Selective enhancement effects of silver salts on the transition metal-catalyzed synthesis of gem-difluorinated heterocyclics using 2,2-difluorohomopropargyl amides

Article abstract of DOI:10.1016/j.jfluchem.2008.05.010

The addition of silver salts had an effect on the catalyst activity in the Pd(0)-catalyzed cyclization-coupling tandem reaction, as well as in the Rh(I)-catalyzed Pauson-Khand reaction. The cationic palladium complex generated from Pd(PPh₃)

Full text of DOI:10.1016/j.jfluchem.2008.05.010

Journal of Fluorine Chemistry 129 (2008) 1047–1051
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Selective enhancement effects of silver salts on the transition
metal-catalyzed synthesis of gem-difluorinated heterocyclics using 2,
2-difluorohomopropargyl amides
*
Satoru Arimitsu, Rebecca L. Bottom, Gerald B. Hammond
Department of Chemistry, University of Louisville, Louisville, KY 40292, USA
A R T I C L E I N F O
A B S T R A C T
Article history:
The addition of silver salts had an effect on the catalyst activity in the Pd(0)-catalyzed cyclization-
coupling tandem reaction, as well as in the Rh(I)-catalyzed Pauson–Khand reaction. The cationic
palladium complex generated from Pd(PPh3)4 (2.5 mol%) with AgSbF6 (1.5 equiv.) activates the triple
Received 14 April 2008
Received in revised form 8 May 2008
Accepted 13 May 2008
Available online 20 May 2008
bond of 2,2-difluoropropargylic amides to give the 4,5-disubstituted 3,3-difluoro-
g-lactams, through a
sequential 5-endo-dig cyclization and cross-coupling reaction. The -lactam was transformed into ring-
g
opened monofluorovinylic compounds after silica-gel chromatography. Pauson–Khand reaction of
fluorinated 1,7-enyne amides using catalytic amounts of [Rh(COD)2]2 (5 mol%) and AgOTf (20 mol%) gave
the corresponding gem-difluorinated bicyclic lactam.
Keywords:
Pauson–Khand
Difluorolactam
Cyclization
ß 2008 Elsevier B.V. All rights reserved.
Difluoropropargyl
Amide
1. Introduction
pargylic amide 1; and the Rh(I)-catalyzed Pauson–Khand reaction
of fluorinated 1,7-enyne 7 (Scheme 2).
The juxtaposition of a carboxy amide – a common group
present in pharmaceuticals and natural products [1] – and fluorine
[2], is known to enhance the biological properties of the parent
molecule. In the past decade, much effort has been spent on the
2. Results and discussion
2.1. Pd(0)-catalyzed tandem cyclization-coupling reaction of amide 1
with organohalides
synthesis of fluorinated carboxy amides. Conversely,
a,a-difluori-
nated lactams are rare. Recently, we reported useful transforma-
tions toward the synthesis of fluorinated lactams (i.e. fluorinated
Tandem reactions are becoming increasingly popular in modern
organicsynthesisbecauseoftheiratom-efficiencyandfewerstepsto
afford final products compared to traditional chemistry [5]. We
investigated the tandem Pd(0)-catalyzed cyclization-coupling
reaction shown in Table 1. This reaction was highly influenced by
silver salts (entries 1–6, Table 1). The use of AgSbF6 (1.5 equiv.)
isoquinolinones, fluorinated
b- and g-lactams) using a catalytic
activation of triple bonds adjacent to a gem-difluoromethylene
group [3]. These synthetic protocols may allow access to
fluorinated drug-like compounds from readily available 2,2-
difluoropropargylic amides (Scheme 1). As expected, fluorine
withdraws electron density from the triple bond [4], making it less
reactive toward electrophiles. In some cases, we have overcome
this decreased reactivity utilizing higher temperatures as well as
microwave irradiation, but these have caused thermal degradation
of the product. An alternative solution is to activate the
electrophile itself. In this paper, we report a selective enhancement
caused by silver salts on the Pd(0)-catalyzed tandem cyclization-
coupling reaction between organohalides and 2,2-difluoropro-
suppressed the formation of by-product 4 [19F NMR
thiscase, the 19F NMR ofthe reaction mixtureshowedonly thesignal
corresponding to product 3a [19F NMR
À104 ppm] (entry 6,
d
À112 ppm]. In
d
Table1)[6]. Followingpurificationbysilica-gelchromatography,the
ring-opened monofluorovinylic product 5a [19F NMR
was obtained in 40% yield (entry 6, Table 1).
d
À116 ppm]
Among the other bases examined, t-BuOK gave the best result.
