acetylene functionalities or highly polar substrates.4 In recent years,
a multitude of homogeneous and heterogeneous5 catalytic methods primarily based on transition metals has been deꢀ
veloped in an attempt to address these limitations.6 Significant progress has been made in the area of (Z)ꢀselective alꢀ
kyne reductions, and a variety of catalytic systems have been developed employing transition metal precatalysts in
combination with hydrogen gas7 or in tandem with transfer hydrogenation agents such as silanes,8 or HCO2H.9 Although
less wellꢀdeveloped in comparison, catalytic systems that provide selective access to the (E)ꢀolefin product have also
been reported,10,11 including Rhꢀ, Ruꢀ, Pdꢀ and Irꢀcatalyzed hydrogenations and transfer hydrogenations. Recently, (E)ꢀ
selective semiꢀreductions catalyzed by base metals have been developed, including a Niꢀcatalyzed transfer hydrogenaꢀ
tion from H3PO210g and an Feꢀcatalyzed hydrogenation.10h Nevertheless, few catalytic systems enable switchable selecꢀ
tivity11 for either the (E)ꢀ or (Z)ꢀolefin isomer in a single transformation12 and, to the best of our knowledge, none are
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 18
switchable under ligand control. We wish to report a nickelꢀcatalyzed transfer hydrogenative semiꢀreduction of alkynes
with formic acid whereby judicious inclusion of a commercially available triphosphine ligand allows for the generation of
either the (E)ꢀ or (Z)ꢀalkene isomer, typically with complete selectivity (>95:5). Importantly, the reaction does not require
purified solvents, reagents or an inert atmosphere, and no additional change to the reaction conditions is necessary in
order to induce the switch in selectivity. Preliminary mechanistic experiments indicate that the reaction initially yields the
(Z)ꢀalkene isomer, which is rapidly isomerized under the reaction conditions by a nickel phosphine complex.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
As a continuation of our previous investigations towards accelerated discovery of metalꢀcatalyzed reaction processes
by screening and deconvoluting complex mixtures of catalyst components,13 a new, unexpected product was isolated
upon subjecting propargylic allylamine 1 to conditions originally intended to promote reductive cyclizationꢀtype reactiviꢀ
ty14 (Scheme 1). Rather, this compound, isolated in 65% yield, was assigned as the (Z)ꢀalkene arising from selective
alkyne semiꢀreduction. No overꢀreduction of the nascent internal olefin or of the pendant allyl group was observed unꢀ
der these reaction conditions, suggesting that such a catalytic system may be able to address some of the issues
commonly encountered using Lindlar’s catalyst. Deconvolution of the reaction components rapidly identified nickel (II)
triflate as the active catalyst, with zinc, formaldehyde and DABCO also necessary for reduction to occur. We hypotheꢀ
sized that the combination of DABCO and formaldehyde would function as a transfer hydrogenation agent akin to amꢀ
monium formate.15 Indeed, upon replacement of these components with formic acid, both the rate and cleanliness of
the reaction notably increased.16 Slight optimization of the reaction conditions established a reliable protocol for the (Z)ꢀ
selective semiꢀreduction of alkynes.17
ACS Paragon Plus Environment

Page 3 of 18
The Journal of Organic Chemistry
Scheme 1. Reaction discovery and deconvolution
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
a Combinatorial discovery and deconvolution of in situꢀgenerated catalysts for semiꢀreduction of alkyne 1. Conversion deꢀ
termined by 1H NMR analysis of the crude mixtures in CDCl3. PMP = paraꢀmethoxyphenylꢀ, DABCO = 1,4ꢀ
diazabicyclo[2.2.2]octane.
Emboldened by this initial discovery, we sought to develop divergent reaction conditions which would allow selective
access to either the (Z)ꢀ or (E)ꢀalkene isomer. Using a model bis(aryl)alkyne, several nickel (II) precursors were shown
to be effective catalysts for this transformation, yet addition of a variety of monoꢀ or bidentate phosphines proved either
detrimental to reactivity, or had no effect on E/Z selectivity (see SI for full optimization information). In contrast, the
presence of tridentate ligand bis(diphenylꢀphosphinoethyl)phenylphosphine (triphos) furnished a 1:1 mix of geometric
isomers (Table 1, entry 3). Switching to NiCl2ꢀdme as a catalyst precursor resulted in complete selectivity for the (E)ꢀ
isomer (entry 4). Finally, reducing the catalyst loadings to 10 mol% had no impact on either conversion levels or on E/Z
selectivities (entries 5 and 6).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Table 1. Ligand Control of E/Z Selectivity
Page 4 of 18
1
2
3
4
5
6
7
8
9
Nickel Source
Ligand
Conversion
(%)a
E/Z
ratio
Entry
(20 mol%)
NiBr2
(20 mol%)
1
2
3
4
5
ꢀ
>95
>95
>95
>95
>95
<5:95
<5:95
50:50
>95:5
<5:95
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NiCl2ꢀdme
ꢀ
NiBr2
triphos
triphos
ꢀ
NiCl2ꢀdme
NiBr2 (10)
NiCl2ꢀdme
6
triphos (10)
>95
>95:5
(10)
aConversion determined by 1H NMR analysis of the crude reaction mixtures in CDCl3. PMP = paraꢀmethoxyphenylꢀ.
With optimal reaction conditions in hand, an evaluation of the reaction generality was undertaken using the NiBr2 sysꢀ
tem to enable the selective preparation of (Z)ꢀalkenes. Upon subjecting the requisite acetylene derivatives to the reacꢀ
tion conditions, the corresponding alkenes were delivered in excellent yields and typically as a single geometric isomer
(Table 2).18 (Z)ꢀStilbene derivatives 2a-i were all delivered in >90% isolated yield, with excellent (Z)ꢀselectivities. Addiꢀ
tionally, substrates bearing reducible functionalities such as a nitrile and OꢀBn, typically unsuitable substrates for relatꢀ
ed nickel catalyzed reductions,19 were smoothly reduced to the desired alkenes 2f and 2g with no competitive nitrile
reduction or OꢀBn deprotection observed. Similarly, a substrate bearing an aryl bromide was also cleanly reduced to
(Z)ꢀstilbene 2h with no evidence of protodebromination.20 A series of olefins 2j-n was also prepared in excellent yields,
with good selectivity for the (Z)ꢀolefin isomer in all cases.
Not all substrates subjected to the reaction conditions proved amenable to reduction. Substrates bearing nitroꢀaryl
groups exhibited no reduction of either alkyne or nitro functionality, even at elevated temperatures. Aldehydes also
proved incompatible with the reaction conditions, yielding a complex mixture of products, presumably as a result of
overꢀreduction.
To explore the ability of the developed catalytic method to selectively deliver (E)ꢀolefins simply by inclusion of triphos
ligand, a further selection of substrates was examined (Table 3). Diarylacetylenes were amenable to the reaction condiꢀ
tions, furnishing the requisite (E)ꢀstilbenes 3a-h in excellent yields and with complete selectivity for the (E)ꢀisomer.
Once more, an OꢀBn substituent was well tolerated by the reaction system (3f), as was an aryl bromide functionality
(3g).
ACS Paragon Plus Environment

Page 5 of 18
The Journal of Organic Chemistry
Table 2. (Z)-Selective alkyne semi-reduction
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aA mixture of alkyne (0.2 mmol), NiBr2 (10 mol%), zinc (1.0 mmol) and HCO2H (1.0 mmol) in 1,4ꢀdioxane (0.5 mL) was
b
c
stirred at 120 °C for 16 h. Isolated yield ꢀ an average of two runs. Reaction performed at 140 °C. d15 mol% NiBr2 was used.
e20 mol% NiBr2 was used. fYield determined by 1H NMR in comparison to 1,3,5ꢀtrimethoxybenzene as internal standard.
