Pd-catalyzed intramolecular addition of active methylene compounds to alkynes with subsequent cross-coupling with (hetero)aryl halides

Article abstract of DOI:10.1039/c9ra08002c

We report an efficient protocol for tandem Pd-catalyzed intramolecular addition of active methylene compounds to alkynes, followed by subsequent cross-coupling with (hetero)aryl bromides and chlorides. The reaction proceeds under mild conditions, providing excellent functional group tolerance, including unprotected OH, NH₂ groups, enolizable ketones, or a variety of heterocycles. Mechanistic studies point towards a catalytic cycle involving oxidative addition, intramolecular nucleophilic addition to the Pd(ii)-activated alkyne, and reductive elimination, with 5-exo-dig cyclization being the rate limiting step.

Full text of DOI:10.1039/c9ra08002c

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Pd-catalyzed intramolecular addition of active
methylene compounds to alkynes with subsequent
cross-coupling with (hetero)aryl halides†
Cite this: RSC Adv., 2019, 9, 40152
b
b
Aleksandra Błocka,a Paweł Woznicki,
Marek Stankevic
ˇ
´
a
*
and Wojciech Chaładaj
We report an efficient protocol for tandem Pd-catalyzed intramolecular addition of active methylene
compounds to alkynes, followed by subsequent cross-coupling with (hetero)aryl bromides and chlorides.
The reaction proceeds under mild conditions, providing excellent functional group tolerance, including
unprotected OH, NH2 groups, enolizable ketones, or a variety of heterocycles. Mechanistic studies point
towards a catalytic cycle involving oxidative addition, intramolecular nucleophilic addition to the Pd(II)-
activated alkyne, and reductive elimination, with 5-exo-dig cyclization being the rate limiting step.
Received 2nd October 2019
Accepted 20th November 2019
DOI: 10.1039/c9ra08002c
rsc.li/rsc-advances
In the late 1980s, Gore disclosed seminal works on a novel
Pd-catalyzed dicarbofunctionalization of unsaturated C–C
Introduction
systems through arylation with iodobenzene and intra-
molecular nucleophilic additions of malonates to alkylidene-
cyclopropanes or alkenes.4 In subsequent accounts, the authors
reported a sequential 5-exo-dig cyclization of malonates and b-
ketoesters tethered to the alkyne moiety, followed by coupling
with aryl iodides.5 The scope of the methodology was further
extended to the use of haloalkynes,6 allyl halides and acetates7
as coupling partners. Recently, we have developed a protocol
enabling the effective reaction of much less active aryl bromides
with acetylenic b-ketoesters.8 A similar strategy, utilizing a 5-
endo-dig cyclization has also been applied to the synthesis of
cyclopentenes9 and indenes.10 Propargylmalonates led to
substituted cyclopropanes via analogous cyclization/coupling
protocol.11 On the other hand, propargyl-b-ketoesters under-
went 5-exo-dig oxocyclization/coupling, leading to the formation
of substituted furan systems due to ambident nature of enolates
of b-ketoesters.12 Interestingly, the analogous transformation
involving homopropargyl-b-ketoesters possessing an internal or
terminal alkyne motif clearly led to either cyclopentenes9 or
dihydropyranes,13 respectively.
The vast majority of the known methodologies utilizing
sequential Pd-catalyzed nucleophilic cyclization and cross
coupling are limited to aryl iodides. Moreover, the functional
group compatibility appeared very narrow, which could possibly
arise from the use of a strong base. Recently, we have addressed
these challenges in a transformation involving acetylenic b-
ketoesters which readily undergo cyclization. Extension of the
scope with respect to activated methylene compounds still
awaits investigation. Although there are examples of such
transformations involving derivatives of ketoesters and malo-
nates (with active aryl iodides), to the best of our knowledge,
cyclization/coupling of haloarenes with acetylenic derivatives of
Palladium complexes emerge as some of the most versatile
homogenous catalysts with a myriad of applications in both
academic and industrial research. The most prominent area of
palladium catalysis, awarded with the 2010 Nobel Price to R.
Heck, A. Suzuki, and E. Negishi,1 covers cross-couplings of
(hetero)aryl or vinyl(pseudo)halides with nucleophilic or
organometallic partners. High efficiency of these and many
other processes (e.g. Wacker oxidation) arises from the facile
interconversion of palladium oxidation states through two-
electron redox chemistry. Besides the most widespread Pd(0)/
Pd(II) cycle, palladium is also able to enter radical processes or
to serve as a carbophilic Lewis acid in redox–neutral trans-
formations. The ability to mediate mechanistically distinct
transformations makes palladium the catalyst of choice for the
design of tandem reactions in which a single metal complex
catalyzes a sequence of transformations.2 In our research, we
are focused on the development of tandem processes
combining the nucleophilic addition to alkynes and subsequent
cross-coupling, which give the access to a wide set of carbo- and
heterocyclic systems.3 In contrast to cross-coupling reactions,
these transformations are highly underdeveloped and suffer
from harsh reaction conditions (e.g. the use of strong bases),
narrow substrate scope (usually limited to active aryl iodides),
and poor functional group tolerance, as well as insufficient
mechanistic understanding.
aInstitute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224
Warsaw, Poland. E-mail: wojciech.chaladaj@icho.edu.pl
bDepartment of Organic Chemistry, Faculty of Chemistry, Marie Curie-Skłodowska
University in Lublin, Gliniana 33, 20-614 Lublin, Poland
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c9ra08002c
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Table
reaction
1 Optimization of the reaction conditions for benchmark
Here, we report an efficient protocol for tandem Pd-catalyzed
intramolecular addition of active methylene compounds to
alkynes and subsequent cross-coupling with (hetero)aryl
bromides and chlorides. The methodology features excellent
tolerance for functionalities present in either reaction partner.
Results and discussion
The reaction of dimethyl pent-4-yn-1-ylmalonate 1 with bro-
mobenzene was chosen as a model transformation for the
development of the reaction conditions. First, a range of Pd-
complexes of mono- and diphosphine ligands were examined
using 3rd-generation Buchwald-type palladacyclic system as
a platform in order to identify an active catalyst system. Opti-
mization revealed XPhos Pd G3 as the pre-catalyst of choice.
Then, the benchmark reaction was evaluated against various
reaction conditions, including base, solvent, catalyst loading,
temperature, and time, among others (Table 1).14 A polar aprotic
solvent appeared to be crucial for the efficiency of the cycliza-
tion. Reactions carried out in moderately polar, or nonpolar
solvents (e.g. dioxane, THF, toluene) failed to proceed at all, or
competitive Sonogashira coupling was observed. The ꢀ best
results were achieved for the reaction run for 24 h at 50 C in
DMF with potassium phosphate as the base. 2 mol% of palla-
dium complex was necessary to achieve a high yield of desired
product 2.
Entry
Solvent
Base
Time
Cat. loading
Yielda
1
2
3
4
5
6
7
8
Toluene
Dioxane
THF
MeCN
DMSO
DMF
DMF
DMF
DMF
DMF
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
t-BuOK
KHMDS
K2CO3
K3PO4
K3PO4
K3PO4
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4h
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
2 mol%
1%
3%
2%
8%
47%
0%
0%
22%
22%
61%
90%
9
10
11
4 h
24 h
DMF
a
Determined by GC with mesitilene as an internal standard.
With satisfactory conditions developed for the model
substrate, we proceeded to investigate the scope of the reaction.
First, we examined the performance of various aryl and heter-
oaryl bromides in the reaction with malonate 1 (Table 2).
malononitrile, cyanoacetates, diketones, as well as substrates
bearing organophosphorus electron-withdrawing functions
have not been reported.
Table 2 Substrate scope: aryl bromidesa
a
Reaction conditions: dimethyl pent-4-yn-1-ylmalonate 1 (0.400 mmol), aryl bromide (0.500 mmol), K3PO4 (0.600 mmol), XPhos Pd G3 (8.0 mmol,
b
2 mol%), DMF (1 ml), 50 ꢀC, 24 h. Run for 4 h.
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Both electron-rich and electron-poor bromoarenes smoothly
The considerably more C–H acidic cyanoacetates, cyano-
underwent the reaction, affording the expected products with malonates, and b-ketoesters appeared to be the more reactive
good to excellent yields and complete stereoselectivity on the substrates, usually providing the appropriate products (32–43)
olenic bond. A range of functional groups including, inter alia, with very good yields (70–96%). The only exception was a reac-
unprotected amines (4), alcohols (12), aldehydes (21), nitriles tion of electron-decient bromoarenes with cyanomalonate and
(20), nitro (25), carbamates (22), or enolizable ketones (7) were t-butyl cyanoacetate, which afforded products (34 and 40) with
well tolerated. Furthermore, sterically hindered o-substituted moderate yields (33–40%). Notably, reactions involving
bromo(hetero)arenes also proved to be complementary reaction electron-decient bromoarenes and all of the above-mentioned
partners (8, 17, 24). The use of various heteroaryl bromides acetylenic substrates proceeded with high, but not complete
enabled the introduction of the heterocyclic moiety to the diastereoselectivity (E/Z selectivity). All reactions involving
product (10–11, 14–16, 18–19, 23), including pharmaceutically electronically neutral, or electron-rich bromoarenes provided
relevant N-heterocyclic motifs (10–11, 14–16, 18–19).
complete selectivity.
Next, we proceeded to examine the scope and limitations
Next, we investigated various phosphorus-substituted acety-
with respect to various acetylenic active methylene compounds lenes as potential reaction partners. We were pleased to nd
(Table 3). Selected derivatives of malonates, cyanoacetates, that esters, ketones, and nitriles bearing phosphoryl or phos-
cyanomalonates, b-ketoesters, and 1,3-diketones were subjected phinoyl functions entered the reaction with bromobenzene,
to the reaction with both electron-poor and electron-rich bro- affording the target cyclopentanes (49–54) with moderate to
moarenes – bromobenzene, p-bromoanisole, and p-bromo- good yields and complete diastereoselectivity. Compound 49
benzonitrile. Transformations with more sterically hindered i- was isolated with a low yield due to difficulties in the isolation
propyl and t-butyl malonates delivered the expected products and purication.
(26–31), although with diminished yields, compared to the less
sterically demanding methyl malonate 1.
Finally, we were pleased to nd that the developed protocol
is also applicable to the remarkably less active aryl chlorides
(Table 4). Both electron-rich and electron-decient chloroar-
enes, as well as heteroaryl chlorides (2-chloropyridine) entered
the reaction, yielding the expected products in moderate to
good yields (39–69%). Interestingly, electron-decient chlor-
oarenes gave products with low diastereoselectivity, in contrast
to their corresponding aryl bromides which provided the
products as single isomers (except 4-nitrobromobenzene).
The postulated mechanism, based on the observations of the
reaction outcome, several control experiments, and literature
data, is depicted in Scheme 1. First, the bromoarene undergoes
fast oxidative addition to Pd(0) complex 57 (formed upon the
activation of the precatalyst with a base)15 leading to the
Table 3 Substrate scope: acetylenic active methylene compoundsa
Table 4 Substrate scope: aryl chloridesa
a
Reaction conditions: acetylenic active methylene compound (0.400
a
mmol), aryl bromide (0.500 mmol), K3PO4 (0.600 mmol), XPhos Pd G3
Reaction conditions: dimethyl pent-4-yn-1-ylmalonate 1 (0.400 mmol),
b
c
(8.0 mmol, 2 mol%), DMF (1 ml), 50 ꢀC, 24 h. Run for 4 h. Run at aryl chloride (0.500 mmol), K3PO4 (0.600 mmol), XPhos Pd G3 (8.0 mmol,
d
80 ꢀC for 24 h. Run at 50 ꢀC for 2 h.
2 mol%), DMF (1 ml), 80 ꢀC, 24 h.
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reactions of bromobenzene with three acetylenic substrates –
derivatives of malonate 1, b-ketoester 65, and b-diketone 68
(Scheme 2b). As expected, malonate 1 reacted signicantly
slower than ketoester 65, providing the corresponding product
in only 21% yield aer 1 h, compared to 90% for 65. This is due
to considerably lower C–H acidity of the malonate. Surprisingly,
under identical conditions, the more C–H acidic b-diketone 68
delivered the product with only 14% yield. Competition exper-
iments, involving pairs of acetylenic substrates (1 equiv. of each)
and bromobenzene (1 equiv.) were also conducted (Scheme 2c).
A reaction involving ketoester 65 and malonate 1 delivered only
the product of the cyclization/coupling of 65, demonstrating the
huge difference in their reactivity. Despite diketone 68 reacting
slower than malonate in a parallel experiment (see: Scheme 2b),
in the competition experiment it provided higher yield of the
corresponding product (60% and 31%, respectively). Similarly,
the cyclization of ketoester and diketone occurred at compa-
rable rates under the competition conditions (42% and 27%,
respectively), in contrast to the parallel experiment (90% vs.
14%). The remarkably slow reaction of diketone 68 could be
attributed either to the lower nucleophilicity of its enolate due
to extended resonance stabilization, or the capability for the
formation of stable complexes with palladium.16 The relatively
stable palladium complex with diketone (or its anion) could
possibly be in tautomeric equilibrium with Pd–alkyne complex
suitable for intramolecular nucleophilic addition leading to 61.
Thus, the involvement of arylpalladium 58 in complexation with
diketone 68 could make it less available for the catalytic trans-
formation of the more reactive ketoester 65 in the competition
experiment.
Competition experiments of malonate 1 with pairs of elec-
tronically divergent bromoarenes revealed the preference for
the reaction with the more electron-decient substrate (Scheme
2e). This stays in contrast with the outcome of the parallel
experiments of 1 with each of the above bromoarenes showing
comparable rates (Scheme 2d). Apparently, oxidative addition is
not a rate limiting step, although in control experiments it
determines the ratio of aryl–Pd(II) intermediates, which in turn
dictates the nal product distribution.
