Palladium-Catalyzed Decarboxylative Benzylation of Acetylides and Enolates

Article abstract of DOI:10.1055/s-0037-1609575

Benzylic alkylation of enolates and acetylides has been achieved through the use of a decarboxylative benzylation strategy. Previous research in this area is often limited by the need for extended conjugation in the electrophiles that are coupled. Herein, we report that the use of 1,1'-bis(diphenylphosphino)ferrocene (dppf) ligand allows the coupling of simple benzyl electrophiles with enolates, while the use of XPhos ligand promotes the decarboxylative couplings of propiolates.

Full text of DOI:10.1055/s-0037-1609575

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–L
special topic
A
en
R. R. P. Torregrosa et al.
Special Topic
Synthesis
Palladium-Catalyzed Decarboxylative Benzylation of Acetylides
and Enolates
PPh2
Robert R. P. Torregrosa
O
O
O
Pd
Fe
Shehani N. Mendis
Alex Davies
PPh2
O
R
R
R
R
R R
Jon A. Tunge*
EDG
EDG
– CO2
35 examples
13–98% yield
The University of Kansas, 2010 Malott Hall, 1251 Wescoe Hall
Dr., Lawrence, KS 66045, USA
tunge@ku.edu
PCy2
i-Pr
i-Pr
Published as part of the Special Topic Modern Coupling
Approaches and their Strategic Applications in Synthesis
Pd
O
i-Pr
R
O
R
R
– CO2
33 examples
24–97% yield
R
Received: 15.05.2018
Accepted after revision: 14.06.2018
Published online: 30.07.2018
the use of preformed organometallics that are more strong-
ly basic.3 Alternatively, decarboxylative benzylation can be
an effective strategy for coupling poorly stabilized nucleo-
philes (pKa ~ 17–29) under formally neutral conditions,
without the need for preformed organometallics (Scheme
1).4,5 For example, we previously communicated the decar-
boxylative arylmethylation of alkynes and ketones under
conditions of palladium catalysis.4a Those studies revealed
that, in general, PBu3 was the best ligand for arylmethyla-
tion of enolates, while Pd(PPh3)4 was the superior catalyst
for arylmethylation of acetylides.6 However, attempts to
couple benzylic electrophiles that lacked extended conjuga-
tion provided only a single successful enolate benzylation
and completely failed to engage in alkyne coupling (Scheme
1). Herein, we report more extensive studies that have re-
sulted in identification of alternative ligands for decarbox-
ylative benzylations.
Previously reported results showed that decarboxylative
arylmethylation of enolates derived from β-keto esters with
Pd/PBu3 was limited to arylmethyl electrophiles that have
extended π-conjugation, while use of 1,1'-bis(diphenyl-
phosphino)ferrocene (dppf) as a ligand provided a single
example of a benzylation from a p-methoxybenzyl ester.4a
Thus, we chose to further investigate dppf as a ligand for
DOI: 10.1055/s-0037-1609575; Art ID: ss-2018-c0342-st
Abstract Benzylic alkylation of enolates and acetylides has been
achieved through the use of a decarboxylative benzylation strategy.
Previous research in this area is often limited by the need for extended
conjugation in the electrophiles that are coupled. Herein, we report
that the use of 1,1'-bis(diphenylphosphino)ferrocene (dppf) ligand al-
lows the coupling of simple benzyl electrophiles with enolates, while
the use of XPhos ligand promotes the decarboxylative couplings of
propiolates.
Key words decarboxylative coupling, acetylide, enolate, benzylation,
palladium
Catalytic benzylic alkylation is a useful strategy for the
introduction of aromatics into bioactive compounds and
their precursors.1,2 Pioneering efforts showed that catalytic
alkylations of benzylic esters could be utilized to avoid the
use of benzyl halides, which are hazardous, corrosive and
lachrymatory. However, the lower reactivity of benzyl es-
ters relative to benzyl halides meant that the reactant ben-
zyl electrophiles typically required extended π-conjugation
for high-yielding reaction.1b–e Moreover, most couplings
have utilized stabilized nucleophiles (pKa < 17)1 or require
O
cat
Pd/PBu3
cat
Pd(PPh3)4
Me
O
Me
Nu
O
Ar
– CO2
– CO2
TMS
EtO
N
cat
Pd(PPh3)4
77%
O
90%
Ph
OMe
No reaction
Scheme 1 Prior catalytic decarboxylative benzylation
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

B
R. R. P. Torregrosa et al.
Special Topic
Synthesis
O
O
O
CpPd(allyl) (10 mol%)
dppf (11 mol%)
R3
O
O
R3
R1 R2
R1 R2
toluene, 110 °C, 15 h
O
MeO
MeO
O
O
O
Ar
Ar
Ar
R3
Ar
Ar
1a 52%
1e R3 = OMe, NR
1f R3 = OCH2CF3 30%a
1d 55%
1b 63%
1c 52%
O
O
O
O
O
O
Ar
Ar
Ar
Ar
Ar
Ar
Ph
Bn
O
O
Et
O
OEt
1g 61%
1h 49%
1i 59%
1j 41%
1k 42%
1l 63%
O
O
O
O
O
O
Ar
Ar
Ar
Ar
Ar
R
Bn Bn
Ar
R
Bn
R
Me
1r 56%
1m 98%
1n R = Me: 59%
1o R = allyl: 56%
1p R = Me, 67%
1q R = Bn, 80%
1s 74%
1t R = Me, 53%
1u R = Bn, 48%
Scheme 2 Decarboxylative benzylation of enolates with dppf-ligated Pd. a Di- and tribenzyl trifluoromethyl ester were also isolated in 10% and 16%
yields, respectively.
enolate benzylation. Treatment of a variety of p-methoxy-
benzyl β-keto esters with 10 mol% CpPd(allyl) and 11 mol%
diphenylphosphinoferrocene (dppf) in toluene at 110 °C,
produced the corresponding α-benzylated ketones in mod-
erate to good yields (Scheme 2). For example α-unsubstitut-
ed β-keto esters underwent decarboxylative coupling to
give alkyl and aryl ketones in moderate yields. Unfortunate-
ly, a methyl ester derivative (R3 = OMe) was unreactive un-
der these conditions; however, the more activated trifluoro-
ethyl ester did provide a low yield of the α-benzylated es-
ter.7 α-Monosubstituted β-keto esters also provided the
product in moderate yield. Finally, α,α-disubstituted β-keto
esters, including cyclic ketones, were able to undergo decar-
boxylative coupling to furnish the α-quaternary benzylated
ketones in moderate to good yield.
O
O
O
CpPd(allyl) (10 mol%)
dppf (11 mol%)
Ar
O
Ar
R
R
toluene, 110 °C
R
R
O
O
O
O
MeO
MeO
O
O
X
Bn
2f 61%
Bn
Bn
Bn
Bn
Bn
Bn Bn
1m p-OMe 98%
2a m-OMe 80%
2b o-OMe NR
2c H 47%a
2g 72%
2h 51%
O
O
O
2d p-CN 23%
2e p-NO2 13%
Bn
Bn
Bn
Bn
N
O
OEt
2j 62%
2k 57%
2i 74%
O
O
O
O
S
Bn
N
Bn
Bn
Bn
Me Me
N
N
Boc
2n 75%
2l 59%
2o 67%
2m 75%
Scheme 3 Scope of benzyl electrophiles. a Impure product, inseperable from protonated ketone.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

C
R. R. P. Torregrosa et al.
Special Topic
Synthesis
O
CpPd(allyl) (5 mol%)
dppf (6 mol%)
Ar
O
Ar
toluene, 110 °C
Ph
Ph
Ph
Ph
Ph
Ph
C5H11
MeO
3a 97% (89)a
3b 78% (78)a
3c 88% (74)
3d 90% (78)
O
Ph
Ph
Ph
N
MeO
N
3e 81% (87)a
3f 89% (90)
3g 88% (75)
3h 88% (74)a
MeO
Ph
TMS
N
Cl
N
Ph
N
3i 87%
3j NRa
3k NR
Scheme 4 Decarboxylative acetylide coupling with dppf ligand. a 10 mol% CpPd(allyl), 11 mol% dppf. b Numbers in parentheses indicate % yield using 5
mol% Pd(PPh3)4.
Next, we assessed the scope of benzyl electrophiles that
are compatible with the dppf-Pd catalyst system. Examina-
tion of the p-substituent effect on the reactivity shows that
a relatively electron-rich benzyl electrophile is required for
efficient decarboxylative coupling. This likely results from
the low stability of the electron-poor π-benzyl intermedi-
O
Pd2dba3 (5 mol%)
XPhos (20 mol%)
Ar
Ar
O
R
R
toluene, 110 °C, 15 h
MeO
O
O
Ph
Ph
Ph
Ph
p-5a 94%
m-5b 67%
o-5c 81%
TMS
5d 95%
5e 81%
5f 97%
O2N
O
F
Ph
Ph
Ph
Me
N
Ph
NC
F
O
H
5h 62%
5g 71%
5i 59%
p-5j 43%
m-5k 24%
TMS
TMS
TMS
N
Ph
O2N
OMe
F
F
NO2
NO2
OMe
5l 31%
5m 70%
5n 90%
5o 47%
TMS
TMS
Ph
Ph
MeO
MeO
OMe
N
Br
5p 25%
5q 94%
5r 81%
5s NR
N
S
N
Boc
N
X
N
Ph
Ph
O
O
Me
Ph
Ph
X = O 5t 79%
X = S 5u 81%
Ph
5v 81%
5w 91%
5x 45%
5y NR
Scheme 5 Decarboxylative acetylide coupling with XPhos ligand
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

D
R. R. P. Torregrosa et al.
Special Topic
Synthesis
O
O
Pd (10 mol%)
ligand (20 mol%)
Ph
Ph
MeO
4a
5a
toluene, 110 °C, 15 h
MeO
PPh2
PPh2
PCy2
PCy2
OMe
PCy2
iPr
Fe
MeO
iPr
CpPd(allyl)
0% conversion
CpPd(allyl) (10 mol%)
72%
XPhos
SPhos
iPr
Pd2dba3 (5 mol%)
77%
Pd2dba3 (5 mol%)
94%
Pd2dba3 (5 mol%)
63%
Equation 1 Ligands for acetylide coupling
ates, making the oxidative addition of the ester more diffi-
cult. While a p-alkoxy group facilitates oxidative addition,
the o-methoxy group completely inhibits the reaction.