Based on 19F NMR yields, DMF appeared to be the best solvent
(entry 10, Table 1), but the isolated yield was lower because the
impurities have a Rf similar to that of the desired product 5a.
With electron-rich aryl iodides, the optimized reaction condi-
tions led to decomposition (entries 1 and 2, Table 2). With an
* Corresponding author. Tel.: +1 502 852 5998; fax: +1 502 852 3899.
E-mail address: gb.hammond@louisville.edu (G.B. Hammond).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.05.010

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S. Arimitsu et al. / Journal of Fluorine Chemistry 129 (2008) 1047–1051
The postulated reaction mechanism is depicted in Scheme 3.
Silver salts can generate the cationic palladium complex after an
oxidative addition of palladium to organohalides [8], thus
coordinating more strongly with a triple bond and inducing a 5-
endo-dig cyclization. Reductive elimination gives the final coupling
product 3. The intrinsic leaving ability of fluorine brings about the
formation of an iminium intermediate [9] that can easily react with
water to yield a hemiaminal, leading to the formation of 5.
2.2. Rh(I)-catalyzed Pauson–Khand reaction of fluorinated 1,7-
dienyne 7
Although there are several publications that report the Pauson–
Khand reaction of fluorinated building blocks, most utilize
stoichiometric amounts of Co2(CO)8 [10], and none of them have
reporteda catalyticversion[11]. Theresultsof our study of the Rh(I)-
catalyzed Pauson–Khand reaction are summarized in Table 3. Under
standard reaction conditions no reaction was observed (entry 1,
Table 3). Instead, we noticed that this reaction was very sensitive to
several experimental parameters (e.g., catalyst, solvent, concentra-
tion, silver salt, and temperature) as described below.
The addition of AgOTf had a crucial effect on the activation of
the rhodium catalyst (compare entries 1 and 2, Table 3) [12]. Other
silver salts did not have this effect (entries 10–13, Table 3) [13]. The
choice of solvent and concentration was also important to prevent
the formation of by-products (mainly the dimer of 8). Our best
conditions produced 8 in 43% isolated yield (entry 5, Table 3).
Utilizing cinnamaldehyde as a CO source did not give the desired
product. Unfortunately, this reaction has strict limitations on the
range of alkynes that can be utilized; for example, no reaction was
observed with a phenyl-substituted alkyne.
Scheme 1. Previously reported synthesis of a,a-difluorinated lactams. (a) Pd(OAc)2
[X = H], (b) TBAF [X = H], (c) [2 + 2 + 2] cycloaddition [R2 = Bn, X = H], (d) (i) enyne
metathesis, (ii) Diels–Alder reaction [R2 = Bn, X = allyl].
electron-deficient aryl iodide, such as 4-nitrophenyl iodide 2d, the
desired product 5d was obtained, albeit in low yield (entry 3,
Table 2). Replacement by allyl bromide 2e resulted only in trace
amounts of product, based on 19F NMR data.
Interestingly, without AgSbF6, the mixture of allyl bromide 2e
and amide 1b furnished the C–N coupling product 6, in good yield
(Eq. (1)) [7].
(1)
Table 1
Screening of Pd(0)-catalyzed tandem reaction of amide 1a with iodobenzene 2a
Entry
Base
Ag salt
Solvent
Yields of 3a/4/5a (%)a
1
2
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
Na2CO3
K2CO3
–
THF
THF
THF
THF
THF
THF
THF
THF
THF
DMF
PhMe
0/52/0
AgNO3
AgClO4
AgOTf
AgBF4
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
0/50/0
3
24/4/0
4
No rxn
0/5/0
5
6
62/0/0 (40)
14/0/19
33/0/0
7
8
9
NaOEt
25/0/0
10
11
t-BuOK
t-BuOK
56/0/0 (33)
21/3/0
a
Yields were determined by 19F NMR; values in parentheses correspond to isolated yield of 5a.

