Intramolecular cyclocarbonylation of cyclopropylidenyl aldehydes mediated by molybdenum carbonyl complex

Article abstract of DOI:10.1055/s-2004-830849

A novel procedure for the synthesis of cis-bicyclic spirocyclopropanelactones from cyclopropylidenyl aldehydes via the molybdenum-mediated cyclocarbonylation is described. The use of (C ₇H₈)Mo(CO)₃ with DMSO to promote the

Full text of DOI:10.1055/s-2004-830849

LETTER
1695
Intramolecular Cyclocarbonylation of Cyclopropylidenyl Aldehydes Mediated
by Molybdenum Carbonyl Complex
Intramolecular
C
h
a
ation of Cy
n
clopropylide
-
nyl
A
lde
M
hydes o Yu,* Young-Taek Hong, Seok-Keun Yoon, Joon-Hwan Lee
Department of Chemistry and Lab for Metal-Catalyzed Reactions (NRL), Sungkyunkwan University, Suwon 440-746, Korea
Fax +82(31)2907075; E-mail: cmyu@chem.skku.ac.kr
Received 9 April 2004
As part of our ongoing efforts to prepare and utilize alle-
Abstract: A novel procedure for the synthesis of cis-bicyclic spiro-
nyl functionalities,7 we have disclosed the cyclization
cyclopropanelactones from cyclopropylidenyl aldehydes via the
strategies using the allenyl-carbonyl moieties through
molybdenum-mediated cyclocarbonylation is described. The use of
transition metal catalysis.8 During the course of this pro-
(C7H8)Mo(CO)3 with DMSO to promote the reaction results in an
efficient and convenient protocol for the three-component assembly gram aimed at finding new synthetic routes and reagents,
in high yields.
we became quite interested in the cyclocarbonylation of
cyclopropylidenyl aldehydes 3 in forming 4 through the
three-component assembly as illustrated in Scheme 1.
Subsequent to previous reports on the utilization of cyclo-
propylidene moiety as a substrate,9 many research groups
have made important contributions in a variety of chemi-
cal transformations including Pauson–Khand reactions,10
Heck-type reactions,11 and cycloadditions.12 To the best of
our knowledge, however, the utilization of the cyclopro-
pylidene functionality as a direct substrate for complex-
ation with transition metals to promote the reaction has
not been described. The realization of an efficient method
in this reaction should be valuable because many useful
applications and functional group transformations can be
foreseen for the cyclopropyl moiety.9
Key words: aldehydes, carbonyl complexes, cyclizations, cyclo-
propane, molybdenum
The availability of efficient synthetic methods in the con-
struction of cyclic systems via organotransition metal cat-
alysts or reagents is of considerable interest in current
organic chemistry. As a consequence, many advances in
the cyclization mediated by transition metals have been
made through a variety of synthetic strategies.1 Of partic-
ular interest is a cyclization strategy between carbonyl
groups and unsaturated bonds to find a practical route for
the preparation of lactones, mainly because the chemical
process could dominate over the classical methods in sim-
ple trial as shown in Scheme 1.2 For example, the use of
titanium-mediated [2+2+1] cycloaddition of d-unsaturat-
ed ketones or aldehydes 1 to form fused g-butyrolactone 2
via cyclocarbonylation, known as hetero-Pauson–Khand
type reaction, has been developed independently by the
laboratories of Buchwald3 and Crowe.4 Recently, Murai
and coworkers reported an elegant atom-economical
method5 in the preparation of a,b-unsaturated g-butyro-
lactones from yne-aldehydes with carbon monoxide
through the ruthenium-catalyzed cyclocarbonylation.6
R1
1) LAH
2) PCC
84–91%
PCC
78%
Pd(dba)2, dppe
3a
3b
3d
OTs
X
NaH, THF, r.t.