Thus, reaction of substituted benzyl esters appears limited
to those with electron donors in the p- or m-position. How-
ever, substrates with that substitution pattern did result in
successful decarboxylative coupling (2f–h; Scheme 3). The
dppf ligand also proved capable of coupling naphthyl-,
quinolinyl-, indolyl-, and thiophenyl-methyl electrophiles
to furnish the arylmethylated coupounds 2i–o in moderate
to good yield.
The success in coupling a wider array of benzyl electro-
philes with enolates using dppf as a ligand inspired us to in-
vestigate the scope of alkyne decarboxylative benzylation
(DcB) using dppf as a ligand. Dppf indeed proved to be an
effective ligand for coupling of arylmethyl electrophiles that
have extended conjugation and, in most cases, provided
products in higher yield than our previous conditions
(Scheme 4).
Unfortunately, dppf failed as a ligand for the benzylation
of an acetylide with an electrophile that lacked extended
conjugation (4a, Eq. 1). Buchwald, and later Li, reported that
benzyl chlorides can undergo couplings in the presence of
XPhos-ligated palladium.6 While Li’s observation that ben-
zyl acetates were unreactive under these conditions was
somewhat discouraging,6c propiolates should be superior
leaving groups due to the inductive withdrawal of the
alkyne substituent. Thus, we chose to investigate the decar-
boxylative coupling with various Buchwald type ligands
(Equation 1). Ultimately, we chose the combination of
Pd2dba3/XPhos catalyst for DcB of simple benzyl propio-
lates.
with simple benzyl electrophiles are even more challeng-
ing, but the dppf ligand has been shown to allow a larger
scope of electrophiles to be coupled relative to our previous
disclosure of PBu3 as a ligand.
Toluene and THF were dried over sodium in the presence of benzo-
phenone indicator. CH2Cl2 and Et2O were dried over activated alumina
on a solvent system purchased from Innovative Technologies, Inc. Pd
catalysts and ligands were purchased from Strem and Sigma–Aldrich.
Other reagents and solvents were also obtained commercially and
used without additional purification. K2CO3 was activated with a mi-
crowave prior to use. CpPd(allyl) was prepared according to a report-
ed procedure.8 The isolated products were purified on silica gel from
Sorbent Technologies (40–63 μm particle size, 60 Å porosity, pH 6.5–
7.5). 1H and 13C NMR spectra were obtained with a Bruker Avance 400
or 500 MHz DRX spectrometer and were referenced to residual protio
solvent signals. FTIR spectra were acquired with a Shimadzu FTIR
8400S spectrophotometer. HRMS was performed with a LCT Premier
TOF mass spectrometer using ESI techniques. Asymmetric analyses
were performed by using gas chromatography with a Shimadzu GC-
17A instrument with an attached AOC-20i auto injector and high-per-
formance liquid chromatography using Shimadzu SCL-10A VP instru-
ment. Reactions that required very high temperatures were per-
formed with a Biotage Initiator Microwave Synthesizer equipped with
a Robot Eight Initiator System. Structural assignments of the isolated
compounds were based on 1H, 13C, DEPT 135, COSY and HSQC spec-
troscopic analyses.
Decarboxylative Benzylation of Ketones; General Procedure
In a flame-dried Schlenk tube under argon, CpPd(allyl) (0.10 mmol)
and dppf (0.11 mmol) were dissolved in toluene (5 mL) and subse-
quently added to the benzyl β-keto ester (1.0 mmol). The resulting
solution was heated at 110 °C with stirring for 15 hours. After cooling
the reaction mixture to r.t., the solution was concentrated in vacuo
and the resulting residue was purified by flash chromatography using
EtOAc/hexanes eluent.
Ultimately, the use of XPhos as a ligand greatly expands
the breadth of arylmethyl electrophiles that are useful DcB
partners.
1-(4-Methoxyphenyl)-4-methylpentan-3-one (1a)9
While benzo-fused propiolates can undergo DcB with
either Pd(PPh3)4 or CpPd(allyl)/dppf catalyst, simple benzyl
propiolates require the use of the electron-rich monoden-
tate Buchwald ligand. Decarboxylative couplings of enolates
Yield: 107 mg (52%); slightly yellow oil.9
1H NMR (500 MHz, CDCl3): δ = 7.12–7.07 (d, J = 8.7 Hz, 2 H), 6.84–6.80
(d, J = 8.7 Hz, 2 H), 3.83–3.74 (s, 3 H), 2.86–2.79 (m, 2 H), 2.76–2.70
(m, 2 H), 2.59–2.52 (m, 1 H), 1.10–1.03 (d, J = 6.9 Hz, 6 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

E
R. R. P. Torregrosa et al.
Special Topic
Synthesis
13C NMR (126 MHz, CDCl3): δ = 214.12, 163.57, 158.03, 133.54,
129.40, 113.99, 55.40, 42.40, 41.18, 29.12, 18.28.
1H NMR (400 MHz, CDCl3): δ = 7.92–7.87 (d, J = 8.3 Hz, 2 H), 7.58–7.51
(m, 1 H), 7.46–7.39 (t, J = 7.6 Hz, 2 H), 7.14–7.08 (d, J = 8.6 Hz, 2 H),
6.87–6.82 (d, J = 8.7 Hz, 2 H), 3.78 (s, 3 H), 3.56–3.43 (m, 2 H), 3.02–
2.88 (m, 2 H), 2.69–2.60 (dd, J = 13.7, 7.7 Hz, 1 H), 2.19 (s, 3 H).
HRMS: m/z [M + Li] calcd for C13H18O2Li: 213.1467; found: 213.1452.
13C NMR (126 MHz, CDCl3): δ = 211.92, 198.75, 158.43, 136.62,
133.19, 130.63, 130.02, 128.77, 128.16, 114.02, 54.92, 49.04, 40.75,
37.18, 30.90.
1-(4-Methoxyphenyl)-4,4-dimethylpentan-3-one (1b)9
Yield: 139 mg (63%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.12–7.08 (d, J = 8.6 Hz, 2 H), 6.84–6.80
(d, J = 8.6 Hz, 2 H), 3.78 (s, 3 H), 2.83–2.78 (m, 2 H), 2.78–2.72 (m,
2 H), 1.14–1.05 (s, 9 H).
HRMS: m/z [M
+ Na] calcd for C19H20O3Na: 319.1310; found:
319.1311.
13C NMR (126 MHz, CDCl3): δ = 215.26, 158.01, 133.77, 129.46,
113.96, 55.40, 44.23, 38.87, 29.35, 26.45.
Ethyl 3-(4-Methoxybenzyl)-3-methyl-4-oxopentanoate (1i)
Yield: 164 mg (59%); slightly yellow oil.
HRMS: m/z [M + H] calcd for C14H21O2: 221.1542; found: 221.1548.
1H NMR (400 MHz, CDCl3): δ = 7.06–6.95 (d, J = 8.6 Hz, 2 H), 6.85–6.77
(d, J = 8.7 Hz, 2 H), 4.15–4.04 (m, 2 H), 3.79 (s, 3 H), 2.87–2.78 (dd, J =
14.9, 9.1 Hz, 2 H), 2.76–2.69 (m, 1 H), 2.38–2.28 (d, J = 16.5 Hz, 1 H),
2.11 (s, 3 H), 1.29–1.20 (m, 6 H).
3-(4-Methoxyphenyl)-1-phenylpropan-1-one (1c)9,10
Yield: 125 mg (52%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 8.00–7.92 (d, J = 8.1 Hz, 2 H), 7.60–7.52
(t, J = 7.4 Hz, 1 H), 7.49–7.42 (m, 2 H), 7.21–7.14 (d, J = 8.4 Hz, 2 H),
6.89–6.81 (d, J = 8.5 Hz, 2 H), 3.79 (s, 3 H), 3.33–3.21 (t, J = 7.7 Hz,
2 H), 3.07–2.96 (t, J = 7.6 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 213.07, 171.71, 158.63, 131.38,
128.46, 113.59, 60.63, 55.37, 50.16, 43.96, 42.53, 27.31, 21.55, 14.31.
HRMS: m/z [M
+ Na] calcd for C16H22O4Na: 301.1416; found:
301.1422.
13C NMR (126 MHz, CDCl3): δ = 199.53, 158.10, 136.96, 133.44,
133.18, 129.49, 128.67, 128.13, 114.06, 55.14, 40.97, 29.35.
3-(4-Methoxybenzyl)-3-methylheptane-2,5-dione (1j)
Yield: 108 mg (41%); slightly yellow oil.