Acetylene derivatives bearing ester functional groups were also smoothly reduced to the corresponding (E)ꢀalkenes
3h, 3i and 3j in high yields. Bisꢀalkene 3k was also generated via this catalytic methodology, albeit in more modest seꢀ
lectivity for the (E)ꢀisomer. Unfortunately, upon subjecting 4ꢀoctyne to the (E)ꢀselective reaction conditions, only the (Z)ꢀ
alkene isomer 3l was detected with poor levels of conversion.
The NiBr2 catalyzed semiꢀreduction system was next applied to a series of terminal alkynes, yielding the expected
terminal olefins in excellent yields (Table 4). Relatively simple olefins 4a-d were isolated as the sole reaction product,
as was estradiol derivative 4e, generated in 88% yield despite the adjacent quaternary carbon center. Additionally, proꢀ
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 18
pargylic allylamine 4f was prepared from the requisite bisꢀalkyne starting material demonstrating the ability to selectiveꢀ
1
2
ly reduce terminal alkynes in the presence of internal alkyne functionalities.
3
4
5
Table 3. (E)-Selective alkyne semi-reduction
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aA mixture of alkyne (0.2 mmol), NiCl2ꢀdme (10 mol%), triphos (10 mol%), zinc (1.0 mmol) and HCO2H (1.0 mmol) in 1,4ꢀ
b
c
d
dioxane (0.5 mL) was stirred at 120 °C for 16 h. Isolated yield ꢀ an average of two runs. Reaction performed at 140 °C. Yꢀ
ield determined by 1H NMR in comparison to 1,3,5ꢀtrimethoxybenzene as internal standard.
ACS Paragon Plus Environment

Page 7 of 18
The Journal of Organic Chemistry
Table 4. Terminal alkyne semiꢀreduction
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
aA mixture of alkyne (0.2 mmol), NiBr2 (10 mol%), zinc (1.0 mmol) and HCO2H (1.0 mmol) in THF (0.5 mL) was stirred at 80
°C for 16 h. bIsolated yield ꢀ an average of two runs.
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
To gain insight into the role of the triphos ligand, an isolated sample of (Z)ꢀstilbene was exposed to both sets of reacꢀ
tion conditions. Upon treatment with NiBr2, zinc and HCO2H at 120 °C for 1 h, no alkene isomerization was observed.
However, upon treatment of (Z)ꢀstilbene with NiCl2ꢀdme and triphos under identical conditions, complete isomerization
to the (E)ꢀalkene was observed after only 1 h at 120 °C (Figure 1). Isomerization was not accomplished by any other
phosphine ligands tested in our initial screen (see SI for details). These observations are highly suggestive of an initial
(Z)ꢀselective alkene reduction followed by rapid Niꢀtriphos catalyzed isomerization.21
Figure 1. Evidence for ‘(Z)ꢀfirst’ reduction mechanism.
In conclusion, a robust catalytic protocol for the selective semiꢀreduction of alkynes using inexpensive nickel precurꢀ
sors, zinc and formic acid is reported. The ability of an in situ generated Niꢀtriphos complex to isomerize (Z)ꢀolefins to
(E)ꢀolefins under simple reaction conditions has also been discovered. The applicability of this catalytic protocol to a
wide range of substrates has been demonstrated providing selective access to a range of terminal, (Z) and (E)ꢀolefins.
The inexpensive nature of the reaction components, the ability to perform the reactions without an inert atmosphere,
and the tunable (E/Z)ꢀselectivity should render this an appealing addition to modern catalytic, chemoselective methodꢀ
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 18
ologies. Ongoing investigations aim to ascertain the nature of the catalytic species involved in these transformations
and to extend the utility of this selective catalyst system in synthesis.
1
2
3
4
5
EXPERIMENTAL SECTION
6
General Information All reagents were used as received without purification. 1,4ꢀDioxane refers to ≥99.5% (GC) (33147ꢀ1L)
and THF refers to ≥99.0% ReagentPlus® (178810ꢀ1L) both purchased from SigmaꢀAldrich. Formic acid refers to 98ꢀ100 grade
and zinc to zinc dust (<10 ꢁm, ≥98.0%) both purchased from SigmaꢀAldrich. Triphos refers to
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
bis(diphenylphosphinoethyl)phenylphosphine (CAS: 23582ꢀ02ꢀ7). NiBr2 and NiCl2 dme are both 98% grade (Aldrich).
ꢀ
General laboratory techniques were used throughout, and no special precautions were taken to exclude air or moisture from
the reactions. Elevated temperatures were achieved by way of a stirrerꢀhotplate, heating block and thermocouple. Where apꢀ
plicable, analytical thin layer chromatography was performed on preꢀcoated aluminium plates (Kieselgel 60 F254 silica). TLC
visualization was carried out with ultraviolet light (254 nm), followed by staining with a 1% aqueous KMnO4 solution. Flash
column chromatography was performed on Kieselgel 60 silica eluting with the solvent system stated.
Nuclear magnetic resonance (NMR) spectra were acquired at 400 MHz (1H), 100 MHz (13C), 376 MHz (19F) at ambient temꢀ
perature in the deuterated solvent stated. All chemical shifts are quoted in parts per million (ppm) relative to the residual solꢀ
vent as the internal standard. GCꢀMS analysis was performed on a GC System connected to a MSD block using a High Resoꢀ
lution Gas Chromatography Column: 30m×0.250mm, 0.25 Micron. High Resolution Mass Spectra were obtained using elecꢀ
trospray ionization (ESI).
General Procedure for Sonogashira Coupling Reaction Starting material alkynes were prepared according to a reported
literature procedure22: To an oven dried Schlenk flask was added PdCl2(PPh3)2 (10 mol%), CuI (10 mol%), and the desired
aryliodide (2.2 mmol). MeCN (3 mL) was then introduced by syringe, followed by phenylacetylene (2.0 mmol), and Et3N (4.0
mmol). The reaction mixture was stirred 16 h at room temperature before being concentrated in vacuo, directly onto silica gel
and purified by flash column chromatography on silica (petroleum ether/diethyl ether) to give the desired arylalkynes; 1ꢀ
Methoxyꢀ4ꢀ(phenylethynyl)benzene,23
1ꢀMethylꢀ3ꢀ(phenylethynyl)benzene,23
1ꢀMethylꢀ2ꢀ(phenylethynyl)benzene,23
4ꢀ
(Phenylethynyl)phenol,24 1ꢀNitroꢀ4ꢀ(phenylethynyl)benzene,24 1ꢀNitroꢀ3ꢀ(phenylethynyl)benzene,24 1ꢀBromoꢀ4ꢀ(phenylethynyl)ꢀ
benzene,25 Methyl 4ꢀ(phenylethynyl)benzoate,26 3ꢀ(Phenylethynyl)benzonitrile,27 4ꢀ(Phenylethynyl)benzaldehyde,23 were all
prepared with analytical data in agreement with the literature.
1ꢀ(Benzyloxy)ꢀ4ꢀ(phenylethynyl)benzene was prepared from 4ꢀ(Phenylethynyl)phenol (1.00 mmol, 0.194 g), K2CO3 (1.10
mmol, 0.152 g), and benzyl bromide (0.900 mmol, 0.107 mL). The reactants were dissolved in acetone and heated to reflux
until TLC analysis indicated consumption of starting material (ca. 4 h). The reaction mixture was then cooled, filtered and diꢀ
luted with EtOAc (30 mL). The organic layer was then washed with sat. aq. NaHCO3 (20 mL), brine (20 mL), dried over
MgSO4, filtered and concentrated in vacuo to give the title compound as an offꢀwhite solid (0.276 g, 97% yield) with analytical
ACS Paragon Plus Environment

Page 9 of 18
The Journal of Organic Chemistry
data in agreement with the literature.28 1H NMR (400 MHz, CDCl3) δ 7.51 (2H, dd, J = 7.5, 1.8 Hz), 7.47 (2H, d, J = 8.6 Hz),
7.45ꢀ7.38 (4H, m), 7.35ꢀ7.32 (4H, m), 6.95 (2H, d, J = 8.6 Hz), 5.09 (2H, s).