HX-R2 (6) 81–92%
R1
R2
5a; R1 = H
7
5b: R1 = Me
MeO2C
MeO2C
H
3e
3c
TsHN
CO2Me
OTBMDS
R'
6a: R' = H; 6d: R' = Me
6e
Me
1) LAH
DIAD, PPh3
Ts
N
Me
2) PCC
87%
6a, CH2Cl2
OH
H
CO2Me
X
67%
X
O
9
8
O
O
O
Transition metals
CO or equivalent
Scheme 2
1
2
4
The starting point of this investigation was the availability
of substrate 3: these compounds were prepared in quantity
by the modified reaction sequences of known pathways12
as outlined in Scheme 2. Vinylic cyclopropyltosylates 5
proved to be useful starting materials to produce 7 via the
palladium-catalyzed substitution with proper nucleophile
6. Compounds 7 were converted to the key starting cyclo-
propylidenyl aldehydes 3a, 3b, 3d, and 3e by the standard
LAH reduction followed by PCC oxidation or direct oxi-
dation of silylether with PCC as described in Scheme 2.
Compound 3c was prepared from 8 by the three-step se-
H
X
X
O
O
3
Scheme 1
SYNLETT 2004, No. 10, pp 1695–1698
0
9
.0
8
.2
0
0
4
Advanced online publication: 15.07.2004
DOI: 10.1055/s-2004-830849; Art ID: U09804ST
© Georg Thieme Verlag Stuttgart · New York

1696
C.-M. Yu et al.
LETTER
quence of Mitsunobu reaction of 8 with 6a to 9, and then could not be realized with catalytic amounts of different
the same reduction and oxidation processes. The stage transition metal complexes, including ruthenium com-
was thus set for the cyclocarbonylation of 3 with inter or plexes, rhodium complexes, and [Ir(COD)Cl]2 under var-
outer carbonyl functionality promoted by a transition met- ious reaction conditions, mainly due to a lack of
al complex. To find optimum conditions for this chemical reactivity. Fortunately, we found that molybdenum carbo-
process, a series of experiments were performed with 3a nyl complexes could promote the reaction process. After
as a model substrate. The cyclocarbonylation was promot- surveying numerous conditions for orienting experiments
ed by transition metal complexes.
as summarized in Table 1, several key findings emerged:
i) 1.5 equivalents of C7H8Mo(CO)3 (cycloheptatrienyl
molybdenum tricarbonyl) was required for optimal condi-
tions in terms of chemical yields and reaction rates; ii) the
introduction of dimethylsulfoxide (DMSO) as an additive
proved to be effective in comparison with other inactive
additives such as H2O, NMO, and HMPA – thus, anhy-
drous conditions were essential;14 iii) 10 equivalents of
DMSO were needed for optimum conditions, since the re-
action with reduced dosage of DMSO resulted in dimin-
ished chemical yield; iv) the use of catalytic amounts of
molybdenum carbonyl complexes turned out to be un-
promising, despite the use of a CO atmosphere under var-
ious pressures; v) the reaction conducted in toluene at 90
°C resulted in the best chemical yields when compared
with other solvents such as THF, MeCN, and DMF. Under
optimal conditions (entry 10 in Table 1), the reaction was
conducted by dropwise addition of 3a (1 equiv) in toluene
and DMSO (10 equiv) at 20 °C to a solution of
C7H8Mo(CO)3 (1.5 equiv) in toluene. After 5 hours at
90 °C, volatile materials were removed under reduced
pressure. Work-up and chromatography gave 4a in 73%
yield.15
Table 1 Preliminary Investigations for Cyclocarbonylation of 3a
H
conditions
H
Ts
N
O
Ts
N
O
O
H
4a
3a
Entry Conditions
Time
(h)
Yield
(%)a
1
2
Ru3(CO)12 (5 mol%), CO (10 atm) 10
N.r.
N.r.
Rh(dppp)ClCO (5 mol%), CO
(1 atm)
12
3
4
Ir(COD)Cl2 (5 mol%), (S)-tolbinap, 16
CO
N.r.