4-(4-Methoxyphenyl)-1-phenylbutan-2-one (1d)11
1H NMR (400 MHz, CDCl3): δ = 7.01–6.93 (d, J = 8.5 Hz, 2 H), 6.85–6.77
(d, J = 8.6 Hz, 2 H), 3.79 (s, 3 H), 2.97–2.87 (d, J = 18.0 Hz, 1 H), 2.82–
2.66 (m, 2 H), 2.52–2.42 (d, J = 18.0 Hz, 1 H), 2.40–2.30 (p, J = 7.1 Hz,
2 H), 2.10 (s, 3 H), 1.22 (s, 3 H), 1.06–0.95 (t, J = 7.3 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 213.97, 209.64, 158.46, 131.40,
128.60, 113.70, 55.36, 50.73, 49.45, 44.14, 36.10, 27.39, 21.82, 7.85.
Yield: 140 mg (55%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.98–7.95 (m, 2 H), 7.58–7.54 (t, J =
7.4 Hz, 1 H), 7.49–7.43 (m, 2 H), 7.21–7.13 (d, J = 8.7 Hz, 2 H), 6.88–
6.80 (d, J = 8.7 Hz, 2 H), 3.79 (s, 3 H), 3.31–3.24 (m, 2 H), 3.05–2.98 (t,
J = 7.7 Hz, 2 H), 2.61 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 199.59, 157.95, 136.86, 133.40,
133.23, 133.18, 129.49, 128.74, 128.72, 128.43, 128.18, 114.00, 55.43,
40.82, 29.35, 26.82.
HRMS: m/z [M
+ Na] calcd for C16H22O3Na: 285.1467; found:
285.1469.
HRMS: m/z [M + Li] calcd for C17H18O2Li: 261.1467; found: 261.1463.
4-(4-Methoxyphenyl)-3,3-dimethylbutan-2-one (1k)
Yield: 85 mg (42%); slightly yellow oil.
2,2,2-Trifluoroethyl 3-(4-Methoxyphenyl)propanoate (1f)
1H NMR (400 MHz, CDCl3): δ = 7.05–6.95 (d, J = 8.6 Hz, 2 H), 6.86–6.74
(d, J = 8.6 Hz, 2 H), 3.80–3.76 (s, 3 H), 2.74 (s, 2 H), 2.09 (s, 3 H), 1.10
(s, 6 H).
13C NMR (126 MHz, CDCl3): δ = 214.23, 158.40, 131.29, 129.83,
113.43, 55.20, 49.01, 44.47, 26.17, 24.12.
Yield: 78 mg (30%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.15–7.08 (d, J = 10.3 Hz, 2 H), 6.87–
6.80 (d, J = 10.4 Hz, 2 H), 4.50–4.39 (m, 2 H), 3.79 (s, 3 H), 2.98–2.88 (t,
J = 7.5 Hz, 2 H), 2.76–2.66 (t, J = 7.6 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 210.78, 139.49, 131.89, 110.38,
109.95, 84.53, 49.49, 27.98, 25.77, 16.88.
FTIR (CH2Cl2): 2928, 1697, 1454, 1356, 1167, 737, 700 cm–1
.
HRMS: m/z [M + Li] calcd for C13H18O2Li: 213.1467; found: 213.1490.
HRMS: m/z [M – H] calcd for C12H12F3O3: 261.0739; found: 261.0715.
3-Benzyl-4-(4-methoxyphenyl)-3-methylbutan-2-one (1l)
4-(4-Methoxyphenyl)-3-methylbutan-2-one (1g)12
Yield: 178 mg (63%); slightly yellow oil.
Yield: 117 mg (61%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.27–7.18 (m, 3 H), 7.10–7.07 (d, J = 8.2
Hz, 2 H), 7.02–6.99 (d, J = 8.8 Hz, 2 H), 6.81–6.78 (d, J = 8.8 Hz, 2 H),
3.78 (s, 3 H), 3.19–3.14 (d, J = 13.3 Hz, 1 H), 3.13–3.09 (d, J = 13.3 Hz, 1
H), 2.62–2.58 (d, J = 13.3 Hz, 1 H), 2.58–2.54 (d, J = 13.3 Hz, 1 H), 1.83
(s, 3 H), 1.11 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 214.6, 158.4, 137.8, 131.3, 130.3,
129.5, 128.1, 126.5, 113.5 55.2, 53.3, 45.7, 45.5, 28.9, 20.4.
1H NMR (400 MHz, CDCl3): δ = 7.13–6.99 (m, 2 H), 6.89–6.77 (m, 2 H),
3.82–3.80 (d, J = 1.3 Hz, 3 H), 3.17–2.90 (m, 1 H), 2.88–2.75 (q, J =
7.0 Hz, 1 H), 2.60–2.48 (dd, J = 12.8, 5.0 Hz, 1 H), 2.10 (s, 3 H), 1.18–
1.04 (m, 3 H).
13C NMR (126 MHz, CDCl3): δ = 212.60, 158.33, 131.75, 131.26,
129.81, 114.00, 113.47, 55.35, 49.15, 38.17, 29.05, 16.35.
HRMS: m/z [M
305.1524.
+ Na] calcd for C19H22O2Na: 305.1518; found:
3-(4-Methoxybenzyl)-1-phenylpentane-1,4-dione (1h)
Yield: 145 mg (49%); slightly yellow oil.
3,3-Dibenzyl-4-(4-methoxyphenyl)butan-2-one (1m)
Yield (0.5 mmol scale): 176 mg (98%); slightly yellow oil.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

F
R. R. P. Torregrosa et al.
Special Topic
Synthesis
1H NMR (500 MHz, CDCl3): δ = 7.27–7.18 (m, 6 H), 7.03 (d, J = 6.8 Hz,
4 H), 6.94 (d, J = 8.7 Hz, 2 H), 6.78 (d, J = 8.7 Hz, 2 H), 3.77 (s, 3 H), 3.04
(s, 4 H), 3.00 (s, 2 H), 1.95 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 214.00, 158.45, 137.79, 131.48,
130.47, 129.54, 129.12, 128.88, 128.55, 126.74, 113.92, 56.45, 55.48,
41.01, 40.45, 29.14.
2-(4-Methoxybenzyl)-2-methylcyclohexanone (1r)14
Yield: 130 mg (56%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.06–6.97 (d, J = 8.6 Hz, 2 H), 6.84–6.75
(d, J = 8.6 Hz, 2 H), 3.77 (s, 3 H), 2.78 (s, 2 H), 2.55–2.40 (m, 2 H), 1.90–
1.78 (m, 3 H), 1.78–1.66 (m, 2 H), 1.57–1.48 (m, 1 H), 1.04–0.96 (s,
3 H).
FTIR (CH2Cl2): 2932, 1699, 1497, 1454, 1250, 1032, 748 cm–1
.
13C NMR (126 MHz, CDCl3): δ = 215.59, 158.00, 131.31, 129.41,
113.21, 55.08, 49.30, 42.09, 38.81, 37.91, 27.17, 22.67, 21.01.
HRMS: m/z [M + H] calcd for C25H26O2: 359.2011; found: 359.2018.
2-Benzyl-2-(4-methoxybenzyl)-2,3-dihydro-1H-inden-1-one (1s)
3-(4-Methoxybenzyl)-3-methylhex-5-en-2-one (1n)
Yield: 253 mg (74%); slightly yellow oil.
Yield: 137 mg (59%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.65–7.59 (d, J = 7.6 Hz, 1 H), 7.40–7.34
(t, J = 7.3 Hz, 1 H), 7.23–7.17 (t, J = 6.6 Hz, 1 H), 7.17–7.11 (t, J = 7.6 Hz,
3 H), 7.11–7.06 (d, J = 6.1 Hz, 4 H), 7.04–6.99 (d, J = 8.1 Hz, 2 H), 6.72–
6.65 (d, J = 6.3 Hz, 3 H), 3.71 (s, 1 H), 3.23–3.10 (t, J = 13.6 Hz, 2 H),
3.03 (s, 2 H), 2.87–2.72 (dd, J = 21.2, 12.7 Hz, 2 H).
1H NMR (500 MHz, CDCl3): δ = 7.04–6.96 (d, J = 8.7 Hz, 2 H), 6.84–6.74
(d, J = 8.7 Hz, 2 H), 5.77–5.62 (m, 1 H), 5.08 (s, 1 H), 5.07–5.03 (d, J =
5.8 Hz, 2 H), 3.77 (s, 3 H), 2.93–2.60 (dd, J = 127.1, 13.7 Hz, 2 H), 2.49–
2.41 (dd, J = 14.0, 7.0 Hz, 1 H), 2.17–2.08 (m, 1 H), 2.05 (s, 3 H), 1.09 (s,
3 H).
13C NMR (126 MHz, CDCl3): δ = 210.68, 158.16, 153.17, 137.29,
137.04, 134.56, 131.40, 130.40, 129.26, 128.13, 127.21, 126.53,
126.07, 123.67, 113.60, 55.46, 55.27, 43.53, 42.74, 34.65.
13C NMR (126 MHz, CDCl3): δ = 213.51, 158.20, 133.97, 131.07,
129.46, 118.46, 113.54, 55.32, 52.44, 43.58, 42.89, 27.31, 20.92.
HRMS: m/z [M
+ Na] calcd for C15H20O2Na: 255.1361; found:
HRMS: m/z [M
+ Na] calcd for C25H24O2Na: 379.1674; found:
255.1364.
379.1657.
