RhI-catalyzed regio- and stereospecific carbonylation of 1-(1-Alkynyl)cyclopropyl ketones: A modular entry to highly substituted 5,6-dihydrocyclopenta[c]furan-4-ones

Article abstract of DOI:10.1002/chem.200900413

A Rh^I-catalyzed regio and stereoselective carbonylation reaction of 2-substituted or 2,3-disubstituted 1-(1-alkynyl)-cyclopropyl ketones, which provides an efficient, highly atom-economic route to synthesize 1,3,5-tri- and 1,3,5,6-tetrasubstitu

Full text of DOI:10.1002/chem.200900413

DOI: 10.1002/chem.200900413
RhI-Catalyzed Regio- and Stereospecific Carbonylation of
1-(1-Alkynyl)cyclopropyl Ketones: A Modular Entry to Highly Substituted
5,6-Dihydrocyclopenta[c]furan-4-ones
Yanqing Zhang,[a] Zuliang Chen,[a] Yuanjing Xiao,[a] and Junliang Zhang*[a, b]
The rich appearance of highly substituted furans as key
structural units in many bioactive natural products and im-
portant pharmaceuticals, and general application as versatile
building blocks in organic synthesis have stimulated many
efforts in exploration of novel methodology.[1,2] Most recent-
ly, much attention has been paid on the development of
metal-catalyzed transformations, including the cyclization of
allenyl ketones,[3] 3-alkyn-1-ones,[3,4] (Z)-2-en-4-yn-1-ols[5]
and 2-(1-alkynyl)-2-alken-1-ones[6] or cycloisomerization of
alkylidenecyclopropyl ketones[7]/cyclopropenyl ketones.[8]
Very recently, 1-(1-alkynyl)-cyclopropyl ketones have been
successfully developed by Schmalz[9a] and Zhang[9b–c] as read-
ily available substrates for efficient construction of highly
substituted furans and other cyclic compounds under the
catalysis of gold(I) complexes (Scheme 1). Our continued
effort to explore new reactions for synthesis of tetrasubsti-
tuted furans with high efficiency,[6e] has led us to target 3,4-
fused bicyclic tetrasubstituted furans[10] as product for inves-
tigation. We envisaged that 1-(1-alkynyl)-cyclopropyl ke-
tones might undergo some interesting transformation initiat-
(1-alkynyl)-cyclopropyl ketones to afford 1,3,5-tri- or 1,3,5,6-
tetrasubstituted 5,6-dihydro-cyclopenta[c]furan-4-ones[12] ini-
À
tiated by the activation of the carbon carbon s bond.
Scheme 1. Previous work and our proposal.
Initially, we tested the carbonylation reaction of 1-(2-
phenyl)-1-(2-phenylethynyl)cyclopropyl methyl ketone 1a in
the presence of 1 atm of CO (balloon) in the presence of
various catalysts (see Supporting Information). After some
attempts, we were pleased to find that the carbonylation re-
action of 1a proceeds very smoothly in 1,2-dichloroethane
at 708C under the catalysis of 5 mol% of [{Rh(CO)2Cl}2]
À
ed by the rhodium(I)-catalyzed activation of the carbon
carbon s bond of cyclopropane ring.[11] Herein we wish to
report our recent result that rhodium(I)-catalyzed a highly
regioselective and stereospecific carbonylation reaction of 1-
(standard conditions) or [{RhACHTNUTRGENNG(U cod)Cl}2] to give 1-methyl-3,5-
diphenyl-5,6-dihydrocyclopenta[c]furan-4-one[12] (2a) in ex-
cellent yields with trace amount of (E)-2-methyl-5-phenyl-3-
styrylfuran (3a). Addition of silver salts led to lower yields
of 2a and higher yields of byproduct 3a. Interestingly by-
product 3a can be afforded as the only major product in
74% isolated yield when the reaction was run under the cat-
[a] Y. Zhang, Z. Chen, Dr. Y. Xiao, Prof. Dr. J. Zhang
Shanghai Key Laboratory of Green Chemistry
and Chemical Processes, Department of Chemistry
East China Normal University
3663 N. Zhongshan Road, Shanghai 200062 (P.R. China)
Fax : (+86)21-6223-3213
E-mail: jlzhang@chem.ecnu.edu.cn
alysis of 5 mol% of [{RhACHTNUGTRNE(UGN cod)Cl}2]/AgPF6 under N2 atmos-
[b] Prof. Dr. J. Zhang
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences, 354 Fenglin Road
Shanghai 200032 (P.R. China)
phere (without CO). The structure of 2a was determined by
single-crystal X-ray diffraction analysis.[13]
With standard reaction conditions in hand, we turned our
attention to studying the reaction scope of this transforma-
tion. Various 2-substituted 1-(1-alkynyl)-cyclopropyl ketones
were studied and the results are summarized in Table 1. Sev-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200900413: For preparative pro-
cedures and spectroscopic data for all new compounds.