1
2
3
4
5
6
7
8
9
NꢀAllylꢀ4ꢀmethylꢀNꢀ(propꢀ2ꢀynꢀ1ꢀyl)benzenesulfonamide To a stirred solution of Nꢀ(Tosyl)Allylamine (4.52 g, 21.4 mmol) and
K2CO3 (4.44 g, 32.1 mmol) in acetone (50 mL) at ambient temperature was added propargyl bromide (3.46 mL, 32.1 mmol)
dropwise and the reaction mixture heated at reflux for 5 h. After allowing to cool, the reaction mixture was quenched with H2O
(40 mL) and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (150 mL), dried over
MgSO4, filtered and concentrated in vacuo to give an offꢀwhite semiꢀsolid. The crude material was dissolved in Et2O (approx.
20 mL) and cooled in the refrigerator overnight to give the title compound as an offꢀwhite crystalline solid (3.36 g, 63% yield)
that was collected by filtration. Analytical data was in agreement with the literature.29 1H NMR: (400 MHz, CDCl3) δ 7.74 (2H,
d, J = 8.3 Hz), 7.29 (2H, d, J = 8.3 Hz), 5.73 (1H, ddt, J = 17.0, 10.1, 6.6 Hz), 5.29 (1H, dt, J = 17.0, 1.3 Hz), 5.24 (1H, dd, J =
10.1, 1.3 Hz), 4.09 (2H, d, J = 2.4 Hz), 3.83 (2H, d, J = 6.6 Hz), 2.43 (3H, s), 2.00 (1H, t, J = 2.4 Hz).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NꢀAllylꢀNꢀ(3ꢀ(4ꢀmethoxyphenyl)propꢀ2ꢀynꢀ1ꢀyl)ꢀ4ꢀmethylbenzenesulfonamide was prepared according to the above general
procedure from NꢀAllylꢀ4ꢀmethylꢀNꢀ(propꢀ2ꢀynꢀ1ꢀyl)benzenesulfonamide and 4ꢀiodoanisole as a pale yellow solid (0.429 g,
86% yield) with analytical data in agreement with the literature.30 1H NMR: (400 MHz, CDCl3) δ 7.82 (2H, d, J = 8.2 Hz), 7.30
(2H, d, J = 7.6 Hz), 7.06 (2H, d, J = 8.7 Hz), 6.81 (2H, d, J = 8.7 Hz), 5.84 (1H, ddt, J = 17.0, 10.2, 6.6 Hz), 5.37 (1H, dd, J =
17.0, 1.1 Hz), 5.30 (1H, d, J = 10.2 Hz), 4.33 (2H, s), 3.92 (2H, d, J = 6.4 Hz), 3.84 (3H, s), 2.40 (3H, s).
4ꢀMethylꢀNꢀ(pentꢀ2ꢀynꢀ1ꢀyl)ꢀNꢀ(propꢀ2ꢀynꢀ1ꢀyl)benzenesulfonamide To a stirred solution of Nꢀ(Tosyl)propargylamine (1.00 g,
4.78 mmol) in DMF (30 mL) at 0 °C was added NaH (0.230 g, 5.74 mmol) in four portions. The reaction mixture was allowed
to stir for 1 h at 0 °C, before 1ꢀbromopentꢀ2ꢀyne (0.640 mL, 6.21 mmol) was added dropwise and the reaction stirred for 4 h,
allowing to warm to room temperature. The reaction was quenched carefully with brine (20 mL), and extracted with Et2O (3 x
30 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an orange oil which
was purified by column chromatography over silica (5% EtOAc in petrol) to give the title compound as a viscous, colorless oil
(0.068 g, 52% yield) with analytical data in agreement with the literature.31 1H NMR (400 MHz, CDCl3) δ 7.72 (2H, d, J = 8.2
Hz), 7.29 (2H, d, J = 8.2 Hz), 4.13 (4H, app. t, J = 2.3 Hz), 2.42 (3H, s), 2.13 (1H, t, J = 2.4 Hz), 2.01 (2H, dddd, J = 9.9, 7.5,
5.1, 2.4 Hz), 0.97 (3H, t, J = 7.5 Hz).
4ꢀMethylꢀNꢀphenylbenzenesulfonamide To a stirred solution of aniline (0.400 g, 4.30 mmol) and Et3N (0.900 mL, 6.50 mmol)
in CH2Cl2 (20 mL) at 0 °C was added TsCl (1.00 g, 5.25 mmol) slowly and the reaction mixture stirred for 1 h at room temperaꢀ
ture. The reaction was quenched with 0.1 M HCl (20 mL) and extracted with CH2Cl2 (3 x 20 mL). The combined organic layers
were washed with brine (30 mL), dried over MgSO4, filtered and concentrated in vacuo to give a white solid (1.02 g, 96% yield)
used without further purification and with analytical data in agreement with the literature.32 1H NMR (400 MHz, CDCl3) δ 7.70ꢀ
7.68 (2H, m), 7.30ꢀ7.25 (4H, m), 7.15 (1H, t, J = 7.5 Hz), 7.12ꢀ7.06 (2H, m), 6.68 (1H, br s), 2.42 (3H, s).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 18
1
2
3
4
5
6
7
8
4ꢀMethylꢀNꢀphenylꢀNꢀ(propꢀ2ꢀynꢀ1ꢀyl)benzenesulfonamide To a stirred solution of 4ꢀMethylꢀNꢀphenylbenzenesulfonamide
(1.00 g, 4.04 mmol) and K2CO3 (0.910 g, 8.08 mmol) in DMF (10 mL) at rt was added propargyl bromide (0.670 mL, 6.06
mmol) dropwise and the reaction mixture stirred for 16 h at room temperature. The reaction mixture was quenched with 0.1 M
HCl (10 mL) and extracted with Et2O (3 x 30 mL). The combined organic layers were then washed with H2O (3 x 15 mL), brine
(15 mL), dried over MgSO4, filtered and concentrated in vacuo to give an offꢀwhite solid (1.07 g, 93% yield) used without furꢀ
ther purification and with analytical data in agreement with the literature.33 1H NMR (400 MHz, CDCl3) δ 7.55 (2H, d, J = 8.2
Hz), 7.32ꢀ7.31 (2H, m), 7.26ꢀ7.22 (5H, m), 4.44 (2H, d, J = 2.4 Hz), 2.42 (3H, s), 2.16 (1H, t, J = 2.4 Hz).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General Procedure for (Z)-selective reduction To an oven dried 10 mL screwꢀtop vial equipped with a magnetic stirrer bar
was added the desired alkyne (0.20 mmol), zinc (1.0 mmol), NiBr2 (10 mol%), 1,4ꢀdioxane (0.5 mL) and HCO2H (1.0 mmol).
The vial was then sealed, transferred to a heating block at 120 °C, and stirred rapidly (1200 rpm) at this temperature for 16 h.
After allowing to cool, the crude reaction mixture was filtered through a celite plug, the filter cake washed with CH2Cl2 and the
reaction mixture concentrated in vacuo to give the desired (Z)ꢀalkene.
(Z)ꢀStilbene (2a) was prepared according to the above general procedure as a colorless oil with analytical data in agreement
with the literature.11b Run 1 ꢀ 0.032 g, 89% yield; Run 2 ꢀ 0.034 g, 94% yield; 1H NMR (400 MHz, CDCl3) δ 7.32ꢀ7.23 (10H, m),
6.65 (2H, s).
(Z)ꢀ1ꢀMethylꢀ2ꢀstyrylbenzene (2b) was prepared according to the above general procedure as a colorless oil with analytical
data in agreement with the literature.11b Run 1 ꢀ 0.035 g, 92% yield; Run 2 ꢀ 0.034 g, 89% yield; 1H NMR (400 MHz, CDCl3) δ
7.22ꢀ7.04 (9H, m), 6.66 (1H, d, J = 12.2 Hz), 6.63 (1H, d, J = 12.2 Hz), 2.28 (3H, s).
