Atropisomerisation in sterically hindered α,β-disubstituted cyclopentenones derived from an intermolecular cobalt(0)-mediated Pauson-Khand reaction

Article abstract of DOI:10.1039/c0ob00264j

4-(2-Phenylethynyl)-2H-chromen-2-one reacts with norbornene and Co ₂(CO)₈ in an intermolecular Pauson-Khand reaction by focused microwave dielectric heating. Two regioisomeric products are formed; the electron-deficient coumarin moie

Full text of DOI:10.1039/c0ob00264j

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Atropisomerisation in sterically hindered a,b-disubstituted cyclopentenones
derived from an intermolecular cobalt(0)-mediated Pauson–Khand reaction†
Benjamin E. Moulton,a Jason M. Lynam,a Anne-Kathrin Duhme-Klair,a Wenxu Zheng,b Zhenyang Lin*b and
Ian J. S. Fairlamb*a
Received 15th June 2010, Accepted 18th August 2010
DOI: 10.1039/c0ob00264j
4-(2-Phenylethynyl)-2H-chromen-2-one reacts with norbornene and Co2(CO)8 in an intermolecular
Pauson–Khand reaction by focused microwave dielectric heating. Two regioisomeric products are
formed; the electron-deficient coumarin moiety preferentially occupies the b-position of the
cyclopentenone ring system, whereas the phenyl occupies the a-position. The sterically hindered
a,b-(2,3)-disubstituted cyclopentenone regioisomeric products exhibit pronounced atropisomerisation,
and the magnitude of the energetic barrier to interconversion between these atropisomers is dependent
on the relative position of the coumarin moieties. Interconversion is slow when the coumarin is found in
the a-position, whereas interconversion is relatively fast when found in the b-position.
Introduction
Intermolecular Pauson–Khand (PK) reactions1 of alkynes with
alkenes (especially norbornene and its derivatives), mediated by
stoichiometric quantities of Co2(CO)8, have been of continued
interest to the academic community, both in terms of applications2
and mechanistic studies.3 Whilst the reactions of internal alkynes
(e.g. 1) under conventional heating are slow, microwave (MW)
heating4 dramatically improves the rate of the reactions. Reaction
of 1,5 norbornene and Co2(CO)8 under MW irradiation generates
two regioisomeric products, 2a or 2b, in 89% yield (ratio =
1 : 3.7; Scheme 1). 2-Pyrone (2H-pyran-2-one) and phenyl moieties
can be considered sterically near equivalent, therefore it was
predicted6 and proven that the major regioisomeric product
possessed the phenyl group in the a-position and the electron-
deficient 2-pyrone in the b-position of the cyclopentenone ring
(2b) (note: a/b notation6a has been used to distinguish between
the two regioisomeric PK cycloadducts in the past; here, 2-pyrone
is the primary ring system).7 Interestingly, 2b participated in
a light induced C3-regioselective 6p-electrocyclisation/oxidative
aromatisation reaction to give 3. In this study we have extended
our investigations to replacement of the 2-pyrone moiety with an
electronically related coumarin (2H-chromen-2-one). The larger
coumarin moiety is expected, on steric grounds, to alter the
regioselectivity of the PK reaction.8 In addition, we anticipated
Scheme 1 PK reaction of 1 with norbornene and Co2(CO)8.
Results and discussion
that PK products containing the coumarin motif could exhibit
Alkynylcoumarin 5 was readily prepared in 62% yield by Sono-
gashira alkynylation of known9 compound 4 using a PdCl2(PPh3)2
precatalyst and CuI co-catalyst at low loadings in the presence
of Et3N (Scheme 2).10 Prior to conducting the PK reaction,
intermediate complex 6 was independently prepared by a reaction
of equimolar quantities of 5 and Co2(CO)8 at 23 ◦C for 16 h,
affording 6 in 77% yield after chromatography on silica gel.
The X-ray crystal structure of 6 (Fig. 1) shows the expected
structural connectivity for this type of complex.11 Labile CO
ligands are found in both cis-equatorial positions, indicated by
atropisomerisation.
aDepartment of Chemistry, University of York, Heslington, York, YO10
5DD, U.K.. E-mail: ijsf1@york.ac.uk; Fax: +44 1904 322516; Tel: +44
1904 324091
bDepartment of Chemistry, The Hong Kong University of Science and
Technology, Clear Water Bay, Kowloon, Hong Kong, P. R. China. E-mail:
chzlin@ust.hk
† Electronic supplementary information (ESI) available: X-Ray diffraction
data, refinement information and Cartesian coordinates. CCDC reference
numbers 780325 and 780326. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c0ob00264j.