Trace
27
Mo(CO)6 (1.2 equiv), toluene,
100 °C
12
12
12
8
5
Mo(CO)6 (1.2 equiv), DMSO
(5 equiv), tolueneb
6
Mo(CO)6 (1.5 equiv), DMSO
(10 equiv), tolueneb
44
With the notion that this approach might lead to a general
and efficient method for the synthesis of 4, we set out to
determine the substituent effects with 3b–d to produce
structurally diverse products. Indeed, the method was suc-
cessful with 3b–d, yielding the bicyclic products 4b–d in
moderate to high yields, as shown in Table 2. Although 4b
was obtained in diastereomerically pure form, the diaste-
reomeric ratio of 4d turned out to be 63:37, presumably
due to a lack of steric bias. The use of 3e as the carbocycle
resulted in high conversion to 4e through the three-com-
ponent assembly.16
7
Mo(CO)6 (1.5 equiv), DMSO
(10 equiv), THFb
21
8
Mo(CO)6 (1.5 equiv), DMSO
(10 equiv), DMFb
8
34
9
Mo(CO)6 (1.5 equiv), NMP
(10 equiv), tolueneb
8
27
10
11
12
13
C7H8Mo(CO)3 (1.5 equiv), DMSO
(10 equiv), 90 °Cc
5
73
C7H8Mo(CO)3 (2 equiv), DMSO
(10 equiv), 60 °Cc
12
7
55
In summary, this paper describes a new procedure for the
synthesis of cis-bicyclic spirocyclopropanelactones 4
from cyclopropylidenyl aldehydes 3 mediated by
C7H8Mo(CO)3 with DMSO in a general and efficient way,
which promises to be widely useful. This unique transfor-
mation accomplishes the cyclization through a three-com-
ponent coupling. Further studies, including synthetic
applications and extension of this method into enantio-
meric pathways, are in progress.
C7H8Mo(CO)3 (2 equiv), DMSO
(5 equiv), 90 °Cc
63
(h6-mesitylene)Mo(CO)3, DMSO,
12
22
90 °Cc
a Refer to isolated products (%).
b At 100 °C.
c In toluene.
Acknowledgment
Initial attempts to cyclize 3a were conducted with various
transition metal complexes, mainly employed for a Pau-
son–Khand type reaction13 of enynes. The results indicat-
ed that the conversion to the corresponding lactone 4a
Generous financial support by grants from the Korea Ministry of
Science and Technology through the National Research Laboratory
program (NRL) and the Center for Molecular Design & Synthesis
(CMDS: KOSEF SRC) at KAIST is gratefully acknowledged.
Synlett 2004, No. 10, 1695–1698 © Thieme Stuttgart · New York

LETTER
Intramolecular Cyclocarbonylation of Cyclopropylidenyl Aldehydes
1697
a
Table 2 Carbocyclization of 3 to 4 Mediated by C7H8Mo(CO)3
Entry
1
Substrate
Product
Time (h)
5
Yield (%)b
73
H
Ts
N
O
H
Ts
N
O
H
H
O
4a
3a
2
5
64
Me
N
Me
N
H
Ts
O
Ts
O
O
H
3b
4b
dr 100:0
3
4
6
6
72
69
Me
Ts
N
O
O
H
Me
Ts
N
O
O
H
H
O
4c
3c
Ts
N
H
O
Ts
N
H
Me
Me
4d
dr 63:37
3d
5
6
77
H
EtO2C
EtO2C
EtO2C
EtO2C
3e
O
H
O
H
O
4e
a Reactions were performed at 90 °C in toluene.
b Isolated yield.
(5) Trost, B. M. Acc. Chem. Res. 2002, 35, 695.
(6) Chatani, N.; Morimoto, T.; Fukumoto, Y.; Murai, S. J. Am.