3-Allyl-3-(4-methoxybenzyl)hex-5-en-2-one (1o)
2-(4-Methoxybenzyl)-2-methyl-3,4-dihydronaphthalen-1(2H)-
one (1t)
Yield: 145 mg (56%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.10–6.95 (d, J = 8.6 Hz, 2 H), 6.89–6.73
(m, 2 H), 5.83–5.65 (m, 2 H), 5.16 (s, 2 H), 5.12–5.06 (d, J = 8.0 Hz,
2 H), 3.79 (s, 3 H), 2.85 (s, 2 H), 2.43–2.23 (ddd, J = 37. 0, 14.1, 7.7 Hz,
4 H), 2.09 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 212.54, 158.34, 133.61, 131.16,
129.27, 118.75, 113.72, 55.85, 55.32, 39.66, 38.17, 27.50.
Yield: 148 mg (53%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 8.11–8.01 (d, J = 7.9 Hz, 1 H), 7.48–7.40
(t, J = 7.5 Hz, 1 H), 7.33–7.27 (t, J = 7.5 Hz, 1 H), 7.24–7.18 (d, J =
7.3 Hz, 1 H), 7.10–7.03 (d, J = 8.5 Hz, 1 H), 6.82–6.75 (d, J = 6.9 Hz,
2 H), 3.77 (s, 3 H), 3.10–3.01 (d, J = 13.6 Hz, 1 H), 3.01–2.94 (t, J =
3.9 Hz, 2 H), 2.81–2.74 (d, J = 13.6 Hz, 1 H), 2.05–1.93 (m, 1 H), 1.90–
1.77 (dt, J = 11.8, 5.9 Hz, 1 H), 1.17–1.13 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 202.33, 158.26, 143.37, 133.23,
131.92, 131.74, 129.73, 128.79, 128.19, 126.80, 113.48, 55.34, 46.04,
41.92, 33.12, 25.61, 22.47.
HRMS: m/z [M
+ Na] calcd for C17H22O2Na: 281.1518; found:
281.1520.
2-(4-Methoxybenzyl)-2-methylcyclopentanone (1p)4a,13
Yield: 146 mg (67%); colorless oil.
HRMS: m/z [M
+ Na] calcd for C19H20O2Na: 303.1361; found:
1H NMR (500 MHz, CDCl3): δ = 7.01 (d, J = 8.7 Hz, 2 H), 6.78 (d, J =
8.7 Hz, 2 H), 3.76 (s, 3 H), 2.78 (d, J = 13.6 Hz, 1 H), 2.51 (d, J = 13.6 Hz,
1 H), 2.26 (ddd, J = 18.8, 8.3, 5.5 Hz, 1 H), 2.08–1.97 (m, 1 H), 1.93 (dt,
J = 12.7, 7.6 Hz, 1 H), 1.83–1.64 (m, 1 H), 1.64–1.56 (m, 2 H), 0.99 (s,
3 H).
13C NMR (126 MHz, CDCl3): δ = 224.02, 158.28, 131.38, 130.27,
113.72, 77.48, 77.23, 76.98, 55.37, 49.86, 41.97, 38.32, 34.77, 22.88,
18.84.
303.1364.
2-Benzyl-2-(4-methoxybenzyl)-3,4-dihydronaphthalen-1(2H)-one
(1u)
Yield: 171 mg (48%); viscous oil.
1H NMR (400 MHz, CDCl3): δ = 8.12–8.05 (d, J = 7.8 Hz, 1 H), 7.46–7.39
(t, J = 8.0 Hz, 1 H), 7.33–7.27 (m, 1 H), 7.24–7.20 (d, J = 7.5 Hz, 2 H),
7.19–7.11 (m, 4 H), 7.09–7.02 (d, J = 8.6 Hz, 2 H), 6.80–6.74 (d, J =
8.6 Hz, 2 H), 3.75 (s, 3 H), 3.36–3.19 (dd, J = 25.8, 13.5 Hz, 2 H), 3.07–
2.96 (t, J = 6.3 Hz, 2 H), 2.68–2.56 (dd, J = 13.4, 10.5 Hz, 2 H), 1.99–
1.84 (t, J = 6.3 Hz, 2 H).
2-Benzyl-2-(4-methoxybenzyl)cyclopentanone (1q)
Yield: 235 mg (80%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.26–7.20 (m, 3 H), 7.12–7.07 (d, J =
6.9 Hz, 2 H), 7.04–6.99 (m, 2 H), 6.82–6.77 (d, J = 8.7 Hz, 2 H), 3.78 (s,
3 H), 3.04–2.91 (dd, J = 20.1, 13.3 Hz, 2 H), 2.62–2.49 (dd, J = 20.6,
13.3 Hz, 2 H), 1.92–1.80 (m, 4 H), 1.36–1.30 (td, J = 7.5, 3.4 Hz, 2 H).
13C NMR (126 MHz, CDCl3): δ = 224.36, 158.69, 137.89, 131.60,
130.70, 129.94, 128.38, 126.76, 113.97, 55.58, 55.09, 43.28, 42.35,
39.88, 30.28, 19.07.
13C NMR (126 MHz, CDCl3): δ = 200.97, 158.27, 143.15, 137.60,
133.29, 132.57, 131.97, 131.06, 129.37, 128.73, 128.20, 128.10,
126.81, 126.46, 113.51, 55.30, 51.07, 41.64, 40.85, 29.22, 25.61.
HRMS: m/z [M
+ Na] calcd for C25H24O2Na: 379.1674; found:
379.1657.
3,3-Dibenzyl-4-(3-methoxyphenyl)butan-2-one (2a)
HRMS: m/z [M
317.1545.
+ Na] calcd for C20H22O2Na: 317.1518; found:
Yield: 287 mg (80%); slightly yellow oil.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

G
R. R. P. Torregrosa et al.
Special Topic
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.31–7.27 (d, J = 1.9 Hz, 2 H), 7.25–7.13
(m, 5 H), 7.09–7.03 (d, J = 8.2 Hz, 4 H), 6.79–6.73 (d, J = 10.4 Hz, 1 H),
6.70–6.63 (d, J = 7.6 Hz, 1 H), 6.56 (s, 1 H), 3.73 (s, 3 H), 3.13–3.01 (d,
J = 9.3 Hz, 6 H), 1.96 (s, 3 H).
1H NMR (500 MHz, CDCl3): δ = 7.27–7.18 (m, 6 H), 7.07–7.02 (d, J =
7.0 Hz, 4 H), 6.77–6.71 (d, J = 8.2 Hz, 1 H), 6.65–6.59 (dd, J = 8.2,
2.0 Hz, 1 H), 6.45–6.40 (d, J = 2.0 Hz, 1 H), 3.84 (s, 3 H), 3.70 (s, 3 H),
3.12–2.98 (m, 6 H), 1.96 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 213.48, 159.33, 139.06, 137.42,
130.19, 129.19, 128.39, 126.60, 122.58, 115.98, 112.14, 56.12, 55.23,
41.17, 40.83, 28.99.
13C NMR (126 MHz, CDCl3): δ = 213.95, 148.41, 147.66, 137.69,
130.21, 129.80, 128.39, 126.59, 122.25, 113.75, 110.90, 56.23, 55.94,
55.79, 41.18, 40.27, 29.03.
HRMS: m/z [M
+
Na] calcd for
C
25H26O2Na: 381.1831; found:
HRMS: m/z [M + Na] calcd for C26H28O3Na: 411.1936; found:
381.1844.
411.1932.
4-(2,2-Dibenzyl-3-oxobutyl)benzonitrile (2d)
3,3-Dibenzyl-4-(naphthalen-2-yl)butan-2-one (2i)
Yield (0.5 mmol scale): 40 mg (23%); slightly yellow oil.
Yield (0.5 mmol scale): 140 mg (74%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.55–7.48 (d, J = 8.4 Hz, 2 H), 7.30–7.23
(m, 6 H), 7.14–7.06 (d, J = 8.4 Hz, 2 H), 7.06–6.98 (m, 4 H), 3.15–3.06
(m, 4 H), 3.05–2.97 (m, 2 H), 2.04 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 212.81, 143.65, 136.77, 131.77,
131.14, 130.12, 128.41, 126.89, 118.84, 110.48, 56.19, 41.48, 40.37,
28.69.
1H NMR (500 MHz, CDCl3): δ = 7.83–7.78 (m, 1 H), 7.76–7.70 (t, J =
8.4 Hz, 2 H), 7.48–7.42 (m, 3 H), 7.30–7.22 (m, 6 H), 7.20–7.16 (dd, J =
8.4, 1.7 Hz, 1 H), 7.09–7.06 (m, 4 H), 3.25 (s, 2 H), 3.20–3.06 (m, 4 H),
1.98 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 213.77, 137.53, 135.17, 133.36,
132.25, 130.32, 128.98, 128.85, 128.78, 128.67, 128.41, 127.80,
127.65, 126.66, 126.17, 125.80, 56.36, 41.30, 40.85, 29.12.
HRMS: m/z [M
+ NH4] calcd for C25H27N2O: 371.2123; found:
371.2054.
HRMS: m/z [M + H] calcd for C28H27O: 379.2062; found: 379.2063.
3,3-Dibenzyl-4-(4-nitrophenyl)butan-2-one (2e)
3,3-Dibenzyl-4-(naphthalen-1-yl)butan-2-one (2j)
Yield: 49 mg (13%); yellow oil.
Yield: 235 mg (62%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 8.12–8.04 (d, J = 8.8 Hz, 2 H), 7.30–7.24
(m, 6 H), 7.17–7.12 (d, J = 8.8 Hz, 2 H), 7.07–7.00 (d, J = 6.6 Hz, 4 H),
3.16 (s, 2 H), 3.14–2.99 (m, 4 H), 2.06 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 212.58, 146.64, 145.90, 136.69,
131.03, 130.11, 128.61, 126.88, 123.31, 56.40, 41.57, 40.05, 28.68.