˚
the longer Co–CO bond lengths, e.g. Co1–COcis-eq (1.8304(17) A)
˚
and Co2–COcis-eq (1.8264(19) A}, and one trans-equatorial position
5398 | Org. Biomol. Chem., 2010, 8, 5398–5403
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
equatorial CO ligands. In terms of the PK reaction, the crystal
structure indicates that the initial ‘CO loss’ could occur from either
cis- or trans-equatorial sites in 6.
PK reaction of 5: A 1,2-dichloroethane (DCE) solution of 5 in
the presence of an equimolar amount of Co2(CO)8 was reacted
at 23 ◦C for 1 h (TLC analysis confirming complete loss of 5).
Norbornene (~ 5 eq.) was then added and the mixture heated in
a CEM Discover microwave at 90 ◦C for 1.5 h, which gave two
isolatable regioisomeric products 7a and 7b in 79% yield in a ratio
of 1 : 1.8, respectively.
It was anticipated that the electron-withdrawing coumarin
moiety would appear preferentially in the b-position of the newly
formed cyclopentenone ring. However, any dominant steric effects
could place the larger coumarin moiety into the a-position. 7b
was predicted to be the major regioisomer based on electronic
grounds and this was confirmed unambiguously as the major
regioisomer crystallised from CDCl3, giving crystals suitable for
X-ray diffraction (Fig. 2).
Scheme 2 PK reactions of 5 with norbornene and Co2(CO)8.
Fig. 2 X-Ray crystal structure of the major regioisomeric product 7b
(determined at 298 K). Thermal ellipsoids are shown at 30% probability.
At 303 K, the 1H NMR spectra of the two regioisomeric prod-
ucts 7a and 7b are markedly different. 7b exhibits broad proton
signals indicative of an exchange process, whereas 7a exhibits
two sets of sharp proton signals sharing similar chemical shifts.
Variable temperature (VT) 1H NMR experiments (500 MHz) for
7b were recorded at 10 K intervals between 223 K and 323 K
(Fig. 3).
At low temperatures, the singlet expected for the C3 proton of
the coumarin in 7b appears as two separate resonances at 6.72
and 6.04 ppm. Increasing the temperature to ca. 293 K results in
coalescence and increasing the temperature to 323 K leads to the
sharpening of the resulting averaged signal. The standard Gibbs’
free energy (DG◦), using the equilibrium constant K derived at
223 K for the two species, is 0.6 kJ mol-1.
Molecular models show that there is restricted rotation about
the single C–C bond connecting the coumarin moiety to the
cyclopentenone framework. The barrier to rotation about this
bond is large enough that, under the appropriate conditions, it
is possible to observe two conformers (atropisomers). The VT
spectra show that increasing temperature allows these conformers
to interconvert thermally. From the spectroscopic data, it is
Fig. 1 X-Ray crystal structure of 6 (determined at 110 K). Thermal
ellipsoids are shown at 50% probability. Inset shows relative CO positions
(‘Cou’ = coumarin).
˚
(Co1–COtrans-eq (1.8302(19) A). The other trans-equatorial position
exhibits a significantly shorter bond distance, e.g. Co2–COtrans-eq
˚
(1.8090(19) A). This difference is likely due to the orientation
and electronic deficiency of the coumarin moiety, relative to each
cobalt atom, which affects the strength of one of the trans-
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 5398–5403 | 5399
©

View Article Online
temperature 1H NMR experiments on 7ain d8-toluene recorded at
higher temperatures showed some line-broadening of the proton
signals, however, no evidence for coalescence was observed up to
◦
65 C. Therefore, the activation energy required for interconver-
sion of the atropisomers derived from 7a is higher than 7b.
DFT calculations at the B3LYP level on the two sets of
atropisomers (derived from both 7a and 7b, Fig. 5) have allowed
the theoretical activation parameters for interconversion of the
atropisomers derived from each regioisomer to be determined.
