Tandem [2+1] cycloaddition-ring expansion of bicyclic alkenes with tertiary propargylic acetates catalyzed by palladium(II)-coordinated phosphinous acid

Article abstract of DOI:10.1055/s-2008-1042919

Palladium-SPO complex catalyzed the tandem [2+1] cycloaddition-ring expansion of norbornene derivatives with tertiary propargylic acetates to afford bicyclo[3.2.1]octadienes. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1042919

LETTER
1071
Tandem [2+1] Cycloaddition–Ring Expansion of Bicyclic Alkenes with
Tertiary Propargylic Acetates Catalyzed by Palladium(II)-Coordinated
Phosphinous Acid
T
andem [2
u
+1] Cycload
l
dition–
i
Ring E
e
xpansion of Bic
y
B
clic Alkene
s
igeault,a Innocenzo de Riggi,a Yves Gimbert,b Laurent Giordano,*a Gérard Buono*a
a
Université d’Aix-Marseille, ECM, Institut des Sciences Moléculaires de Marseille (ISM2), CNRS UMR 6263; Avenue Escadrille
Normandie Niemen, Case A 62, 13397 Marseille Cedex 20, France
Fax +33(491)282742; E-mail: gerard.buono@univ-cezanne.fr; E-mail: laurent.giordano@univ-cezanne.fr
Université Joseph Fourier de Grenoble, Département de Chimie Moléculaire, UMR CNRS 5250, ICMG FR-2607, 38041 Grenoble
Cedex 9, France
b
Received 22 December 2007
nylidenecyclopropanes catalyzed by palladium(II)-
coordinated phosphinous acid. We firstly decided to re-
examine the reaction of tertiary acetates 2a and 2b with
norbornadiene 1a in the presence of 5 mol% of Pd(OAc)2
associated with cyclohexylphenylphosphine oxide (1:2
molar ratio) at room temperature using toluene instead of
THF as solvent.10 In contrast with the reaction carried out
in THF (Table 1, entries 1 and 2) the expected cycload-
ducts 3a and 3b were obtained in lower yield, 22% and
8%, respectively (Table 1, entries 3 and 5). However, 1H
NMR analysis of the crude reaction mixture revealed a
complete conversion (based on 2) and the formation of a
new adduct 4 obtained as a 9:1 mixture of diastereomers.
The structure of 4a and 4b were established by 1H NMR
and 13C NMR and the exo stereochemistry of the acetoxy
group for the major diastereomer 4b was assigned by
comparison with literature data.12 Interestingly, when the
reaction was performed at 60 °C for 60 hours, 3a and 4a
were obtained with an overall yield of 86% and the molar
ratio of 4a/3a raised to 3.8:1 (Table 1, entry 4). The vari-
ation of the molar ratio in favor of 4a when increasing the
temperature suggested 3a as a precursor of 4a. Indeed, 3a
could react with AcOH released in the medium during the
first step of the reaction (Scheme 1). It is important to note
that the reaction performed with Ph3P in place of SPO
ligands did not afford 3.13
Abstract: Palladium–SPO complex catalyzed the tandem [2+1] cy-
cloaddition–ring expansion of norbornene derivatives with tertiary
propargylic acetates to afford bicyclo[3.2.1]octadienes.