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COMMUNICATION
Table 1. Synthesis of 1,3,5-trisubstituted 5,6-dihydrocyclopenta[c]furan-4-
ones.[a]
Entry
1: R1/R2/R3
t [h]
Yield [%] 2
1[b]
2
3
4
5
Me/1-naphthyl/Ph (1b)
Me/n-C4H9/Ph (1c)
42
22
17
24
22
40
18
21
49
52
18
2b (84)
2c (80)
2d (79)
2e (69)
2 f (76)
2g (86)
2h (94)
2i (86)
2j (82)
2k (87)
eral points are noteworthy: 1) under standard reaction con-
ditions, various substituted 3,4-fused bicyclic furans could be
prepared in good to excellent yields with high regioselectivi-
ty; 2) various substituents and functional groups could be in-
troduced to R1, R2 position and the reactions proceeded
smoothly; 3) the cyclopropyl group at the R2 position of
substrates 1d and 1i was kept untouched, demonstrating the
inertness of the isolated unactived cyclopropane ring under
the reaction conditions; 4) when R3 is not an aryl group, it
Me/1-cyclohexenyl/Ph (1d)
Me/cyclopropyl/Ph (1e)
Me/Ph/4-MeOPh (1 f)
Me/4-MeOPh/4-MeOPh (1g)
Ph/Ph/Ph (1h)
Ph/cyclopropyl/Ph (1i)
Ph/n-C4H9/Ph (1j)
Me/AcOC2H4/Ph (1k)
Ph/Ph/H (1l)
6
7
8
9
10[c]
11
2l (50, 84[d]
)
[a] All reactions were carried out using 1 (0. 5 mmol) under standard
conditions and yield is isolated yield. [b] 5 mol% of [{Rh(cod)Cl}2] was
used as catalyst. [c] Another 5 mol% of [{Rh(cod)Cl}2] was added after
reacting 19 h. [d] 5 mol% of [RhCl(CO)(PPh3)2] was used as catalyst.
was found that [RhCl(CO)ACHTNUGTRENUNG(PPh3)2] (84%) is a much better
catalyst than the corresponding [{Rh(CO)2Cl}2] (50% yield).
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Table 2. Synthesis of 1,3,5,6-tetrasubstituted 5,6-dihydrocyclopenta[c]fur-
an-4-ones.
Entry
4: R1/R2/R3/R4
t [h]
Yield [%] 5
1[a]
2
Me/Ph/Ph/PhCO (4a)
Ph/Ph/Ph/PhCO (4b)
20
17
40
42
10
22
37
28
5a (50)
5b (90)
5c (43)
5d (38)
5e (85)
5 f (95)
5g (68)
5h (90)
3[a,b]
4[a,b]
5
Ph/cyclopropyl/Ph/PhCO (4c)
Ph/n-C4H9/Ph/PhCO (4d)
Ph/4-MeOPh/Ph/PhCO (4e)
Ph/4-NO2Ph/Ph/PhCO (4 f)
Ph/1-naphthyl/Ph/PhCO (4g)
Ph/Ph/Ph/EtOCO (4h)
6
7
8
Reactions of (1R*,2R*)-1m and its diastereoisomer
(1R*,2S*)-1m were examined to determine whether the
configuration of substituted cyclopropane ring affects the re-
action pathway. To our surprise, the reactions of (1R*,2R*)-
1m could indeed give the desired carbonylation product 2m
in 87% isolated yield under the catalysis of 5 mol%
[a] 20–40% of the corresponding trisubstituted furans 6 were isolated as
a mixture of E/Z isomer. [b] The reaction was run at reflux.