Fig. 3 VT 1H NMR (500 ;MHz) spectra of 7b in CDCl3 between
6.8–5.8 ppm for temperatures 223 K to 323 K. * Trace impurity.
possible to obtain the activation parameters for the observed
exchange process for 7b.
Using gNMR software,12 we were able to simulate the line
shape of the experimentally observed spectra to gain the rate
constants for the exchange process at a number of temperatures.
An Arrhenius plot of 1/T against lnk gives a straight line with
slope –Ea/R, allowing the activation energy to be estimated
(55.3 kJ mol-1). In addition, an Eyring plot of ln(k/T) against
1/T afforded a straight line plot (Fig. 4, R2 = 0.9964) from which
the enthalpy (DH‡ = (51.8 1.79) kJ mol-1) and entropy DS‡ =
(-11.85 6.52) J mol-1K-1 of activation were determined. The small
DS‡ value is in keeping with exchange being intramolecular, and
the DH‡ value indicates that the barrier to rotation is primarily
enthalpic. These data indicate that the free energy of activation
(DG‡) at 303 K is (55.4 2.66) kJ mol-1.
Fig. 5 Relative free energies calculated for the four atropisomers of 7.
The theoretical values for the activation parameters for isomer
7b are in good agreement with the experimentally observed
values, with a difference in DG‡ of 0.6 kJ mol-1 between the
value calculated for TS-1 and the experimentally-determined value
(Fig. 6). The interconversion of 7aA → 7aB is calculated to be less
favoured than that of 7bA → 7bB, with DG‡ being ca. 23 kJ mol-1
higher. This difference supports the experimental observation that
no exchange is observed at room temperature for 7a. Substituting
DH‡ = Ea − RT
the calculated value of DH‡ for 7a into
allows the
activation energy for the interconversion to be estimated. At 303 K,
the activation energy for the process is approximately 75.7 kJ mol-1.
This is 20 kJ mol-1 higher than the value calculated for the major
isomer 7b (from the Arrhenius plot).
By substituting the calculated values of DH‡ and DS‡ into
ln(k /T) = ln k / h −(DH‡/RT) +(DS‡/R)
(
)
equation
, the rate con-
B
stant for the exchange process could be estimated at various
temperatures. From the values calculated for 7b, an estimated
rate constant of 2240 s-1 at 303 K was determined. The estimated
rate constant by gNMR at 303 K was determined to be 1960 s-1,
showing a reasonable correlation between the calculated and
observed values. From the values calculated for 7a, a rate constant
of approximately 0.2 s-1 is estimated, confirming that at room
temperature, exchange is expected to be slow on the NMR
timescale.
The relative energies obtained for the four atropisomers indicate
that the regioisomer with the coumarin moiety in the a-position is
the energetically most favourable regioisomer, with a difference of
7.3 kJ mol-1 between the two lowest energy atropisomers 7aA and
Fig. 4 Eyring plot of ln (k/T) vs. 1/T for rate constants obtained by
simulation of 1H NMR spectra at temperatures between 223 K and 323 K
for compound 7b.
For the minor isomer 7a, the two separate atropisomers 7aA
and 7aB are clearly distinguishable at room temperature, and
there is no indication of an exchange process occurring. Variable
‡ Neither regioisomer 7a or 7b undergoes a natural ligand-inducted 6p-
electrocyclisation/oxidative aromatisation reaction (in contrast to 2b).
5400 | Org. Biomol. Chem., 2010, 8, 5398–5403
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
Fig. 6 Theoretically determined energetic parameters for both of the regioisomeric products 7a and 7b. For each process, two different transition state
structures were calculated considering the clockwise and anticlockwise rotations about the single C–C bond connecting the coumarin moiety to the
cyclopentenone framework.
7bA (for each regioisomer). The calculations also show that the
two atropisomers of 7b are closer in energy than the two isomers
of 7a, with 7bA being 4.7 kJ mol-1 more stable than 7bB, and 7aA
being 7.6 kJ mol-1 more stable than 7aB.
or transition states. Calculations of intrinsic reaction coordinates
(IRC)15 were also performed on transition states to confirm that
such structures are indeed connecting two minima. The standard
6-31G basis set was used.16 All calculations were carried out with
the Gaussian 03 software package.17
Conclusions
In this paper we have demonstrated that 4-(2-phenylethynyl)-2H-
chromen-2-one 5 reacts with norbornene and Co2(CO)8 in an
intermolecular Pauson–Khand reaction. The electron deficient
moiety preferentially occupies the b-position of the cyclopen-
tenone. However, both regioisomeric cyclopentenone products
7a and 7b exhibit atropisomerisation. The magnitude of the
energetic barrier to interconversion between these atropisomers
is dependent on the relative position of the coumarin substituent.