Key words: palladium, secondary phosphine oxides, tertiary prop-
argylic acetate, bicyclic alkene, tandem reaction
Secondary Phosphine Oxides (SPO) are excellent preli-
gands for transition metals.1 To date, the SPO are largely
employed as preligands in catalytic reactions.2 The pio-
neering work involving SPO for transition-metal-cata-
lyzed cross-coupling reactions was reported by Li.3 Since
2001, the field of application of SPO in cross-coupling re-
actions has considerably extended.4 Transition-metal-co-
ordinated chiral phosphinous acid have also found
applications in asymmetric allylic amination5 or
alkylation6 and asymmetric hydrogenation of imines7 or
functionalized olefins.8 Recently, a bridged phosphinous
acid dimer POPd1 (Figure 1) proved to be an efficient cat-
alyst for the conjugate addition of arylsiloxanes to a wide
range of a,b-unsaturated substrates.9
t-Bu t-Bu
t-Bu t-Bu
Cl
O
P
P
O
H
Pd
Pd
H
O
P
P
O
Cl
t-Bu
t-Bu
t-Bu t-Bu
This observation was supported by the reaction of 3a and
AcOH in the presence of Pd(OAc)2/CyPhP(O)H as a cat-
alytic system affording 4a as a single adduct in 48% yield
(Scheme 2).14
POPd1
Figure 1 Li’s catalyst
In our previous works, we reported that palladium or plat-
inum–phosphinous acid catalysts are active for the [2+1]
cycloaddition of terminal alkynes and norbornene deriva-
tives.10,11 These classes of complexes also show an activ-
ity in a [4+2] cycloaddition involving alkylidenecyclo-
propanes.11 These results led us to examine the behavior
of vinylidenecyclopropanes in the presence of nucleo-
philic reagent and catalytic amounts of Pd(OAc)2/SPO. In
this letter, we describe the direct preparation of bicyc-
lo[3.2.1]octadienes via an in situ rearrangement of alle-
However, under these conditions the diastereomeric ex-
cess decrease to 68%, probably due to a large amount of
AcOH (1 equiv) compared to the catalytic system (0.05
equiv). Finally, using the tertiary acetate 2b in the same
conditions, 4b was obtained selectively in 60% yield
(Table 1, entry 6). Secondly, having established the feasi-
bility of this transformation, various bicyclic alkenes were
tested to extend the scope of the above reaction (Table 2).
Almost all bicyclic substrates were transformed into their
corresponding bicyclo[3.2.1]octadienes 4. For instance,
norbornene 1c and functionalized norbornadienes 1d–g
afforded 4d–g in moderate yields. However, the whole
transformation should be considered as two successive
steps with fairly good yields (Table 2, entries 1–6). It is
SYNLETT 2008, No. 7, pp 1071–1075
x
x.
x
x.
2
0
0
8
Advanced online publication: 17.03.2008
DOI: 10.1055/s-2008-1042919; Art ID: G41707ST
© Georg Thieme Verlag Stuttgart · New York

1072
J. Bigeault et al.
LETTER
Table 1 Synthesis of Bicyclo[3.2.1]octadiene 4 from Tertiary Acetates 2 and Norbornadiene 1aa
R
R
R
Pd(OAc)2, SPO
R
+
OAc
+
48 h
R
R
AcO
4a
1a
2a R, R = -(CH2)5-
2b R, R = Me
3a
3b
4b
O
SPO =
P
H
1/2/Pd/SPO = 2:1:0.05:0.1
Ph
Cy
Entry
Alkyne
2a
Solvent
THF
Temp (°C)
Product
3a
Yield (%)b
1
2
3
25
25
25
64
27
2b
THF
3b,
2a
Toluene
3a
4a
22
33
4
5
6
2a
2b
2b
Toluene
Toluene
Toluene
60
25
60
3a
4a
18
68
3b
4b
8
32
3b
4b
≤ 5
60
a All reactions were carried out with 1 mmol of 2a or 2b for 48 h.
b Isolated yield.
R
1a
R
R
Pd(OAc)2, SPO
Pd(OAc)2, SPO
AcOH
+
+
R
AcO
R
3
4
OAc
R
2
Scheme 1 A possible formation of bicyclo[3.2.1]octadiene 4 from alkyne 2 and norbornadiene 1a
worth noting that these reaction conditions were suitable
for every compound except for 7-tert-butoxynorborna-
diene (1h, Table 2, entry 7). In this case, the possibility of
the coordination of the oxygen atom carried by tert-but-
oxy group and the double bond of the norbornadiene moi-
ety could yield a stable complex 5, unreactive for the
[2+1] cycloaddition (Figure 2).15
Pd(OAc)2, CyPhP(O)H
toluene, 60 °C, 60 h
+
AcOH
3a
AcO
4a 48%, de = 68%
Scheme 2 Pd(OAc)2–SPO-catalyzed rearrangement of allenyl-
idenecyclopropane
A possible pathway for the palladium-catalyzed [2+1] cy-
cloaddition of norbornadiene 1a with tertiary propargylic
acetates 2 was proposed in our previous work.10 The
mechanism of the present ring expansion involving Pd(II)
cationic species A as the active catalyst is suggested
(Scheme 3).16 Complex A is able to coordinate the allene
partner by the most available endo face to give B. At this
stage, the activation of the double bond branched on cy-
clopropane ring generates a cyclopropyl cation C which
rearranges into an allylic cation D. Nucleophilic attack of
the acetate17 and protonolysis of D release the product 4
and the active catalyst A.