1H NMR (500 MHz, CDCl3): δ = 7.97–7.93 (dd, J = 6.2, 3.5 Hz, 1 H),
7.89–7.85 (dd, J = 6.1, 3.4 Hz, 1 H), 7.77–7.73 (d, J = 8.2 Hz, 1 H), 7.53–
7.48 (dd, J = 6.4, 3.3 Hz, 2 H), 7.42–7.37 (t, J = 7.7 Hz, 1 H), 7.25–7.18
(m, 7 H), 7.06–7.00 (m, 4 H), 3.48 (s, 2 H), 3.28–3.16 (m, 4 H), 1.81 (s,
3 H).
13C NMR (126 MHz, CDCl3): δ = 214.40, 137.31, 133.91, 133.40,
132.74, 130.44, 128.95, 128.56, 128.36, 127.31, 126.62, 126.28,
125.85, 125.16, 123.42, 55.66, 41.66, 36.47, 29.16.
HRMS: m/z [M+] calcd for C24H23NO3: 373.1678; found: 373.1727.
3,3-Dibenzyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)butan-2-one
(2f)
HRMS: m/z [M + H] calcd for C28H27O: 379.2062; found: 379.2059.
Yield (0.5 mmol scale): 117 mg (61%); slightly yellow oil.
Ethyl 3-Methyl-4-oxo-3-(quinolin-4-ylmethyl)pentanoate (2k)
1H NMR (500 MHz, CDCl3): δ = 7.28 (s, 2 H), 7.24–7.19 (m, 4 H), 7.08–
7.04 (d, J = 8.1 Hz, 4 H), 6.97–6.76 (m, 2 H), 6.72–6.67 (s, 1 H), 3.10–
3.07 (d, J = 4.7 Hz, 1 H), 3.07 (s, 3 H), 3.05–3.04 (d, J = 5.6 Hz, 1 H),
3.04–2.96 (s, 2 H), 2.77–2.63 (d, J = 25.9 Hz, 4 H), 2.04 (s, 1 H), 1.97 (s,
3 H), 1.79–1.74 (m, 3 H).
13C NMR (126 MHz, CDCl3): δ = 213.87, 137.74, 136.80, 135.29,
134.23, 131.13, 130.31, 128.98, 128.66, 128.31, 127.34, 126.51, 56.21,
41.03, 40.62, 29.53, 29.10, 23.33.
Yield: 171 mg (57%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 8.87–8.79 (d, J = 4.2 Hz, 1 H), 8.22–8.15
(d, J = 8.4 Hz, 1 H), 8.08–8.00 (d, J = 8.4 Hz, 1 H), 7.79–7.71 (t, J =
7.2 Hz, 1 H), 7.60–7.53 (t, J = 7.7 Hz, 1 H), 7.33–7.28 (d, J = 4.2 Hz,
1 H), 4.17–4.10 (q, J = 7.2 Hz, 2 H), 3.64 (s, 2 H), 2.81 (s, 3 H), 2.06 (s,
3 H), 1.27–1.22 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 210.99, 171.65, 130.13, 128.81,
127.16, 124.31, 123.80, 61.32, 51.87, 39.50, 35.72, 28.28, 14.44.
HRMS: m/z [M + H] calcd for C28H31O: 383.2375; found: 383.2347.
HRMS: m/z [M + H] calcd for C18H22NO3: 300.1600; found: 300.1618.
4-(Benzo[d][1,3]dioxol-5-yl)-3,3-dibenzylbutan-2-one (2g)
3-Allyl-3-(quinolin-4-ylmethyl)hex-5-en-2-one (2l)
Yield ( 0.5 mmol scale): 134 mg (72%); slightly yellow oil.
Yield: 165 mg (59%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.28–7.20 (m, 6 H), 7.08–7.01 (d, J =
8.3 Hz, 4 H), 6.72–6.67 (d, J = 8.0 Hz, 1 H), 6.55–6.47 (m, 2 H), 5.92 (s,
2 H), 3.06 (s, 4 H), 2.98 (s, 2 H), 1.98 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 213.66, 147.60, 146.19, 137.42,
130.95, 130.24, 128.39, 126.60, 123.40, 110.65, 107.99, 101.03, 56.28,
40.76, 28.90.
1H NMR (500 MHz, CDCl3): δ = 8.84–8.70 (d, J = 4.5 Hz, 1 H), 8.14–7.98
(m, 2 H), 7.77–7.65 (m, 1 H), 7.62–7.50 (m, 1 H), 7.20–7.09 (d, J =
4.5 Hz, 1 H), 5.75–5.61 (m, 2 H), 5.17–5.01 (m, 4 H), 3.37 (s, 2 H),
2.54–2.41 (m, 4 H), 2.02 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 212.24, 149.81, 148.63, 144.32,
132.95, 130.43, 129.44, 128.61, 126.80, 123.84, 122.17, 119.74, 55.17,
38.68, 36.06, 27.49.
HRMS: m/z [M
+ NH4] calcd for C25H28NO3: 390.2069; found:
390.2077.
HRMS: m/z [M + H] calcd for C19H22NO: 280.1701; found: 280.1694.
3,3-Dibenzyl-4-(3,4-dimethoxyphenyl)butan-2-one (2h)
Yield: 198 mg (51%); slightly yellow oil.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

H
R. R. P. Torregrosa et al.
Special Topic
Synthesis
3,3-Dibenzyl-4-(quinolin-6-yl)butan-2-one (2m)
1-methyl-4-(3-phenylprop-2-ynyl)naphthalene (3b)4a
Yield (0.5 mmol scale): 142 mg (75%); slightly yellow oil.
Yield: 200 mg (78%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 8.91–8.83 (d, J = 3.3 Hz, 1 H), 8.04–7.94
(dd, J = 13.4, 8.4 Hz, 2 H), 7.41–7.33 (m, 3 H), 7.28–7.21 (q, J = 8.7,
7.6 Hz, 6 H), 7.07–7.01 (d, J = 7.6 Hz, 4 H), 3.25 (s, 2 H), 3.18–3.03 (q,
J = 14.9 Hz, 4 H), 2.00 (s, 3 H)
1H NMR (400 MHz, CDCl3): δ = 8.14–8.11 (dd, J = 6.6, 3.2 Hz, 1 H),
8.07–8.03 (dd, J = 7.6, 2.1 Hz, 1 H), 7.60–7.53 (td, J = 6.3, 5.8, 2.4 Hz,
3 H), 7.47–7.41 (dd, J = 6.0, 2.3 Hz, 2 H), 7.32–7.27 (m, 4 H), 4.20 (s,
2 H), 2.70 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 213.50, 150.27, 147.38, 137.30,
136.25, 135.92, 132.45, 130.27, 129.25, 128.34, 128.02, 126.64,
121.31, 56.44, 41.35, 40.34, 29.00.
13C NMR (126 MHz, CDCl3): δ = 133.66, 132.77, 131.57, 131.47,
130.51, 128.11, 127.63, 126.29, 125.70, 125.46, 125.37, 124.85,
123.83, 123.62, 87.57, 83.18, 23.55, 19.49.
HRMS: m/z [M + H] calcd for C27H26NO: 380.2014; found 380.2005.
FTIR (CH2Cl2): 2995, 2246, 1686, 1390, 1094, 758, 432 cm–1
.
HRMS: m/z [M + H] calcd for C20H17: 257.1330; found: 257.1328.
tert-Butyl 3-(2,2-Dibenzyl-3-oxobutyl)-1H-indole-1-carboxylate
(2n)
1-(Oct-2-ynyl)naphthalene (3c)4a
Yield (0.5 mmol scale): 175 mg (75%); colorless solid.
Yield: 208 mg (88%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 8.15 (s, 1 H), 7.42–7.33 (m, 3 H), 7.27–
7.20 (m, 7 H), 7.12–7.02 (t, J = 3.7 Hz, 4 H), 3.28–3.09 (m, 4 H), 3.06 (s,
2 H), 2.01 (s, 3 H), 1.71 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 213.46, 137.16, 130.33, 128.48,
126.74, 124.69, 123.36, 122.57, 119.03, 116.75, 115.22, 56.13, 41.51,
28.98, 28.60, 28.38.
1H NMR (500 MHz, CDCl3): δ = 8.04 (d, J = 8.4 Hz, 1 H), 7.86 (d, J =
7.7 Hz, 1 H), 7.75 (d, J = 8.2 Hz, 1 H), 7.64 (d, J = 6.6 Hz, 1 H), 7.51 (dt,
J = 20.8, 7.5 Hz, 2 H), 7.46–7.42 (m, 1 H), 3.98 (s, 2 H), 2.23 (t, J =
7.1 Hz, 2 H), 1.57–1.50 (m, 2 H), 1.42–1.36 (m, 2 H), 1.33 (dd, J = 14.1,
7.2 Hz, 2 H), 0.89 (t, J = 7.2 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 133.65, 133.39, 131.51, 128.62,
127.28, 125.39, 123.44, 83.69, 77.19, 30.71, 28.82, 23.23, 22.27, 18.55,
13.87.
HRMS: m/z [M + Na] calcd for C31H33NO3Na: 490.2358; found:
490.2333.
FTIR (CH2Cl2): 2930, 2230, 1597, 1510, 1396, 987, 769 cm–1
.
3,3-Dimethyl-4-(thiophen-2-yl)butan-2-one (2o)
HRMS: m/z [M + H] calcd for C18H20: 237.1643; found: 237.1634.