Interconversion is slow when the coumarin is found in the a-
position, whereas interconversion is relatively fast when found in
the b-position. It is interesting to note this is a rare instance13
where atropisomerisation has been observed in the formation of
PK-type cyclopentenone products.
General experimental details
Solvents were dried where necessary using standard procedures
prior to use and stored under an argon atmosphere. DCE refers to
1,2-dichloroethane. Nitrogen gas was oxygen-free and was dried
immediately prior to use by passage through an 80 cm column
containing sodium hydroxide pellets andsilica. Argongas was used
directly via balloon transfer or on a Schlenk line. TLC analysis
was performed routinely using Merck 5554 aluminium backed
silica plates. Compounds were visualised using UV light (254 nm)
1
and a basic aqueous solution of potassium permanganate. H
NMR spectra were recorded at either 400 MHz using a JEOL
ECX 400 spectrometer, with13C NMR spectra recorded on the
same instrument at 100 MHz (1H decoupled); or at 500 MHz on
a Bruker AV 500 spectrometer, with 13C NMR spectra recorded
on the same instrument at 125 MHz (1H decoupled). Chemical
shifts are reported in parts per million (d) relative to CHCl3
at d 7.24 (1H) or 77.0 (13C). Coupling constants (J values) are
reported in Hertz (Hz), and spin multiplicities are indicated by the
following symbols: s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet), br (broad). Full details of the X-ray diffraction studies
are given in the ESI.†
Experimental section
Computational studies by DFT
Density functional theory (DFT) calculations at the B3LYP level14
were performed to calculate the structures of the isomers and the
transition states. Frequency calculations were also performed to
confirm the characteristics of the calculated structures as minima
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 5398–5403 | 5401
©

View Article Online
4-(2-Phenylethynyl)-2H-chromen-2-one
(5). 4-Bromo-2H-
to 7 : 3, v/v) to afford two regioisomeric products 7a (52 mg, 28%)
and 7b (93 mg, 52%).
chromen-2-one 4 (1.0 g, 4.7 mmol) and phenylacetylene (580 mg,
0.62 mL, 5.6 mmol), PdCl2(PPh3)2 (33 mg, 1 mol%), CuI (27 mg,
3 mol%) and dry acetonitrile (7 mL) were added to an oven
dried Schlenk tube charged with a magnetic stirrer bead. Dry
triethylamine (1.5 eq.) was added and the reaction was heated at
reflux for 16 h. On completion, the reaction mixture was washed
with H2O (10 mL), extracted with CH2Cl2 (3 ¥ 20 mL), dried over
MgSO4, filtered and the solvent removed in vacuo. Purification by
recrystallisation from hot EtOH, afforded the title compound as
a cream solid (720 mg, 62%). M.p. > 119 C (decomposes). H
NMR (400 MHz, CDCl3): d = 6.63 (s, 1H; coumarin), 7.34–7.38
(m, 2H; coumarin), 7.41–7.47 (m, 3H; Ph), 7.57 (ddd, J = 8.2, 7.4,
1.6 Hz, 1H; coumarin), 7.65 (m, 2H; Ph), 7.96 (dd, J = 8.2 Hz,
1.6 Hz, 1H; coumarin). 13C NMR (100.5 MHz, CDCl3): d = 82.8
(4◦), 102.1 (4◦), 117.0 (CH), 118.4 (CH), 118.4 (4◦), 121.1 (4◦),
124.5 (CH), 126.7 (CH), 128.7 (CH), 130.2 (CH), 132.2 (CH),
132.3 (CH), 137.2 (4◦), 153.5 (4◦), 160.2 (4◦). nmax (CH2Cl2, cm-1)
2211, 1751, 1730, 1719, 1607, 1557, 1491, 1451, 1374, 1324,
1250, 1189, 1146, 1126, 936. LR(ESI-MS): m/z: 247{(MH)+,
100}. HR(ESI-MS): m/z: calcd for C17H11O2: 247.0754; found:
247.0750 [M+H]+.
