2,3,4- or 2,3,5-trisubstituted furans: Catalyst-controlled highly regioselective ring-opening cycloisomerization reaction of cyclopropenyl ketones

Article abstract of DOI:10.1021/ja036616g

2,3,4- or 2,3,5-trisubstituted furans were highly regioselectively formed from the cycloisomerization reaction of the same starting cyclopropenes 1 via the subtle choice of the transition metal halides. Under the catalysis of 5 mol % PdCl₂(CH

Full text of DOI:10.1021/ja036616g

Published on Web 09/18/2003
2,3,4- or 2,3,5-Trisubstituted Furans: Catalyst-Controlled Highly
Regioselective Ring-Opening Cycloisomerization Reaction of Cyclopropenyl
Ketones
Shengming Ma* and Junliang Zhang
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. China
Received June 11, 2003; E-mail: masm@mail.sioc.ac.cn
Cyclopropenes,1 highly strained but readily accessible carbocyclic
molecules, have been shown to possess useful reactivity in organic
Table 1. MXn-Catalyzed Cycloisomerization of Cyclopropenyl
Ketone 1aa
synthesis.2 In the past several years, more and more attention has
been paid to the transition metal-catalyzed reaction of cyclopro-
penes. Two kinds of reaction patterns of cyclopropenes, that is,
the direct oxidative addition of the C-C σ bond2b,3c and metalation
(hydrometalation,3a,b carbometalation,4,5 and bismetalation3b) of the
CdC bond, have been disclosed for their interaction with transition
metals (Scheme 1). It is obvious that there is an attractive but often
troublesome regioselectivity issue when R1 is different from R4.5,6
entry
catalyst
solvent/T (°C)
t (h)
2/3b
yield (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
no
acetone/reflux
acetone/reflux
acetone/reflux
acetone/reflux
acetone/reflux
acetone/reflux
acetone/reflux
acetone/reflux
acetone/reflux
CH3CN/80
AcOEt/reflux
Cl(CH2) 2Cl/80
CHCl3/reflux
acetone/reflux
CH3CN/80
19
24
24
12
14
12
11
17
12
17
17
11
18
12
9
0
7
CoCl2
NiBr2
FeCl3
65:35
20:80
99:1
98:2
98:2
94:6
94:6
20
25
61
58
60
53
trace
25
64
66
71d
75
91d
Scheme 1
RuCl3‚3H2O
RhCl3‚3H2O
PdCl2
PdBr2(PhCN)2
PdI2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
CuCl2
88:12
94:6
96:4
98:2
12:88
<1:99
CuI
a The reaction was carried out using 1a (0.5 mmol) and catalyst (5 mol
1
%) in solvent (2.0 mL). b The ratio was determined by H NMR analysis
of the crude reaction mixture. c Unless otherwise specified, isolated yields
of two isomers. d Isolated yield of the major isomer.
After observing some interesting chemistry with methylenecy-
clopropanes (MCPs),7 we showed high interest in the transition
metal halide-mediated reaction of cyclopropenes, which also have
an active CdC bond in the three-membered ring. Although the
chloropalladation of cyclopropenes with a stoichiometric amount
of PdCl2(CH3CN)2 leading to an allylpalladium species has been
disclosed,8 no catalytic reaction has been reported. Herein, we wish
to report a highly regioselective ring-opening cycloisomerization
of cyclopropenyl ketones 1, in which the subtle application of CuI
and PdCl2(CH3CN)2 addressed the issue of regioselectivity leading
to corresponding 2,3,4- or 2,3,5-trisubstituted furans, respectively.
Initially, we tested the halometalation of cyclopropenyl ketone
1a9 in the presence of a number of transition metal halides (MXn)
(Table 1). NiBr2 and CoCl2 are less effective with low regioselec-
tivity (entries 2-3, Table 1), while FeCl3 showed high regioselec-
tivity with a low yield (entry 4, Table 1). RhCl3‚3H2O, RuCl3‚
3H2O, PdBr2(PhCN)2, and PdCl2 showed higher activity to give
2a in good yields with high regioselectivities (entries 5-8, Table
1). After numerous screenings, we were pleased to find that the
reaction applying 5 mol % PdCl2(CH3CN)2 as the catalyst and
CHCl3 as the solvent (Conditions A) gave 2a in 71% yield with
very high regioselectivity (98:2) (entry 13, Table 1). Both yields
and regioselectivities in other solvents such as CH3CN, AcOEt,
and ClCH2CH2Cl are lower (entries 10-12, Table 1). After further
Figure 1.
study, we were excited to find that the reaction of 1a in CH3CN at
80 °C under the catalysis of 5 mol % CuI (Conditions B) for 9 h
gave 3a with an excellent regioselectivity (>99:1) in 91% yield
(entry 15, Table 1).