Another factor used for better understanding the reaction
mechanism is the stereochemical outcome of the trans-
formation. All of the reactions with malonates proceeded with
complete diastereoselectivity, arising from anti-carbopallada-
tion of the alkyne moiety. Similarly, other acetylenic active
methylene compounds delivered the corresponding products as
single isomers, unless electron-decient bromoarenes (e.g. p-
bromobenzonitrile) were used as coupling partners. In this
case, the isomer with the alternate conguration on the double
bond was formed to some extent, suggesting an alternative
pathway for these sets of substrates (Scheme 1, dashed lines).
Scheme 1 Plausible mechanism.
formation of aryl–Pd(II) species 58 which coordinates to the
alkyne moiety. Then, intramolecular nucleophilic addition to
the activated unsaturated system occurs, providing vinyl–Pd(II)
species 60 which undergoes facile reductive elimination
affording the expected product 61 and reconstituting the Pd(0)
complex 57. Although the above mechanism seems viable for
the majority of the investigated reactions, for some specic
combinations of substrates, alternative scenarios should also be
considered. For instance, the formation of chelate 62 (possibly
being in equilibrium with 59), in which palladium is bound by
both alkyne and active methylene moieties, could facilitate the
insertion of the Pd–arene to the alkyne (syn-carbometallation),
and thus rationalize the formation of some amount of another
diastereoisomer of the product with altered conguration at the
exocyclic double bond (64).
Oxidative addition to Pd(0) ligated to a single electron-rich
monophosphine is fast. In fact, oxidative addition of bro-
moarene to XPhos–Pd(0) complex proceeds within minutes at
room temperature, as observed by 31P NMR spectroscopy.
Reductive elimination from Pd complexes of sterically
demanding ligands is also facile. In particular, we have recently
shown that the reductive elimination is not a rate-limiting step
in the XPhos–Pd-catalyzed tandem cyclization/coupling of 3-
acetylenic b-ketoesters with aryl bromides (Scheme 2a).8 The
tandem reaction of ketoester 65 with bromobenzene is much
slower than Negishi coupling of compound 66 with diphe-
nylzinc, both proceeding through reductive elimination from
a common intermediate 67. This points towards the conclusion
that the cyclization step is a bottleneck of the transformation. In
order to shed more light on the inuence of the structure of
reagents on the reaction outcome, we compared the rate of
Experimental
All manipulations were performed in a nitrogen-lled glove-
box or under an argon atmosphere using Schlenk techniques,
unless mentioned otherwise. Flash chromatography was per-
formed using Merck silica gel 60 (230–400 mesh). TLC analysis
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Scheme 2 Control experiments.
of reaction mixtures was performed on Merck silica gel 60 recorded with a Bruker AV 400 spectrometer. 1H and 13C
F254 TLC plates and visualized with cerium molybdate stain chemical shis are given in ppm relative to TMS. Solvent
(Hanessian's stain). 1H, 13C{1H}, and 19F NMR spectra were signals were used as references (CDCl3dH ¼ 7.26 ppm, dC
¼
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77.0 ppm) and the chemical shi converted to the TMS scale. ¼ 7.2, 2.5 Hz, 2H), 2.40 (t, J ¼ 6.9 Hz, 2H), 1.84 (p, J ¼ 7.1 Hz,
Coupling constants (J) are reported in Hz, and the following 2H); 13C NMR (101 MHz, CDCl3) d 171.4, 141.0, 137.6, 128.7,
abbreviations were used to denote multiplets: s ¼ singlet, d ¼ 128.2, 127.4, 126.8, 65.4, 52.8, 35.7, 32.0, 24.8; IR (CH2Cl2): 3053,
doublet, t ¼ triplet, q ¼ quartet, quint ¼ quintet, m ¼ multi- 3024, 2953, 2878, 2842, 1733, 1431, 1263, 1152, 773, 696 cmꢂ1
;
plet (denotes a complex pattern), dd ¼ doublet of doublets, dt HRMS (ESI) m/z calcd for
¼ doublet of triplets and br ¼ broad signal. Infrared spectra 297.1097.
were recorded with a Jasco FTIR-6200 spectrometer. Electron
C16H18O4Na 297.1103; found
ionization high-resolution mass spectra (EI-HR) were recorded Dimethyl (2E)-2-(4-methoxybenzylidene)cyclopentane-1,1-
with an Autospec Premier (Waters Inc) mass spectrometer dicarboxylate (3)
using the narrow-range high-voltage scan technique with low-
Prepared in reaction of dimethyl 4-pentenylmalonate and 4-
bromoanisole following general procedure (110 mg, yield 91%)
or in reaction with 4-chloroanisole following modied general
boiling peruorokerosene (PFK) as internal standard. Samples
were introduced by using a heated direct insertion probe.
Electrospray ionization high-resolution mass spectra (ESI-HR)
were recorded with MALDISynapt G2-S HDMS (Waters Inc)
mass spectrometer equipped with an electrospray ion source
and q-TOF type mass analyzer. ESI-MS spectra were recorded
in the positive ion mode (source parameters: capillary voltage
3.15 kV, sampling cone 25 V, source temperature 120 ꢀC,
ꢀ
procedure (run at 80 C) (81 mg, yield 67%). Product was iso-
lated as oil aer column chromatography on silica gel (15 g, hex/
AcOEt 80 : 20). 1H NMR (400 MHz, CDCl3) d 7.31–7.26 (m, 2H),
6.89–6.84 (m, 2H), 6.63 (t, J ¼ 2.6 Hz, 1H), 3.80 (s, 3H), 3.76 (s,
6H), 2.69 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.38 (t, J ¼ 6.9 Hz, 2H), 1.83 (p,
J ¼ 7.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.5, 158.4, 138.7,
130.4, 129.9, 126.8, 113.6, 65.3, 55.2, 52.7, 35.7, 31.9, 24.8; IR
(CH2Cl2): 2954, 2838, 1732, 1606, 1512, 1435, 1251, 1177, 1033,
826 cmꢂ1; HRMS (ESI): m/z calcd for C17H20O5Na 327.1208;
found 327.1196.
ꢀ
desolvation temperature 150 C).
Unless otherwise noted, all commercially available
compounds (ABCR, Acros, Fluorochem, TCI, Sigma-Aldrich,
Strem) were used as received. Phosphine ligands were
purchased from Aldrich or Fluorochem, Pd(OAc)2 was
purchased from Strem. Buchwald-type 3rd-generation pallada-
cyclic precatalysts (Ligand Pd G3) were prepared following
literature procedures,15 and showed similar reactivity to the
commercial samples (XPhos Pd G3 was compared with
commercial samples). Dimethyl pent-4-yn-1-ylmalonate 1 and
other acetylenic active methylene compounds were synthesized
by alkylation of dimethyl malonate or other C–H acids with 1-
iodo-pentyne, according to typical literature procedures.
Dimethyl (2E)-2-(4-aminobenzylidene)cyclopentane-1,1-
dicarboxylate (4)
Prepared in reaction of dimethyl 4-pentenylmalonate and 4-
bromoaniline following general procedure (63 mg, yield 55%).
Product was isolated as oil aer column chromatography on
silica gel (15 g, hex/AcOEt 80 : 20 / 70 : 30) 1H NMR (400
MHz, CDCl3) d 7.16 (d, J ¼ 8.4 Hz, 2H), 6.64 (d, J ¼ 8.4 Hz, 2H),
6.57 (t, J ¼ 2.3 Hz, 1H), 3.75 (s, 6H), 2.68 (td, J ¼ 7.2, 2.4 Hz,
2H), 2.36 (t, J ¼ 7.0 Hz, 2H), 1.82 (p, J ¼ 7.1 Hz, 2H); 13C NMR
(101 MHz, CDCl3) d 171.7, 145.3, 137.2, 129.9, 128.2, 127.2,
114.7, 65.3, 52.7, 35.8, 31.9, 24.9; IR (CH2Cl2): 3467, 3378,
2953, 1728, 1623, 1516, 1264, 1180, 1153, 825, 526 cmꢂ1; MS
(EI): m/z (%) ¼ 290(21), 289(67)[M+], 231(29), 230(100), 229(21),
202(19), 171(30), 170(94), 143(21), 106(22), 73(38), 57(28),
55(17), 43(23); HRMS (EI): m/z calcd for C16H19NO4 289.1314;
found 289.1316.
General procedure A for Pd-catalyzed carbocyclization-
coupling of aryl bromides with acetylenic active methylene
compounds
In a drybox, a 4 ml screw-cap vial was charged with XPhos Pd G3
(6.8 mg, 8 mmol), aryl halide (0.5 mmol), K3PO4 (127.2 mg, 0.6
mmol), DMF (1 ml), and a magnetic stirring bar. Then, acety-
lenic active methylene compound (e.g. dimethyl pent-4-yn-1-
ylmalonate 1) was added (0.4 mmol), the vial was tightly
sealed and removed from drybox. The reaction mixture was
stirred for 24 h at 50 ꢀC in a heating block, then cooled to room
temperature, quenched with 20 ml of an NH4Cl solution, added
to 10 ml of water, and extracted with MTBE (3 ꢁ 10 ml). The
combined organic phases were dried with Na2SO4, ltered, and
concentrated. The crude product was puried by column
chromatography on silica gel.
Dimethyl (2E)-2-(4-(dimethylamino)benzylidene)
cyclopentane-1,1-dicarboxylate (5)
Prepared in reaction of dimethyl 4-pentenylmalonate and 4-
bromo-N,N-dimethylaniline following general procedure
(85 mg, yield 67%). Product was isolated as oil aer column
chromatography on silica gel (15 g, hex/AcOEt 90 : 10 /
70 : 30). 1H NMR (400 MHz, CDCl3) d 7.29–7.24 (m, 2H), 6.70 (d,
J ¼ 8.8 Hz, 2H), 6.60 (t, J ¼ 2.3 Hz, 1H), 3.76 (s, 6H), 2.96 (s, 6H),
2.72 (td, J ¼ 7.2, 2.4 Hz, 2H), 2.38 (t, J ¼ 7.0 Hz, 2H), 1.83 (p, J ¼
Dimethyl (2E)-2-benzylidenecyclopentane-1,1-dicarboxylate (2)
Prepared in reaction of dimethyl 4-pentenylmalonate and bro- 7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.8, 149.3, 136.5,
mobenzene following general procedure (105 mg, 90%) or in 129.7, 127.2, 126.2, 112.1, 65.3, 52.6, 40.4, 35.8, 31.9, 24.9; IR
reaction with chlorobenzene following modied general (CH2Cl2): 2952, 2881, 2804, 1730, 1608, 1522, 1434, 1355, 1247,
procedure (run at 80 C) (71 mg, yield 65%). Product was iso- 1162, 1064, 813, 530 cmꢂ1; MS (EI): m/z (%) ¼ 318(21), 317(69)
ꢀ
lated as oil aer column chromatography on silica gel (15 g, hex/ [M+], 259(29), 258(100), 199(20), 198(49), 171(12), 153(9),
1
AcOEt 95 : 5). H NMR (400 MHz, CDCl3) d 7.37–7.30 (m, 4H), 134(13), 77(5), 59(7); HRMS (EI): m/z calcd for C18H23NO4
7.24–7.19 (m, 1H), 6.71 (t, J ¼ 2.4 Hz, 1H), 3.78 (s, 6H), 2.72 (td, J 317.1627; found 317.1636.
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69%). Product was isolated as oil aer column chromatography
on silica gel (15 g, hex/AcOEt 90 : 10). 1H NMR (400 MHz, CDCl3)
d 7.84–7.79 (m, 4H), 7.52 (dd, J ¼ 8.5, 1.4 Hz, 1H), 7.48–7.44 (m,
2H), 6.90 (t, J ¼ 2.3 Hz, 1H), 3.82 (s, 6H), 2.84 (td, J ¼ 7.2, 2.5 Hz,
2H), 2.46 (t, J ¼ 7.0 Hz, 2H), 1.89 (p, J ¼ 7.0 Hz, 2H); 13C NMR
(101 MHz, CDCl3) d 171.4, 141.5, 135.1, 133.3, 132.23, 128.0,
127.6, 127.6, 127.5, 126.8, 126.0, 125.8, 65.5, 52.8, 35.7, 32.1,
24.8; IR (CH2Cl2): 3053, 2953, 2879, 1732, 1434, 1262, 1065,
1016, 817, 748, 477 cmꢂ1; HRMS (ESI): m/z calcd for C20H20O4Na
347.1248; found 347.1259.
Dimethyl (2E)-2-(4-(triuoromethyl)benzylidene)
cyclopentane-1,1-dicarboxylate (6)
Prepared in reaction of dimethyl 4-pentenylmalonate and 4-bro-
mobenzotriuoride following general procedure (91 mg, yield
67%) or in reaction with 4-chlorobenzotriuoride following
ꢀ
modied general procedure (run at 80 C) (76 mg, yield 56%).
Product was isolated as oil aer column chromatography on
silica gel (15 g, hex/AcOEt/DCM 86 : 9.5 : 0.5). 1H NMR (400 MHz,
CDCl3 d 7.58 (d, J ¼ 8.2 Hz, 2H), 7.43 (d, J ¼ 8.2 Hz, 2H), 6.74 (s,
1H), 3.78 (s, 6H), 2.71 (td, J ¼ 7.2, 2.5 Hz, 2H), 2.41 (t, J ¼ 7.0 Hz,
2H), 1.85 (p, J ¼ 7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.1,
143.8, 141.1, 128.8, 128.6 (q, J ¼ 32.5 Hz), 126.3, 125.0 (q, J ¼ 3.6
Hz), 124.2 (q, J ¼ 271.8 Hz) 65.5, 52.9, 35.6, 32.1, 24.7; 19F NMR
(376 MHz, CDCl3) d ꢂ62.52; IR (CH2Cl2): 2956, 1735, 1615, 1435,
1327, 1265, 1125, 1068, 830, 598 cmꢂ1; MS (EI): m/z (%) ¼ 343(12),
342(39)[M+], 323(18), 310(24), 283(40), 282(61), 252(25), 251(83),
250(41), 224(27), 223(100), 159(37), 77(14), 59(38); HRMS (EI): m/z
calcd for C17H17F3O4 342.1079; found 342.1084.