Data for (3aRS,4SR,7RS,7aSR)-6-Methyl-4-(1-oxo-3-phenyl-
3a,4,5,6,7,7a-hexahydro-1H -4,7-methanoinden-2-yl)-2H -chro-
men-2-one (7a). M.p. > 88 ◦C (decomposes). 1H NMR
(500 MHz, 303 K, CDCl3) (quoted as a mixture of atropisomers):
d = 1.08 (d, J = 10.8 Hz, 0.8H; H-8). 1.22–1.27 (m, 1.8H; H-
8), 1.39 (d, J = 10.8 Hz, 1H; H-8), 1.44–1.52 (m, 3.6H; H-5,6-
endo), 1.67–1.80 (m, 3.6H; H-5,6-exo), 2.24–2.28 (br, 1.8H; H-7a),
2.60 (d, J = 5.4 Hz, 1H), 2.62–2.66 (m, 1.6H; H-7 + H-4), 2.66–
2.69 (br, 1H; H-7), 3.39 (d, J = 5.4 Hz, 1H; H-3a), 3.43 (d, J =
5.4 Hz, 0.8H; H-3a), 6.00 (s, 0.8H; C3-coumarin), 6.45 (s, 1H;
C3-coumarin), 6.88–6.95 (m, 1.8H), 7.26–7.33 (m, 9.8H), 7.34–
7.41 (m, 3.6H), 7.43–7.47 (d, 1H), 7.55–7.59 (m, 1H). 13C NMR
(125 MHz, 303 K, CDCl3): d = 28.6 (CH2), 28.7 (CH2), 28.9 (CH2),
29.1 (CH2), 31.7 (CH2), 32.4 (CH2), 38.7 (CH), 39.2 (CH), 39.4
(CH), 39.8 (CH), 50.7 (CH), 51.5 (CH), 54.4 (CH), 54.7 (CH),
116.5 (CH), 116.8 (4◦), 117.2 (CH), 117.4 (CH), 117.7 (CH), 118.7
(4◦), 123.8 (CH), 124.6 (CH), 125.8 (CH), 126.3 (CH), 128.2 (CH),
128.3 (CH), 129.0 (CH), 131.0 (CH), 131.7 (CH), 132.2 (CH),
133.0 (4◦), 133.6 (4◦), 136.6 (4◦), 138.4 (4◦), 147.6 (4◦), 149.6
(4◦), 153.9 (4◦), 154.1 (4◦), 160.2 (4◦), 160.3 (4◦), 172.7 (4◦), 174.1
(4◦), 206.1 (4◦), 206.6 (4◦). nmax (CH2Cl2, cm-1) 2963, 2877, 1755,
1723, 1695, 1628, 1606, 1559, 1450, 1380, 1371, 1327, 1198, 1183.
LR(ESI-MS): m/z: 369{(MH)+, 100}. HR(ESI-MS): m/z: calcd
for C25H21O3: 369.1485; found: 369.1493 [M+H]+.