[RhCl(CO)
N
results of 5a and 5b. Effects of other three groups R1, R2,
and R3 to the reaction are similar to the case of trisubstitut-
ed 5,6-dihydrocyclopenta[c]furan-4-ones.
other catalysts such as [{Rh(CO)2Cl}2] give only 3m’), but
(1R*,2S*)-1m did not afford the expected product under the
similar conditions; instead, a trisubstituted furan 3mꢀ was
obtained in 72% yield through a direct cycloisomerization
reaction.
Furthermore, we are pleased to find that various trans-
1,2,5,6-tetrasubstituted 5,6-dihydrocyclopenta[c]furan-4-ones
could be synthesized from the corresponding 2,3-disubstitut-
ed 1-(1-alkynyl)-cyclopropyl ketones with high efficiency
(Table 2). It is interesting to find that this RhI-catalyzed car-
bonylation is regiospecific (as a single regioisomer, no other
carbonylation product were observed) and stereospecific
with the retention of stereochemistry, which is determined
by the X-ray structure of 4a and 5a (Figure 1).[13] Residue
R4 does not affect the reaction pathway via comparison the
A plausible mechanism is depicted in Scheme 2. Regiose-
lective oxidative addition[11] of the C1 C2 bond of cyclopro-
À
pane of (1R*,2R*)-1m generates rhodacyclobutane 7, the
configuration of which might favor to undergo a rapid cyclo-
isomerization to fused furan-derived rhodacyclopentane 8.
Insertion of carbon monoxide generates fused furan deriva-
tive rhodacyclohexanone 9 and subsequent reductive elimi-
nation furnishes the carbonylation product. However, The
intermediate rhodacyclobutane 10, generated from the other
diastereoisomer (1R*,2S*)-1m does not afford the expected
bicyclic rhodacyclopentane 8 (the reason is not clear yet),
instead, a 1,2-allenyl ketone 11 may be produced via a
tandem process involving b-hydride elimination, reductive
Chem. Eur. J. 2009, 15, 5208 – 5211
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www.chemeurj.org
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J. Zhang et al.
Experimental Section
Typical procedure for the synthesis of 2a (Scheme 1): The solution of 1-
(2-phenyl-1-(2-phenylethynyl)cyclopropyl)ethanone (1a; 65.0 mg,
0.25 mmol) and [{RhCl(CO)2}2] (4.9 mg, 0.0125 mmol) in 1,2-dichloroe-
tane (5 mL) was degassed and then recharged with CO. Then the reac-
tion mixture was stirred at 708C and the TLC analysis showed the reac-
tion was complete after 22 h. The reaction mixture was concentrated
under reduced temperature and the residue was purified by column chro-
matography on silica gel to give 2a (68.0 mg, 94%). M.p.139–1418C;
1H NMR (300 MHz, CDCl3): d = 8.28–8.22 (m, 2H), 7.48–7.39 (m, 2H),
7.39–7.31 (m, 3H), 7.31–7.25 (m, 3H), 4.22 (dd, J=8.7, 4.8 Hz, 1H), 3.38
(dd, J=16.2, 8.7 Hz, 1H), 2.99 (dd, J=16.2, 4.8 Hz, 1H), 2.41 ppm (s,
3H); 13C NMR (75 MHz, CDCl3): d = 197.54, 149.80, 142.88, 140.27,
130.77, 129.36, 129.30, 128.81, 128.73, 127.85, 127.09, 125.48, 124.99, 61.02,
27.44, 12.30 ppm; MS (EI): m/z: 288 [M+] (100); HRMS: m/z: calcd for
C20H16O2: 288.1150, found: 288.1149.
Acknowledgements
Financial supports from 973 program (2009CB825300), NSFC
(20702015), Shanghai Shuguang Program (07SG27), Shanghai Pujiang
Program (07pj14039) and Shanghai Leading Academic Discipline Project
(B409) are greatly appreciated.
À
Keywords: carbonylation · C C activation · cyclization ·
regioselectivity · rhodium
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Highly Substituted 5,6-Dihydrocyclopenta[c]furan-4-ones
COMMUNICATION
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Received: February 15, 2009
Published online: April 9, 2009
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