(Z)ꢀ1ꢀMethylꢀ3ꢀstyrylbenzene (2c) was prepared according to the above general procedure as a yellow liquid with analytical
data in agreement with the literature.8d Run 1 ꢀ 0.033 g, quant. yield; Run 2 ꢀ 0.038 g, quant. yield; 1H NMR (400 MHz, CDCl3)
δ 7.32ꢀ7.23 (6H, m), 7.17ꢀ7.11 (2H, m), 7.07 (1H, t, J = 7.7 Hz), 6.62 (2H, s), 2.31 (3H, s).
(Z)ꢀ4ꢀStyrylphenol (2d) was prepared according to the above general procedure with 15 mol% NiBr2 as a yellow solid with
1
analytical data in agreement with the literature.8e Run 1 ꢀ 0.041 g, quant. yield; Run 2 ꢀ 0.039 g, quant. yield; H NMR (400
MHz, CDCl3) δ 7.32ꢀ7.30 (4H, m), 7.28ꢀ7.23 (1H, m), 7.18 (2H, d, J = 8.6 Hz), 6.72 (2H, d, J = 8.6 Hz), 6.56 (2H, s), 4.80 (1H,
br s).
(Z)ꢀ1ꢀMethoxyꢀ4ꢀstyrylbenzene (2e) was prepared according to the above general procedure as an offꢀwhite solid with analytiꢀ
1
cal data in agreement with the literature.34 Run 1 ꢀ 0.046 g, quant. yield; Run 2 ꢀ 0.044 g, 100% yield; H NMR (400 MHz,
CDCl3) δ 7.33ꢀ7.22 (7H, m), 6.80 (2H, d, J = 8.7 Hz), 6.60ꢀ6.53 (2H, m), 3.83 (3H, s).
ACS Paragon Plus Environment

Page 11 of 18
The Journal of Organic Chemistry
(Z)ꢀ1ꢀ(Benzyloxy)ꢀ4ꢀstyrylbenzene (2f) was prepared according to the above general procedure with analytical data in agreeꢀ
1
2
1
ment with the literature.9f Run 1 ꢀ 0.058 g, quant. yield; Run 2 ꢀ 0.051 g, 89% yield; H NMR (400 MHz, CDCl3) δ 7.48ꢀ7.43
3
4
(5H, m), 7.33ꢀ7.22 (5H, m), 6.87 (2H, d, J = 8.5 Hz), 6.56 (2H, s), 5.08 (2H, s).
5
6
7
8
(Z)ꢀ3ꢀStyrylbenzonitrile (2g) was prepared according to the above general procedure as a yellow oil with analytical data in
1
agreement with the literature.35 Run 1 ꢀ 0.039 g, 98% yield; Run 2 ꢀ 0.042 g, quant. yield; H NMR (400 MHz, CDCl3) δ 7.55
9
(1H, s), 7.50 (2H, t, J = 8.3 Hz), 7.35 (1H, t, J = 7.8 Hz), 7.30ꢀ7.28 (3H, m), 7.23ꢀ7.21 (2H, m), 6.78 (1H, d, J = 12.2 Hz), 6.59
(1H, d, J = 12.2 Hz).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(Z)ꢀ1ꢀBromoꢀ4ꢀstyrylbenzene (2h) was prepared according to the above general procedure with 15 mol% NiBr2 as a yellow
solid with analytical data in agreement with the literature.34 Run 1 ꢀ 0.049 g, 98% yield; Run 2 ꢀ 0.050 g, quant. yield; 1H NMR:
(400 MHz, CDCl3) δ 7.34 (2H, d, J = 8.5 Hz), 7.24ꢀ7.20 (5H, m), 7.11 (2H, d, J = 8.5 Hz), 6.63 (1H, d, J = 12.2 Hz), 6.51 (1H,
d, J = 12.2 Hz).
(Z)ꢀMethyl 4ꢀstyrylbenzoate (2i) was prepared according to the above general procedure with 20 mol% NiBr2 as an offꢀwhite
1
solid with analytical data in agreement with the literature.11e Run 1 ꢀ 0.045 g, quant. yield; Run 2 ꢀ 0.043 g, quant. yield; H
NMR (400 MHz, CDCl3) δ 7.89 (2H, d, J = 8.1 Hz), 7.30 (2H, d, J = 8.1 Hz), 7.22 (5H, br s), 6.71 (1H, d, J = 12.2 Hz), 6.61
(1H, d, J = 12.2 Hz), 3.90 (3H, s).
(Z)ꢀNꢀAllylꢀNꢀ(3ꢀ(4ꢀmethoxyphenyl)allyl)ꢀ4ꢀmethylbenzenesulfonamide (2j) was prepared according to a slight modification of
the above general procedure on 0.1 mmol scale at 140 °C with 20 mol% NiBr2 as a 4:1 Z/E mixture; Run 1 ꢀ 0.031 g, 91%
yield; Run 2 ꢀ 0.028 g, 85% yield; 1H NMR (400 MHz, CDCl3, only (Z)ꢀisomer signals reported) δ 7.68 (2H, d, J = 8.2 Hz), 7.28
(2H, d, J = 8.0 Hz), 7.08 (2H, d, J = 8.6 Hz), 6.85 (2H, d, J = 8.6 Hz), 6.47 (1H, d, J = 11.7 Hz), 5.56 (1H, ddt, J = 16.9, 10.3,
6.5 Hz), 5.39 (1H, dt, J = 11.9, 6.2 Hz), 4.97 (1H, d, J = 10.5 Hz), 4.92 (1H, m), 4.09 (2H, d, J = 6.4 Hz), 3.81 (3H, s), 3.75
(2H, d, J = 6.3 Hz), 2.43 (3H, s); 13C NMR (125 MHz, CDCl3, only (Z)ꢀisomer signals reported) δ 158.8, 143.2, 137.4, 132.5,
131.9, 130.0, 129.7, 128.8, 127.3, 125.5, 119.0, 113.7, 55.3, 49.8, 44.6, 21.5; HRMS (ESI+) C20H23NO3S ([M+Na]+) found
380.1290; expected 380.1291 (+0.3 ppm).
(Z)ꢀPentaꢀ1,4ꢀdienꢀ1ꢀylbenzene (2k) was prepared according to the above general procedure at 140 °C with 15 mol% NiBr2 as
a colorless oil with analytical data in agreement with the literature.36 Run 1 ꢀ 0.025 g, 89% yield; Run 2 ꢀ 0.031 g, quant. yield;
1H NMR (400 MHz, CDCl3) δ 7.40ꢀ7.26 (5H, m), 6.58 (1H, d, J = 11.5 Hz), 5.97 (1H, ddt, J = 16.9, 10.4, 6.0 Hz), 5.76 (1H, dt,
J = 11.5, 7.6 Hz), 5.18 (1H, dd, J = 17.2, 1.6 Hz), 5.11 (1H, d, J = 10.4 Hz), 3.12 (2H, t, J = 6.7 Hz).
(Z)ꢀEthyl 3ꢀphenylacrylate (2l) was prepared according to the above general procedure as a colorless liquid with analytical
data in agreement with the literature.35 Isolated as a 3:1 Z/E isomer mixture; Run 1 ꢀ 0.045 g, quant. yield; Run 2 ꢀ 0.042 g,
1
quant. yield; H NMR (400 MHz, CDCl3, only (Z)ꢀisomer signals reported) δ 7.58 (2H, dd, J = 7.5, 1.7 Hz), 7.36ꢀ7.32 (3H, m),
6.95 (1H, d, J = 12.6 Hz), 5.95 (1H, d, J = 12.6 Hz), 4.18 (2H, q, J = 7.1 Hz), 1.24 (3H, t, J = 7.1 Hz).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 18
(Z)ꢀMethyl octꢀ2ꢀenoate (2m) was prepared according to the above general procedure as a colorless liquid with analytical data
in agreement with the literature.11c Run 1 ꢀ 0.018 g, 53% yield; Run 2 ꢀ 0.028 g, 82% yield; 1H NMR (400 MHz, CDCl3) δ 6.23
(1H, dt, J = 11.5, 7.5 Hz), 5.77 (1H, d, J = 11.5 Hz), 3.71 (3H, s), 2.65 (1H, qd, J = 7.4, 1.3 Hz), 1.45ꢀ1.42 (2H, m), 1.35ꢀ1.29
(5H, m), 0.88 (3H, t, J = 6.7 Hz).