Ph Cy
O
P
O
Pd
Cy
H
5
P
O
Ph
Figure 2 Formation of a possible stable complex 5
Synlett 2008, No. 7, 1071–1075 © Thieme Stuttgart · New York

LETTER
Tandem [2+1] Cycloaddition–Ring Expansion of Bicyclic Alkenes
1073
Table 2 Pd–SPO-Catalyzed Tandem [2+1] Cycloaddition–Ring Expansion of 1 with 2ba
Entry
1
Alkene
Time (h)
48
Product (de, %)
Yield (%)b
60
AcO
1a
4b (80)
2
3
24
60
54
55
AcO
1c
4c (80)
Ac
O
Ac
O
AcO
AcO
AcO
1d
4d (95)
AcO
AcO
AcO
AcO
4
5
60
50
53
33
AcO
1e
4e (93)
MeO2CO
MeO2CO
MeO2CO
MeO2CO
AcO
1f
4f (92)
Ph
Ph
6
7
60
14
49
AcO
4g (95)
t-BuO
1g
t-BuO
NR
AcO
1h
4h
a All reactions were carried out with 1 mmol of 2b at 60 °C in toluene. Ratio: 1/2b/Pd/CyPhP(O)H = 2:1:0.05:0.1.
b Isolated yield.
We intended to compare the effect of Ph3P ligand and acetoxypalladation (ii). Intermediate E isomerizes to a p-
SPO on the outcome of the reaction of 3a with AcOH. allyl Pd F precursor of 4 whereas intermediate G under-
When using Pd(0)/PPh3 as a catalyst, the reaction was not goes reductive elimination to afford the ketone 6 after hy-
selective, affording 4a together with 6 (Scheme 4).
drolysis.
Although the Pd(0)/Ph3P catalyzes this rearrangement In conclusion, a new tandem [2+1] cycloaddition–ring ex-
with modest selectivity, it turns out that the SPO ligands pansion of norbornene derivatives with tertiary propargyl-
showed a better efficiency and selectivity for the second ic acetates using a Palladium–SPO complex as a catalyst
step of this reaction. On the basis of these results, another have been developed. This simple catalytic procedure pro-
mechanistic pathway involving HPd(OAc)(PPh3)2 must vides various functionalized bicyclo[3.2.1]octadienes.
be considered (Scheme 5).18
Since enantiomerically enriched SPO preligands20 can be
used for this transformation, an asymmetric domino reac-
tion is expected to occur. These studies will be reported in
due course.
The formation of both products could be explained by two
distinct elemental steps: A hydropalladation (i)19 and an
Synlett 2008, No. 7, 1071–1075 © Thieme Stuttgart · New York

1074
J. Bigeault et al.
LETTER
O
Pd(OAc)2
+
P
Ph
H
Cy
AcOH, AcO–
Cy
Ph
O
P
P
AcO
R
H
Pd +
Cy
R
R
4
R
O
A
Ph
3
AcOH, AcO–
Cy
O
Ph
P
[Pd] =
H
Pd
P
R
O
Ph
Cy
B
R
+
[Pd]
[Pd]+
D
R
R
R
+
R
[Pd]
C
Scheme 3 Proposed reaction pathway for the palladium–SPO-catalyzed ring expansion of 3
Pd(0), AcOH (1 equiv)
toluene, 75 °C, 24 h
+
O
AcO
3a
4a
6
Pd(dba)2 (5 mol%)/PPh3 (20 mol%)
Pd(OAc)2 (5 mol%)/PPh3 (25 mol%)
36%, de = 54%
22%, de = 33%
18%
11%
Scheme 4 Palladium(0)-catalyzed ring expansion of 3a
R
R
R
(L)2Pd(H)OAc
H
R
Pd(L)2(OAc)
R
i
Pd(L)2(OAc)
R
E
F
R
AcO
4
L = PPh3
R
OAc
3
ii
O
+ AcO–
R
(L)2Pd(H)OAc,
AcO–
R
(H)(L)2Pd
6
G
R
R
Scheme 5 Possible pathway for Pd(0)-catalyzed ring expansion of 3
Typical Procedure
solution of 1 (2 mmol) and 2-methybut-3-yn-2-yl acetate (2b, 1
mmol, 125.1 mg), respectively, in 1 mL and 2 mL of dry and de-
gassed toluene were added successively. The resulting mixture was
stirred at 60 °C for 24–60 h. The solvent was then concentrated in
vacuum to afford a yellow or dark crude mixture. Purification of the
In a 10mL flame-dried Schlenk flask, Pd(OAc)2 (11.2 mg, 0.05
mmol, 5 mol%) and CyPhP(O)H (0.1 mmol, 20.8 mg, 10 mol%)
were dissolved under argon in dry and degassed toluene (2 mL),
then, the resulting yellow solution was stirred at r.t. After 30 min, a
Synlett 2008, No. 7, 1071–1075 © Thieme Stuttgart · New York

LETTER
Tandem [2+1] Cycloaddition–Ring Expansion of Bicyclic Alkenes
1075
crude by flash chromatography using Et2O–light PE as eluent af-
(3) (a) Li, G. Y.; Zheng, G.; Noonan, A. F. J. Org. Chem. 2001,
forded 33–60% of 4.