S. Arimitsu et al. / Journal of Fluorine Chemistry 129 (2008) 1047–1051
1049
Scheme 2. Possible new synthetic routes to fluorinated heterocyclics.
Table 2
Synthetic limitations of the Pd(0)-catalyzed tandem reaction
Entry
1
R-X
Isolate yields of 5 (%)
Decompo. (5b)
2
Decompo. (5c)
3
4
31 (5d)
Trace (5e)
Table 3
Screening of Rh(I)-catalyzed Pauson–Khand reaction
Entry
Catalyst
Ag salt
Solvent (X M)
Temperature
Timea (h)
Isolate yields of 8 (%)
b
1
2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Ir(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
–
THF (0.1)
70
70
r.t.
70
70
70
70
70
70
70
70
70
70
24
1
No rxn
22
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgSbF6
AgBF4
AgClO4
AgNO3
THF (0.1)
3
THF (0.1)
15
15
6
No rxn
No rxn
43
4
THF (0.1)
5
THF (0.02)
1,4-Dioxane (0.02)
DMF (0.02)
PhMe (0.02)
1,2-DCEc (0.02)
THF (0.02)
THF (0.02)
THF (0.02)
THF (0.02)
6
6
No rxn
No rxn
No rxn
Trace
Trace
Trace
Trace
No rxn
7
6
8
6
9
6
10
11
12
13
6
6
6
6
a
The reaction progress was monitored by TLC and/or GC–MS.
COD = 1,5-cyclooctadiene.
b
c
1,2-Dichloroethane.

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S. Arimitsu et al. / Journal of Fluorine Chemistry 129 (2008) 1047–1051
Scheme 3. Proposed mechanism for the Pd(0)-catalyzed tandem reaction of 1 with 2.
3. Conclusion
(0.48 mmol, 1.5 equiv.) and fluorinated amide 1a (0.32 mmol) into
which phenyl iodide (0.48 mmol, 1.5 equiv.) in THF (3.2 mL, 0.1 M)
was added via syringe. The vial was then placed in a CEM Discover
microwave synthesizer at 100 8C for 10 min (at 150 W, 250 psi
max); the temperature was monitored by computer during the
reaction. After cooling to room temperature, the reaction was
quenched with aqueous NH4Cl (50 mL, 1/1 = water/saturated
aqueous NH4Cl). The mixture was extracted with ethyl acetate
and the combined organic extracts were washed with brine and
dried over anhydrous MgSO4. 19F NMR yield of the desired product
3a was obtained after the removal of solvents. The final compound
was isolated by silica-gel column chromatography eluted with
hexane/ethyl acetate (5/1) yielding 5a (0.051 mg, 40%) as a pale
yellow solid.
The addition of silver salts was investigated in the Pd(0)-
catalyzed cyclization-coupling tandem reaction and in the Rh(I)-
catalyzed Pauson–Khand reaction. Both cationic transition metal
complexes activate the triple bond of 2,2-difluoropropargylamide.
In both cases there are limitations on the scope of substrates that
can be utilized. These reactions underscored the unique electronic
properties of electron-deficient triple bonds and insinuate
promising protocols that could turn unreactive triple bonds into
useful synthetic handles.
4. Experimental
4.1. General
4.2.1. 2-Fluoro-4-oxo-3,4-diphenyl-but-2-enoic acid benzylamide
1H, 13C and 19F NMR spectra were recorded at 500, 126 and
470 MHz respectively, using CDCl3 as a solvent. The chemical shifts
(5a)
mp 86–89 8C; 1H NMR (CDCl3)
d: 4.52 (s) and 4.53 (s) for 2H,
are reported in TM (ppm) values relative to CHCl3 (
d
7.26 ppm for 1H
6.73 (bs, 1H), 7.13 (s, 1H), 7.19 (s, 1H), 7.24–7.30 (m, 8H), 7.30 (t,
NMR and
d
77.0 ppm for 13C NMR) and CFCl3 (
d
0 ppm for 19F NMR).