◦
1
[l2-4-(2-Phenylethynyl)-2H-chromen-2-one]-hexacarbonyl di-
cobalt (6). Equimolar quantities of dicobalt octacarbonyl
(239 mg, 0.7 mmol) and the alkyne 5 (720 mg, 0.7 mmol) were
added to a Schlenk tube containing a magnetic stirrer bead. Dry
THF (6 mL per mmol) was added and the reaction was stirred
Data for (3aRS,4SR,7RS,7aSR)-6-Methyl-4-(1-oxo-2-phenyl-
3a,4,5,6,7,7a-hexahydro-1H -4,7-methanoinden-3-yl)-2H -chro-
men-2-one (7b). M.p. > 196 ◦C (decomposes). 1H NMR
(500 MHz, 303 K, CDCl3): d = 1.15 (d, J = 10.6 Hz, 1H; H-8),
1.28–1.34 (m (overlapping d, J = 10.6 Hz), 2H; H-8), 1.37–1.43 (m,
1H; H-5,6-endo), 1.63–1.74 (m, 2H; H-5,6-exo), 2.12–2.28 (br, 1H;
H-4), 2.60 (d, J = 5.5 Hz, 1H; H-7a), 2.69 (br, 1H; H-7), 3.01 (d, J =
5.5 Hz, 1H; H-3a), 5.72–6.65 (br, 1H), 7.04–7.24 (m, 6H), 7.38–
7.42 (m, 2H), 7.44–7.62 (br s, 1H). 13C NMR (125 MHz, 303 K,
CDCl3): d = 28.4 (CH2), 28.8 (CH2), 31.6 (br, CH2), 37.6 (CH), 40.0
(CH), 52.0 (br, CH), 54.1 (CH), 114.4 (4◦), 117.5 (CH), 124.5 (br,
4◦), 125.9 (4◦), 128.3 (CH), 128.4 (CH), 128.8 (CH), 129.8 (br, 4◦),
132.5 (CH), 145.9 (br, CH), 153.8 (4◦), 156.3 (4◦), 159.9 (4◦), 207.2
(4◦). nmax (CH2Cl2, cm-1) 2963, 2877, 1726, 1707, 1606, 1562, 1494,
1450, 1372, 1322, 1183, 1105. LR(ESI-MS): m/z: 391{(MNa)+,
100}. HR(ESI-MS): m/z: calcd for C25H20NaO3: 391.1305; found:
391.1318 [M+Na]+.
◦
for 16 h at room temperature (23 C). The solvent was removed
in vacuo and the crude product purified by chromatography on
silica gel eluting with hexane–ethyl acetate mixtures (1 : 0 to 9 : 1,
v/v), which afforded the title compound as a black crystalline
1
solid (286 mg, 77%). H NMR (500 MHz, CDCl3): d = 6.82 (s,
1H; coumarin), 7.04 (ddd, J = 8.3, 7.3, 1.1 Hz, 1H; coumarin),
7.33 (dd, J = 8.0, 1.4 Hz, 1H; coumarin), 7.35–7.39 (m, 3H; Ph),
7.41 (dd, J = 8.3, 1.0 Hz, 1H; coumarin), 7.44–7.46 (m, 2H;
Ph), 7.50 (ddd, J = 8.6, 7.3, 1.1 Hz, 1H; coumarin). 13C NMR
(125 MHz, CDCl3): d = 82.3 (4◦), 95.9 (4◦), 116.7 (CH), 117.4 (4◦),
117.5 (CH), 123.7 (CH), 126.4 (CH), 128.7 (CH), 129.3 (CH),
129.9 (CH), 132.2 (CH), 137.0 (4◦), 153.4 (4◦), 154.4 (4◦), 160.8
(4◦), 198.2 (br, M–CO). nmax (CH2Cl2, cm-1) 2097, 2064, 2037,
1716, 1606, 1549, 1350, 1271, 1264, 1188. LR(ESI-MS): m/z:
533{(MH)+, 100}. HR(ESI-MS): m/z: calcd for C23H11Co2O8:
532.9112; found: 532.9091 [M+H]+. Found – C, 51.83; H, 1.98.
C23H10Co2O8 requires C, 51.91; H, 1.89.
Acknowledgements
Pauson–Khand reaction of compound 5. Equimolar quantities
of dicobalt octacarbonyl (171 mg, 0.5 mmol) and compound 5
(124 mg, 0.5 mmol) were added to a microwave tube containing
a magnetic stirrer bar. 1,2-Dichloroethane (2 mL) was added and
the reaction mixture was stirred for 60 min at room temperature
(23 ◦C). After this time, norbornene (235 mg, 2.5 mmol) was added
and the reaction tube was placed in a microwave reactor (100 W,
This work has been supported by the EPSRC (DTA award to
B.E.M.) and the Royal Society (U.R.F. to I.J.S.F.). We are grateful
to Dr A. C. Whitwood (York) for discussion and assistance with
X-ray analysis. Mr. R. A. Jennings is thanked for assistance with
the preparation of compound 5.