1
2
3
4
5
6
7
8
(Z)ꢀPropꢀ1ꢀenꢀ1ꢀylbenzene (2n) was prepared according to the above general procedure at 140 °C with 20 mol% NiBr2 with
9
analytical data in agreement with the literature.8e Run 1 ꢀ 70% 1H NMR yield relative to 1,3,5ꢀtrimethoxybenzene (0.1 mmol) as
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
1
an internal standard; Run 2 ꢀ 84% H NMR yield relative to 1,3,5ꢀtrimethoxybenzene (0.1 mmol) as an internal standard; H
NMR (400 MHz, CDCl3) δ 7.43ꢀ7.22 (5H, m), 6.47 (1H, dd, J = 11.6, 1.7 Hz), 5.82 (1H, dq, J = 11.6, 7.2 Hz), 1.93 (3H, dd, J =
7.2, 1.8 Hz).
General Procedure for (E)-selective reduction To an oven dried 10 mL screwꢀtop vial equipped with a magnetic stirrer bar
was added the desired alkyne (0.20 mmol), zinc (1.0 mmol), NiCl2ꢀdme (10 mol%), triphos (10 mol%), 1,4ꢀdioxane (0.5 mL)
and HCO2H (1.0 mmol). The vial was then sealed, transferred to a heating block at 120 °C, and stirred rapidly (1200 rpm) at
this temperature for 16 h. After allowing to cool, the crude reaction mixture was filtered through a celite plug, the filter cake
washed with CH2Cl2 and the reaction mixture concentrated in vacuo to give the desired (E)ꢀalkene.
(E)ꢀStilbene (3a) was prepared according to the above general procedure as a white solid with analytical data in agreement
with the literature.11b Run 1 0.042 g, quant. yield; Run 2 0.047 g, quant. yield; 1H NMR (400 MHz, CDCl3) δ 7.59ꢀ7.56 (4H, m),
7.44ꢀ7.39 (4H, m), 7.34ꢀ7.29 (2H, m), 7.17 (2H, s).
(E)ꢀ1ꢀMethylꢀ2ꢀstyrylbenzene (3b) was prepared according to the above general procedure as a white solid with analytical
data in agreement with the literature.11b Run 1 ꢀ 0.038 g, quant. yield; Run 2 ꢀ 0.028 g, 74% yield; 1H NMR (400 MHz, CDCl3) δ
7.64 (1H, d, J = 7.0 Hz), 7.57 (2H, d, J = 7.4 Hz), 7.41 (1H, t, J = 7.6 Hz), 7.38 (1H, d, J = 16.2 Hz), 7.32 (1H, d, J = 7.4 Hz),
7.25ꢀ7.22 (4H, m), 7.05 (1H, d, J = 16.2 Hz), 2.44 (3H, s).
(E)ꢀ1ꢀMethylꢀ3ꢀstyrylbenzene (3c) was prepared according to the above general procedure as a white solid with analytical
data in agreement with the literature.37 Run 1 ꢀ 0.040 g, quant. yield; Run 2 ꢀ 0.043 g, quant. yield; 1H NMR (400 MHz, CDCl3)
δ 7.57 (2H, d, J = 7.2 Hz), 7.43ꢀ7.37 (4H, m), 7.31 (2H, t, J = 7.7 Hz), 7.15 (2H, s), 7.13 (1H, m), 2.44 (3H, s).
(E)ꢀ4ꢀStyrylphenol (3d) was prepared according to the above general procedure as a yellow solid with analytical data in
agreement with the literature.38 Run 1 ꢀ 0.034 g, 89% yield; Run 2 ꢀ 0.039 g, quant. yield; H NMR (400 MHz, CDCl3) δ 7.49
1
(2H, d, J = 8.1 Hz), 7.41 (2H, d, J = 8.1 Hz), 7.35 (2H, t, J = 7.4 Hz), 7.26ꢀ7.23 (1H, m), 7.05 (1H, d, J = 16.3 Hz), 6.97 (1H, d,
J = 16.3 Hz), 6.84 (2H, d, J = 8.0 Hz), 4.89 (1H, br s).
(E)ꢀ1ꢀMethoxyꢀ4ꢀstyrylbenzene (3e) was prepared according to the above general procedure as an offꢀwhite white solid with
analytical data in agreement with the literature.11b Run 1 ꢀ 0.049 g, quant. yield; Run 2 ꢀ 0.043 g, 99% yield; H NMR (400
1
ACS Paragon Plus Environment

Page 13 of 18
The Journal of Organic Chemistry
MHz, CDCl3) δ 7.51ꢀ7.46 (4H, m), 7.35 (2H, t, J = 7.6 Hz), 7.24 (1H, t, J = 7.3 Hz), 7.07 (1H, d, J = 16.3 Hz), 6.99 (1H, d, J =
1
16.3 Hz), 6.93ꢀ6.89 (2H, m), 3.84 (3H, s).
2
3
4
5
6
7
8
(E)ꢀ1ꢀ(Benzyloxy)ꢀ4ꢀstyrylbenzene (3f) was prepared according to the above general procedure as a yellow solid with analytiꢀ
1
cal data in agreement with the literature.39 Run 1 ꢀ 0.058 g, quant. yield; Run 2 ꢀ 0.064 g, quant. yield; H NMR (400 MHz,
9
CDCl3) δ 7.55ꢀ7.36 (14H, m), 6.95 (2H, m), 5.09 (2H, s).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(E)ꢀ1ꢀBromoꢀ4ꢀstyrylbenzene (3g) was prepared according to the above general procedure as a white solid with analytical
data in agreement with the literature.34 Run 1 ꢀ 0.042 g, 82% yield; Run 2 ꢀ 0.055 g, quant. yield; 1H NMR (400 MHz, CDCl3) δ
7.52ꢀ7.47 (4H, m), 7.39ꢀ7.35 (4H, m), 7.30ꢀ7.28 (1H, m), 7.10 (1H, d, J = 16.3 Hz), 7.04 (1H, d, J = 16.3 Hz).
(E)ꢀMethyl 4ꢀstyrylbenzoate (3h) was prepared according to the above general procedure as a white solid with analytical data
in agreement with the literature.34 Run 1 0.045 g, 94% yield; Run 2 0.047 g, 98% yield; 1H NMR (400 MHz, CDCl3) δ 8.07 (2H,
d, J = 8.3 Hz), 7.60 (4H, app. dd, J = 12.0, 8.0 Hz), 7.43 (2H, t, J = 7.5 Hz), 7.36ꢀ7.30 (1H, m), 7.26 (1H, d, J = 16.4 Hz), 7.18
(1H, d, J = 16.4 Hz), 3.97 (3H, s).
Ethyl cinnamate (3i) was prepared according to the above general procedure as a colorless liquid with analytical data in
agreement with the literature.35 Run 1 ꢀ 0.040 g, quant. yield; Run 2 ꢀ 0.042 g, quant. yield; 1H NMR (400 MHz, CDCl3) δ 7.69
(1H, d, J = 16.0 Hz), 7.54ꢀ7.52 (2H, m), 7.39ꢀ7.37 (3H, m), 6.45 (1H, d, J = 16.0 Hz), 4.27 (2H, q, J = 7.1 Hz), 1.34 (3H, t, J =
7.1 Hz).
(E)ꢀMethyl octꢀ2ꢀenoate (3j) was prepared according to the above general procedure as a 1:1 E/Z mix with analytical data in
1
agreement with the literature.36 Run 1 ꢀ 0.047 g, quant. yield; Run 2 ꢀ 0.047 g, quant. yield; H NMR (400 MHz, CDCl3, a 1:1
E/Z mixture – only the characteristic (E)ꢀolefinic protons are reported) δ 7.01 (1H, dt, J = 15.6, 7.0 Hz), 5.86 (1H, d, J = 15.6
Hz).