Dimethyl (2E)-2-(pyridin-3-ylmethylidene)cyclopentane-1,1-
dicarboxylate (10)
Prepared in reaction of dimethyl 4-pentenylmalonate and 3-
bromopyridine following general procedure (92 mg, yield 84%).
Product was isolated as oil aer column chromatography on
silica gel (15 g, hex/AcOEt 80 : 20 / 70 : 30). 1H NMR (400 MHz,
CDCl3) d 8.56 (d, J ¼ 2.0 Hz, 1H), 8.41 (dd, J ¼ 4.8, 1.5 Hz, 1H),
7.61 (dt, J ¼ 7.9, 1.7 Hz, 1H), 7.24–7.19 (m, 1H), 6.64 (t, J ¼
2.4 Hz, 1H), 3.75 (s, 6H), 2.67 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.37 (t, J ¼
7.0 Hz, 2H), 1.82 (p, J ¼ 7.0 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d 171.0, 150.0, 147.7, 143.6, 135.1, 133.2, 124.0, 123.0, 65.4, 52.8,
35.6, 32.0, 24.7; IR (CH2Cl2): 3027, 2953, 2879, 1732, 1567, 1434,
1266, 1065, 1021, 804, 710 cmꢂ1; HRMS (ESI): m/z calcd for
Dimethyl (2E)-2-(4-acetylbenzylidene)cyclopentane-1,1-
dicarboxylate (7)
Prepared in reaction of dimethyl 4-pentenylmalonate and 4-bro-
moacetophenone following general procedure (57 mg, yield 45%)
or in reaction with 4-chloroacetophenone following modied
ꢀ
general procedure (run at 80 C) (75 mg, yield 60%, isomer E/Z
C
15H17NO4 276.1212; found 276.1232.
55 : 45). Product was isolated as oil aer column chromatography
1
on silica gel (15 g, hex/AcOEt 90 : 10 / 80 : 20). H NMR (400
Dimethyl (2E)-2-(pyridin-2-ylmethylidene)cyclopentane-1,1-
MHz, CDCl3): d 7.92–7.88 (m, 2H), 7.43–7.38 (m, 2H), 6.73 (t, J ¼
2.6 Hz, 1H), 3.76 (s, 6H), 2.71 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.57 (s, 3H),
2.39 (t, J ¼ 6.9 Hz, 2H), 1.84 (p, J ¼ 7.1 Hz, 2H); 13C NMR (101
MHz, CDCl3): d 197.5, 171.0, 144.0, 142.2, 135.2, 128.7, 128.2,
126.6, 65.6, 52.8, 35.6, 32.2, 26.5, 24.7; IR (CH2Cl2): 2954, 1732,
1682, 1602, 1435, 1360, 1268, 590 cmꢂ1; HRMS (ESI): m/z calcd for
C18H20O5Na 339.1208; found: 339.1201.
dicarboxylate (11)
Prepared in reaction of dimethyl 4-pentenylmalonate and 2-
bromopyridine following general procedure (64 mg, yield 58%)
or in reaction with 2-cꢀhloropyridine following modied general
procedure (run at 80 C) (60 mg, yield 55%). Product was iso-
lated as oil aer column chromatography on silica gel (15 g, hex/
AcOEt 80 : 20 / 70 : 30). 1H NMR (400 MHz, CDCl3) d 8.57 (dd, J
¼ 4.8, 1.9, 0.9 Hz, 1H), 7.59 (td, J ¼ 7.7, 1.9 Hz, 1H), 7.28–7.20
(m, 1H), 7.07–7.02 (m, 1H), 6.74 (t, J ¼ 2.7 Hz, 1H), 3.74 (s, 6H),
2.94 (td, J ¼ 7.3, 2.6 Hz, 2H), 2.37 (t, J ¼ 6.9 Hz, 2H), 1.82 (p, J ¼
7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.1, 156.4, 149.1,
146.1, 135.8, 126.6, 124.07, 121.0, 65.8, 52.8, 35.6, 32.7, 24.6; IR
(CH2Cl2): 3050, 2954, 2280, 1732, 1584, 1438, 1433, 1263, 1151,
Dimethyl (2E)-2-(2-methoxybenzylidene)cyclopentane-1,1-
dicarboxylate (8)
Prepared in reaction of dimethyl 4-pentenylmalonate and 2-
bromoanisole following general procedure (88 mg, yield 73%)
or in reaction with 2-chloroanisole following modied general
procedure (run at 80 C) (63 mg, yield 51%). Product was iso- 738, 747 cmꢂ1; HRMS (ESI): m/z calcd for C15H17NO4 276.1236;
lated as oil aer column chromatography on silica gel (15 g, hex/ found 276.1223.
ꢀ
1
AcOEt 85 : 15). H NMR (400 MHz, CDCl3) d 7.34 (dd, J ¼ 7.6,
1.7 Hz, 1H), 7.23–7.17 (m, 1H), 6.97 (t, J ¼ 2.6 Hz, 1H), 6.92 (td, J
Dimethyl (2E)-2-(4-(hydroxymethyl)benzylidene)cyclopentane-
¼ 7.5, 1.2 Hz, 1H), 6.85 (dd, J ¼ 8.3, 1.1 Hz, 1H), 3.81 (s, 3H), 3.78
1,1-dicarboxylate (12)
(s, 6H), 2.64 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.39 (t, J ¼ 6.9 Hz, 2H), 1.80
Prepared in reaction of dimethyl 4-pentenylmalonate and 4-
bromobenzyl alcohol following general procedure (72 mg, yield
60%). Product was isolated as oil aer column chromatography
(p, J ¼ 7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.5, 157.0,
140.5, 128.9, 128.1, 126.7, 122.3, 120.0, 110.5, 64.9, 55.5, 52.6,
35.7, 31.8, 24.7; IR (CH2Cl2): 2953, 2839, 1732, 1597, 1487, 1461,
on silica gel (15 g, hex/AcOEt 60 : 40). 1H NMR (400 MHz, CDCl3)
1436, 1248, 1136, 755 cmꢂ1; HRMS (ESI): m/z calcd for
d 7.34–7.27 (m, 4H), 6.67 (t, J ¼ 2.5 Hz, 1H), 4.64 (s, 2H), 3.75 (s,
C
17H20O5Na 327.1208; found 327.1203.
6H), 2.68 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.37 (t, J ¼ 6.9 Hz, 2H), 2.11 (s,
1H), 1.82 (p, J ¼ 7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.4,
141.0, 139.5, 136.9, 128.8, 127.1, 126.7, 65.4, 64.8, 52.8, 35.7,
32.0, 24.7; IR (CH2Cl2): 3426, 2953, 2877, 1730, 1435, 1265, 1163,
Dimethyl (2E)-2-(naphthalen-2-ylmethylidene)cyclopentane-
1,1-dicarboxylate (9)
Prepared in reaction of dimethyl 4-pentenylmalonate and 2- 1013 cmꢂ1; HRMS (ESI): m/z calcd for C17H20O5Na 327.1208;
bromonaphthalene following general procedure (90 mg, yield found 327.1205.
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(td, J ¼ 7.1, 2.4 Hz, 2H), 2.37 (t, J ¼ 6.9 Hz, 2H), 1.83 (p, J ¼
7.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.4, 147.5, 146.4,
139.3, 131.9, 127.1, 123.0, 108.6, 108.1, 100.9, 65.3, 52.7, 35.7,
31.9, 24.8; IR (CH2Cl2): 2963, 2890, 1730, 1491, 1442, 1254, 1038,
930, 809 cmꢂ1; MS (EI): m/z (%) ¼ 319(25), 318(81)[M+], 260(18),
259(63), 258(38), 231(29), 227(23), 200(31), 199(100), 169(36),
141(34), 135(30), 115(27), 77(13), 59(21); HRMS (EI): m/z calcd
for C17H18O6 318.1103; found 318.1095.
Dimethyl (2E)-2-(4-chlorobenzylidene)cyclopentane-1,1-
dicarboxylate (13)
Prepared in reaction of dimethyl 4-pentenylmalonate and 1-
bromo-4-chlorobenzene following general procedure (70 mg,
57%). Product was isolated as oil aer column chromatography
on silica gel (15 g, hex/AcOEt 90 : 10). 1H NMR (400 MHz,
CDCl3): d 7.31–7.23 (m, 4H), 6.65 (t, J ¼ 2.5 Hz, 1H), 3.76 (s, 6H),
2.66 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.38 (t, J ¼ 6.9 Hz, 2H), 1.88–1.80
(m, 2H); 13C NMR (101 MHz, CDCl3): d 171.2, 141.7, 136.0, 132.5,
129.9, 128.3, 126.3, 65.4, 52.8, 35.7, 32.0, 24.7; IR (CH2Cl2): 2953,
1733, 1491, 1434, 1265, 821, 519 cmꢂ1; HRMS (ESI): m/z calcd
for C16H17O4ClNa 331.0713; found 331.0706.
Dimethyl (2E)-2-(2-(methoxycarbonyl)benzylidene)
cyclopentane-1,1-dicarboxylate (17)
Prepared in reaction of dimethyl 4-pentenylmalonate and
methyl 2-bromobenzoate following general procedure (102 mg,
yield 77%). Product was isolated as oil aer column chroma-
tography on silica gel (15 g, hex/AcOEt 90 : 10 / 70 : 30).1H
NMR (400 MHz, CDCl3) d 7.89 (dd, J ¼ 7.8, 1.4 Hz, 1H), 7.48–7.39
(m, 2H), 7.30–7.25 (m, 1H), 7.19 (t, J ¼ 2.6 Hz, 1H), 3.85 (s, 3H),
3.80 (s, 6H), 2.49 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.38 (t, J ¼ 6.9 Hz, 2H),
1.77 (p, J ¼ 7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.3,
167.5, 141.1, 138.9, 131.4, 130.3, 129.8, 129.3, 126.9, 126.7, 64.4,
52.7, 51.9, 35.8, 31.3, 24.6; IR (CH2Cl2): 2953, 1729, 1598, 1569,
1434, 1257, 1127, 1078, 777, 740 cmꢂ1; MS (EI): m/z (%) ¼ 332(8)
[M+], 301(12), 300(24), 273(23), 268(12), 241(42), 240(100),
213(38), 182(27), 181(72), 153(32), 128(17), 115(18), 91(12),
77(14), 59(23); HRMS (EI): m/z calcd for C18H20O6 332.1260;
found 332.1255.
Dimethyl (2E)-2-(isoquinolin-5-ylmethylidene)cyclopentane-
1,1-dicarboxylate (14)
Prepared in reaction of dimethyl 4-pentenylmalonate and 5-
bromoisoquinoline following general procedure (93 mg, yield
72%). Product was isolated as oil aer column chromatography
1
on silica gel (15 g, hex/AcOEt 70 : 30 / 60 : 40). H NMR (400
MHz, CDCl3) d 9.21 (s, 1H), 8.53 (d, J ¼ 6.0 Hz, 1H), 7.82 (dd, J ¼
15.3, 6.9 Hz, 2H), 7.61–7.52 (m, 2H), 7.19 (s, 1H), 3.82 (s, 6H),
2.49–2.42 (m, 4H), 1.75 (p, J ¼ 7.0 Hz, 2H); 13C NMR (101 MHz,
CDCl3) d 171.2, 152.7, 144.2, 143.2, 134.3, 134.1, 129.5, 128.6,
126.7, 126.5, 123.7, 117.5, 64.6, 52.9, 35.9, 31.6, 24.4; IR
(CH2Cl2): 2953, 1732, 1617, 1584, 1434, 1261, 1152, 832, 762,
475 cmꢂ1; MS (EI): m/z (%) ¼ 326(12), 325(57)[M+], 275(9),
267(4), 234(75), 207(30), 206(100), 204(26), 156(13), 142(14),
98(2), 77(6), 43(12); HRMS (EI): m/z calcd for C19H19NO4
325.1314, found: 325.1317.
Dimethyl (2E)-2-(1,3-benzothiazol-5-ylmethylidene)
cyclopentane-1,1-dicarboxylate (18)
Prepared in reaction of dimethyl 4-pentenylmalonate and 5-
bromobenzothiazole following general procedure (69 mg, yield
52%). Product was isolated as orange solid aer column chro-
matography on silica gel (15 g, hex/AcOEt 75 : 25). 1H NMR (400
MHz, CDCl3) d 8.97 (s, 1H), 8.11 (d, J ¼ 1.7 Hz, 1H), 7.88 (d, J ¼
8.4 Hz, 1H), 7.41 (dd, J ¼ 8.4, 1.7 Hz, 1H), 6.85 (t, J ¼ 2.6 Hz, 1H),
3.78 (s, 6H), 2.78 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.41 (t, J ¼ 6.9 Hz, 2H),
1.86 (p, J ¼ 7.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.3,
154.3, 153.6, 141.9, 136.1, 132.0, 126.8, 126.8, 123.1, 121.3, 65.4,
52.8, 35.7, 32.1, 24.8; IR (CH2Cl2): 2952, 1731, 1540, 1438, 1264,
1153, 1065, 849 cmꢂ1; MS (EI): m/z (%) ¼ 332(21), 331(62)[M+],
272(10), 241(20), 240(62), 213(29), 212(100), 186(18), 152(14),
148(28), 59(14); HRMS (EI): m/z calcd for C17H17NO4S: 331.0878;
found 331.0885.