Yield: 122 mg (67%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.16–7.07 (d, J = 4.2 Hz, 1 H), 6.90 (s,
2-(3-Phenylprop-2-ynyl)naphthalene (3d)4a
1 H), 6.74 (s, 1 H), 3.04 (s, 2 H), 2.13 (s, 3 H), 1.17 (s, 6 H).
13C NMR (126 MHz, CDCl3): δ = 213.46, 139.95, 127.01, 126.72,
124.17, 48.81, 39.39, 26.01, 24.59.
Yield: 218 mg (90%); slightly yellow solid.
1H NMR (500 MHz, CDCl3): δ = 7.87 (s, 1 H), 7.82 (dd, J = 7.3, 2.1 Hz,
2 H), 7.50 (dd, J = 8.4, 1.8 Hz, 1 H), 7.48 (dd, J = 3.3, 1.2 Hz, 1 H), 7.47
(d, J = 1.9 Hz, 1 H), 7.45 (dd, J = 2.0, 0.8 Hz, 1 H), 7.43 (dd, J = 6.7,
1.4 Hz, 1 H), 7.30 (dt, J = 4.7, 2.4 Hz, 3 H), 3.99 (s, 2 H).
HRMS: m/z [M + Li] calcd for C10H14OSLi: 189.0925; found: 189.0922.
13C NMR (126 MHz, CDCl3): δ = 134.54, 133.86, 132.68, 132.01,
128.59, 128.53, 128.21, 127.98, 126.84, 126.56, 126.46, 125.92,
123.97, 87.70, 83.05, 26.46.
Decarboxylative Benzylation of Alkynes to Form 3a–l; General
Procedure
In a flame-dried Schlenk tube under argon, CpPd(allyl) (0.05 mmol)
and dppf (0.06 mmol) were dissolved in toluene (5 mL) and added to
the benzyl propiolic ester (1.0 mmol). The reaction was stirred at
110 °C for 15 hours or until reaction completion was indicated by TLC.
After cooling to r.t., the mixture was concentrated in vacuo and puri-
fied by flash chromatography using hexane and EtOAc as eluent.
FTIR (CH2Cl2): 3053, 2251, 1694, 1489, 1269, 812, 690 cm–1
.
HRMS: m/z [M + H] calcd for C19H14: 243.1174; found: 243.1174.
2-Methoxy-6-(3-phenylprop-2-ynyl)naphthalene (3e)4a
Yield: 220 mg (81%); slightly yellow oil.
Note on storage of benzylic alkynes: We observed that some of the
isolated benzylic alkynes –especially quinolinyl methyl alkynes – de-
composed over time when stored at r.t. To avoid the risk of decompo-
sition and degradation, all benzylic alkynes were also stored in a
freezer after isolation.
1H NMR (400 MHz, CDCl3): δ = 7.81 (s, 1 H), 7.77–7.70 (d, J = 9.2 Hz,
2 H), 7.49 (s, 3 H), 7.36–7.29 (t, J = 3.4 Hz, 3 H), 7.19–7.11 (m, 2 H),
4.02–3.95 (d, J = 2.8 Hz, 2 H), 3.95–3.87 (d, J = 3.9 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 157.55, 133.51, 131.96, 131.72,
129.26, 129.10, 128.39, 127.88, 127.14, 126.17, 123.80, 118.99,
105.79, 87.75, 82.83, 55.44, 25.91.
1-Methoxy-4-(3-phenylprop-2-ynyl)naphthalene (3a)4a
FTIR (CH2Cl2): 2935, 2359, 2332, 1606, 1265, 1229, 756 cm–1
.
Yield: 264 mg (97%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 8.35 (d, J = 8.3 Hz, 1 H), 8.04 (d, J =
8.3 Hz, 1 H), 7.64–7.56 (m, 2 H), 7.56–7.50 (m, 1 H), 7.46 (dd, J = 7.0,
2.6 Hz, 2 H), 7.33–7.27 (m, 3 H), 6.79 (d, J = 7.8 Hz, 1 H), 4.15 (s, 2 H),
3.99 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 154.87, 132.23, 131.61, 128.18,
127.73, 126.64, 125.89, 125.61, 125.06, 124.35, 123.77, 123.24,
122.63, 103.29, 87.63, 83.24, 55.40, 23.20.
HRMS: m/z [M + H] calcd for C20H17O: 273.1279; found: 273.1266.
3-(3-Phenylprop-2-ynyl)quinoline (3f)4a
Yield: 216 mg (89%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 8.92 ppm (d, J = 2.2 Hz, 1 H), 8.19 (s,
1 H), 8.09 (d, J = 8.4 Hz, 1 H), 7.81 (d, J = 8.1 Hz, 1 H), 7.70–7.66 (m,
1 H), 7.54 (t, J = 7.5 Hz, 1 H), 7.46 (dd, J = 5.8, 3.8 Hz, 2 H), 7.31 (dd, J =
4.4, 2.2 Hz, 3 H), 4.01 (s, 2 H).
FTIR (CH2Cl2): 2938, 2359, 2332, 1489, 1437, 1119, 756 cm–1
HRMS: m/z [M + H] calcd for C20H16O: 273.1279; found: 273.1273.
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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R. R. P. Torregrosa et al.
Special Topic
Synthesis
13C NMR (126 MHz, CDCl3): δ = 150.97, 147.07, 134.21, 131.64,
129.61, 129.15, 129.08, 128.29, 128.11, 127.98, 127.51, 126.82,
122.95, 85.81, 83.65, 23.25.
1H NMR (400 MHz, CDCl3): δ = 7.47–7.40 (dd, J = 6.6, 3.0 Hz, 2 H),
7.35–7.31 (m, 2 H), 7.31–7.28 (dd, J = 4.8, 2.1 Hz, 3 H), 6.92–6.84 (d,
J = 8.6 Hz, 2 H), 3.81 (s, 3 H), 3.77 (s, 2 H).
FTIR (CH2Cl2): 3057, 2924, 2177, 1691, 1267, 432 cm–1
.
13C NMR (126 MHz, CDCl3): δ = 158.50, 131.76, 129.07, 128.92,
128.36, 123.71, 114.03, 88.16, 82.45, 55.58, 24.66.
FTIR (CH2Cl2): 2928, 2835, 2359, 2191, 1670, 1510, 1037, 756 cm–1
HRMS: m/z [M + H] calcd for C18H13N: 244.1126; found: 244.1122.
.
6-(3-Phenylprop-2-ynyl)quinoline (3g)4a
HRMS: m/z [M + H] calcd for C16H15O: 223.1123; found: 223.1097.
Yield: 214 mg (88%); slightly yellow oil.
1-Methoxy-3-(3-phenylprop-2-ynyl)benzene (5b)6c
1H NMR (500 MHz, CDCl3): δ = 8.88 (d, J = 4.2 Hz, 1 H), 8.13 (d, J =
8.2 Hz, 2 H), 8.08 (d, J = 8.6 Hz, 1 H), 7.85 (s, 1 H), 7.73 (dd, J = 8.6,
1.8 Hz, 1 H), 7.47 (dd, J = 6.7, 2.9 Hz, 3 H), 7.38 (dd, J = 8.3, 4.2 Hz,
1 H), 7.30 (dd, J = 5.0, 2.0 Hz, 1 H), 4.00 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 150.36, 147.72, 135.94, 135.34,
131.85, 130.30, 129.88, 128.42, 128.18, 126.25, 123.44, 121.22, 86.87,
83.38, 25.97.
Yield: 149 mg (67%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.50–7.40 (m, 2 H), 7.32–7.28 (m, 3 H),
7.28–7.24 (m, 2 H), 7.03–6.94 (m, 2 H), 6.83–6.77 (m, 1 H), 3.83 (s,
3 H), 3.81 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 159.93, 138.46, 131.77, 129.65,
128.40, 128.37, 127.97, 123.77, 120.47, 113.84, 112.19, 87.49, 82.84,
55.37, 25.90.
FTIR (CH2Cl2): 2926, 2199, 1595, 1277, 827, 692 cm–1
.
HRMS: m/z [M + H] calcd for C18H13N: 244.1126; found: 244.1125.
1-Methoxy-2-(3-phenylprop-2-ynyl)benzene (5c)
5-Methoxy-2-(3-phenylprop-2-ynyl)benzofuran (3h)4a
Yield: 180 mg (81%); slightly yellow oil.
Yield: 207 mg (88%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.62–7.57 (dd, J = 7.5, 1.5 Hz, 1 H),
7.50–7.44 (m, 2 H), 7.33–7.28 (m, 3 H), 7.27–7.23 (m, 1 H), 7.03–6.94
(td, J = 7.5, 1.0 Hz, 1 H), 6.91–6.81 (d, J = 8.1 Hz, 1 H), 3.87 (s, 3 H), 3.79
(s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 156.89, 131.80, 129.04, 128.34,
127.94, 127.83, 125.24, 124.02, 120.66, 110.07, 87.70, 82.84, 55.50,
20.22.
1H NMR (400 MHz, CDCl3): δ = 7.57–7.51 (d, J = 7.5 Hz, 1 H), 7.51–7.43
(m, 3 H), 7.37–7.29 (s, 3 H), 7.27 (s, 1 H), 7.25–7.20 (m, 1 H), 6.74–
6.68 (s, 1 H), 3.98 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 155.10, 153.56, 131.82, 128.38,
128.12, 123.71, 123.13, 122.85, 120.58, 111.06, 103.38, 83.92, 82.67,
20.04.
FTIR (CH2Cl2): 3060, 2940, 2370, 2230, 1604, 1484, 1243, 1103,
FTIR (CH2Cl2): 3057, 2932, 2359, 2220, 1599, 1165, 752 cm–1
.
755 cm–1
.
