Transition-metal-catalyzed rearrangement of allenyl sulfides: A route to furan derivatives

Article abstract of DOI:10.1002/anie.200604299

(Chemical Equation Presented) Mass migration: Allenyl sulfides undergo 1,4-migration of the phenylsulfanyl group when catalyzed by a transition-metal complex to give furan derivatives (see scheme). Evidence suggests that the reaction proceeds via a metal

Full text of DOI:10.1002/anie.200604299

Angewandte
Chemie
DOI: 10.1002/anie.200604299
Synthetic Methods
Transition-Metal-Catalyzed Rearrangement of Allenyl Sulfides:
A Route to Furan Derivatives**
Lingling Peng, Xiu Zhang, Ming Ma, and Jianbo Wang*
Allene chemistry has attracted considerable attention in
recent years. In particular, the transition-metal-catalyzed
reaction of allene derivatives bearing an a substituent, such
as hydroxy, carbonyl, carboxy, thio (sulfanyl), and amino
groups, has led to many synthetically useful transforma-
tions.[1,2] One important reaction among them is the transi-
tion-metal-catalyzed cyclization of allenyl ketones to afford
compounds and propargyl sulfide. We report herein the
preliminary results of this study.
furans in a straightforward manner [Eq. (1)].[3] Furans are
The allenyl sulfide 1a, which can be easily obtained by a
CuI- or RhII-catalyzed reaction of methyl phenyldiazoacetate
and phenyl propargyl sulfide,[7,9] was treated with various
transition-metal catalysts (Table 1). AuCl or [Au(PPh3)Cl],
Table 1: Reaction of 1a with various transition-metal complexes.
important heterocycles and are present as key structural units
in many biologically important natural products and pharma-
ceutical substances.[4] Furans are also widely used as building
blocks in organic synthesis.[5] The development of novel and
efficient approaches to furan derivatives has been an active
research area over the past decade.[6]
In relation to our investigation on [2,3]-sigmatropic
rearrangements of sulfide ylides generated from metal
carbenes and propargylic sulfides,[7] we have studied the
transition-metal-catalyzed reaction of allenyl sulfides. The
reaction proceeds through 1,4 migration of the sulfanyl group
to afford furan derivatives [Eq. (2)].[8] The reaction presum-
ably involves a metal carbene intermediate, which is trapped
intramolecularly by a carbonyl group. Based on this trans-
formation, we have developed a one-pot sequential catalytic
process that gives furan products directly from diazocarbonyl
Entry
Catalyst[a]
T [8C]
t [h]
Yield [%][b]
1
2
3
4
5
6
7
8
9
AuCl
80
80
80
80
80
80
80
80
25
17
12
17
4.5
12
4.5
4.5
1
trace[c]
n.r.[c]
n.r.
67
trace
73
50
93
88
[Au(PPh3)Cl]
AuCl+AgOTf
Rh2(O2CCF3)4
Rh2(OAc)4
PtCl2
[Ru(PPh3)3Cl2]
[{RuCl2(p-cymene)}2]
[{RuCl2(p-cymene)}2]
23
[a] Reactions were carried out with 5 mol% catalyst except for
RhII catalysts, of which 1 mol% was used. [b] Yield of isolated product
after column chromatography. [c] Most of the starting material was
recovered. n.r.=no reaction. The best result is highlighted in bold.
[*] L. Peng, X. Zhang, Dr. M. Ma, Prof. Dr. J. Wang
Beijing National Laboratory of Molecular Sciences (BNLMS)
Green Chemistry Center (GCC) and
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
Ministry of Education
which are efficient catalysts for the cycloisomerization of a-
thioallenes,[2a] were not effective with 1a (Table 1, entries 1,
2); RhII carboxylates were next examined: Rh2(O2CCF3)4 was
found to effectively catalyze the reaction of 1a in toluene at
808C to afford furan 2a in 67% yield (Table 1, entry 4).
Rh2(OAc)4 gave only trace amount of 2a (Table 1, entry 5)
and treatment of 1a with 5 mol% of PtCl2 gave 2a in a slightly
higher yield compared to Rh2(O2CCF3)4 (Table 1, entry 6).
RuII complexes were also tested (Table 1, entries 7–9). To our
delight, [{RuCl2(p-cymene)}2] was highly efficient and
afforded 2a with an excellent yield in 1 h at 808C in toluene
(Table 1, entry 8). The reaction also occurred at room
temperature, but it took much longer (Table 1, entry 9).