Dimethyl (2E)-2-(quinolin-5-ylmethylidene)cyclopentane-1,1-
dicarboxylate (15)
Prepared in reaction of dimethyl 4-pentenylmalonate and 5-
bromoquinoline following general procedure (68 mg, yield
52%). Product was isolated as oil aer column chromatography
1
on silica gel (15 g, hex/AcOEt 70 : 30 / 60 : 40). H NMR (400
MHz, CDCl3) d 8.88 (dd, J ¼ 4.2, 1.6 Hz, 1H), 8.41–8.36 (m, 1H),
7.99 (d, J ¼ 8.4 Hz, 1H), 7.67–7.62 (m, 1H), 7.44–7.37 (m, 2H),
7.18 (s, 1H), 3.81 (s, 6H), 2.44 (td, J ¼ 7.0, 2.1 Hz, 4H), 1.73 (p, J ¼
7.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.3, 150.1, 148.3,
144.1, 135.4, 133.2, 128.7, 128.6, 126.8, 126.0, 124.1, 120.9, 64.5,
52.9, 35.9, 31.5, 24.4; IR (CH2Cl2): 2952, 1731, 1593, 1572, 1434,
1254, 1148, 806 cmꢂ1; MS (EI): m/z (%) ¼ 326(10), 325(41)[M+],
265(23), 248(20), 235(27), 234(73), 207(35), 206(100), 204(36),
152(9), 142(24), 59(11); HRMS (EI): m/z calcd for C19H19NO4
325.1314; found 325.1312.
Dimethyl (2E)-2-((2-methyl-1,3-benzoxazol-5-yl)methylidene)
cyclopentane-1,1-dicarboxylate(19)
Prepared in reaction of dimethyl 4-pentenylmalonate and 5-
bromo-2-methyl-1,3-benzoxazole following general procedure
(118 mg, yield 89%). Product was isolated as oil aer column
chromatography on silica gel (15 g, hex/AcOEt 70 : 30). 1H NMR
Dimethyl (2E)-2-(1,3-benzodioxol-5-ylmethylidene)
cyclopentane-1,1-dicarboxylate (16)
Prepared in reaction of dimethyl 4-pentenylmalonate and 4- (400 MHz, CDCl3) d 7.61 (d, J ¼ 2.0 Hz, 1H), 7.37 (d, J ¼ 8.4 Hz,
bromo-1,2-methylenedioxybenzene following general proce- 1H), 7.23 (dd, J ¼ 8.5, 1.8 Hz, 1H), 6.77 (t, J ¼ 2.6 Hz, 1H), 3.75 (s,
dure (112 mg, yield 88%). Product was isolated as oil aer 6H), 2.70 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.59 (s, 3H), 2.37 (t, J ¼ 6.9 Hz,
column chromatography on silica gel (15 g, hex/AcOEt 70 : 30 2H), 1.82 (p, J ¼ 7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 171.3,
/ 50 : 50). 1H NMR (400 MHz, CDCl3) d 6.87 (s, 1H), 6.83–6.74 164.2, 149.8, 141.6, 140.6, 134.1, 127.1, 125.9, 119.0, 109.6, 65.3,
(m, 2H), 6.59 (t, J ¼ 2.3 Hz, 1H), 5.93 (s, 2H), 3.76 (s, 6H), 2.67 52.7, 35.7, 31.9, 24.8, 14.4; IR (CH2Cl2): 3456, 2954, 1732, 1578,
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1434, 1265, 919, 812 cmꢂ1; MS (EI): m/z (%) ¼ 330(15), 329(45)
[M+], 269(37), 252(23), 238(59), 211(30), 210(100), 169(33),
146(28), 141(31), 115(23), 91(5), 77(9), 59(19); HRMS (EI): m/z
calcd for C18H19NO5 329.1263; found 329.1274.
Dimethyl (2E)-2-(thiophen-2-ylmethylidene)cyclopentane-1,1-
dicarboxylate (23)
Prepared in reaction of dimethyl 4-pentenylmalonate and 2-
bromothiophene following general procedure (53 mg, yield
47%). Product was isolated as oil aer column chromatography
1
on silica gel (15 g, hex/AcOEt 98 : 2 / 90 : 10). H NMR (400
Dimethyl (2E)-2-(4-cyanobenzylidene)cyclopentane-1,1-
MHz, CDCl3) d 7.31–7.27 (m, 1H), 7.04–7.01 (m, 2H), 6.93 (t, J ¼
2.7 Hz, 1H), 3.76 (s, 6H), 2.69 (td, J ¼ 7.3, 2.6 Hz, 2H), 2.40 (t, J ¼
6.9 Hz, 2H), 1.90 (p, J ¼ 7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3)
d 171.1, 141.3, 138.7, 127.4, 126.9, 125.6, 120.8, 65.3, 52.8, 36.1,
dicarboxylate (20)
Prepared in reaction of dimethyl 4-pentenylmalonate and 4-
bromobenzonitrile following general procedure (73 mg, yield
62%) or in reaction with 4-chlorobenzonitrile following modi-
ed general procedure (run at 80 ꢀC) (47 mg, yield 39%, isomer
E/Z 56 : 44). Product was isolated as oil aer column chroma-
tography on silica gel (15 g, hex/AcOEt 98 : 2 / 90 : 10). 1H
NMR (400 MHz, CDCl3) d 7.60 (d, J ¼ 8.3 Hz, 2H), 7.41 (d, J ¼
8.3 Hz, 2H), 6.71 (t, J ¼ 2.4 Hz, 1H), 3.76 (s, 6H), 2.68 (td, J ¼ 7.2,
2.5 Hz, 2H), 2.39 (t, J ¼ 6.9 Hz, 2H), 1.89–1.80 (m, 2H); 13C NMR
(101 MHz, CDCl3) d 170.8, 145.1, 142.0, 131.9, 129.1, 126.1,
118.9, 110.1, 65.6, 52.9, 35.5, 32.2, 24.7; IR (CH2Cl2): 2955, 2225,
1732, 1604, 1435, 1264, 1115, 826, 555 cmꢂ1; HRMS (ESI): m/z
calcd for C17H17NO4Na 322.1055; found: 322.1045.
32.2, 24.5; IR (CH2Cl2): 2952, 1731, 1433, 1261, 1148, 701 cmꢂ1
;
MS (EI): m/z (%) ¼ 280(53)[M+], 222(36), 221(100), 220(84),
190(21), 189(62), 167(30), 161(87), 128(32), 115(20), 97(52),
77(23), 59(32); HRMS (EI): m/z calcd for C14H16O4S 280.0769;
found 280.0761.
Dimethyl (2E)-2-(2-chlorobenzylidene)cyclopentane-1,1-
dicarboxylate (24)
Prepared in reaction of dimethyl 4-pentenylmalonate and 1-
chloro-2-bromobenzene following general procedure (114 mg,
yield 93%). Product was isolated as oil aer column chroma-
1
Dimethyl (2E)-2-(4-formylbenzylidene)cyclopentane-1,1-
tography on silica gel (15 g, hex/AcOEt 90 : 10). H NMR (400
dicarboxylate (21)
MHz, CDCl3) d 7.40–7.34 (m, 2H), 7.24–7.19 (m, 1H), 7.18–7.13
(m, 1H), 6.95 (t, J ¼ 2.6 Hz, 1H), 3.79 (s, 6H), 2.58 (td, J ¼ 7.2,
Prepared in reaction of dimethyl 4-pentenylmalonate and 4-
bromobenzaldehyde following general procedure (62 mg, yield
51%). Product was isolated as oil aer column chromatography
2.6 Hz, 2H), 2.39 (t, J ¼ 6.9 Hz, 2H), 1.81 (p, J ¼ 7.0 Hz, 2H); 13
C
NMR (101 MHz, CDCl3) d 171.1, 142.9, 135.7, 133.7, 129.6, 129.3,
128.1, 126.2, 124.5, 64.7, 52.8, 35.7, 31.6, 24.7; IR (CH2Cl2): 2953,
1733, 1590, 1436, 1258, 1138, 751, 606 cmꢂ1; MS (EI): m/z (%) ¼
310(22), 308(48)[M+], 276(27), 249(42), 248(48), 219(42), 217(83),
213(94), 191(48), 189(100), 153(65), 125(62), 115(26), 77(27);
HRMS (EI) m/z calcd for C16H17O4Cl 308.0815; found 308.0819.
1
on silica gel (15 g, hex/AcOEt 90 : 10 / 80 : 20). H NMR (400
MHz, CDCl3) d 9.97 (s, 1H), 7.83 (d, J ¼ 7.9 Hz, 2H), 7.48 (d, J ¼
7.9 Hz, 2H), 6.75 (t, J ¼ 2.8 Hz, 1H), 3.77 (d, J ¼ 1.1 Hz, 6H), 2.72
(td, J ¼ 7.3, 2.6 Hz, 2H), 2.42–2.37 (m, 2H), 1.85 (p, J ¼ 7.1 Hz,
2H); 13C NMR (101 MHz, CDCl3) d 191.7, 171.0, 144.8, 143.7,
134.6, 129.6, 129.1, 126.6, 65.6, 52.9, 35.6, 32.3, 24.8; IR
(CH2Cl2): 2954, 2840, 1731, 1696, 1602, 1565, 1434, 1264, 1168,
822, 792, 523 cmꢂ1; MS (EI): m/z (%) ¼ 303(17), 302(63)[M+],
270(41), 243(42), 242(50), 213(21), 211(99), 210(54), 183(73),
Dimethyl (2E)-2-(4-nitrobenzylidene)cyclopentane-1,1-
dicarboxylate (25)
156(27), 155(100), 153(49), 128(33), 115(31), 91(37), 77(27), Prepared in reaction of dimethyl 4-pentenylmalonate and 4-
59(33); HRMS (EI): m/z calcd for C17H18O5 302.1154; found bromonitrobenzene following modied general procedure (run
302.1159.
at 80 ꢀC) (61 mg, yield 48%, isomer E/Z 20 : 80) or with 4-
chloronitrobenzene following modied general procedure (run
at 80 ꢀC) (50 mg, yield 40%, isomer E/Z 45 : 55). Product was
isolated as oil aer column chromatography on silica gel (15 g,
Dimethyl (2E)-2-(3-((tert-butoxycarbonyl)amino)benzylidene)
cyclopentane-1,1-dicarboxylate (22)
1
hex/AcOEt 75 : 25). H NMR (400 MHz, CDCl3) d 8.14–8.08 (m,
Prepared in reaction of dimethyl 4-pentenylmalonate and N- 4H), 5.41–5.38 (m, 1H), 3.67 (s, 6H), 3.64 (q, J ¼ 2.3 Hz, 2H),
(tert-butoxycarbonyl)-3-bromoaniline following general proce- 2.57–2.51 (m, 2H), 2.40–2.33 (m, 2H); 13C NMR (101 MHz,
dure (148 mg, yield 95%). Product was isolated as oil aer CDCl3) d 171.2, 170.5, 147.5, 146.5, 146.4, 145.3, 143.5, 139.9,
column chromatography on silica gel (15 g, hex/AcOEt 85 : 15 134.1, 123.0, 129.2, 124.9, 123.4, 122.9, 67.6, 64.0, 52.6, 52.5,
/ 80 : 20). 1H NMR (400 MHz, CDCl3) d 7.39 (s, 1H), 7.24–7.16 39.4, 35.0, 35.0, 33.9, 30.4, 22.6. Indicative signals of minor
1
(m, 2H), 7.00 (dt, J ¼ 7.2, 1.7 Hz, 1H), 6.65 (t, J ¼ 2.7 Hz, 1H), isomer: H NMR (400 MHz, CDCl3) d 7.49–7.45 (m, 2H), 7.37–
6.60 (s, 1H), 3.75 (s, 6H), 2.70 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.37 (t, J ¼ 7.32 (m, 2H), 6.67 (t, J ¼ 2.4 Hz, 1H), 3.47 (s, 6H), 2.68 (td, J ¼
6.9 Hz, 2H), 1.81 (p, J ¼ 7.1 Hz, 2H), 1.50 (s, 9H); 13C NMR (101 7.6, 2.2 Hz, 2H), 2.44 (t, J ¼ 7.0 Hz, 2H), 1.76 (p, J ¼ 7.3 Hz, 2H);
MHz, CDCl3) d 171.3, 152.7, 141.4, 138.4, 138.3, 128.6, 127.2, MS (EI): m/z (%) ¼ 319(36)[M+], 287(33), 260(48), 259(100),
123.4, 118.7, 117.1, 80.3, 65.4, 52.7, 35.7, 32.0, 28.3, 24.8; IR 229(28), 228(99), 227(48), 200(73), 154(66), 128(31), 115(30),
(CH2Cl2): 3361, 2976, 2955, 1729, 1538, 1435, 1237, 1160, 1065, 106(14), 90(19), 77(25), 59(49), 39(16); IR (CH2Cl2): 2953, 2854,
888, 737, 693, 463 cmꢂ1; HRMS (EI): m/z calcd for C21H27NO6 1732, 1597, 1519, 1434, 1346, 1266, 1156, 1066, 857 cmꢂ1; HRMS
389.1736; found 389.1736.
(EI): m/z calcd for C16H17NO6 319.1056; found 319.1057.
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33.8, 30.3, 21.6, 21.6; MS (EI): m/z (%) ¼ 355(11)[M+], 313(7),
269(20), 227(54), 209(30), 180(40), 154(19), 116(29), 77(10),
57(11); HRMS (EI): m/z calcd for C21H25NO4 355.1784; found
355.1781.