J = 7.5 Hz, 2H), 7.54 (t, J = 7.5 Hz, 1H), 7.90 (d, J = 7.0 Hz, 2H); 19F
Coupling constants are reported in hertz (Hz). All air and/or
moisture sensitive reactions were carried out under argon
atmosphere. Solvents (tetrahydrofuran, DMF) were dried using a
commercial purification system. Toluene and 1,2-dichloroethane
were distilled over CaH2, and 1,4-dioxane was distilled over
benzophenone/Na. All other commercial reagents were obtained
from major chemical suppliers and used without further purifica-
NMR (CDCl3)
(CDCl3)
d
: À116.08 (s) and À116.15 (s) for 1F; 13C NMR
d
: 43.8 108.57, 108.60, 125.9, 127.1, 127.8, 127.9, 128.1,
128.6, 128.7, 128.8, 133.8, 136.8, 136.9, 155.4 (d, J = 295.3 Hz),
158.9 (d, J = 29.8 Hz), 187.9; IR (CCl4) cmÀ1: 3346, 3314, 3965,
3032, 2925, 2387, 2317, 1666, 1527, 1282.
4.2.2. 2-Fluoro-3-(4-nitrophenyl)-4-oxo-4-phenyl-but-2-enoic acid
tion. 19F NMR yield in the mixture was obtained using
trifluoromethylbenzene as the internal reference.
a
,a
,
a
-
benzylamide (5d)
Viscous oil; 1H NMR (CDCl3)
d
: 4.49 (s) and 4.50 (s) for 2H, 6.81
(bs, 1H), 7.08 (bs, 2H), 7.18–7.13 (m, 7H), 7.42 (t, J = 7.5 Hz, 2H),
4.2. General procedure of Pd(0)-catalyzed tandem cyclization-
7.53 (t, J = 7.5 Hz, 1H), 7.89 (d, J = 8.0 Hz, 2H); 19F NMR (CDCl3)
d:
coupling reaction of amide 1a with organohalide 2
À115.8 (s) and À115.9 (s) for 1F; 13C NMR (CDCl3)
d: 43.9, 108.7 (d,
J = 2.8 Hz), 121.4, 123.6, 125.9, 127.9, 128.3, 128.7, 128.8, 128.9,
133.9, 136.7, 136.9, 155.4 (d, J = 295.3 Hz), 158.9 (d, J = 29.8 Hz),
188.0; IR (CCl4) cmÀ1: 3321, 3063, 3033, 2928, 2352, 2319, 1715,
1661, 1521, 1448, 1277.
An oven-dried microwave vial (10 mL size) equipped with a stir
bar, under argon atmosphere, was charged with t-BuOK
(0.38 mmol, 1.2 equiv.), Pd(PPh3)4 (0.008 mmol, 2.5 mol%), AgSbF6

S. Arimitsu et al. / Journal of Fluorine Chemistry 129 (2008) 1047–1051
1051
4.3. General procedure for the Pd(0)-catalyzed allyl-N coupling of
4.4.1. 2-Benzyl-4,4-difluoro-1,2,7,7a-tetrahydro-4H-[2]pyrindine-
fluorinated amide 1b
3,6-dione (8)
Oil; 1H NMR (CDCl3)
d: 2.07 (d, J = 19.0 Hz, 1H), 2.63 (dd, J = 6.5,
An oven-dried microwave vial (10 mL size) equipped with a
stir bar, under argon atmosphere, was charged with t-BuOK
(0.66 mmol, 1.5 equiv.), Pd(PPh3)4 (0.044 mmol, 10 mol%) and
fluorinated amide 1b (0.44 mmol). Allyl bromide (1.32 mmol,
3.0 equiv.) in THF (2.2 mL, 0.2 M) was added via syringe. The vial
was then placed in a CEM Discover microwave synthesizer at
100 8C for 1 h (at 150 W, 250 psi max); the temperature was
monitored by computer during the reaction. After cooling to
room temperature, the reaction was quenched with aqueous
NH4Cl (50 mL, 1/1 = water/saturated aqueous NH4Cl). The
mixture was extracted with ethyl acetate and the combined
organic extracts were washed with brine and dried over
anhydrous MgSO4. After the removal of solvents, the final
compound was isolated by silica-gel column chromatography
eluted with hexane/ethyl acetate (40/1) to furnish 6 (0.116 mg,
79%) as a pale yellow liquid [14].