(E)ꢀPentaꢀ1,4ꢀdienꢀ1ꢀylbenzene (3k) was prepared according to the above general procedure as a 3:1 E/Z mixture with analytꢀ
1
ical data in agreement with the literature.40 Run 1 ꢀ 0.061 g, quant. yield; Run 2 ꢀ 0.050 g, 87% yield; H NMR (400 MHz,
CDCl3, a 3:1 E/Z mixture – only the characteristic (E)ꢀolefinic protons are reported) δ 6.41 (1H, dt, J = 15.9, 1.4 Hz), 6.22 (1H,
dt, J = 15.9, 6.7 Hz).
General Procedure for Terminal Alkyne Reduction To an oven dried 10 mL screwꢀtop vial equipped with a magnetic stirrer
bar was added the desired alkyne (0.20 mmol), zinc (1.0 mmol), NiBr2 (10 mol%), THF (0.5 mL) and HCO2H (1.0 mmol). The
vial was then sealed, transferred to a heating block at 80 °C, and stirred rapidly (1200 rpm) at this temperature for 16 h. After
allowing to cool, the crude reaction mixture was filtered through a celite plug, the filter cake washed with CH2Cl2 and the reacꢀ
tion mixture concentrated in vacuo to give the desired alkene.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 18
Styrene (4a) was prepared from phenylacteylene according to the above general procedure to give a colorless oil with analytiꢀ
cal data in agreement with a commercially available sample; Run 1: 0.009 g, 45% yield; Run 2: 0.021 g, quant. yield; 1H NMR:
(400 MHz, CDCl3) δ 7.41 (2H, d, J = 7.5 Hz), 7.33 (2H, t, J = 7.4 Hz), 7.27ꢀ7.26 (1H, m), 6.72 (1H, dd, J = 17.6, 10.9 Hz), 5.75
(1H, d, J = 17.6 Hz), 5.25 (1H, d, J = 10.9 Hz).
1
2
3
4
5
6
7
8
9
NꢀAllylꢀ4ꢀmethylꢀNꢀphenylbenzenesulfonamide (4b) was prepared according to the above general procedure as an offꢀwhite
solid with analytical data in agreement with the literature.41 Run 1 ꢀ 0.050 g, 86% yield; Run 2 ꢀ 0.054 g, 93% yield; mp 65 °C
{lit. 69 °C}; 1H NMR (400 MHz, CDCl3) δ 7.53 (2H, d, J = 8.1 Hz), 7.33ꢀ7.28 (5H, m), 7.08 (2H, app. dd, J = 7.4, 1.8 Hz), 5.78
(1H, ddt, J = 16.8, 10.4, 6.4 Hz), 5.13ꢀ5.07 (2H, m), 4.22 (2H, d, J = 6.2 Hz), 2.47 (3H, s).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N,NꢀDiallylꢀ4ꢀmethylbenzenesulfonamide (4c) was prepared according to the above general procedure to give a colorless oil
with analytical data in agreement with the literature.42 Run 1 ꢀ 0.052 g, quant. yield; Run 2 ꢀ 0.044 g, 88% yield; 1H NMR (400
MHz, CDCl3) δ 7.71 (2H, d, J = 8.1 Hz), 7.30 (2H, d, J = 8.1 Hz), 5.66ꢀ5.56 (2H, m), 5.15ꢀ5.12 (4H, m), 3.80 (4H, d, J = 6.1
Hz), 2.43 (3H, s).
2ꢀMethoxyꢀ6ꢀvinylnaphthalene (4d) was prepared according to the above general procedure as a white solid with analytical
data in agreement with the literature.43 Run 1 ꢀ 0.037 g, quant. yield; Run 2 ꢀ 0.040 g, quant. yield; 1H NMR (400 MHz, CDCl3)
δ 7.72 (3H, m), 7.61 (1H, dd, J = 8.8, 1.3 Hz), 7.15ꢀ7.12 (2H, m), 6.85 (1H, dd, J = 17.6, 10.9 Hz), 5.82 (1H, d, J = 17.6 Hz),
5.28 (1H, d, J = 10.9 Hz), 3.92 (3H, s).
(8R,9S,13S,14S,17R)ꢀ13ꢀMethylꢀ17ꢀvinylꢀ7,8,9,11,12,13,14,15,16,17ꢀdecahydroꢀ6Hꢀcyclopenta[a]phenanthreneꢀ3,17ꢀdiol (4e)
was prepared according to the above general procedure as a white solid with analytical data in agreement with the literature.37
Run 1 ꢀ 0.046 g, 77% yield; Run 2 ꢀ 0.059 g, 98% yield; 1H NMR (400 MHz, MeOD) δ 7.06 (1H, d, J = 8.3 Hz), 6.53 (1H, dd, J
= 8.3, 2.6 Hz), 6.48 (1H, br s), 6.11 (1H, dd, J = 17.3, 10.9 Hz), 5.16 (1H, dd, J = 17.3, 1.5 Hz), 5.11 (1H, dd, J = 10.9, 1.5 Hz),
3.33ꢀ3.31 (2H, m), 2.80ꢀ1.30 (13H, m), 0.94 (3H, s).
NꢀAllylꢀ4ꢀmethylꢀNꢀ(pentꢀ2ꢀynꢀ1ꢀyl)benzenesulfonamide 4f was prepared according to the above general procedure as a colorꢀ
1
less oil with analytical data in agreement with the literature.31 Run 1 ꢀ 0.057 g, quant. yield; Run 2 ꢀ 0.034 g, 61% yield; H
NMR (400 MHz, CDCl3) δ 7.74 (2H, d, J = 8.1 Hz), 7.29 (2H, d, J = 8.1 Hz), 5.74 (1H, ddt, J = 17.0, 10.2, 6.5 Hz), 5.27 (1H, d,
J = 17.0 Hz), 5.22 (1H, d, J = 10.2 Hz), 4.05 (2H, s), 3.80 (2H, d, J = 6.4 Hz), 2.42 (3H, s), 1.92 (2H, q, J = 7.5 Hz), 0.90 (3H, t,
J = 7.5 Hz).
ASSOCIATED CONTENT
Supporting Information
ACS Paragon Plus Environment

Page 15 of 18
The Journal of Organic Chemistry
Supporting Information including reaction optimization details and spectra is also provided. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
2
3
4
5
AUTHOR INFORMATION
6
7
Corresponding Author
8
9
* moran@unistra.fr
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACKNOWLEDGMENT
This work was supported in part by a LabEx CSC “Chemistry of Complex Systems” grant. E.R. thanks the
Leverhulme Trust for a fellowship.
REFERENCES
[1] (a) Lindlar, H. Helv. Chim. Acta 1952, 35, 446ꢀ450. (b) Lindlar, H.; Dubuis, R. Org. Synth. 1966, 46, 89.
[2] (a) Fürstner, A.; Guth, O.; Rumbo, A.; Siedel, G. J. Am. Chem. Soc. 1999, 121, 11108ꢀ11113. (b) M. Fouche, L. Rooney, A. G.
M. Barrett J. Org. Chem. 2012, 77, 3060ꢀ3070.
[3] (a) Ulan, J. G.; Maier, W. F.; Smith, D. A. J. Org. Chem. 1987, 52, 3132ꢀ3142. (b) Kluwer, A. M.; Koblenz, T. S.; Jonischkeit, T.;
Woelk, K.; Elsevier, C. J. J. Am. Chem. Soc. 2005, 127, 15470ꢀ15480.