HRMS: m/z [M + Na] calcd for C17H12ONa: 255.0786; found: 255.0869.
HRMS: m/z [M – H] calcd for C16H13O: 221.0966; found: 221.0962.
6-(3-(Trimethylsilyl)prop-2-ynyl)quinoline (3i)4a
5-(3-Phenylprop-2-ynyl)benzo[d][1,3]dioxole (5d)6c
Yield: 208 mg (87%); white solid.
Yield: 224 mg (95%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 8.91–8.81 (d, J = 4.1 Hz, 1 H), 8.17–8.09
(d, J = 8.3 Hz, 1 H), 8.09–7.96 (d, J = 8.8 Hz, 1 H), 7.76 (s, 1 H), 7.71–
7.61 (d, J = 8.7 Hz, 1 H), 7.44–7.31 (dd, J = 8.2, 4.2 Hz, 1 H), 3.81 (s,
2 H), 0.22 (s, 9 H).
13C NMR (126 MHz, CDCl3): δ = 150.29, 147.58, 135.80, 134.90,
130.19, 129.69, 128.22, 126.16, 121.43, 103.76, 87.90, 26.29, 0.02.
1H NMR (500 MHz, CDCl3): δ = 7.48–7.42 (dd, J = 6.5, 3.2 Hz, 2 H),
7.33–7.27 (m, 3 H), 6.97–6.90 (d, J = 1.5 Hz, 1 H), 6.89–6.83 (dd, J =
8.0, 1.6 Hz, 1 H), 6.80–6.75 (m, 1 H), 5.95 (s, 2 H), 3.75 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 147.92, 146.42, 131.69, 130.58,
128.81, 128.30, 127.98, 127.05, 123.65, 120.90, 108.70, 108.35,
101.12, 87.69, 82.69, 25.30.
FTIR (CH2Cl2): 2959, 2359, 2176, 1645, 1250, 1022, 847 cm–1
.
HRMS: m/z [M + H] calcd for C15H18NSi: 240.1209; found: 240.1198.
Prop-1-yne-1,3-diyldibenzene (5e)15,16
Yield: 156 mg (81%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.52–7.40 (m, 4 H), 7.38–7.32 (t, J =
7.6 Hz, 2 H), 7.32–7.28 (m, 3 H), 7.27 (s, 1 H), 3.84 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 136.89, 131.78, 128.69, 128.37,
Decarboxylative Benzylation of Alkynes to Form 5a–x; General
Procedure
In a flame-dried Schlenk tube under argon, Pd2(dba)3 (0.05 mmol)
and XPhos (0.20 mmol) were dissolved in toluene (5 mL) and added to
the benzyl propiolic ester (1.0 mmol). The reaction was stirred at
110 °C for 15 hours or until reaction completion was indicated by TLC.
After cooling to r.t. the mixture was concentrated in vacuo and puri-
fied by flash chromatography using hexane and EtOAc as eluent.
128.10, 127.96, 126.77, 123.79, 87.65, 82.78, 25.89.
Trimethyl((4-(3-phenylprop-2-ynyl)phenyl)ethynyl)silane (5f)
Yield (0.5 mmol scale): 140 mg (97%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.49–7.40 (dt, J = 5.0, 3.2 Hz, 4 H),
7.37–7.33 (d, J = 7.9 Hz, 2 H), 7.33–7.28 (dd, J = 4.9, 1.9 Hz, 3 H), 3.82
(s, 2 H), 0.25 (s, 9 H).
13C NMR (126 MHz, CDCl3): δ = 137.38, 132.26, 131.78, 128.41,
128.08, 127.97, 123.51, 121.58, 105.11, 94.08, 86.88, 83.14, 25.85,
0.15.
Note on storage of benzylic alkynes: We observed that some of the
isolated benzylic alkynes – especially quinolinyl methyl alkynes – de-
composed over time when stored at r.t. To avoid the risk of decompo-
sition and degradation, all benzylic alkynes were stored in a freezer
after isolation.
1-Methoxy-4-(3-phenylprop-2-ynyl)benzene (5a)
FTIR (CH2Cl2): 2959, 2349, 2156, 1599, 1489, 1250, 864, 690 cm–1
HRMS: m/z [M + NH4] calcd for C20H24NSi: 306.1678; found: 306.1640.
.
Yield: 209 mg (94%); slightly yellow oil.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

J
R. R. P. Torregrosa et al.
Special Topic
Synthesis
N-(4-(3-Phenylprop-2-ynyl)phenyl)acetamide (5g)
1H NMR (400 MHz, CDCl3): δ = 8.10–8.05 (d, J = 7.6 Hz, 1 H), 7.65–7.57
(m, 1 H), 7.27 (s, 1 H), 3.69 (s, 2 H), 0.21 (s, 9 H).
13C NMR (126 MHz, CDCl3): δ = 155.58, 153.48, 135.00, 125.49,
118.66, 102.01, 89.18, 29.85, 25.43, 0.09.
FTIR (CH2Cl2): 2959, 2392, 2179, 1622, 1539, 1350, 844, 760 cm–1
Yield: 177 mg (71%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.49–7.41 (td, J = 10.1, 9.2, 3.7 Hz,
4 H), 7.38–7.33 (d, J = 8.0 Hz, 2 H), 7.32–7.27 (m, 3 H), 7.23–7.17 (m,
1 H), 3.78 (s, 2 H), 2.19–2.14 (m, 3 H).
.
13C NMR (126 MHz, CDCl3): δ = 168.36, 136.53, 132.86, 131.69,
130.24, 129.54, 128.64, 128.38, 127.99, 123.72, 120.23, 87.58, 82.81,
25.34, 24.75.
HRMS: m/z [M + NH4] calcd for C12H18FN2O2Si: 269.1122; found:
269.1132.
FTIR (CH2Cl2): 3303, 3059, 2349, 2197, 1666, 1537, 1319, 1020, 756,
(3-(2-Methoxy-4-nitrophenyl)prop-1-ynyl)trimethylsilane (5m)
692 cm–1
.
Yield: 184 mg (70%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.89–7.85 (dd, J = 8.3, 2.1 Hz, 1 H),
7.71–7.68 (d, J = 8.4 Hz, 1 H), 7.68–7.67 (d, J = 2.1 Hz, 1 H), 3.92 (s,
3 H), 3.65 (s, 2 H), 0.21 (s, 9 H).
HRMS: m/z [M + H] calcd for C17H16NO: 250.1232; found: 250.1237.
4-(3-Phenylprop-2-ynyl)benzonitrile (5h)17
13C NMR (126 MHz, CDCl3): δ = 156.74, 147.79, 132.63, 128.92,
Yield: 135 mg (62%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.67–7.57 (d, J = 8.1 Hz, 2 H), 7.57–7.48
(d, J = 7.9 Hz, 2 H), 7.48–7.38 (dd, J = 6.5, 3.1 Hz, 3 H), 7.36–7.28 (dd,
J = 4.4, 2.1 Hz, 2 H), 3.87 (s, 2 H).
115.74, 104.57, 102.10, 88.55, 55.76, 20.51, 0.07.
FTIR (CH2Cl2): 2959, 2179, 1526, 1493, 1416, 1288, 1094, 1034, 845,
760 cm–1
.
13C NMR (126 MHz, CDCl3): δ = 142.45, 132.52, 131.78, 128.91,
HRMS: m/z [M + NH4] calcd for C13H21N2O3Si: 281.1321; found:
128.48, 128.37, 123.18, 119.01, 110.81, 85.27, 83.91, 25.98.
281.1329.
1-(Difluoromethoxy)-4-(3-phenylprop-2-ynyl)benzene (5i)
1-(2-Nitro-4-(3-(trimethylsilyl)prop-2-ynyl)phenyl)pyrrolidine
(5n)
Yield: 152 mg (59%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.47–7.37 (m, 4 H), 7.34–7.27 (m, 3 H),
7.13–7.05 (d, J = 8.5 Hz, 2 H), 6.68–6.31 (t, J = 74.1 Hz, 1 H), 3.80 (s,
2 H).
13C NMR (126 MHz, CDCl3): δ = 149.96, 133.94, 131.71, 129.45,
128.42, 128.11, 119.94, 117.93, 116.12, 114.06, 86.92, 83.05, 25.11.
Yield: 272 mg (90%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.77–7.68 (d, J = 2.1 Hz, 1 H), 7.38–7.29
(dd, J = 8.7, 2.0 Hz, 1 H), 6.92–6.83 (d, J = 8.8 Hz, 1 H), 3.57 (s, 2 H),
3.24–3.16 (t, J = 6.4 Hz, 4 H), 2.04–1.91 (p, J = 3.6 Hz, 4 H), 0.19 (s,
9 H).
13C NMR (126 MHz, CDCl3): δ = 141.88, 136.85, 132.83, 125.86,
123.80, 116.29, 103.82, 87.59, 50.58, 25.89, 24.88, 0.21.
FTIR (CH2Cl2): 2959, 2199, 1703, 1603, 1508, 1223, 1018, 758,
692 cm–1
.
FTIR (CH2Cl2): 2959, 2176, 2118, 1630, 1463, 1306, 845, 760 cm–1
.
HRMS: m/z [M + NH4] calcd. for C16H16F2NO: 276.1200; found:
276.1171.
HRMS: m/z [M
+ H] calcd for C16H23N2O2Si: 303.1529; found:
303.1531.
1-Nitro-4-(3-phenylprop-2-ynyl)benzene (5j)
1-Fluoro-2-methoxy-4-(3-phenylprop-2-ynyl)benzene (5o)
Yield: 102 mg (43%); orange oil.