20.0 Hz, 1H), 2.93 (dt, J = 2.5, 11.5 Hz, 1H), 3.33–3.38 (m, 1H), 3.55
(dd, J = 7.0, 11.5 Hz, 1H), 4.45 (d, J = 14.5 Hz, 1H), 4.73 (d, J = 14.5 Hz,
1H), 6.44 (bs, 1H), 7.18–7.20 (m, 2H), 7.26–7.31 (m, 3H); 19F NMR
(CDCl3)
d
: À92.8 (d, J = 304.0 Hz, 1F), À116.3 (d, J = 300.7 Hz, 1F); 13
C
NMR (CDCl3)
d: 36.0 (d, J = 4.7 Hz), 38.9, 51.0, 51.8, 107.0 (dd,
J = 237.7, 250.1 Hz), 128.27, 128.35, 129.1, 131.0, 134.8, 160.6 (t,
J = 29.6 Hz), 165.6(dd, J = 22.1,24.9 Hz), 204.4;IR(CCl4) cmÀ1:3432,
3356, 3087, 3032, 2919, 2850, 1959, 1722, 1680, 1451, 1066; MS m/z
(%): 227 (34, M+), 260 (15), 156 (9), 133 (11), 91 (100).
Acknowledgement
The authors are grateful to the National Science Foundation
(CHE-0513483) for its financial support.
References
4.3.1. N-Allyl-N-benzyl-2,2-difluoro-4-phenyl-3-butynamide (6)
[1] A.K. Ghose, V.N. Viswanadhan, J.J. Wendoloski, J. Comb. Chem. 1 (1999) 55–68.
[2] For general reviews, see:
Oil; 1H NMR (CDCl3)
d: 0.89 (t, J = 6.5 Hz, 3H), 1.24–1.58 (m, 8H),
(a) K. Uneyama, Organofluorine Chemistry, Blackwell, Oxford, 2006;
(b) R.D. Chambers, Fluorine in Organic Chemistry, Blackwell, Oxford, 2004;
(c) P. Kirsch, Modern Fluoroorganic Chemistry, Wiley–VCH, Weinheim, 2004;
(d) B. Koksch, N. Sewald, H.-D. Jakubke, K. Burger, in: I. Ojima, J.R. McCarthy, J.T.
Welch (Eds.), Biomedical Frontiers of Fluorine Chemistry, American Chemical
Society, Washington, DC, 1996.
2.17–2.21 (m, 1H), 2.31–2.35 (m, 1H), 3.93 (d, J = 5.5 Hz) and 4.05
(d, J = 5.0 Hz) for 2H, 4.63 (s) and 4.76 (s) for 2H, 5.11 (d, J = 17.0 Hz)
and 5.22 (d, J = 17.0 Hz) for 1H, 5.21 (d, J = 10.0 Hz) and 5.30 (d,
J = 10.0 Hz) for 1H, 5.71–5.83 (m, 1H), 7.23–7.39 (m, 5H); 19F NMR
(CDCl3)
d
: À83.98 (s) and À84.68 (s) for 2F; 13C NMR (CDCl3)
d:
´
[3] (a) S. Fustero, B. Fernandez, P. Bello, C. del Pozo, S. Arimitsu, G.B. Hammond, Org.
Lett. 9 (2007) 4251–4253;
13.9, 18.5, 22.4, 27.4, 28.4, 31.1, 47.8, 48.0, 49.1, 50.1, 71.4 (t,
J = 37.9 Hz), 71.5 (t, J = 37.7 Hz), 93.6 (t, J = 6.0 Hz), 93.8 (t,
J = 6.0 Hz), 105.9 (t, J = 240.2 Hz), 106.1 (t, J = 240.9 Hz), 118.2,
119.1, 127.2, 127.6, 127.8, 128.0, 128.66, 128.69, 131.1, 132.3,
135.4, 136.0, 161.4 (t, J = 28.4 Hz), 161.6 (t, J = 28.3 Hz); IR (neat)
cmÀ1: 2931, 2861, 2250, 1686, 1444, 1222, 1072; MS m/z (%): 334
(100, M++H), 276 (12), 91 (65); HRMS (FAB) calcd. for C20H25F2NO
(M+): 333.1904, found: 334.1989 (M++H).