[4] van Laren, M. W.; Elsevier, C. J. Angew. Chem. Int. Ed 1999, 38, 3715ꢀ3717.
[5] For further heterogeneous catalysts based on Pd, see: (a) Li, J.; Hua R.; Liu, T. J. Org. Chem. 2010, 75, 2966ꢀ2970. (b) Slack,
E. D.; Gabriel, C. M.; Lipshutz, B. H. Angew. Chem., Int. Ed. 2014, 126, 14275ꢀ14278. For Ni, see: (c) Brown, C. A. J. Org. Chem.
1970, 35, 1900ꢀ1904. (d) Alonso, F.; Osante, I.; Yus, M. Adv. Synth. Catal. 2006, 348, 305ꢀ308. (e) Alonso, F.; Osante, I.; Yus, M.
Tetrahedron 2007, 63, 93ꢀ102. For Au, see: (f) Yan, M.; Jin, T.; Ishikawa, Y.; Minato, T.; Fujita, T.; Chen, LꢀY.; Bao, M.; Asao, N.;
Chen, MꢀW.; Yamamoto, Y. J. Am. Chem. Soc. 2012, 134, 17536ꢀ17542. (g) Wag, Y. S.; Asao, N. J. Org. Chem. 2015, 80, 847ꢀ851.
[6] For a comprehensive review of the area see: Oger, C.; Balas, L.; Durand, T.; Galano, J.ꢀM. Chem. Rev. 2013, 113, 1313ꢀ1350
and references therein.
[7] For selected examples of transition metalꢀcatalyzed (Z)ꢀselective alkyne hydrogenations, see: (a) Schrock, R. R.; Osborn, J. A.
J. Am. Chem. Soc. 1976, 98, 2143ꢀ2147. (b) Blum, Y.; Czarkie, D.; Rahamim, Y.; Shvo, Y. Organometallics 1985, 4, 1459ꢀ1461. (c)
van Laren, M. W.; Elsevier, C. J. Angew. Chem., Int. Ed. Engl. 1999, 38, 3715ꢀ3717. (d) Kluwer, A. M.; Koblenz, T. S.; Jonischkeit, T.;
Woelk, K.; Elsevier, C. J. J. Am. Chem. Soc. 2005, 127, 15470ꢀ15480. (e) La Pierre, H. S.; Arnold, J.; Toste, F. D. Angew. Chem. Int.
Ed. 2011, 50, 3900ꢀ3903.
[8] For transition metalꢀcatalyzed, (Z)ꢀselective alkyne semiꢀreductions using silanes, see: (a) Trost, B. M.; Braslau, R. Tetrahedron
Lett. 1989, 30, 4657ꢀ4660. (b) Semba, K.; Fujihara, T.; Xu, T.; Terao, J.; Tsuji, Y. Adv. Synth. Catal. 2012, 354, 1542ꢀ1550. (c) Whitꢀ
taker, A. M.; Lalic, G. Org. Lett. 2013, 15, 1112ꢀ1115. (d) Enthaler, S.; Haberberger, M.; Irran, E. Chem. Asian J. 2011, 6, 1613ꢀ1623.
(e) Wang, GꢀH.; Bin, HꢀY.; Sun, M.; Chen, SꢀW.; Liu, JꢀH.; Zhong, CꢀM. Tetrahedron, 2014, 70, 2175-2179. NaBH4 has been emꢀ
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 18
ployed in a similar fashion: (f) Choi, J.; Yoon, N.ꢀM. Tetrahedron Lett. 1996, 37, 1057ꢀ1060. (g) Lee, S. E.; Vyle, J. S.; Williams, D. M.;
Grasby, J. A. Tetrahedron Lett. 2000, 41, 267ꢀ270.
1
2
3
4
5
6
7
8
9
[9] For transition metalꢀcatalyzed, (Z)ꢀselective alkyne semiꢀreductions using HCO2H or HCO2H generated in situ, see: (a) Tani, K.;
Ono, N.; Okamoto, S.; Sato, F. J. Chem. Soc., Chem. Commun. 1993, 386ꢀ387. (b) Hauwert, P.; Maestri, G.; Sprengers, J. W.; Caꢀ
tellani, M.; Elsevier, C. J. Angew. Chem. Int. Ed. 2008, 47, 3223ꢀ3226. (c) Belger, C.; Neisius, N. M.; Plietker, B. Chem. Eur. J. 2010,
16, 12214ꢀ12220. (d) Broggi, J.; Jurcik, V.; Songis, O.; Poater, A.; Cavallo, L.; Slawin, A. M. Z.; Cazin, C. S. J. J. Am. Chem. Soc.
2013, 135, 4588−4591. (e) Drost, R. M.; Bouwens, T.; van Leest, N. P.; de Bruin, B.; Elsevier, C. J. ACS Catal. 2014, 4, 1349ꢀ1357.
(f) Li, J.; Jua, R.; Liu, T. J. Org. Chem. 2010, 75, 2966ꢀ2970.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[10] For (E)ꢀselective reductions catalyzed by Rh see: (a) Burch, R. R.; Muetterties, E. L.; Teller, R. G.; Williams, J. M. J. Am.
Chem. Soc. 1982, 104, 4257ꢀ4258. For Ru see: (b) Trost, B. M.; Ball, Z. T.; Joege, T. J. Am. Chem. Soc. 2002, 124, 7922ꢀ7923. (c)
Fürstner, A. Radkowski, K. Chem. Commun. 2002, 2182ꢀ2183. (d) Radkowski, K.; Sundaraju, B.; Fürstner, A. Angew. Chem. Int. Ed.
2013, 52, 355ꢀ360. (e) Michaelides, I. N.; Dixon, D. J. Angew. Chem., Int. Ed. 2013, 52, 806ꢀ808. For Ir see: (f) Tani, K.; Iseki, A.;
Yamagata, T. Chem. Commun. 1999, 1821ꢀ1822. For Ni see: (g) Chen, T.; Xiao, J.; Zhou, Y.; Yin, S.; Han, LꢀB. J. Organomet. Chem.
2014, 749, 51ꢀ54. For Fe see: (h) Srimani, D. DiskinꢀPosner, Y.; BenꢀDavid, Y.; Milstein, D. Angew. Chem. Int. Ed. 2013, 52, 14131ꢀ
14134. For reduction with Na2S see: (i) Chen, Z.; Luo, M.; Wen, Y.; Luo, G.; Liu, L. Org. Lett. 2014, 16, 3020ꢀ3023.
[11] For catalytic reduction systems that offer switchable (E)/(Z) selectivity under similar reaction conditions, see: (a) Barriosꢀ
Francisco, R.; Garcia, J. J. Inorg. Chem. 2009, 48, 386ꢀ393. (b) Luo, F.; Pan. C.; Wang, W.; Ye. Z.; Cheng, J. Tetrahedron, 2010,
1399ꢀ1403. (c) Shen, R.; Chen, T.; Zhao, Y.; Qiu, R.; Zhou, Y.; Yin, S.; Wang, X.; Goto, M. Han, LꢀB. J. Am. Chem. Soc. 2011, 133,
17037ꢀ17044. (d) Li, J.; Hua, R. Chem. Eur. J. 2011, 17, 8462ꢀ8465. (e) Schabel, T.; Belger, C.; Plietker, B. Org. Lett. 2013, 15,
2858ꢀ2861. (f) Liu, Y.; Hu, L.; Chen, H.; Du, H. Chem. Eur. J. 2015, 21, 3495ꢀ3501.
[12] For examples of (E)ꢀ or (Z)ꢀ selective alkyne semiꢀreductions via a twoꢀstep hydrosilylation/desilylation procedure, see: (a)
Yong, L.; Kirleis, K.; Butenschoen, H. Adv. Synth. Catal. 2006, 348, 833ꢀ836. (b) Belger, C.; Plietker, B. Chem. Commun. 2012, 48,
5419ꢀ5421.