Chem. Soc. 1998, 120, 5335.
References
(1) For excellent discussions, see: (a)Ojima, I.; Tzamarioudaki,
M.; Li, Z.; Donovan, R. Chem Rev. 1996, 96, 635.
(b) Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96,
49. (c) Trost, B. M.; Toste, F. D.; Pinkerton, A. B. Chem.
Rev. 2001, 101, 2067. (d) Aubert, C.; Buisine, O.; Malacria,
M. Chem. Rev. 2002, 102, 813.
(2) For general discussions, see: (a) Transition Metals for
Organic Synthesis, Vol I; Beller, M.; Bolm, C., Eds.; Wiley-
VCH: Weinheim, 1998. (b) Transition Metals for Organic
Synthesis, Vol II; Beller, M.; Bolm, C., Eds.; Wiley-VCH:
Weinheim, 1998.
(3) (a) Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem. Soc.
1995, 117, 6785. (b) Kablaoui, N. M.; Buchwald, S. L. J.
Am. Chem. Soc. 1996, 118, 3182. (c) Kablaoui, N. M.; Hick,
F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 5818.
(d) Kablaoui, N. M.; Hick, F. A.; Buchwald, S. L. J. Am.
Chem. Soc. 1997, 119, 4424.
(4) (a) Crowe, W. E.; Vu, A. T. J. Am. Chem. Soc. 1996, 118,
1557. (b) Mandal, S. M.; Amin, S. R.; Crowe, W. E. J. Am.
Chem. Soc. 2001, 123, 6457.
(7) (a) Yu, C.-M.; Yoon, S.-K.; Baek, K.; Lee, J.-Y. Angew.
Chem. Int. Ed. 1998, 37, 2392. (b) Yu, C.-M.; Kim, Y.-M.;
Kim, J.-M. Synlett 2003, 1518.
(8) (a) Kang, S.-K.; Hong, Y.-T.; Lee, J.-H.; Kim, W.-Y.; Lee,
I.; Yu, C.-M. Org. Lett. 2003, 5, 2813. (b) Kang, S.-K.;
Kim, K.-J.; Hong, Y.-T. Angew. Chem. Int. Ed. 2002, 41,
1584. (c) Kang, S.-K.; Kim, K.-J.; Yu, C.-M.; Hwang, J.-W.;
Do, Y.-K. Org. Lett. 2001, 3, 2851.
(9) For a review see: Goti, A.; Cordero, F. M.; Brandi, A. In
Small Ring Compounds in Organic Synthesis V; de Meijere,
A., Ed.; Springer: Berlin, 1996, 1–98.
(10) (a) Stolle, A.; Becker, H.; Salauen, J.; de Meijere, A.
Tetrahedron Lett. 1994, 35, 3521. (b) Takano, S.; Inomata,
K.; Ogasawara, K. J. Chem. Soc., Chem. Commun. 1992,
169.
(11) Ang, K. H.; Braese, S.; Steinig, A. G.; Meyer, F. E.;
Liebaria, A.; Voigt, K.; de Meijere, A. Tetrahedron 1996,
52, 11503.
Synlett 2004, No. 10, 1695–1698 © Thieme Stuttgart · New York

1698
C.-M. Yu et al.
LETTER
(12) (a) Estieu, K.; Paugam, R.; Ollivier, J.; Salauen, L. J. Org.
Chem. 1997, 62, 8276. (b) Ferrara, M.; Cordero, F. M.; Goti,
A.; Brandi, A.; Estieu, K.; Paugam, R.; Ollivier, J.; Salaun,
J. Eur. J. Org. Chem. 1999, 2725. (c) Pisaneschi, F.;
Cordero, F. M.; Goti, A.; Paugam, R.; Ollivier, J.; Brandi,
A.; Salaun, J. Tetrahedron: Asymmetry 2000, 11, 897.
(13) For a review see: Gibson, S. E.; Stevenazzi, A. Angew.