A reaction mechanism is proposed in Scheme 1: the
phenylsulfanyl group attacks the terminal carbon atom of the
metal-activated allene moiety to give a five-membered
College of Chemistry
Peking University
Beijing 100871 (P.R. China)
Fax: ( +86)10-6275-1708
E-mail: wangjb@pku.edu.cn
Homepage: http://www.chem.pku.edu.cn/physicalorganic/
home.htm
[**] The project is supported by the Natural Science Foundation of
China (Grant No. 20572002, 20521202, 20225205, 20390050) and
the Ministry of Education of China (Cheung Kong Scholars
Program).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Communications
crossover experiment with a mixture of 1a and 3 as the
substrates resulted in the isolation of furan derivatives, 2a and
4 (Scheme 2). No crossover products were detected, which
suggests that migration of the sulfanyl group is intramolecular
in accordance with the mechanism proposed in Scheme 1.
Scheme 1. Mechanistic hypothesis for the formation of furans accord-
ing to Equation (2).
Scheme 2. Crossover experiment with two different allenyl sulfides.
thiolanium ion species, B. Metal carbenes, C and D, are then
generated from B through 1,4 migration of the phenylsulfanyl
group. These metal carbenes can be viewed as metal-
stabilized allylic cations with resonance structure E. There-
fore, trans/cis isomerization occurs readily, and C and D are in
rapid equilibrium. From C, the carbonyl oxygen atom
interacts with the electron-deficient carbene carbon atom,
which leads to the formation of 2a. This step, to afford a
carbonyl ylide, is a well-known process in transition-metal-
catalyzed reactions of diazo compounds.[9b,c,10] Moreover,
Hashmi and co-workers recently reported that the reaction
of gold carbene species with a carbonyl oxygen atom is the
key step in the synthesis of arene oxides and arenes by gold-
catalyzed reaction of furans.[11]
Second, the allenyl sulfide 5, in which the methoxycar-
bonyl group of 1a is replaced with a phenyl group, was
investigated (Scheme 3). The PtCl2-catalyzed reaction gave
The selective attack of the terminal position of the allene
moiety by the phenylsulfanyl group may be attributed to the
favorable formation of a five-membered ring. However, the
possibility cannot be ruled out that this attack may arise from
efficient generation of a metal carbene and its subsequent
reactions. Attack of the internal double bond will not
Scheme 3. Catalytic reaction with allenyl sulfide, 5.
À
indene derivative 6, presumably formed through formal C H
generate
a
metal carbene species. Besides, from
D
insertion of the metal carbene intermediate 8.[12] When 5 was
subjected to [{RuCl2(p-cymene)}2], 1,3-butadiene derivative 7
was identified as the major product. The formation of 7 can be
rationalized by 1,2-sulfur migration from the metal carbene
intermediate.[14] Although extensive investigation is still
required to firmly establish the reaction mechanism, these
experiments provide evidence to support the hypothesis
shown in Scheme 1.
À
(Scheme 1) formal insertion into an aromatic C H bond by
metal carbenes should give indene derivatives.[12] No indene
products are observed in this process as the reaction of an
electron-deficient metal carbene with a carbonyl oxygen atom
À
is more favorable than formal insertion into an aromatic C H
bond.[9b,c,10]
The key point of this mechanism is the formation of metal
carbene intermediates. Although there are rare precedents,
metal carbenes have been supposed to be intermediates in
transition-metal-catalyzed reactions of allenes.[2h,3c,d] Hashmi
and co-workers have suggested a palladium carbene inter-
mediate in a palladium(II)-catalyzed reaction of allenyl
ketones.[3c,d] In a similar transition-metal-catalyzed reaction
of propargyl acetate, metal carbenes have been suggested as
intermediates.[13]
The scope of this catalytic reaction is demonstrated by a
series of allenyl sulfides, 1b–p, 9, 11a,b, and allenyl selenide
13, which are summarized in Table 2and Scheme 4. The
tertiary allenyl sulfides 1b–p (Table 2), which bear various
substituents, all gave good to excellent yields of the corre-
sponding furan products under the optimized reaction con-
ditions with [{RuCl2(p-cymene)}2] as catalyst. Cyclic tertiary
allenyl sulfide 9 also worked well under the same conditions.
However, for secondary allenyl sulfides 11a and 11b the
RuII catalyst gave a complex mixture, while catalysis with
To substantiate the above-hypothesized reaction mecha-
nism, several experiments have been carried out. First, the
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Table 2: [{RuCl2(p-cymene)}2]-catalyzed reaction of 2b–p.