´
(b) S. Arimitsu, B. Fernandez, C. del Pozo, S. Fustero, G.B. Hammond, J. Org. Chem.
73 (2008) 2656–2661.
[4] S. Arimitsu, G.B. Hammond, J. Org. Chem. 72 (2007) 8559–8561.
[5] Review for tandem reaction, see:
J.-C. Wasilke, S.J. Obrey, R.T. Baker, G.C. Bazan, Chem. Rev. 105 (2005) 1001–1020;
Example of transition metal catalyzed cyclization-coupling reactions, see:
(a) G. Balme, D. Bouyssi, T. Lomberget, N. Monteiro, Synthesis 14 (2003) 2115–
2134;
(b) G. Battistuzzi, S. Cacchi, G. Fabrizi, Eur. J. Org. Chem. (2002) 2671–2681.
[6] Product 4a has been reported. See Ref. [3a]
[7] (a) J. Yin, S.L. Buchwald, Org. Lett. 2 (2000) 1101–1104;
(b) S.E. Bystro¨m, R. Aslanian, J.-E. Ba¨ckvall, Tetrahedron Lett. 26 (1985) 1749–1752.
[8] (a) Y. Hu, Y. Zhang, Z. Yang, R. Fathi, J. Org. Chem. 67 (2002) 2365–2386;
(b) G. Zou, Y.K. Reddy, J.R. Falck, Tetrahedron Lett. 42 (2001) 7213–7215 (and
references therein).
4.4. General procedure for the Rh(I)-catalyzed Pauson–Khand
reaction of fluorinated 1,7-dienyne 7
An oven-dried two-necked round bottom flask (50-mL size)
equipped with a condenser was loaded with (S)-BINAP (0.03 mmol,
10 mol%), [Rh(COD)2]2 (0.015 mmol, 5 mol%) and THF (2 mL) under
argon; then the argon was replaced by carbon monoxide in a
plastic balloon, and the whole reaction mixture was stirred for
30 min at 40 8C. AgOTf (0.06 mmol, 20 mol%) was added into the
reaction mixture and stirred for another 30 min at 40 8C. After the
fluorinated 1,7-dienyne 7 (0.3 mmol) was added with the aid of
THF (13 mL, 0.2 M as a total concentration), the reaction mixture
was stirred at 70 8C for additional 6 h. The organic solvent was
removed from the resulting solution and the residue was charged
on silica-gel column chromatography using hexane/Et2O (1/3) as
eluent to afford 8 (0.133 mg, 43%). The enantiomeric excess of the
product 8 was not determined.
[9] For a similar example, see:
Y. Wang, S. Zhu, Org. Lett. 5 (2003) 745–748.
[10] (a) R. Nadano, J. Ichikawa, J. Chem. Lett. 36 (2007) 22–23;
(b) S. Harthong, T. Billard, B.R. Langlois, Synthesis 13 (2005) 2253–2263;
(c) A. Ferry, T. Billard, B.R. Langlois, Synlett 6 (2005) 1027–1029;
(d) M. Ishizaki, D. Suzuki, O. Hoshino, J. Fluorine Chem. 111 (2001) 81–90.
[11] For examples of Rh(I)-catalyzed Pauson–Khand reaction see:
(a) K. Fuji, T. Morimoto, K. Tsutsumi, K. Kakiuchi, Angew. Chem. Int. Ed. 42 (2003)
2409–2411;
(b) N. Jeong, B.K. Sung, Y.K. Choi, J. Am. Chem. Soc. 122 (2000) 6771–6772 (and
references cited therein).
[12] Silver salts have been reported to enhance Rh(I)-catalyzed (e.g. [Rh(CO)2Cl]2,
[RhCl(CO2)]2) Pauson–Khand reaction, see:
(a) K.M. Brummond, B. Mitasev, Org. Lett. 6 (2004) 2245–2248;
(b) Ref. [11b]..
[13] T. Shibata, N. Toshida, K. Takagi, J. Org. Chem. 67 (2002) 7446–7450 (and
references cited therein).
[14] Product 6 has been reported. See Ref. [3b]