Some typical examples for this regioselective transformation are
summarized in Table 2. Several types of substituents such as 1-alkyl,
tert-butyl, and phenyl groups could be introduced (entries 1-8,
Table 2). The introduction of the PhSO2 group as R2 provided us
further evidence for the regioselectivity, since we established the
structures of 2h10 and 3h11 by X-ray diffraction studies (Figure 1).
A possible rationale for this regioselectivity is depicted in Scheme
2. In the presence of a catalytic amount of PdCl2(CH3CN)2 (cycle
A), the regioselective chloropalladation8 of the CdC bond of the
9
12386
J. AM. CHEM. SOC. 2003, 125, 12386-12387
10.1021/ja036616g CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Regioselective Cycloisomerization of Cyclopropene
Ketones 1 under Conditions A and B
In conclusion, we have developed a regioselective cycloisomer-
ization of cyclopropenyl ketones 1 leading to 2,3,4-trisubstituted
furans or 2,3,5-trisubstituted furans by using the catalyst CuI or
PdCl2(CH3CN)2, respectively. Further studies into the scope,
mechanism, and synthetic applications of this transformation are
being carried out in our laboratory.
Acknowledgment. Financial support from the National Science
Foundation of China, the Major State Basic Research Development
Program (Grant No. G2000077500), and the Chinese Academy of
Sciences is greatly appreciated. S.M. is the recipient of the 1999
Qiu Shi Award for Young Chinese Scientific Workers issued by
the Hong Kong Qiu Shi Foundation of Science and Technology
(1999-2003). This work is dedicated to Professor Xian Huang on
the occasion of his 70th birthday.
cyclopropenyl ketones 1
1
2
3
entry
R /R /R
cond./t(h)
yielda (2:3)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
TBSO(CH2)2/CO2Et/CH3 (1b)
Ac/3
B/10
A/3
(2b) 65 (95:5)
(3b) 85 (<1:99)
(2c) 60 (96:4)
(3c) 83 (<1:99)
(2d) 66 (98:2)
(3d) 80 (<1:99)
(2e) 73 (99:1)
(3e) 89 (1:99)
(2f) 50 (98:2)d
(3f) 80 (<1:99)
(2g) 78 (95:5)
(3g) 80 (<1:99)
(2h) 88 (99:1)
(3h) 96 (<1:99)
1b
TBSOCH2/CO2Et/CH3 (1c)
1c
B/10
A/13
B/4.5
A/10
B/2.5
Ac/24
B/10
Ac/3
B/6
t-Bu/CO2Et/CH3 (1d)
1d
Ph/CO2Et/CH3 (1e)
Supporting Information Available: Experimental procedures and
characterization data of all new compounds (PDF and CIF). This
material is available free of charge via the Internet at http://pubs.acs.org.
1e
n-C5H11/CO2Et/Ph (1f)
1f
n-C4H9/COMe/CH3 (1g)
References
1g
n-C4H9/SO2Ph/CH3 (1h)
Ac/5
B/10
(1) For a review, see: Baird, M. S. Cyclopropenes: Synthesis: By Construc-
tion of the System. Houben-Weyl; Thieme: Stuttgart, Germany, 1997;
E17d/2, p 2695.
(2) For reviews, see: (a) Binger, P.; Bu¨ch, H. M. Top. Curr. Chem. 1987,
135, 77. (b) Jennings, P. W.; Johnoson, L. L. Chem. ReV. 1994, 94, 2241.
(c) Baird, M. S. Cyclopropenes: Transformations. Houben-Weyl; Thi-
eme: Stuttgart, Germany, 1997; E17d/2, p 2781. (d) Nakamura, M.; Isobe,
H.; Nakamura, E. Chem. ReV. 2003, 103, 1295.
1h
a Isolated yield of the major isomer. b The ratio was determined by H
NMR analysis of the crude reaction mixture. c CH2Cl2 was used as the
solvent. d Unidentified product was also formed.