1H NMR (400 MHz, CDCl3): δ = 8.30–8.15 (d, J = 8.7 Hz, 2 H), 7.64–7.56
(dd, J = 8.9, 2.1 Hz, 2 H), 7.50–7.43 (dd, J = 6.6, 3.0 Hz, 2 H), 7.38–7.30
(dd, J = 8.7, 4.2 Hz, 3 H), 3.96 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 147.12, 144.17, 131.79, 129.08,
128.96, 128.50, 128.42, 123.96, 123.12, 85.56, 83.92, 25.99.
Yield: 113 mg (47%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.50–7.41 (t, J = 3.5 Hz, 2 H), 7.34–7.28
(d, J = 3.8 Hz, 3 H), 7.21–7.06 (dd, J = 25.1, 11.3 Hz, 2 H), 6.98–6.87 (t,
J = 8.6 Hz, 1 H), 3.89 (s, 3 H), 3.77 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 131.79, 128.40, 128.08, 123.58,
FTIR (CH2Cl2): 2853, 2349, 1597, 1518, 1344, 1109, 858, 756 cm–1
.
115.92, 113.78, 87.09, 83.08, 56.69, 25.01.
FTIR (CH2Cl2): 2932, 2349, 2039, 1518, 1277, 1122, 1027 cm–1
.
HRMS: m/z [M – H] calcd for C15H10NO2: 236.0712; found: 236.0708.
HRMS: m/z [M + H] calcd for C16H14FO: 241.1029; found: 241.1023.
1-Nitro-3-(3-phenylprop-2-ynyl)benzene (5k)
3-(3-Phenylprop-2-ynyl)pyridine (5p)
Yield: 57 mg (24%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 8.31 (s, 1 H), 8.16–8.10 (dd, J = 7.9,
1.9 Hz, 1 H), 7.81–7.73 (m, 1 H), 7.56–7.49 (t, J = 7.9 Hz, 1 H), 7.49–
7.44 (td, J = 4.2, 2.2 Hz, 2 H), 7.35–7.29 (t, J = 3.2 Hz, 3 H), 3.94 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 139.03, 134.30, 131.83, 129.60,
128.49, 128.40, 123.16, 122.07, 85.66, 84.02, 25.70.
Yield: 48 mg (25%); orange oil.
1H NMR (400 MHz, CDCl3): δ = 8.70–8.62 (m, 2 H), 8.56–8.47 (d, J =
4.2 Hz, 1 H), 7.81–7.73 (d, J = 7.9 Hz, 1 H), 7.51–7.39 (m, 1 H), 7.36–
7.29 (dt, J = 4.9, 2.5 Hz, 5 H), 3.84 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 149.46, 148.33, 135.65, 132.55,
FTIR (CH2Cl2): 3080, 2920, 2210, 1594, 1354, 1101, 757 cm–1
.
131.78, 128.45, 128.25, 123.60, 123.33, 86.23, 83.25, 23.00.
HRMS: m/z [M + H] calcd for C14H12N: 194.0970; found: 194.0971.
HRMS: m/z [M + NH4] calcd for C15H15N2O2: 255.1134; found:
255.1178.
(3-(4-Methoxyphenyl)prop-1-ynyl)trimethylsilane (5q)
(3-(4-Fluoro-3-nitrophenyl)prop-1-ynyl)trimethylsilane (5l)
Yield: 205 mg (94%); colorless solid.
Yield: 78 mg (31%); slightly yellow oil.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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R. R. P. Torregrosa et al.
Special Topic
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.24 (s, 2 H), 6.91–6.82 (d, J = 8.5 Hz,
2 H), 3.81 (s, 3 H), 3.58 (s, 2 H), 0.19 (s, 9 H).
FTIR (CH2Cl2): 3134, 3057, 2361, 2203, 1699, 1488, 1061, 914,
756 cm–1
.
13C NMR (126 MHz, CDCl3): δ = 158.51, 128.97, 128.43, 114.02,
HRMS: m/z [M + H] calcd for C12H8NO: 184.0762; found: 184.0774.
104.91, 86.62, 55.29, 25.33, 0.26.
FTIR (CH2Cl2): 2960, 2170, 2125, 1614, 1509, 1243, 1036, 840 cm–1
.
5-(3-Phenylprop-2-ynyl)oxazole (5x)
Yield: 82 mg (45%); slightly yellow oil.
HRMS: m/z [M – H] calcd for C13H17OSi: 217.1049; found: 217.1066.
1H NMR (400 MHz, CDCl3): δ = 7.83 (s, 1 H), 7.51–7.38 (d, J = 5.8 Hz,
2 H), 7.36–7.28 (t, J = 2.8 Hz, 3 H), 7.27 (s, 1 H), 7.03 (s, 1 H), 3.88 (s,
2 H).
13C NMR (126 MHz, CDCl3): δ = 150.76, 147.91, 131.84, 128.45,
123.40, 122.94, 82.81, 82.55, 17.34.
2-Methoxy-1-(3-phenylprop-2-ynyl)naphthalene (5r)
Yield: 220 mg (81%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 8.20–8.15 (d, J = 8.8 Hz, 1 H), 7.84–7.78
(d, J = 10.3 Hz, 1 H), 7.59–7.51 (t, J = 7.7 Hz, 1 H), 7.41–7.35 (t, J =
7.5 Hz, 1 H), 7.35–7.29 (m, 2 H), 7.24–7.19 (dd, J = 4.4, 2.1 Hz, 3 H),
4.21 (s, 1 H), 4.01 (s, 1 H).
FTIR (CH2Cl2): 3134, 3057, 2361, 2203, 1699, 1488, 1061, 914,
756 cm–1
.
13C NMR (126 MHz, CDCl3): δ = 154.13, 133.01, 131.79, 129.44,
128.93, 128.54, 128.16, 127.61, 126.78, 124.07, 123.82, 123.67,
118.31, 113.87, 88.67, 80.24, 57.09, 15.54.
HRMS: m/z [M + H] calcd for C12H8NO: 184.0762; found: 184.0756.
FTIR (CH2Cl2): 2934, 2210, 1949, 1626, 1512, 1089, 756, 692 cm–1
.
Funding Information
HRMS: m/z [M + H] calcd for C20H17O: 273.1279; found: 273.1282.
We thank the National Science Foundation (CHE-1465172) and the
Kansas Bioscience Authority Rising Star program for financial sup-
port. Support for the NMR instrumentation was provided by NSF Aca-
demic Research Infrastructure Grant No. 9512331, NIH Shared
Instrumentation Grant No. S10RR024664, and NSF Major Research In-
2-(3-Phenylprop-2-ynyl)furan (5t)17
Yield: 144 mg (79%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.47–7.39 (m, 2 H), 7.38–7.33 (m, 1 H),
7.32–7.27 (t, J = 3.2 Hz, 3 H), 6.37–6.24 (d, J = 33.9 Hz, 2 H), 4.01–3.50
(s, 2 H).
strumentation Grant No. 0320648.
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13C NMR (126 MHz, CDCl3): δ = 150.45, 141.90, 131.83, 131.75,
128.49, 128.37, 128.33, 128.14, 123.44, 110.60, 110.43, 106.38, 84.64,
81.98, 19.59.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1609575.
FTIR (CH2Cl2): 3057, 2924, 2189, 1657, 1597, 1315, 1070, 756 cm–1
.
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HRMS: m/z [M – H] calcd for C13H9O: 181.0653; found: 181.0638.
References
2-(3-Phenylprop-2-ynyl)thiophene (5u)17,18
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Yield: 161 mg (81%); slightly yellow oil.
1H NMR (500 MHz, CDCl3): δ = 7.51–7.41 (dd, J = 6.5, 3.0 Hz, 2 H),
7.36–7.28 (dd, J = 6.4, 2.7 Hz, 3 H), 7.23–7.17 (dd, J = 5. 1, 1.1 Hz, 1 H),
7.06–7.00 (d, J = 4.5 Hz, 1 H), 7.00–6.93 (m, 1 H), 4.01 (s, 2 H).
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128.13, 127.00, 125.20, 124.25, 123.47, 86.82, 82.46, 20.81.
tert-Butyl 2-(3-Phenylprop-2-ynyl)-1H-pyrrole-1-carboxylate (5v)
Yield: 228 mg (81%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.50–7.39 (m, 2 H), 7.32–7.27 (t, J =
2.8 Hz, 3 H), 7.26 (s, 1 H), 6.37–6.31 (t, J = 2.2 Hz, 1 H), 6.15–6.11 (t, J =
3.3 Hz, 1 H), 4.01 (s, 2 H), 1.68–1.56 (s, 9 H).
13C NMR (126 MHz, CDCl3): δ = 149.40, 131.82, 130.12, 128.32,
127.93, 123.81, 121.70, 112.70, 110.15, 86.81, 84.12, 81.84, 27.93,
20.33.
FTIR (CH2Cl2): 2978, 2931, 2359, 1740, 1491, 1340, 1119, 756 cm–1
.
HRMS: m/z [M + Na] calcd for C18H19NO2: 304.1313; found: 304.1313.
4-(3-Phenylprop-2-ynyl)oxazole (5w)
Yield: 167 mg (91%); slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.86 (s, 1 H), 7.69–7.65 (dd, J = 2.4,
1.4 Hz, 1 H), 7.47–7.41 (m, 2 H), 7.33–7.28 (m, 3 H), 3.74 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ = 151.36, 136.92, 135.67, 131.81,
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2001, 123, 4155. (b) Qian, M.; Negishi, E. Tetrahedron Lett. 2005,
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128.40, 128.22, 123.31, 84.99, 82.17, 18.02.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L