Chem. Int. Ed. 2003, 42, 1800; and references cited therein.
(14) (a) Jeong, N.; Lee, S. J. Tetrahedron Lett. 1993, 34, 4027.
(b) Brummond, K. M.; Kerekes, A. D.; Wan, H. J. Org.
Chem. 2002, 67, 5156.
(15) General Procedure: A flame-dried sealed tube containing
C7H8Mo(CO)3 (152.0 mg, 0.56 mmol) was evacuated and
carefully purged with argon three times and then charged
with 3a (103.0 mg, 0.37 mmol) in dry toluene (3 mL).
Freshly distilled DMSO (0.27 mL, 289 mg, 3.80 mmol) was
then added at 20 °C. After stirring at 20 °C for 1 h, the
reaction mixture was heated and allowed to proceed at 90 °C
for 5 h. The resulting mixture was treated with EtOAc. The
combined organics were washed with H2O (3 ×) and brine
(1 ×). The organic layer was dried over anhyd MgSO4,
filtered, and concentrated under reduced pressure. The crude
product was purified by flash column chromatography
(EtOAc–hexane, 1:1) to give 4a (83.0 mg, 0.27 mmol, 73%)
as a colorless oil: Rf = 0.37 (EtOAc–hexane, 1:1).
7.30 (d, 2 H, J = 8.2 Hz), 7.70 (d, 2 H, J = 8.2 Hz). 13C NMR
(125 MHz, CDCl3): d = 177.8, 144.3, 135.6, 130.1, 127.4,
80.3, 61.2, 53.3, 53.1, 25.4, 22.0, 21.8, 18.6, 12.2.
Compound 4c: 1H NMR (500 MHz, CDCl3): d = 0.83 (ddd,
1 H, J = 4.5, 7.3, 9.6 Hz), 1.03 (s, 3 H), 1.06 (ddd, 1 H,
J = 4.5, 7.3, 10.1 Hz), 1.11 (ddd, 1 H, J = 4.5, 7.3, 9.6 Hz),
1.31 (ddd, 1 H, J = 4.5, 7.3, 10.1 Hz), 2.45 (s, 3 H), 2.97 (d,
1 H, J = 10.1 Hz), 3.09 (d, 1 H, J = 10.1 Hz), 3.45 (dd, 1 H,
J = 1.7, 11.9 Hz), 3.58 (dd, 1 H, J = 5.3, 11.9 Hz), 4.56 (dd,
1 H, J = 1.7, 5.3 Hz), 7.35 (d, 2 H, J = 8.2 Hz), 7.68 (d, 2 H,
J = 8.2 Hz). 13C NMR (125 MHz, CDCl3): d = 178.4, 144.5,
132.6, 130.1, 128.0, 86.2, 58.4, 53.7, 47.4, 28.9, 21.8, 20.6,
14.0, 12.3. Compound 4d: (major) 1H NMR (500 MHz,
CDCl3): d = 0.99 (m, 1 H), 1.05 (m, 2 H), 1.33 (m, 1 H), 1.45
(d, 3 H, J = 6.8 Hz), 2.44 (s, 3 H), 2.84 (ddd, 1 H, J = 5.6,
6.2, 7.9 Hz), 3.37 (dd, 1 H, J = 4.5, 7.9 Hz), 3.40 (dd, 1 H,
J = 4.5, 6.2 Hz), 4.13 (dq, 1 H, J = 6.2, 7.3 Hz), 4.87 (dd, 1