1
Scheme 2
(3) (a) Nakamura, I.; Bajracharya, G. B.; Yamamoto, Y. J. Org. Chem. 2003,
68, 2297. (b) Liao, L.; Fox, J. M. J. Am. Chem. Soc. 2002, 124, 14322.
(c) Cho, S. H.; Liebeskind, L. S. J. Org. Chem. 1987, 52, 2631.
(4) (a) Nakamura, M.; Hirai, A.; Nakamura, E. J. Am. Chem. Soc. 2000, 122,
978. (b) Kubota, K.; Mori, S.; Nakamura, M.; Nakamura, E. J. Am. Chem.
Soc. 1998, 120, 13334. (c) Section IV.B.1 in ref 2d.
(5) For a ligand effect on switching the regioselectivity in allylzincation of
1-trimethylsilyl (Ge, Sn)-cyclopropenone acetals, see: Nakamura, M.;
Inoue, T.; Sato, A.; Nakamura, E. Org. Lett. 2000, 2, 2193.
(6) For control of regioselectivity by the metallic complexes of different
oxidation states, see: Padwa, A.; Kassir, J. M.; Xu, S. L. J. Org. Chem.
1991, 56, 6971.
(7) Ma, S.; Zhang, J. Angew. Chem., Int. Ed. 2003, 42, 184.
(8) (a) Mushak, P.; Battiste, M. A. J. Organomet. Chem. 1969, 17, P46. (b)
Battiste, M. A.; Friedrich, L. E.; Fiato, R. A. Tetrahedron Lett. 1975, 45.
(9) The starting materials 1 were prepared in moderate yields by the rhodium-
catalyzed cyclopropanation reaction of alkynes according to the following
reference except that the corresponding diazo compounds were used
instead of iodonium ylides, see: Batsila, C.; Kostakis, G.; Hadjiarapoglou,
L. P. Tetrahedron Lett. 2002, 43, 5997.
(10) X-ray data for compound 2h: C15H18O3S, MW ) 278.35, orthorhombic,
space group Pca2(1), Mo KR, final R indices [I > 2σ(I)], R1 ) 0.0446,
wR2 ) 0.0598, a ) 12.0416 (9) Å, b ) 15.7116 (11) Å, c ) 15.1600
(11) Å, R ) 90°, â ) 90°, γ ) 90°, V ) 2868.2 (4) Å3, T ) 293 (2) K,
Z ) 8, reflections collected/unique: 16 943/6492 (Rint ) 0.0555), no
observation [I > 2σ(I)] 3776, parameters 425. CCDC 211695 contains
the supplementary crystallographic data.
cyclopropenyl ketone 1 (path a) would afford the palladium
intermediate 4, which would undergo â-decarbopalladation to afford
delocalized intermediate 5. Subsequent intramolecular endo-mode
insertion of the CdC bond into the oxygen-palladium bond of
intermediate 5 would afford a cyclic palladium intermediate 6,
which would undergo â-halide elimination to afford 2 and regener-
ate palladium(II) species. On the other hand, in the presence of a
catalytic amount of CuI, it would proceed according to cycle B.
The opposite regioselective iodocupration of the CdC bond of 1
(path b) and subsequent â-decarbocupration gave delocalized
intermediate 8. The intramolecular endo-mode insertion of the
CdC bond into the oxygen-copper bond of intermediate 8 and
subsequent â-halide elimination of intermediate 9 afforded 3 and
regenerated CuI.
(11) X-ray data for compound 3h: C15H18O3S, Mw ) 278.35, triclinic, Space
group P-1, Mo KR, final R indices [I > 2σ(I)], R1 ) 0.0488, wR2 )
0.1119, a ) 7.9303 (11) Å, b ) 9.6961 (13) Å, c ) 11.1246 (11) Å, R
) 68.445 (2)°, â ) 81. 980 (3)°, γ ) 66.606 (2)°, V ) 730.16 (17) Å3,
T ) 293 (2) K, Z ) 2, reflections collected/unique: 4497/3261 (Rint
)
0.0589), No Observation [I > 2σ(I)] 2119, parameters 245. CCDC 211696
contains the supplementary crystallographic data.
JA036616G
9
J. AM. CHEM. SOC. VOL. 125, NO. 41, 2003 12387