◦
90 C). Any build-up in pressure was released from the vessel at
Notes and references
10 min intervals during the first hour of the reaction. The reaction
was monitored by TLC analysis and heated until the intermediate
cobalt complex (6) could no longer be detected. On completion,
the solvent was removed in vacuo and the crude products purified
by chromatography on silica gel eluting with hexane–EtOAc (1 : 0
1 For recent reviews, see: (a) S. E. Gibson and A. Stevenazzi, Angew.
Chem., Int. Ed., 2003, 42, 1800; (b) M. Rodriguez Rivero, J. Adrio and
J. C. Carretero, Synlett, 2005, 26; (c) K. H. Park and Y. K. Chung,
Synlett, 2005, 545; (d) C. J. Scheuermann ne´e Taylor and B. D. Ward,
New J. Chem., 2008, 32, 1850.
5402 | Org. Biomol. Chem., 2010, 8, 5398–5403
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
2 Recent selected applications, see: (a) J. T. Shaw, Nat. Prod. Rep., 2009,
26, 11; (b) E. V. Banide, P. Oulie and M. J. McGlinchey, Pure Appl.
Chem., 2009, 81, 1; (c) J. R. Green, Eur. J. Org. Chem., 2008, 6053;
(d) C. Olier, N. Azzi, G. Gil, S. Gastaldi and M. P. Bertrand, J. Org.
Chem., 2008, 73, 8469; (e) S. E. Gibson, K. A. C. Kaufmann, J. W.
Loch and A. Miyazaki, Pure Appl. Chem., 2008, 80, 903; (f) N. P. Pera,
U. J. Nilsson and N. Kann, Tetrahedron Lett., 2008, 49, 2820; (g) M. R.
Coogan and D. S. Wilkins, J. Chem. Res. (S), 2008, 516–519; (h) A.
Vazquez-Romero, J. Rodriguez, A. Lledo, X. Verdaguer and A. Riera,
Org. Lett., 2008, 10, 4509; (i) A. Coleman and M. T. Pryce, Inorg. Chem.,
2008, 47, 10980; (j) S. Horn and M. O. Senge, Eur. J. Org. Chem., 2008,
4881.
3 Intermediates in the PK reactions, see: (a) M. E. Krafft, I. L. Scott,
R. H. Romero, S. Feibelmann and C. E. Van Pelt, J. Am. Chem. Soc.,
1993, 115, 7199. Intermediates generated by photochemical means,
see: (b) C. M. Gordon, M. Kiszka, I. R. Dunkin, W. J. Kerr, J. S. Scott
and J. Gebicki, J. Organomet. Chem., 1998, 554, 147. Phosphine ligated
intermediates, see: (c) Y. Gimbert, F. Robert, A. Durif, M.-T. Averbuch,
N. Kann and A. E. Greene, J. Org. Chem., 1999, 64, 3492. On the
reactivity of the alkene partner in PK reactions, see: (d) M. A. Perica`s,
J. Balsells, J. Castro, I. Marchueta, A. Moyano, A. Riera, J. Vazquez
and X. Verdaguer, Pure Appl. Chem., 2002, 74, 167; (e) E. V. Banide, H.
Mu¨ller-Bunz, A. R. Manning, P. Evans and M. J. McGlinchey, Angew.
Chem., Int. Ed., 2007, 46, 2907; (f) M. K. Pallerla, G. P. A. Yap and J. M.
Fox, J. Org. Chem., 2008, 73, 6137. Other highly relevant mechanistic
studies, see: (g) S. E. Gibson, D. J. Hardick, P. R. Haycock, K. A. C.
Kaufmann, A. Miyazaki, M. J. Tozer and A. J. P. White, Chem.–Eur. J.,
2007, 13, 7099; (h) S. E. Gibson, K. A. C. Kaufmann, P. R. Haycock,
A. J. P. White, D. J. Hardick and M. J. Tozer, Organometallics, 2007,
26, 1578; (i) S. E. Gibson, K. A. C. Kaufmann, L. A. Loch, J. W. Steed
and A. J. P. White, Chem.–Eur. J., 2005, 11, 2566.
4 Stoichiometric intermolecular PK reactions involving internal alkyne
substrates are assisted by microwave heating. Note: the regioisomeric
distribution is similar using conventional heating. For use of microwave
heating in PK reactions, see: (a) M. Iqbal, N. Vyse, J. Dauvergne and
P. Evans, Tetrahedron Lett., 2002, 43, 7859; (b) E. Fager-Jokela, E.
Kaasalainen, K. Leppanen, J. Tois and J. Helaja, Tetrahedron, 2008,
64, 10381.