[13] Wolf, E.; Richmond, E.; Moran, J. Chem. Sci. 2015, 6, 2501ꢀ2505.
[14] For reviews on transitionꢀmetal catalyzed cycloisomerizations, see (a) Trost, B. M; Krische, M. J. Synlett 1998, 1ꢀ16. (b) Lloydꢀ
Jones, G. C. Org. Biomol. Chem. 2003, 1, 215ꢀ236. (c) Aubert, C.; Fensterbank, L.; Garcia, P.; Malacria, M.; Simonneau, A. Chem.
Rev. 2011, 111, 1954ꢀ1993. (d) Yamamoto, Y. Chem. Rev. 2012, 112, 4736ꢀ4769. For selected nickelꢀcatalyzed examples of eneꢀ
yne cycloisomerization, see (e) Radetich, B.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120, 8007ꢀ8008. (f) Ikeda, Sꢀi.; Daimon, N.;
Sanuki, R.; Odashima, K. Chem. Eur. J. 2006, 12, 1797ꢀ1806. (g) Boeing, C.; Hahne, J.; Francio, G.; Leitner, W. Adv. Synth. Catal.
2008, 350, 1073ꢀ1080. (h) Chen, M.; Weng, Y.; Guo, M.; Zhang, H.; Lei. A. Angew. Chem. Int. Ed. 2008, 47, 2279ꢀ2282.
[15] (a) Iyer, S.; Sattar, A. K. Synth. Commun. 1998, 28, 1721ꢀ1725. (b) Ram, S.; Ehrenkaufer, R. E. Synthesis, 1998, 91ꢀ95.
[16] For recent examples of nickel catalyzed transfer hydrogenation using HCO2H see: (a) Yang, P.; Xu, H.; Zhou, J. Angew.
Chem. Int. Ed. 2014, 53, 122210ꢀ12213. (b) Xu, H.; Yang, P.; Chuanprasit, P.; Hirao, H.; Zhou, J. Angew. Chem. Int. Ed. 2015, 54,
5112ꢀ5116.
[17] Previous NiCl2/zinc reductions of a variety of functional groups have been disclosed: Nose, A.; Kudo, T. Chem. Pharm. Bull.
1990, 38, 2097ꢀ2101, however to the best of our knowledge not with alkynes.
ACS Paragon Plus Environment

Page 17 of 18
The Journal of Organic Chemistry
1
[18] Greater than 95:5 (E)ꢀ or (Z)ꢀselectivity is assigned on the basis of being unable to detect the minor geometric isomer by H
NMR analysis. In addition, GCꢀMS analysis of crude olefin (Z)ꢀ2a (tR 5.53 min) also revealed <5% of the (E)ꢀolefin isomer. Similarly,
GCꢀMS analysis of crude olefin (E)ꢀ3a (tR 6.30 min) showed no residual (Z)ꢀolefin, and <5% of overꢀreduced alkane.
[19] (a) Oikawa, Y.; Tanaka, T.; Horita, K.; Yonemitsu, O. Tetrahedron Lett. 1984, 25, 5397ꢀ5400. (b) Caddick, S.; Judd, D. B.;
Lewis, A. K. de K.; Reich, M. T.; Williams, M. R. V. Tetrahedron, 2003, 59, 5417ꢀ5423.
[20] Molander, G. A.; Cavalcanti, L. N.; GarciaꢀGarcia, C. J. Org. Chem. 2013, 78, 6427ꢀ6439.
[21] For examples of transitionꢀmetal catalyzed E/Z olefin isomerization see: (a) Yu, J.; Gaunt, M.; Spencer, J. B. J. Org. Chem.
2002, 67, 4627ꢀ4629. (b) Kim, I. S.; Dong, G. R.; Jung, Y. H. J. Org. Chem. 2007, 72, 5424ꢀ5426. (c) Canovese, L.; Santo, C.; Visenꢀ
tin, F. Organometallics 2008, 27, 3577ꢀ3581. (d) Gauthier, D.; Lindhart, A. T.; Olsen, E. P. K.; Overgaard, J.; Skyrdstrup, T. J. Am.
Chem. Soc. 2010, 132, 7998ꢀ8009. (e) Tan, E. H. P.; LloydꢀJones, G. C.; Harvey, J. N.; Lennox, A. J. J.; Mills, B. M. Angew. Chem.
Int. Ed. 2011, 50, 9602ꢀ9606.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[22] Chatzopoulou, E.; Davies, P. W. Chem. Comm. 2013, 49, 8617ꢀ8619.
[23] Gallop, C. W. D.; Chen, M.ꢀT.; Navarro, O. Org. Lett. 2014, 16, 3724ꢀ3727.
[24] Sagadevan, A.; Hwang, K. C. Adv. Synth. Catal. 2012, 18, 3421ꢀ3427.
[25] Liang, B.; Dai, M.; Chen, J.; Yang, Z. J. Org. Chem. 2005, 70, 391ꢀ393.
[26] Monnier, F.; Turtaunt, F.; Duroure, L.; Taillefer, M. Org. Lett. 2008, 10, 3203ꢀ3206.
[27] Huang, H.; Jiang, H.; Chen, K.; Liu, H. J. Org. Chem. 2008, 73, 9061ꢀ9064.
[28] Bizier, N. P.; Wackerly, J. W.; Braunstein, E. D.; Zhang, M.; Nodder, S. T.; Carlin, S. M.; Katz, J. L. J. Org. Chem. 2013, 78,
5987ꢀ5998.
[29] Sylvester, K. T.; Chirik, P. J. J. Am. Chem. Soc. 2009, 131, 8772ꢀ8774.
[30] Lin, A.; Zhang, Z.ꢀW.; Yang, J. Org. Lett. 2014, 16, 386ꢀ389.
[31] Ota, K.; Lee, S. I.; Tang, JꢀM.; Takachi, M. Nakai, H.; Morimoto, T.; Sakurai, H.; Kataoka, K.; Chatani, N. J. Am. Chem. Soc.
2009, 131, 15203ꢀ15211.
[32] Barluenga, J.; Fananas, F. J.; Sanz, R.; Marcos, C.; Ignacio, J. M. Chem. Comm. 2005, 933ꢀ935.
[33] Lee, S. I.; Park, S. Y.; Chung, Y. K. Adv. Synth. Catal. 2006, 348, 2531ꢀ2539.
[34] Cella, R.; Stefani, H. A. Tetrahedron, 2006, 62, 5656ꢀ5662.
[35] Ito, Y.; Kajita, T.; Kunimoto, K.; Mastuura, T. J. Org. Chem. 1989, 54, 587ꢀ591.
[36] Lee, KꢀY.; Kim, HꢀS.; Mo, JꢀT.; Lee, PꢀH. Chem. Asian J. 2011, 6, 2147ꢀ2157
[37] Sarkar, S.; Jana, M.; Tadigoppula, N. RSC Advances, 2013, 3, 18755ꢀ18758.
[38] Cui, X.; Li, Z.; Tao, CꢀZ.; Xu, Y.; Li, J.; Liu, L.; Guo, QꢀX. Org. Lett. 2006, 8, 2467ꢀ2470.
[39] Patel, K. N.; Kamath, B. V.; Bedekar, A. V. Tetrahedron Lett. 2013, 54, 80ꢀ84.
[40] Krasovskiy, A. L.; Haley, S.; Voigtritter, K.; Lipshutz, B. H. Org. Lett. 2014, 16, 4066ꢀ4069.
[41] Carnahan, F. L.; Hurd, C. D. J. Am. Chem. Soc. 1930, 52, 4586ꢀ4595.
[42] Lipshutz, B. H.; Ghorai, S. Org. Lett. 2009, 11, 705ꢀ708.
[43] Yabe, Y.; Yamada, T.; Nagata, S.; Sawama, Y.; Monguci, Y.; Sajiki, H. Adv. Synth. Catal. 2012, 354, 1264ꢀ1268.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 18
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
18
ACS Paragon Plus Environment