All new compounds exhibited satisfactory 1H NMR, 13C NMR, and
IR spectral data. The following physical data are representative.
66, 8677. (b) Li, G. Y. Angew. Chem. Int. Ed. 2001, 40,
1513. (c) Li, G. Y.; Fagan, P. J.; Watson, P. L. Angew.
Chem. Int. Ed. 2001, 40, 1106.
(4) For a review, see: Ackermann, L.; Born, R.; Spatz, J. H.;
Althammer, A.; Gschrei, C. J. Pure Appl. Chem. 2006, 78,
209.
(5) Nemoto, T.; Matsuda, T.; Akimoto, Y.; Fukuyama, T.;
Hamada, Y. Org. Lett. 2005, 7, 4447.
(6) (a) Dai, W.-M.; Yeung, K. K. Y.; Leung, W. H.; Haynes, R.
K. Tetrahedron: Asymmetry 2003, 14, 2821. (b) Nemoto,
T.; Matsumoto, T.; Matsuda, T.; Hitomi, T.; Hatano, K.;
Hamada, Y. J. Am. Chem. Soc. 2004, 126, 3690.
(c) Nemoto, T.; Matsuda, T.; Matsumoto, T.; Hamada, Y.
J. Org. Chem. 2005, 70, 7172.
(7) Jiang, X.; Minnaard, A. J.; Hessen, B.; Feringa, B. L.;
Duchateau, A. L. L.; Andrien, J. G. O.; Boogers, J. A. F.; de
Vries, J. G. Org. Lett. 2003, 5, 1503.
(8) Jiang, X.; van den Berg, M.; Minnaard, A. J.; Feringa, B. L.;
de Vries, J. G. Tetrahedron: Asymmetry 2004, 15, 2223.
(9) Lerebour, R.; Wolf, C. Org. Lett. 2007, 9, 2737.
(10) Bigeault, J.; Giordano, L.; Buono, G. Angew. Chem. Int. Ed.
2005, 44, 4753.
(11) Bigeault, J.; Giordano, L.; de Riggi, I.; Gimbert, Y.; Buono,
G. Org. Lett. 2007, 9, 3567.
(12) Goering, H. L.; Kantner, S. S. J. Org. Chem. 1984, 49, 422.
(13) (a) See ref. 10, 11. (b) Tenaglia, A.; Giordano, L.; Buono,
G. Org. Lett. 2006, 8, 4315.
(14) Reaction carried out without Pd(OAc)2/CyPhP(O)H as a
catalytic system did not proceed at all.
3-(2-Methyl-propenyl)-exo-bicyclo[3.2.1]oct-3,6-dien-2-yl Ace-
tate (4b)
Diastereomeric excess: 80%; yield 60%; pale yellow oil. TLC:
Rf = 0.48 (Et2O–light PE, 1:9). IR (thin film, NaCl plate): nmax
=
3059, 3028, 2971, 2945, 2867, 1737, 1648, 1446, 1368, 1327, 1239,
1015, 974 cm–1. ESI-MS (low resolution): m/z calcd for C14H18O2
[M + H]+: 219; found: 219 [M + H]+, 236 [M + NH4]+, 241 [M +
Na]+.