H, J = 5.6, 7.3 Hz), 7.34 (d, 2 H, J = 8.2 Hz), 7.71 (d, 2 H,
J = 8.2 Hz). 13C NMR (125 MHz, CDCl3): d = 178.7, 144.4,
133.7, 130.1, 127.5, 86.5, 62.1, 51.6, 43.6, 25.6, 21.8, 18.7,
17.9, 12.1. Compound 4d (minor) 1H NMR (500 MHz,
CDCl3): d = 0.88 (m, 1 H), 1.05 (m, 2 H), 1.18 (m, 1 H), 1.37
(d, 3 H, J = 6.7 Hz), 2.42 (s, 3 H), 2.63 (ddd, 1 H, J = 5.1,
6.5, 7.9 Hz), 3.19 (dd, 1 H, J = 7.9, 11.0 Hz), 3.20 (dd, 1 H,
J = 5.1, 11.0 Hz), 3.68 (dq, 1 H, J = 6.7, 11.0 Hz), 4.66 (dd,
1 H, J = 6.5, 11.0 Hz), 7.31 (d, 2 H, J = 8.2 Hz), 7.69 (d, 2
H, J = 8.2 Hz). 13C NMR (125 MHz, CDCl3): d = 177.7,
144.3, 135.1, 130.1, 128.0, 82.8, 60.2, 52.6, 42.0, 24.9, 21.8,
18.2, 15.2, 12.8. Compound 4e: 1H NMR (500 MHz,
CDCl3): d = 1.05 (m, 2 H), 1.25 (t, 3 H, J = 7.0 Hz), 1.26 (t,
3 H, J = 7.0 Hz), 1.27 (m, 1 H), 1.35 (m, 1 H), 2.24 (dd, 1 H,
J = 9.3, 13.8 Hz), 2.43 (dd, 1 H, J = 6.2, 13.8 Hz), 2.66 (dd,
1 H, J = 2.5, 14.9 Hz), 2.72 (dd, 1 H, J = 5.9, 14.9 Hz), 2.76
(ddd, 1 H, J = 6.2, 7.0, 9.3 Hz), 5.11 (ddd, 1 H, J = 2.5, 5.9,
7.0 Hz), 4.18 (q, 2 H, J = 7.0 Hz), 4.20 (q, 2 H, J = 7.0 Hz).
13C NMR (125 MHz, CDCl3): d = 179.5, 171.4, 170.7, 82.4,
62.2, 60.6, 44.8, 41.3, 38.7, 26.5, 18.9, 14.2, 12.7.
(16) 1H NMR and 13C NMR data: Compound 4a: 1H NMR (500
MHz, CDCl3): d = 1.03 (dt, 2 H, J = 3.1, 5.6 Hz), 1.31 (dt, 2
H, J = 3.1, 8.2 Hz), 2.45 (s, 3 H), 2.82 (ddd, 1 H, J = 3.9, 8.2,
7.6 Hz), 3.06 (dd, 1 H, J = 7.6, 10.4 Hz), 3.19 (dd, 1 H,
J = 3.9, 10.4 Hz), 3.22 (dd, 1 H, J = 5.3, 11.5 Hz), 3.61 (d, 1
H, J = 11.5 Hz), 5.06 (ddd, 1 H, J = 0.6, 5.3, 8.2 Hz), 7.35 (d,
2 H, J = 8.2 Hz), 7.69 (d, 2 H, J = 8.2 Hz). 13C NMR (125
MHz, CDCl3): d = 178.6, 144.6, 132.1, 130.1, 128.2, 79.7,
54.6, 52.3, 44.1, 24.8, 21.8, 18.4, 13.0. Compound 4b: 1H
NMR (500 MHz, CDCl3): d = 1.29 (d, 3 H, J = 6.7 Hz), 2.42
(s, 3 H), 2.42 (dd, 1 H, J = 3.7, 6.8 Hz), 3.73 (dq, 1 H,
J = 3.7, 6.7 Hz), 3.74 (dd, 1 H, J = 4.5, 13.2 Hz), 3.86 (dd, 1
H, J = 0.8, 13.2 Hz), 5.01 (ddd, 1 H, J = 0.8, 4.5, 6.8 Hz),
Synlett 2004, No. 10, 1695–1698 © Thieme Stuttgart · New York