Di(propan-2-yl) (2E)-2-benzylidenecyclopentane-1,1-
dicarboxylate (26)
Prepared
in
reaction
of
dipropan-2-yl
2-pent-4-
ynylpropanedioate and bromobenzene following modied
general procedure (run at 80 ꢀC) (56 mg, yield 42%). Product was
isolated as oil aer column chromatography on silica gel (15 g,
Di-tert-butyl (2E)-2-benzylidenecyclopentane-1,1-dicarboxyl-
ate (29)
1
hex/AcOEt 95 : 5). H NMR (400 MHz, CDCl3) d 7.34–7.32 (m,
Prepared in reaction of di-tert-butyl pent-4-yn-1-ylpropanedioate
and bromobenzene following modied general procedure (run
at 80 C) (37 mg, yield 26%). Product was isolated as oil aer
4H), 7.23–7.18 (m, 1H), 6.76 (t, J ¼ 2.6 Hz, 1H), 5.10 (hept, J ¼
6.3 Hz, 2H), 2.70 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.36 (t, J ¼ 6.9 Hz, 2H),
1.82 (p, J ¼ 7.1 Hz, 2H), 1.28 (dd, J ¼ 6.3, 4.1 Hz, 12H); 13C NMR
(101 MHz, CDCl3) d 170.3, 141.2, 137.9, 128.6, 128.1, 127.2,
126.6, 68.8, 65.2, 35.6, 32.1, 24.7, 21.6, 21.5; IR (CH2Cl2): 3450,
2980, 2875, 1722, 1449, 1374, 1251, 1104, 909, 777, 699,
517 cmꢂ1. MS (EI): m/z (%) ¼ 330(27)[M+], 244(35), 202(59),
201(72), 184(54), 183(57), 173(44), 155(100), 129(43), 115(29),
91(56), 77(25), 43(95); HRMS (EI): m/z calcd for C20H26O4
330.1831; found 330.1822.
ꢀ
column chromatography on silica gel (25 g, hex/AcOEt 98 : 2).
1H NMR (400 MHz, CDCl3) d 7.36–7.29 (m, 4H), 7.23–7.17 (m,
1H), 6.77 (t, J ¼ 2.6 Hz, 1H), 2.68 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.30 (t, J
¼ 6.9 Hz, 2H), 1.79 (p, J ¼ 7.0 Hz, 2H), 1.50 (s, 18H); 13C NMR
(101 MHz, CDCl3) d 169.9, 141.5, 138.1, 128.6, 128.1, 127.0,
126.5, 81.2, 66.51, 35.7, 32.1, 27.9, 24.6; MS (EI): m/z (%) ¼
247(3), 246(12), 202(34), 185(14), 184(21), 183(11), 155(21),
142(7), 129(14), 115(13), 106(9), 91(16), 79(16), 57(100), 41(34);
IR (CH2Cl2): 3054, 2977, 2930, 1725, 1599, 1368, 1270, 1166,
1128, 845, 696, 515 cmꢂ1; HRMS (EI): m/z calcd for C22H30O4
358.2144; found 358.2115.
Di(propan-2-yl) (2E)-2-(4-methoxybenzylidene)cyclopentane-
1,1-dicarboxylate (27)
Prepared
in
reaction
of
dipropan-2-yl
2-pent-4-
ynylpropanedioate and 4-bromoanisole following modied
general procedure (run at 80 ꢀC) (68 mg, yield 47%). Product was
isolated as oil aer column chromatography on silica gel (15 g,
Di-tert-butyl (2E)-2-(4-methoxybenzylidene)cyclopentane-1,1-
dicarboxylate (30)
Prepared in reaction of di-tert-butyl pent-4-yn-1-ylpropanedioate
and 4-bromoanisole following modied general procedure (run
1
hex/AcOEt 90 : 10). H NMR (400 MHz, CDCl3) d 7.29–7.24 (m,
2H), 6.88–6.84 (m, 2H), 6.68 (t, J ¼ 2.6 Hz, 1H), 5.08 (hept, J ¼
6.2 Hz, 2H), 3.80 (s, 3H), 2.67 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.33 (t, J ¼
6.9 Hz, 2H), 1.81 (p, J ¼ 7.1 Hz, 2H), 1.26 (dd, J ¼ 6.3, 4.0 Hz,
12H); 13C NMR (101 MHz, CDCl3) d 170.4, 158.3, 139.0, 130.7,
129.9, 126.7, 113.6, 68.7, 65.1, 55.2, 35.6, 32.0, 24.7, 21.6, 21.5;
IR (CH2Cl2): 2979, 2936, 1724, 1607, 1511, 1466, 1250, 1103, 827,
530 cmꢂ1; MS (EI): m/z (%) ¼ 361(14), 360(43) [M+], 317(11),
273(36), 232(32), 231(100), 214(33), 213(30), 185(53), 171(12),
159(13), 135(17), 121(28), 115(21), 43(50), 41(24); HRMS (EI): m/z
calcd for C21H28O5 360.1937; found 360.1936.
ꢀ
at 80 C) (35 mg, yield 23%). Product was isolated as oil aer
column chromatography on silica gel (25 g, hex/AcOEt 90 : 10).
1H NMR (400 MHz, CDCl3) d 7.29–7.25 (m, 2H), 6.88–6.84 (m,
2H), 6.69 (t, J ¼ 2.5 Hz, 1H), 3.80 (s, 3H), 2.65 (td, J ¼ 7.2, 2.6 Hz,
2H), 2.27 (t, J ¼ 6.9 Hz, 2H), 1.78 (p, J ¼ 7.1 Hz, 2H), 1.48 (s,
18H); 13C NMR (101 MHz, CDCl3) d 170.1, 158.3, 139.3, 130.9,
129.9, 126.4, 113.6, 81.2, 66.5, 55.2, 35.7, 32.1, 27.9, 27.7, 24.6;
IR (CH2Cl2) 3449, 2977, 2934, 1725, 1607, 1511, 1456, 1368,
1251, 1167, 1129, 1036, 848, 828 cmꢂ1; MS (EI): m/z (%) ¼ 388(7)
[M+], 276(22), 232(40), 231(100), 214(25), 203(11), 185(36),
171(12), 121(21), 115(15), 91(4), 77(8), 57(96), 43(12), 41(33);
HRMS (EI): m/z calcd for C23H32O5 388.2250; found 388.2242.
Di(propan-2-yl) (2E)-2-(4-cyanobenzylidene)cyclopentane-1,1-
dicarboxylate (28)
Di-tert-butyl (2E)-2-(4-cyanobenzylidene)cyclopentane-1,1-
dicarboxylate (31)
Prepared
in
reaction
of
dipropan-2-yl
2-pent-4-
ynylpropanedioate and 4-bromobenzonitrile following modi-
ed general procedure (run at 80 ꢀC) (37 mg, yield 26%, isomer Prepared in reaction of di-tert-butyl pent-4-yn-1-ylpropanedioate
E/Z 75 : 25). Product was isolated as oil aer column chroma- and 4-bromobenzonitrile following modied general procedure
tography on silica gel (25 g, hex/AcOEt 95 : 5). 1H NMR (400 (run at 80 C) (54 mg, yield 35%, isomer E/Z 35 : 65). Product
ꢀ
MHz, CDCl3) d 7.55–7.49 (m, 4H), 6.62 (t, J ¼ 2.2 Hz, 1H), 4.81 was isolated as oil aer column chromatography on silica gel
(hept, J ¼ 6.3 Hz, 2H), 2.68 (td, J ¼ 7.6, 2.2 Hz, 2H), 2.43 (t, J ¼ (25 g, hex/AcOEt 95 : 5). 1H NMR (400 MHz, CDCl3) d 7.55–7.50
7.0 Hz, 2H), 1.76 (p, J ¼ 7.2 Hz, 2H), 1.13 (d, J ¼ 6.2 Hz, 6H), 1.04 (m, 4H), 6.57 (t, 1H), 2.65 (td, J ¼ 7.5, 2.3 Hz, 3H), 2.37 (t, J ¼
(d, J ¼ 6.3 Hz, 6H); 13C NMR (101 MHz, CDCl3) d 169.6, 144.7, 6.9 Hz, 2H), 1.76–1.69 (m, 2H), 1.28 (s, 18H). 13C NMR (101
132.1, 131.5, 130.2, 129.3, 125.2, 110.1, 69.5, 64.3, 39.8, 35.8, MHz, CDCl3) d 169.2, 145.0, 141.8, 131.5, 129.5, 124.7, 109.9,
22.7, 21.4, 21.3; IR (CH2Cl2): 2981, 2937, 2226, 1724, 1604, 1375, 109.8, 81.9, 65.3, 40.5, 36.5, 27.6, 22.7; indicative signals of
1
1265, 1102, 1128, 845, 696, 515 cmꢂ1; Indicative signals of minor isomer: H NMR (400 MHz, CDCl3) d 7.61–7.56 (m, 2H),
1
minor isomer (Z): H NMR (400 MHz, CDCl3) d 7.59–7.55 (m, 7.42–7.37 (m, 2H), 6.76 (t, J ¼ 2.6 Hz, 1H), 2.29 (t, J ¼ 6.9 Hz, 2H),
2H), 7.35–7.30 (m, 2H), 5.23 (p, J ¼ 2.1 Hz, 1H), 5.05 (hept, J ¼ 1.84–1.76 (m, 2H), 1.47 (s, 18H); 13C NMR (101 MHz, CDCl3)
6.3 Hz, 2H), 3.61–3.55 (m, 2H), 2.55–2.48 (m, 2H), 2.37–2.30 (m, d 169.36, 145.66, 142.49, 131.90, 129.00, 125.56, 119.06, 81.62,
2H), 1.25 (dd, J ¼ 6.3, 5.1 Hz, 12H); 13C NMR (101 MHz, CDCl3) 66.83, 35.46, 32.37, 27.84, 24.48; IR (CH2Cl2): 3434, 2978, 2933,
d 170.5, 145.8, 141.7, 140.6, 133.3, 119.1, 110.1, 69.0, 68.0, 35.3, 2226, 1724, 1604, 1456, 1368, 1128, 1065, 844, 555 cmꢂ1; MS
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(EI): m/z (%) ¼ 384(1)[M+], 327(4), 283(10), 271(13), 254(9), 116(28), 77(8), 57(100), 43(16), 41(28); HRMS (ESI): m/z calcd for
227(42), 210(15), 180(13), 153(11), 116(12), 77(3), 57(100), 43(6),
41(23).
C19H20N2O2Na 331.1525; found 331.1397.
Propan-2-yl (2E)-2-benzylidene-1-cyanocyclopentane-
tert-Butyl (2E)-2-benzylidene-1-cyanocyclopentanecarboxylate
carboxylate (35)
(32)
Prepared in reaction of propan-2-yl 2-cyanohept-6-ynoate and
Prepared in reaction of tert-butyl 2-cyanohept-6-ynoate and bromobenzene following modied general procedure (run for 4
bromobenzene following general procedure (82 mg, yield 73%). h) (80 mg, yield 75%). Product was isolated as oil aer column
1
Product was isolated as oil aer column chromatography on chromatography on silica gel (15 g, hex/AcOEt 95 : 5). H NMR
1
silica gel (15 g, hex/AcOEt 90 : 10). H NMR (400 MHz, CDCl3) (400 MHz, CDCl3) d 7.39–7.30 (m, 4H), 7.29–7.24 (m, 1H), 6.84 (t,
d 7.39–7.31 (m, 4H), 7.29–7.24 (m, 1H), 6.85 (t, J ¼ 2.6 Hz, 1H), J ¼ 2.6 Hz, 1H), 5.10 (hept, J ¼ 6.3 Hz, 1H), 2.82–2.68 (m, 2H),
2.78–2.71 (m, 2H), 2.59–2.50 (m, 1H), 2.32–2.24 (m, 1H), 2.14– 2.61–2.53 (m, 1H), 2.35–2.26 (m, 1H), 2.16–2.05 (m, 1H), 2.03–
2.03 (m, 1H), 2.01–1.90 (m, 1H), 1.52 (s, 9H); 13C NMR (101 MHz, 1.91 (m, 1H), 1.32 (t, J ¼ 6.5 Hz, 6H); 13C NMR (101 MHz, CDCl3)
CDCl3) d 166.7, 141.3, 136.4, 128.6, 128.5, 128.3, 127.5, 127.1, d 167.4, 141.0, 136.3, 128.6, 128.4, 127.6, 127.4, 119.9, 70.9, 52.9,
120.1, 83.8, 53.6, 36.4, 30.8, 27.7, 25.1; MS (EI): m/z (%) ¼ 283(1) 36.6, 30.8, 25.1, 21.4, 21.4; IR (CH2Cl2): 2981, 2241, 1737, 1450,
[M+], 182(37), 153(10), 128(12), 115(15), 102(5), 91(17), 77(12), 1376, 1237, 1103, 762, 695, 513 cmꢂ1; MS (EI): m/z (%) ¼ 270(3),
57(100), 43(12), 41(26); IR (CH2Cl2): 3447, 2978, 2877, 2240, 269(14), 184(5), 183(62), 182(82), 155(5), 129(22), 115(20),
2214, 1737, 1449, 1370, 1256, 1150, 840, 695, 513 cmꢂ1; HRMS 102(8), 91(24), 77(18), 52(13), 43(100); HRMS (EI) m/z calcd for
(EI): m/z calcd for C18H21NO2 283.1572; found 283.1564.