Table 3: One-pot sequential catalytic reactions with two catalysts.
Yield [%][a]
Entry
Diazo substrate 15, Ar, R
t[a]
Yield [%][b]
Entry
Allene 1, R, R’
t
1
2
3
4
5
6
7
8
9
15a, C6H5, OMe
1 h
1 h
1.5 h
10 min
30 min
3 h
2 h
2 h
1 h
81
90
72
83
84
50
73
62
82
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1b, 4-ClC6H4, OMe
1c, 2,4-Cl2C6H3, OMe
1d, 4-MeOC6H4, OMe
1e, 3-MeC6H4, OMe
1 f, 1-naphthyl, OMe
1g, 3-ClC6H4, Me
1h, 2-ClC6H4, Me
1i, 2-thienyl, OEt
1j, Ph, H
1 h
95
74
91
81
70
80
78
93
99
98
98
83
60
60
74
15b, 4-ClC6H4, OMe
15c, 2,4-Cl2C6H3, OMe
15d, 4-MeOC6H4, OMe
15e, 3-MeC6H4, OMe
15 f, 1-naphthyl, OMe
15g, 3-ClC6H4, Me
15h, 2-ClC6H4, Me
15i, 2-thienyl, OEt
1.5 h
10 min
30 min
3 h
2 h
2 h
1 h
1 h
1 h
1 h
1k, 4-BrC6H4, H
1l, 4-MeOC6H4, H
[a] Reaction time for second step. [b] Yields of isolated products after
column chromatography.
=
À
1m, trans-CH3CH CH , OEt
1 h
1n, CH3C(O), CH3
1o, EtOC(O), OEt
1p, Me, H
48 h
23 h
12 h
Recently, the use of a single transition-metal catalyst to
mediate two or more transformations in a single synthetic
operation has emerged as a new research area.[16] We have
observed that [{RuCl2(p-cymene)}2] can also catalyze the
reaction of a-diazocarbonyl compounds with propargyl
sulfide to afford allenyl sulfides. Naturally, [{RuCl2(p-
cymene)2}] was then tested as a single catalyst in this one-
pot sequential catalytic reaction. As shown in Table 4, with
[a] Yields of isolated products after column chromatography.
Table 4: One-pot sequential catalytic reactions with one catalyst.
Entry
Diazo substrate 15, Ar
t
Yield [%][a]
1
2
3
4
8
6
7
5
15a, C6H5
1 h
1 h
18 h
30 min
1 h
1 h
1 h
1 h
52
67
15b, 4-ClC6H4
15c, 2,4-Cl2C6H3
15d, 4-MeOC6H4
15q, 3-MeOC6H4
15r, 4-MeC6H4
15 s, 3-ClC6H4
15t, 4-BrC6H4
[b]
–
–
[b]
Scheme 4. Catalytic reaction with allenyl sulfides, 9, 11a,b, and allenyl
selenide 13.
68
45
61
54
5 mol% of PtCl2 afforded the furan products 12a and 12b in
moderate yields, together with a complex mixture as by-
products (Scheme 4). No products as a result of direct furan
formation without migration of the sulfanyl group could be
identified.[15] It is noteworthy that the catalytic reaction with
allenyl selenide 13 also proceeded with the RuII catalyst.
As the allenyl sulfides are obtained from the CuI- or RhII-
catalyzed reactions of a-diazocarbonyl compounds and
propargyl sulfide, it is conceivable that a one-pot reaction
may be possible by carrying out the two catalytic reactions
without separation of the allenyl sulfides (Table 3). Thus, the
reaction of diazo compounds 15a–i with propargyl sulfide 16
was first catalyzed with 1 mol% Rh2(OAc)4 in toluene at
608C. After the [2,3]-sigmatropic rearrangement was com-
pleted, 5 mol% of [{RuCl2(p-cymene)}2] was added and the
reaction mixture was heated to 808C. As shown in Table 3, the
one-pot reaction worked well with various diazo substrates
and gave the furan products in high yields.
[a] Yields of isolated products after silica-gel column chromatography.
[b] Diazo compound decomposed, but no furan product was identified.
the exception of two substrates (Table 4, entries 3, 4), the
RuII complex catalyzed the two reactions sequentially and
gave the corresponding furan products in moderate yields.
The two exceptions arose because of inefficiency and low
selectivity of the first catalytic reaction, that is, the generation
of the allenyl sulfide. Finally, as Rh2(O2CCF3)4 can also
catalyze the allenyl sulfide rearrangement (Table 1, entry 4),
we attempted its use as the only catalyst in the one-pot
reaction. The corresponding furan product was obtained,
however, the yield was low with isolation of a considerable
amount of allenyl sulfide.