5 On a general note, there appears to be limited number of unsymmetrical
diarylethynes that undergo efficient intermolecular PK reactions, see:
(a) S. E. Gibson and N. Mainolfi, Angew. Chem., Int. Ed., 2005, 44,
3022; (b) S. Laschat, A. Becheanu, T. Bell and A. Baro, Synlett, 2005,
2547.
6 (a) F. Robert, A. Milet, Y. Gimbert, D. Konya and A. E. Greene, J. Am.
Chem. Soc., 2001, 123, 5396; (b) T. J. M. de Bruin, A. Milet, F. Robert,
Y. Gimbert and A. E. Greene, J. Am. Chem. Soc., 2001, 123, 7184.
7 B. E. Moulton, H. Dong, C. T. O’Brien, S. B. Duckett, Z. Lin and I. J. S.
Fairlamb, Org. Biomol. Chem., 2008, 6, 4523.
8 On the regioselectivity in PK reactions, see: (a) M. E. Krafft, R. H.
Romero and I. L. Scott, J. Org. Chem., 1992, 57, 5277; (b) M. E.
Krafft, R. H. Romero and I. L. Scott, Synlett, 1995, 577; (c) T. J. M.
de Bruin, C. Michel, K. Vekey, A. E. Greene, Y. Gimbert and A. Milet,
J. Organomet. Chem., 2006, 691, 4281–4288. Effect on regioselectivity
using sterically bulky alkenes, see: (d) V. Derdau, S. Laschat and P. G.
Jones, Eur. J. Org. Chem., 2000, 681. Also see ref. 6.
9 Y. Kato, S. Okada, K. Tomimoto and T. Mase, Tetrahedron Lett., 2001,
42, 4849–4851.
10 (a) I. J. S. Fairlamb, A. F. Lee, F. Loe-Mie, E. H. Niemela¨, C. T. O’Brien
and A. C. Whitwood, Tetrahedron, 2005, 61, 9827–9838; (b) I. J. S.
Fairlamb, L. R. Marrison, J. M. Dickinson, F.-J. Lu and J.-P. Schmidt,
Bioorg. Med. Chem., 2004, 12, 4285–4299; (c) J. C. Collings, A. C.
Parsons, L. Porre`s, A. Beeby, A. S. Batsanov, J. A. K. Howard, D. P.
Lydon, P. J. Low, I. J. S. Fairlamb and T. B. Marder, Chem. Commun.,
2005, 2666–2668.
11 (a) F. A. Cotton, J. D. Jamerson and B. R. Stults, J. Am. Chem.
Soc., 1976, 98, 1774; (b) M. F. D’Agostino, C. S. Frampton and M. J.
McGlinchey, Organometallics, 1990, 9, 2972.
12 gNMR software package (version 5.1, P. H. M. Budzelaar,
Department of Chemistry, University of Manitoba), see: http://home.
cc.umanitoba.ca/~budzelaa/gNMR/gNMR.html (last accessed
03/06/2010).
13 M. McLaughlin, M. Takahashi and G. C. Micalizio, Angew. Chem.,
Int. Ed., 2007, 46, 3912. This paper details the Ti-mediated alkoxide-
directed intermolecular [2+2+1] annulation of an ortho-substituted
aromatic imine with an internal alkyne alkoxide which delivers an
atropisomeric lactam product in good diastereoselectivity.
14 (a) A. D. Becke, J. Chem. Phys., 1993, 98, 5648; (b) B. Miehlich, A.
Savin, H. Stoll and H. Preuss, Chem. Phys. Lett., 1989, 157, 200; (c) C.
Lee, W. Yang and G. Parr, Phys. Rev., 1988, B37, 785.
15 (a) K. Fukui, J. Phys. Chem., 1970, 74, 4161; (b) K. Fukui, Acc. Chem.
Res., 1981, 14, 363.
16 P. C. Hariharan and J. A. Pople, Theor. Chim. Acta, 1973, 28,
213.
17 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C.
Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci,
M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M.
Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E.
Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi,
C. Pomelli, J. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P.
Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D.
Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K.
Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S.
Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz,
I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y.
Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. G. Johnson,
W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople, GAUSSIAN 03
(Revision B.05), Gaussian, Inc., Wallingford, CT, 2004.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 5398–5403 | 5403
©