C17H19NO2 269.1416; found 269.1422.
tert-Butyl (2E)-1-cyano-2-(4-methoxybenzylidene)
Propan-2-yl (2E)-1-cyano-2-(4-methoxybenzylidene)
cyclopentanecarboxylate (33)
cyclopentanecarboxylate (36)
Prepared in reaction of tert-butyl 2-cyanohept-6-ynoate and 4- Prepared in reaction of propan-2-yl 2-cyanohept-6-ynoate and 4-
bromoanisole following modied general procedure (run at 80 bromoanisole following modied general procedure (run for 4
ꢀC) (121 mg, yield 96%). Product was isolated as oil aer column h) (86 mg, yield 72%). Product was isolated as oil aer column
chromatography on silica gel (15 g, hex/AcOEt 80 : 20).1H NMR chromatography on silica gel (15 g, hex/AcOEt 90 : 10). 1H NMR
(400 MHz, CDCl3) d 7.32–7.23 (m, 2H), 6.93–6.85 (m, 2H), 6.77 (t, (400 MHz, CDCl3) d 7.31–7.23 (m, 2H), 6.92–6.84 (m, 2H), 6.76 (t,
J ¼ 2.6 Hz, 1H), 3.80 (s, 3H), 2.78–2.64 (m, 2H), 2.58–2.46 (m, J ¼ 2.6 Hz, 1H), 5.08 (hept, J ¼ 6.3 Hz, 1H), 3.80 (s, 3H), 2.80–
1H), 2.31–2.20 (m, 1H), 2.13–2.01 (m, 1H), 2.00–1.88 (m, 1H), 2.64 (m, 2H), 2.59–2.49 (m, 1H), 2.33–2.22 (m, 1H), 2.15–2.04
1.51 (s, 9H); 13C NMR (101 MHz, CDCl3) d 166.9, 158.9, 138.9, (m, 1H), 2.01–1.89 (m, 1H), 1.31 (t, J ¼ 6.3 Hz, 6H); 13C NMR (101
129.9, 129.2, 126.6, 120.3, 113.8, 83.7, 55.17, 53.60, 36.5, 30.7, MHz, CDCl3) d 167.5, 159.0, 138.6, 129.9, 129.0, 126.8, 120.0,
27.7, 25.1; IR (CH2Cl2): 2978, 2935, 2838, 2240, 1735, 1607, 1512, 113.8, 70.7, 55.2, 52.9, 36.5, 30.7, 25.1, 21.4, 21.3. IR (CH2Cl2):
1462, 1370, 1253, 1152, 1034, 836, 513 cmꢂ1; MS (EI): m/z (%) ¼ 2981, 2937, 2240, 1736, 1606, 1512, 1465, 1253, 1178, 1103,
313(10)[M+], 213(65), 212(75), 198(28), 167(32), 121(16), 115(14), 1034, 831, 531 cmꢂ1; MS (EI): m/z (%) ¼ 299(19)[M+], 256(4),
91(8), 77(13), 57(100), 43(11), 41(27); HRMS (EI): m/z calcd for 212(100), 198(10), 170(12), 121(13), 115(12), 91(6), 77(10),
C
19H23NO3 313.1678; found 313.1680.
43(52); HRMS (EI): m/z calcd for C18H21NO3 299.1521; found
299.1527.
tert-Butyl (2E)-1-cyano-2-(4-cyanobenzylidene)cyclopentane-
carboxylate (34)
Propan-2-yl (2E)-1-cyano-2-(4-cyanobenzylidene)
cyclopentanecarboxylate (37)
Prepared in reaction of tert-butyl 2-cyanohept-6-ynoate and 4-
bromobenzonitrile following modied general procedure (run Prepared in reaction of propan-2-yl 2-cyanohept-6-ynoate and 4-
at 80 ꢀC) (40 mg, yield 33%, isomer E/Z 23 : 77). Product was bromobenzonitrile following modied general procedure (run
isolated as oil aer column chromatography on silica gel (15 g, for 4 h) (83 mg, yield 70%, isomer E/Z 20 : 80). Product was
1
hex/AcOEt 90 : 10). H NMR (400 MHz, CDCl3) d 7.61–7.56 (m, isolated as oil aer column chromatography on silica gel (15 g,
1
2H), 7.35–7.29 (m, 2H), 5.49–5.45 (m, 1H), 3.58 (dq, J ¼ 16.6, hex/AcOEt 90 : 10). H NMR (400 MHz, CDCl3) d 7.60–7.55 (m,
2.1 Hz, 1H), 3.46 (dq, J ¼ 16.5, 2.2 Hz, 1H), 2.66–2.57 (m, 1H), 2H), 7.32–7.27 (m, 2H), 5.50 (p, J ¼ 1.9 Hz, 1H), 4.95 (hept, J ¼
2.54–2.44 (m, 3H), 1.45 (s, 9H); 13C NMR (101 MHz, CDCl3) 6.3 Hz, 1H), 3.61–3.52 (m, 1H), 3.48–3.40 (m, 1H), 2.67–2.58 (m,
d 166.7, 143.3, 138.5, 134.0, 132.2, 132.1, 130.1, 129.0, 110.6, 1H), 2.56–2.46 (m, 2H), 1.26–1.21 (m, 6H); 13C NMR (101 MHz,
84.1, 56.7, 36.1, 34.61, 31.0, 27.6; Indicative signals of minor CDCl3) d 167.3, 143.1, 138.2, 134.3, 132.7, 132.4, 132.2, 132.1,
isomer (Z): 1H NMR (400 MHz, CDCl3) d 7.66–7.60 (m, 2H), 7.41 130.0, 129.4, 129.0, 127.8, 118.6, 118.5, 110.6, 71.0, 56.0, 36.1,
(d, J ¼ 8.3 Hz, 2H), 6.82 (t, J ¼ 2.7 Hz, 1H), 2.73 (td, J ¼ 7.3, 34.5, 31.0, 21.4, 21.3, 21.3, 21.3; indicative signals of minor
2.6 Hz, 2H), 2.32–2.24 (m, 1H), 2.14–2.03 (m, 1H), 2.02–1.91 (m, isomer (Z): 1H NMR (400 MHz, CDCl3) d 7.78–7.72 (m, 1H), 7.71–
1H), 1.50 (s, 9H); 13C NMR (101 MHz, CDCl3) d 166.2, 145.3, 7.65 (m, 1H), 7.65–7.57 (m, 1H), 7.40 (d, J ¼ 8.4 Hz, 1H), 6.81 (t, J
140.7, 119.6, 118.5, 110.9, 84.3, 53.9, 36.4, 25.0; IR (CH2Cl2): ¼ 2.7 Hz, 1H), 5.08 (p, J ¼ 6.2 Hz, 1H), 2.77–2.70 (m, 1H), 2.36–
3059, 2879, 2935, 2228, 1736, 1606, 1370, 1254, 1152 cmꢂ1; MS 2.26 (m, 2H), 2.16–2.05 (m, 1H), 2.03–1.95 (m, 1H), 1.95–1.88
(EI): m/z (%) ¼ 308(1)[M+], 252(10), 208(26), 207(30), 153(6), (m, 1H), 1.32–1.27 (m, 6H); 13C NMR (101 MHz, CDCl3) d 166.8,
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160.8, 145.0, 143.3, 142.5, 140.6, 125.8, 119.3, 118.2, 112.2,
110.9, 110.81, 110.2, 53.2, 37.1, 36.4, 35.5, 34.1, 25.0, 22.3; IR
(CH2Cl2): 3452, 3060, 2983, 2938, 2228, 1738, 1606, 1326, 1248,
1178, 1104, 834, 553 cmꢂ1; MS (EI): m/z (%) ¼ 294(7)[M+],
252(10), 208(63), 204(34), 180(18), 153(15), 140(19), 116(45),
104(16), 89(20), 77(14), 43(100); HRMS (EI): m/z calcd for
(E)-Methyl 1-acetyl-2-(4-methoxybenzylidene)cyclopentane-
carboxylate (41)
Prepared in reaction of methyl 2-acetylhept-6-ynoate and 4-
bromoanisole following modied general procedure (run for 2
h) (yield: 79%). Product was isolated as oil aer column chro-
matography on silica gel (15 g column, 90 : 10 / 80 : 20
hexanes/EtOAc). 1H NMR (400 MHz, CDCl3) d 7.33–7.26 (m, J ¼
8.7 Hz, 2H), 6.91–6.85 (m, 2H), 6.53 (t, J ¼ 2.4 Hz, 1H), 3.81 (s,
3H), 3.77 (s, 3H), 2.79–2.59 (m, 2H), 2.44 (dt, J ¼ 13.5, 6.9 Hz,
1H), 2.25 (s, 3H), 2.24–2.13 (m, 1H), 1.90–1.76 (m, 2H); 13C NMR
(101 MHz, CDCl3) d 204.3, 172.0, 158.5, 139.2, 130.2, 129.9,
127.1, 113.7, 72.2, 55.2, 52.6, 34.4, 31.9, 26.7, 24.8; IR (CH2Cl2):
2954, 1737, 1712, 1606, 1512, 1461, 1435, 1355, 1251, 1177,
1034, 826, 531 cmꢂ1; MS (EI), m/z (%): 288 (24, M+), 245 (79), 229
(16), 214 (50), 185 (100), 171 (16), 159 (14), 141 (13), 128 (14), 121
(24), 115 (23), 77 (10), 43 (32); HRMS (EI): m/z calcd for
C
18H18N2O2 294.1368; found 294.1363.
(2E)-2-Benzylidenecyclopentane-1,1-dicarbonitrile (38)
Prepared in reaction of pent-4-yn-1-ylpropanedinitrile and bro-
mobenzene following modied general procedure (run for 4 h)
(72 mg, yield 87%). Product was isolated as oil aer column
chromatography on silica gel (15 g, hex/AcOEt 90 : 10). 1H NMR
(400 MHz, CDCl3) d 7.44–7.31 (m, 5H), 6.99 (t, J ¼ 2.7 Hz, 1H),
2.83 (td, J ¼ 7.3, 2.7 Hz, 2H), 2.50 (t, J ¼ 6.9 Hz, 2H), 2.15 (p, J ¼
7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 136.5, 135.0, 129.9,
128.8, 128.7, 128.6, 128.4, 115.4, 40.3, 38.8, 29.3, 24.3; IR
(CH2Cl2): 3058, 3029, 2953, 2246, 1492, 1449, 1194, 921, 760,
694, 512 cmꢂ1; MS (EI): m/z (%) ¼ 208(100)[M+], 207(55),
180(47), 153(30), 115(69), 102(21), 91(33), 77(26), 51(28), 39(26);
HRMS (EI): m/z calcd for C14H12N2 208.1000; found 208.1006.
C
17H20O4: 288.1362. Found 288.1364.
(E)-Methyl 1-acetyl-2-(4-cyanobenzylidene)cyclopentane-
carboxylate (42)
Prepared in reaction of methyl 2-acetylhept-6-ynoate and 4-
bromobenzonitrile following modied general procedure (run
for 2 h) (yield: 75%, E/Z 91 : 9) Product was isolated as oil aer
column chromatography on silica gel (15 g column, 9 : 1 / 8 : 2
hexanes/EtOAc). 1H NMR (400 MHz, CDCl3) d 7.63–7.56 (m, 2H),
7.40 (d, J ¼ 8.3 Hz, 2H), 6.57 (t, J ¼ 2.5 Hz, 1H), 3.78 (s, 3H), 2.76–
2.59 (m, 2H), 2.53–2.43 (m, 1H), 2.24 (s, 3H), 2.22–2.14 (m, 1H),
1.91–1.75 (m, 2H); 13C NMR (101 MHz, CDCl3) d 202.9, 171.3,
145.4, 141.9, 132.0, 129.1, 126.2, 118.9, 110.2, 72.4, 52.9, 34.3,
32.3, 26.8, 24.7; indicative signals of Z isomer: 1H NMR (400
MHz, CDCl3) d 7.52–7.48 (m, 2H), 7.28 (d, J ¼ 8.1 Hz, 2H), 6.68
(s, 1H), 3.40 (s, 3H), 2.06 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 204.3, 145.2, 141.3, 131.6, 125.4, 110.5, 70.3, 52.3, 38.4, 35.8,
23.1; IR (CH2Cl2): 2954, 2880, 2842, 2226, 1738, 1713, 1604,
1503, 1433, 1357, 1239, 1177, 1153, 1129, 886, 827, 555; HRMS
(ESI): m/z calcd for C17H17NO3Na ([M + Na]+): 306.1106. Found
306.1107.
(2E)-2-(4-Methoxybenzylidene)cyclopentane-1,1-dicarbo-
nitrile (39)
Prepared in reaction of pent-4-yn-1-ylpropanedinitrile and 4-
bromoanisole following modied general procedure (run for
4 h) (86 mg, yield 91%). Product was isolated as oil aer
column chromatography on silica gel (15 g, hex/AcOEt
80 : 20). 1H NMR (400 MHz, CDCl3) d 7.34–7.28 (m, 2H),
6.95–6.89 (m, 3H), 3.83 (s, 3H), 2.79 (td, J ¼ 7.3, 2.7 Hz, 2H),
2.47 (t, J ¼ 6.9 Hz, 2H), 2.13 (p, J ¼ 7.1 Hz, 2H); 13C NMR (101
MHz, CDCl3) d 159.6, 133.8, 130.2, 129.3, 127.7, 115.6, 114.0,
55.2, 40.3, 38.8, 29.2, 24.4; IR (CH2Cl2): 2956, 2839, 2246,
1606, 1513, 1463, 1254, 1179, 1032, 890, 829, 531 cmꢂ1; MS
(EI): m/z (%) ¼ 239(29), 238(100)[M+], 237(27), 223(16),
210(29), 195(21), 170(19), 160(40), 145(40), 129(25), 115(27),
91(17), 77(20), 51(17), 43(13), 39(18); HRMS (EI): m/z calcd for
C
15H14N2O 238.1106; found 238.1111.