Major Diastereomer
1H NMR (200 MHz, CDCl3): d = 1.68 (d, J = 1.3 Hz, 3 H), 1.69 (d,
J = 1.3 Hz, 3 H), 1.83–1.92 (m, 1 H), 1.97 (d, J = 9.6 Hz, 1 H), 2.03
(s, 3 H), 2.69–2.75 (m, 1 H, H1), 2.81–2.87 (m, 1 H), 4.97 (d, J = 1.3
Hz, 1 H, HCO), 5.28 (m, 1 H), 5.86 (dd, J = 3.1, 5.5 Hz, 1 H), 6.10
(d, J = 6.6 Hz, 1 H), 6.48 (dd, J = 2.8, 5.5 Hz, 1 H). 13C NMR (50
MHz, CDCl3): d = 19.4 (q), 21.2 (q), 26.4 (q), 38.4 (t), 39.2 (d), 43.7
(d), 70.9 (d), 123.5 (d), 129.5 (d), 130.5 (s), 135.6 (s), 136.9 (d)
145.4 (d), 170.4 (s).
Minor diastereomer
NMR signals from the exo/endo mixture: H NMR (200 MHz,
CDCl3): d = 1.69–1.71 (m, 6 H), 3.19 (td, J = 5.1, 2.8 Hz, 1 H), 5.46
(d, J = 5.5 Hz, 1 H, HCO), 5.74 (dd, J = 5.5, 2.6 Hz, 1 H). 13C NMR
(50 MHz, CDCl3): d = 19.5 (q), 20.7 (q), 21.1 (q), 39.0 (d), 44.2 (t),
71.4 (d), 123.4 (d), 129.4 (d), 131.9 (s), 135.6 (d).
1
(15) For a similar observation, see: Lautens, M.; Fagnou, K.;
Yang, D. J. Am. Chem. Soc. 2003, 125, 14884.
(16) For a similar proposed mechanism with TiCl4 as Lewis acid,
see: Huang, X.; Su, C.; Liu, Q.; Song, Y. Synlett 2008, 229.
(17) The exo selectivity for the nucleophilic attack of the acetate
is well established. See: Battiste, M. A.; Coxon, J. M.;
Edelman, R. Tetrahedron Lett. 1972, 45, 4577.
(18) For the formation of HPd(OAc)(PPh3)2, see: (a) Trost, B.;
Rise, F. J. Am. Chem. Soc. 1987, 109, 3161. (b) Trost, B.;
Schmidt, T. J. Am. Chem. Soc. 1988, 110, 2301.
(19) For a recent example concerning the Pd(0)-catalyzed
reaction of vinylidenecyclopropanes with acetic acid, see:
Lu, J.-M.; Shi, M. Tetrahedron 2006, 62, 9115.
(20) For the enantioselective synthesis of SPO, see: (a) Leyris,
A.; Nuel, D.; Giordano, L.; Achard, M.; Buono, G.
Tetrahedron Lett. 2005, 46, 8673. (b) Leyris, A.; Bigeault,
J.; Nuel, D.; Giordano, L.; Buono, G. Tetrahedron Lett.
2007, 48, 5247.
Acknowledgment
We are grateful to CNRS and ANR project ‘SPOs Preligands’ (Con-
tract No. BLAN07-1_190839) for financial support. J. B. thanks
MENRT for the doctoral fellowship. We also think Dr. J. Leclaire
(Ecole centrale Marseille, France) and Dr. A. Tenaglia (CNRS) for
useful suggestions.
References and Notes
(1) (a) Roudhill, D. M.; Sperline, R. P.; Beaulieu, W. B. Coord.
Chem. Rev. 1978, 26, 263. (b) Walther, B. Coord. Chem.
Rev. 1984, 60, 67. (c) Appleby, T.; Woollins, J. D. Coord.
Chem. Rev. 2002, 235, 121.
(2) For reviews, see: (a) Ackermann, L. Synthesis 2006, 1557.
(b) Dubrovina, N. V.; Börner, A. Angew. Chem. Int. Ed.
2004, 43, 5883.
Synlett 2008, No. 7, 1071–1075 © Thieme Stuttgart · New York

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