1-((2E)-1-Benzoyl-2-benzylidenecyclopentyl)ethanone (43)
(E)-Methyl 1-acetyl-2-benzylidenecyclopentanecarboxylate (40)
Prepared in reaction of 2-(pent-4-ynyl)-1-phenylbutane-1,3-
Prepared in reaction of methyl 2-acetylhept-6-ynoate and bro- dione and bromobenzene following modied general proce-
mobenzene following modied general procedure (run for 2 h) dure (run at 80 ꢀC) (55 mg, yield 45%). Product was isolated as
(yield: 80%) product was isolated as oil aer column chro- oil aer column chromatography on silica gel (15 g, hex/AcOEt
1
matography on silica gel (15 g, 95 : 5 / 90 : 10 hexanes/ 90 : 10). H NMR (400 MHz, CDCl3) d 7.83–7.78 (m, 2H), 7.54–
1
EtOAc). H NMR (400 MHz, CDCl3) d 7.37–7.32 (m, 4H), 7.27– 7.49 (m, 1H), 7.44–7.39 (m, 2H), 7.36–7.31 (m, 4H), 7.26–7.21
7.20 (m, 1H), 6.60 (t, J ¼ 2.5 Hz, 1H), 3.78 (s, 3H), 2.80–2.63 (m, (m, 1H), 2.90–2.80 (m, 2H), 2.79–2.69 (m, 1H), 2.34 (s, 3H), 2.32–
2H), 2.50–2.41 (m, 1H), 2.26 (s, 3H), 2.25–2.16 (m, 1H), 1.89– 2.24 (m, 1H), 1.92–1.84 (m, 2H); 13C NMR (101 MHz, CDCl3)
1.75 (m, 2H); 13C NMR (101 MHz, CDCl3) d 204.0, 171.8, 141.5, d 204.8, 199.2, 142.2, 137.4, 135.5, 132.5, 129.3, 128.8, 128.6,
137.4, 128.6, 128.2, 127.6, 126.9, 72.2, 52.6, 34.4, 32.0, 26.8, 128.3, 128.2, 127.0, 77.2, 34.9, 31.8, 27.4, 24.8; IR (CH2Cl2): 3056,
24.8; IR (CH2Cl2): 3410, 2953, 1737, 1714, 1493, 1447, 1433, 3025, 2959, 2876, 1683, 1597, 1446, 1258, 1231, 735, 696,
1356, 1238, 697 cmꢂ1; MS (EI), m/z (%): 258 (7, M+), 216 (80), 516 cmꢂ1; MS (EI): m/z (%) ¼ 304(5)[M+], 262(13), 233(12),
184 (100), 167 (13), 155 (86), 141 (19), 128 (34), 115 (29), 105 199(11), 182(13), 155(10), 128(15), 105(100), 91(19), 77(48),
(14), 91 (35), 77 (23), 43 (46); HRMS (EI): m/z calcd for 51(15), 43(32); HRMS (EI) m/z calcd for C21H20O2 304.1463;
C
16H18O3: 258.1256. Found 258.1255.
found 304.1462.
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183(4), 155(6), 128(7), 115(7), 105(100), 91(13), 77(44), 51(11);
1-((2E)-1-Benzoyl-2-(4-methoxybenzylidene)cyclopentyl)
HRMS (EI): m/z calcd for C26H22O2 366.1620; found 366.1620.
ethanone (44)
Prepared in reaction of 2-(pent-4-ynyl)-1-phenylbutane-1,3-
dione and 4-bromoanisole following modied general proce-
dure (run at 80 ꢀC) (78 mg, yield 60%). Product was isolated as
oil aer column chromatography on silica gel (15 g, hex/AcOEt
((2E)-1-Benzoyl-2-(4-methoxybenzylidene)cyclopentyl)(phenyl)
methanone (47)
Prepared in reaction of 2-(pent-4-ynyl)-1,3-diphenylpropane-1,3-
dione and 4-bromoanisole following modied general proce-
dure (run at 80 ꢀC) (88 mg, yield 56%). Product was isolated as
oil aer column chromatography on silica gel (25 g, hex/AcOEt/
1
80 : 20). H NMR (400 MHz, CDCl3) d 7.81–7.76 (m, 2H), 7.52–
7.47 (m, 1H), 7.42–7.36 (m, 2H), 7.29–7.24 (m, 2H), 6.90–6.85
(m, 2H), 6.40 (t, J ¼ 2.5 Hz, 1H), 3.80 (s, 3H), 2.87–2.74 (m, 2H),
2.73–2.66 (m, 1H), 2.32 (s, 3H), 2.29–2.22 (m, 1H), 1.92–1.82 (m,
2H); 13C NMR (101 MHz, CDCl3) d 204.9, 199.4, 158.6, 139.9,
135.6, 132.4, 130.2, 129.9, 129.2, 128.3, 128.2, 113.7, 77.2, 55.2,
34.9, 31.7, 27.3, 24.9; IR (CH2Cl2): 3059, 2968, 2837, 1684, 1605,
1511, 1446, 1251, 1177, 1032, 880, 829, 701 cmꢂ1; MS (EI): m/z
(%) ¼ 334(25)[M+], 292(50), 291(34), 229(100), 187(33), 135(26),
121(31), 105(89), 77(57), 43(51); HRMS (EI) m/z calcd for
1
dioxane 85 : 10 : 5). H NMR (400 MHz, CDCl3) d 7.84–7.80 (m,
4H), 7.49–7.43 (m, 2H), 7.40–7.34 (m, 4H), 7.27–7.22 (m, 2H),
6.89–6.84 (m, 2H), 6.34 (t, J ¼ 2.5 Hz, 1H), 3.78 (s, 3H), 2.92–2.87
(m, 2H), 2.65 (t, J ¼ 7.2 Hz, 2H), 1.88 (p, J ¼ 7.3 Hz, 2H); 13C NMR
(101 MHz, CDCl3) d 199.2, 158.4, 140.8, 136.2, 132.3, 130.3,
130.0, 129.3, 128.3, 128.3, 113.5, 75.5, 55.1, 36.7, 31.9, 24.3; IR
(CH2Cl2): 3058, 2956, 2836, 1687, 1659, 1606, 1510, 1251, 1177,
1033, 828, 701, 531 cmꢂ1; MS (EI): m/z (%) ¼ 397(5)[M+], 369(15),
292(33), 291(100), 274(25), 263(19), 155(11), 135(19), 105(75),
91(13), 77(54), 51(15); HRMS (EI): m/z calcd for C27H24O3
396.1725; found 396.1719.
C
22H22O3 334.1569; found 334.1574.
4-(((1E)-2-Acetyl-2-benzoylcyclopentylidene)methyl)benzo-
nitrile (45)
4-(((1E)-2,2-Dibenzoylcyclopentylidene)methyl)benzonitrile
(48)
Prepared in reaction of 2-(pent-4-ynyl)-1-phenylbutane-1,3-
dione and 4-brombenzonitrile following modied general
procedure (run at 80 ꢀC) (51 mg, yield 40%, isomer E/Z 70 : 30).
Product was isolated as oil aer column chromatography on
Prepared in reaction of 2-(pent-4-ynyl)-1,3-diphenylpropane-1,3-
dione and 4-bromobenzonitrile following modied general
1
ꢀ
procedure (run at 80 C) (63 mg, yield 40%). Product was iso-
silica gel (25 g, hex/AcOEt 90 : 10). H NMR (400 MHz, CDCl3)
lated as oil aer column chromatography on silica gel (25 g, hex/
AcOEt 90 : 10). 1H NMR (400 MHz, CDCl3) d 7.81–7.76 (m, 4H),
7.59–7.56 (m, 2H), 7.50–7.45 (m, 2H), 7.40–7.34 (m, 6H), 6.38 (t, J
¼ 2.6 Hz, 1H), 2.88 (td, J ¼ 7.4, 2.6 Hz, 2H), 2.69 (t, J ¼ 7.2 Hz,
2H), 1.90 (p, J ¼ 7.3 Hz, 2H); 13C NMR (101 MHz, CDCl3) d 198.5,
147.3, 142.0, 135.8, 132.6, 131.9, 129.3, 129.2, 128.5, 128.5,
127.2, 118.9, 110.1, 75.7, 36.6, 32.2, 24.2; IR (CH2Cl2): 3361,
3060, 2961, 2226, 1659, 1601, 1446, 1265, 1225, 1178, 879, 832,
736, 701, 554 cmꢂ1; MS (EI): m/z (%) ¼ 391(1)[M+], 287(2),
285(7), 269(4), 201(6), 153(3), 130(4), 105(100), 77(40), 51(10);
HRMS (EI): m/z calcd for C27H21NO2 391.1572; found 391.1586.
d 7.77–7.73 (m, 2H), 7.65–7.58 (m, 2H), 7.46–7.38 (m, 5H), 6.45
(t, J ¼ 2.6 Hz, 1H), 2.88–2.69 (m, 4H), 2.31 (s, 3H), 1.95–1.82 (m,
2H); 13C NMR (101 MHz, CDCl3) d 204.3, 198.2, 145.9, 141.9,
135.3, 132.8, 132.1, 132.0, 130.3, 129.2, 129.1, 128.9, 128.6,
128.5, 127.1, 35.0, 32.1, 27.4, 24.8; indicative signals of minor
isomer (Z): 1H NMR (400 MHz, CDCl3) d 7.57 (d, J ¼ 1.9 Hz, 1H),
7.56–7.50 (m, 5H), 7.36–7.30 (m, 3H), 5.41 (p, J ¼ 2.0 Hz, 1H),
2.58–2.35 (m, 6H), 2.24 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 206.5, 199.4, 145.3, 135.2, 133.6, 133.0, 118.8, 110.3, 79.3, 35.4,
33.3, 31.1, 27.3; IR (CH2Cl2): 3058, 2962, 2226, 1695, 1692, 1603,
1446, 1357, 1232, 700, 553 cmꢂ1; MS (EI): m/z (%) ¼ 329(1)[M+],
287(39), 286(16), 258(8), 153(9), 127(6), 116(12), 105(100),
77(48), 51(15), 43(30); HRMS (EI): m/z calcd for C22H19NO2
329.1416; found 329.1404.
Ethyl (2E)-2-benzylidene-1-(diethylphosphono)
cyclopentanecarboxylate (49)
Prepared in reaction of ethyl 2-(diethylphosphono)hept-6-
ynoate and bromobenzene following general procedure
(20 mg, yield 14%). Product was isolated as oil aer HPLC
chromatography (DCM/MeOH 99,5 : 0,5 / 99 : 1). 1H NMR
((2E)-1-Benzoyl-2-benzylidenecyclopentyl)(phenyl)methanone
(46)
Prepared in reaction of 2-(pent-4-ynyl)-1,3-diphenylpropane-1,3- (400 MHz, CDCl3) d 7.36–7.29 (m, 4H), 7.27–7.17 (m, 1H), 6.98
dione and bromobenzene following modied general procedure (7.01–6.94 (m, 1H), 4.28–4.10 (m, 6H), 2.79–2.68 (m, 1H), 2.69–
ꢀ
(run at 80 C) (71 mg, yield 49%). Product was isolated as oil 2.59 (m, 1H), 2.58–2.45 (m, 1H), 2.45–2.33 (m, 1H), 2.01–1.87
aer column chromatography on silica gel (25 g, hex/AcOEt (m, 1H), 1.84–1.73 (m, 1H), 1.34–1.25 (m, 9H); 13C NMR (101
1
95 : 5). H NMR (400 MHz, CDCl3) d 7.85–7.81 (m, 4H), 7.50– MHz, CDCl3) d 170.5, 140.3 (d, J ¼ 7.7 Hz), 137.9 (d, J ¼ 3.9 Hz),
7.45 (m, 2H), 7.41–7.36 (m, 4H), 7.34–7.28 (m, 4H), 7.24–7.20 128.7 (d, J ¼ 1.8 Hz), 128.2, 127.5 (d, J ¼ 7.5 Hz), 126.7, 63.3 (d, J
(m, 1H), 6.41 (t, J ¼ 2.5 Hz, 1H), 2.92 (td, J ¼ 7.4, 2.5 Hz, 2H), ¼ 6.9 Hz), 62.9 (d, J ¼ 7.3 Hz), 61.6, 58.9 (d, J ¼ 143.8 Hz), 33.7
2.68 (t, J ¼ 7.2 Hz, 2H), 1.89 (p, J ¼ 7.3 Hz, 2H); 13C NMR (101 (d, J ¼ 3.4 Hz), 32.7 (d, J ¼ 5.3 Hz), 29.7, 25.4 (d, J ¼ 6.3 Hz), 16.5
MHz, CDCl3) d 199.0, 143.1, 137.6, 136.2, 132.4, 129.3, 128.9, (d, J ¼ 5.7 Hz), 14.0; 31P NMR (162 MHz, CDCl3) d 23.4; IR
128.8, 128.4, 128.1, 126.8, 75.5, 36.7, 32.0, 24.2; IR (CH2Cl2): (CH2Cl2): 3233, 2979, 2928, 1728, 1446, 1248, 1025, 966, 759,
3059, 3026, 2959, 1689, 1659, 1597, 1447, 1264, 1125, 697 cmꢂ1
;
698, 572 cmꢂ1; MS (EI): m/z (%) ¼ 367(16), 366(41)[M+], 293(33),
MS (EI): m/z (%) ¼ 366(2)[M+], 262(7), 261(20), 245(12), 244(21), 229(42), 184(33), 183(82), 156(30), 155(100), 129(26), 115(29),
40164 | RSC Adv., 2019, 9, 40152–40167
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105(23), 91(38), 77(25), 43(8); HRMS (EI): m/z calcd for 13C NMR (101 MHz, CDCl3) d 138.6 (d, J ¼ 6.6 Hz), 136.3 (d, J ¼
C
19H27O5P 366.1596; found 366.1604.
3.4 Hz), 132.8 (d, J ¼ 8.4 Hz), 132.7 (d, J ¼ 2.9 Hz), 132.6 (d, J ¼
2.6 Hz), 131.9 (d, J ¼ 8.5 Hz), 129.9 (d, J ¼ 97.2 Hz), 128.85 (d, J ¼
11.7 Hz), 128.78 (d, J ¼ 6.6 Hz), 128.5 (d, J ¼ 1.9 Hz), 128.4 (d, J ¼
101.2 Hz), 128.21 (d, J ¼ 12.4 Hz), 128.15, 127.3, 121.6 (d, J ¼ 2.8
Hz), 47.5 (d, J ¼ 64.7 Hz), 34.4, 31.8, 25.3 (d, J ¼ 2.2 Hz); 31P NMR
(162 MHz, CDCl3) d 30.4; IR (CH2Cl2): 3057, 2961, 2871, 2230,
1438, 1203, 1115, 725, 695, 607, 548, 526 cmꢂ1; MS (EI): m/z (%)
Dipropan-2-yl ((2E)-2-benzylidene-1-cyanocyclopentyl)
phosphonate (50)
Prepared in reaction of dipropan-2-yl (1-cyanohex-5-yn-1-yl)
phosphonate and bromobenzene following general procedure
(88 mg, yield 63%). Product was isolated as oil aer column
chromatography on silica gel (15 g, hex/AcOEt 60 : 40). 1H NMR
(400 MHz, CDCl3) d 7.37–7.28 (m, 4H), 7.27–7.18 (m, 1H), 6.98–
6.91 (m, 1H), 4.86–4.73 (m, 2H), 2.80–2.61 (m, 2H), 2.54–2.41
(m, 1H), 2.37–2.25 (m, 1H), 2.14–2.03 (m, 1H), 1.89–1.77 (m,
1H), 1.39–1.27 (m, 12H); 13C NMR (101 MHz, CDCl3) d 138.1 (d, J
¼ 8.1 Hz), 136.5 (d, J ¼ 3.7 Hz), 128.5 (d, J ¼ 2.0 Hz), 128.3 (d, J ¼
7.7 Hz), 128.2, 127.2, 119.8 (d, J ¼ 6.4 Hz), 73.0 (d, J ¼ 7.2 Hz),
73.0 (d, J ¼ 7.2 Hz), 46.1 (d, J ¼ 148.1 Hz), 34.6 (d, J ¼ 4.6 Hz),
31.3 (d, J ¼ 3.6 Hz), 24.8 (d, J ¼ 4.1 Hz), 24.0 (d, J ¼ 3.3 Hz), 24.0
(d, J ¼ 3.3 Hz), 23.6 (d, J ¼ 3.9 Hz), 23.5 (d, J ¼ 3.8 Hz); 31P NMR
(162 MHz, CDCl3) d 16.7; IR (CH2Cl2): 3458, 3253, 2981, 2936,
2235, 1450, 1387, 1255, 1103, 989, 762, 696, 585 cmꢂ1; MS (EI):
m/z (%) ¼ 348(3), 347(10)[M+], 305(9), 264(20), 263(68), 210(10),
183(50), 182(100), 181(12), 166(32), 155(22), 129(19), 115(22),
91(25), 77(15), 51(7); HRMS (EI): m/z calcd for C19H26NO3P
347.1650; found 347.1647.
¼
384(12), 383(28)[M+], 382(6), 258(4), 202(25), 201(100),
182(15), 154(9), 115(7), 91(8), 77(25), 51(13); HRMS (EI): m/z
calcd for C25H22NOP 383.1439; found 383.1428.
Ethyl (2E)-2-benzylidene-1-(diphenylphosphoryl)
cyclopentanecarboxylate (53)
Prepared in reaction of ethyl 2-(diphenylphosphoryl)hept-6-
ynoate and bromobenzene following general procedure
(83 mg, yield 52%). Product was isolated as oil aer column
chromatography on silica gel (15 g, hex/AcOEt 60 : 40 /
1
50 : 50). H NMR (400 MHz, CDCl3) d 7.97–7.89 (m, 2H), 7.88–
7.80 (m, 2H), 7.54–7.47 (m, 2H), 7.46–7.38 (m, 4H), 7.34–7.28
(m, 2H), 7.24–7.18 (m, 3H), 6.50 (p, J ¼ 7.0 Hz, 1H), 4.22–4.06
(m, 2H), 2.69–2.51 (m, 2H), 2.47–2.34 (m, 1H), 1.85–1.68 (m,
2H), 1.28–1.22 (m, 1H), 1.11 (t, J ¼ 7.1 Hz, 3H); 13C NMR (101
MHz, CDCl3) d 171.0 (d, J ¼ 2.0 Hz), 140.5 (d, J ¼ 6.5 Hz), 137.6
(d, J ¼ 3.2 Hz), 133.1 (d, J ¼ 8.7 Hz), 132.2 (d, J ¼ 8.7 Hz), 131.9
(d, J ¼ 97.4 Hz), 131.68 (d, J ¼ 2.8 Hz), 131.65 (d, J ¼ 2.8 Hz),
131.1 (d, J ¼ 100.3 Hz), 128.63, 128.61, 128.56 (d, J ¼ 7.0 Hz),
128.2 (d, J ¼ 11.7 Hz), 128.1, 127.7 (d, J ¼ 11.7 Hz), 61.6, 61.2 (d, J
Diethyl ((2E)-1-acetyl-2-benzylidenecyclopentyl)phosphonate
(51)
Prepared in reaction of diethyl (2-oxooct-7-yn-3-yl)phosphonate
and bromobenzene following general procedure (60 mg, yield
45%). Product was isolated as oil aer column chromatography
on silica gel (15 g, hex/AcOEt/dioxane 45 : 45 : 10). 1H NMR (400
MHz, CDCl3) d 7.36–7.31 (m, 4H), 7.26–7.18 (m, 1H), 7.01–6.96
(m, 1H), 4.22–4.05 (m, 4H), 2.74–2.64 (m, 2H), 2.51–2.38 (m,
1H), 2.37 (s, 3H), 2.35–2.23 (m, 1H), 1.96–1.83 (m, 1H), 1.77–1.65
(m, 1H), 1.33–1.29 (m, 3H), 1.26 (td, J ¼ 7.1, 0.6 Hz, 3H); 13C
NMR (101 MHz, CDCl3) d 203.8, 140.5 (d, J ¼ 6.6 Hz), 137.6 (d, J
¼ 3.7 Hz), 128.6 (d, J ¼ 1.8 Hz), 128.2, 128.2 (d, J ¼ 7.4 Hz), 126.8,
¼ 65.9 Hz), 33.4, 33.1 (d, J ¼ 2.9 Hz), 25.7 (d, J ¼ 5.1 Hz), 13.7; 31
P
NMR (162 MHz, CDCl3) d 34.1, 31.2; IR (CH2Cl2): 3431, 3057,
2959, 1721, 1438, 1228, 1113, 724, 697, 549 cmꢂ1; MS (EI): m/z
(%) ¼ 431(18), 430(36)[M+], 357(10), 301(7), 288(6), 229(12),
219(32), 202(59), 201(100), 184(68), 183(46), 155(59), 129(24),
105(23), 91(32), 77(25), 43(8); HRMS (EI): m/z calcd for
C
27H27O3P 430.1698; found 430.1705.
66.7 (d, J ¼ 139.8 Hz), 63.3 (d, J ¼ 7.0 Hz), 62.5 (d, J ¼ 7.3 Hz), 1-((2E)-2-Benzylidene-1-(diphenylphosphoryl)cyclopentyl)
32.7 (d, J ¼ 0.9 Hz), 32.6 (d, J ¼ 4.2 Hz), 27.5, 25.0, 24.9 (d, J ¼ 6.9 ethanone (54)
Hz), 16.4 (d, J ¼ 5.8 Hz), 16.3 (d, J ¼ 5.8 Hz); 31P NMR (162 MHz,
Prepared in reaction of 3-(diphenylphosphoryl)oct-7-yn-2-one
and bromobenzene following general procedure (81 mg, yield
CDCl3) d 23.8, 23.8; IR (CH2Cl2): 3455, 3230, 2980, 1706, 1445,
1227, 1049, 1024, 956, 760, 698, 599 cmꢂ1; MS (EI): m/z (%) ¼
51%). Product was isolated as oil aer column chromatography
336(4)[M+], 295(29), 294(100), 266(15), 237(13), 220(5), 156(31),
on silica gel (15 g, hex/AcOEt/dioxane 45 : 45 : 10). 1H NMR (400
155(84), 128(22), 115(19), 105(11), 91(29), 77(16), 43(29); HRMS
MHz, CDCl3) d 7.94–7.79 (m, 4H), 7.54–7.46 (m, 2H), 7.46–7.38
(m, 4H), 7.36–7.30 (m, 2H), 7.27–7.19 (m, 3H), 6.68 (s, 1H), 2.75–
(EI): m/z calcd for C18H25O4P 336.1490; found 336.1502.
2.65 (m, 1H), 2.62–2.52 (m, 2H), 2.42 (s, 3H), 2.38–2.28 (m, 1H),
1.76–1.63 (m, 2H); 13C NMR (101 MHz, CDCl3) d 205.3, 140.8 (d,
(2E)-2-Benzylidene-1-(diphenylphosphoryl)cyclopentane-
carbonitrile (52)
J ¼ 5.7 Hz), 137.5 (d, J ¼ 2.8 Hz), 133.0 (d, J ¼ 9.2 Hz), 132.6 (d, J
Prepared in reaction of 2-(diphenylphosphoryl)hept-6-ynenitrile ¼ 8.6 Hz), 131.8 (d, J ¼ 2.7 Hz), 131.7 (d, J ¼ 2.7 Hz), 131.6 (d, J ¼
and bromobenzene following general procedure (62 mg, yield 97.8 Hz), 131.0 (d, J ¼ 97.8 Hz), 129.3 (d, J ¼ 6.5 Hz), 128.6,
41%). Product was isolated as oil aer column chromatography 128.21, 128.17 (d, J ¼ 11.4 Hz), 128.0 (d, J ¼ 11.9 Hz), 127.0, 68.8
on silica gel (15 g, hex/AcOEt 50 : 50). 1H NMR (400 MHz, CDCl3) (d, J ¼ 64.4 Hz), 32.8 (d, J ¼ 3.7 Hz), 32.7, 28.3, 25.4 (d, J ¼ 5.5
d 8.28–8.18 (m, 2H), 8.05–7.96 (m, 2H), 7.67–7.52 (m, 4H), 7.51– Hz); 31P NMR (162 MHz, CDCl3) d 35.80, 34.60; IR (CH2Cl2):
7.41 (m, 2H), 7.35–7.26 (m, 2H), 7.26–7.18 (m, 1H), 7.15 (d, J ¼ 3378, 3058, 2960, 2925, 2854, 1699, 1437, 1179, 1112, 750, 722,
7.2 Hz, 2H), 5.97–5.91 (m, 1H), 2.89–2.70 (m, 2H), 2.65–2.51 (m, 696, 543 cmꢂ1; MS (EI): m/z (%) ¼ 400(24)[M+], 359(42),
1H), 2.44–2.29 (m, 1H), 2.23–2.11 (m, 1H), 1.90–1.75 (m, 1H); 358(100), 281(16), 219(24), 202(47), 201(98), 182(45), 167(53),
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155(40), 128(34), 115(25), 105(21), 91(36), 77(63), 51(33), 43(65); including acetylenic derivatives of malonates, cyanomalonates,
HRMS (EI): m/z calcd for C26H25O2P 400.1592; found 400.1587. b-ketoesters, b-diketones, cyanoacetates, and organophos-
phorus compounds. Mechanistic studies revealed a plausible
mechanism comprising oxidative addition of haloarene,
nucleophilic addition to alkyne activated by coordination to
aryl–Pd(II), and reductive elimination. However, for the trans-
formations of less C–H acidic substrates (e.g. b-ketoesters, b-
diketones) and electron-decient haloarenes, an alternative
path involving syn-carbometallation may operate in parallel.
Dimethyl (2E)-2-(4-uorobenzylidene)cyclopentane-1,1-
dicarboxylate (55)
Prepared in reaction of dimethyl 4-pentenylmalonate and 1-
chloro-4-uorobenzene following modied general procedure
ꢀ
(run at 80 C) (74 mg, yield 63%). Product was isolated as oil
aer column chromatography on silica gel (15 g, hex/AcOEt
1
90 : 10). H NMR (400 MHz, CDCl3) d 7.33–7.27 (m, 2H), 7.04–
Conflicts of interest
6.97 (m, 2H), 6.66 (t, J ¼ 2.7 Hz, 1H), 3.76 (s, 6H), 2.66 (td, J ¼
7.2, 2.6 Hz, 2H), 2.38 (t, J ¼ 6.9 Hz, 2H), 1.83 (p, J ¼ 7.1 Hz, 2H);
13C NMR (101 MHz, CDCl3) d 171.3, 162.8, 161.5 (d, J ¼ 246.8
Hz), 140.6 (d, J ¼ 2.1 Hz), 133.7 (d, J ¼ 3.3 Hz), 130.2 (d, J ¼ 8.0
There are no conicts to declare.
Hz), 126.3, 115.0 (d, J ¼ 21.5 Hz), 65.3, 52.7, 35.7, 31.8, 24.7; 19
F
Acknowledgements
NMR (376 MHz, CDCl3) d ꢂ114.96; IR (CH2Cl2): 2954, 2879,
2842, 1733, 1603, 1508, 1434, 1227, 1190, 1159, 1098, 1065,
1014, 929, 885, 827, 773, 523 cmꢂ1. MS (EI): m/z (%) ¼ 293(6)
[M+], 292(32), 260(13), 233(32), 232(44), 201(65), 200(21),
173(100), 146(23), 133(18), 109(44), 77(7), 59(16), 43(4); HRMS
(EI): m/z calcd for C16H17O4F 292.1111; found 292.1117.
Financial support from the Polish National Science Centre
(Grant decision DEC-2016/22/E/ST5/00537) is gratefully
acknowledged.
Notes and references
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´
´
248, 2365–2379; (b) R. P. Herrera and E. Marques-Lopez,
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d 7.99–7.95 (m, 2H), 7.40–7.36 (m, 2H), 6.72 (t, J ¼ 2.6 Hz, 1H),
3.88 (s, 3H), 3.76 (s, 6H), 2.70 (td, J ¼ 7.2, 2.6 Hz, 2H), 2.38 (t, J ¼
7.0 Hz, 2H), 1.83 (p, J ¼ 7.1 Hz, 2H); 13C NMR (101 MHz, CDCl3)
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51.9, 35.6, 32.1, 24.7; indicative signals of minor isomer (Z): 1H
NMR (400 MHz, CDCl3) d 7.95–7.89 (m, 2H), 7.35 (s, 1H), 6.65 (d,
J ¼ 2.3 Hz, 1H), 3.87 (s, 3H), 3.43 (s, 5H), 2.67–2.62 (m, 2H), 2.42
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34.8, 22.5, 14.0; IR (CH2Cl2): 2963, 2843, 1724, 1606, 1565, 1435,
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MS (EI): m/z (%) ¼ 333(9)[M+], 332(39), 301(24), 273(24), 272(43),
242(32), 241(100), 240(48), 214(30), 213(98), 181(32), 155(35),
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