In summary, we have reported an unprecedented
1,4 migration of the sulfanyl group in a transition-metal-
catalyzed reaction of allenyl sulfides. The reaction gives
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1907

Communications
112, 2382; Angew. Chem. Int. Ed. 2000, 39, 2285; f) S. Ma, J.
Zhang, L. Lu, Chem. Eur. J. 2003, 9, 2447.
[4] For a recent review, see: X. L. Hou, Z. Yang, H. N. C. Wong in
Progress in Heterocyclic Chemistry, Vol. 15 (Eds.: G. W. Gribble,
T. L. Gilchrist), Pergamon, Oxford, 2003, p. 167.
[5] For a review, see: B. H. Lipshutz, Chem. Rev. 1986, 86, 795.
[6] Reviews on the synthesis of furan derivatives: a) X. L. Hou,
H. Y. Cheung, T. Y. Hon, P. L. Kwan, T. H. Lo, S. Y. T. Tong,
H. N. C. Wong, Tetrahedron 1998, 54, 1955; b) S. F. Kirsch, Org.
Biomol. Chem. 2006, 4, 2076; c) B. A. Beay, Chem. Soc. Rev.
1999, 28, 209; d) S. Cacchi, J. Organomet. Chem. 1999, 576, 42 ;
e) R. C. D. Brown, Angew. Chem. 2005, 117, 872; Angew. Chem.
Int. Ed. 2005, 44, 850; f) for a recent report on furan synthesis
with Au-catalyzed reaction of alkynyl cyclopropyl ketones, see:
J. Zhang, H.-G. Schmalz, Angew. Chem. 2006, 118, 6856; Angew.
Chem. Int. Ed. 2006, 45, 6704.
multisubstituted furan products in good to excellent yields.
Furthermore, in combination with a metal-catalyzed [2,3]-
sigmatropic rearrangement, a one-pot sequential catalytic
transformation of a-diazocarbonyl compounds to furan
derivatives has been developed.[17] This one-pot catalytic
process is highly atom-economic and involves remarkable
bond reorganizations.
Received: October 20, 2006
Revised: December 14, 2006
Published online: February 2, 2007
Keywords: allenes · carbenes · diazo compounds · heterocycles ·
.
synthetic methods
[7] a) M. Ma, L. Peng, C. Li, X. Zhang, J. Wang, J. Am. Chem. Soc.
2005, 127, 15016; b) X. Zhang, M. Ma, J. Wang, Tetrahedron:
Asymmetry 2003, 14, 891.
[1] For recent reviews, see: a) N. Krause, A. S. K. Hashmi in Modern
Allene Chemistry, Vol. 2, Wiley-VCH, Weinheim, 2004, chap. 15;
b) A. Hoffmann-Röder, N. Krause, Org. Biomol. Chem. 2005, 3,
387; c) A. S. K. Hashmi, Angew. Chem. 2000, 112, 3737; Angew.
Chem. Int. Ed. 2000, 39, 3590; d) A. Hoffmann-Röder, N.
Krause, Angew. Chem. 2002, 114, 3057; Angew. Chem. Int. Ed.
2002, 41, 2933; e) R. Zimmer, C. U. Dinesh, E. Nandanan, F. A.
Khan, Chem. Rev. 2000, 100, 3067; f) J. A. Marshall, Chem. Rev.
2000, 100, 3163; g) S. Ma, Acc. Chem. Res. 2002, 35, 701; h) R.
Bates, V. Satcharoen, Chem. Soc. Rev. 2002, 31, 12; i) L. Sydnes,
Chem. Rev. 2003, 103, 1133; j) L. Brandsma, N. A. Nedolya,
Synthesis 2004, 735; k) M. Tius, Acc. Chem. Res. 2003, 36, 284;
l) L.-L. Wei, H. Xiong, R. P. Hsung, Acc. Chem. Res. 2003, 36,
773; m) X. Lu, C. Zhang, Z. Xu, Acc. Chem. Res. 2001, 34, 535;
n) S. Ma, Chem. Rev. 2005, 105, 2829; o) B. M. Trost, Acc. Chem.
Res. 2002, 35, 695; p) S. Ma, Eur. J. Org. Chem. 2004, 1175.
[2] For selected recent examples, see: a) N. Morita, N. Krause,
Angew. Chem. 2006, 118, 1930; Angew. Chem. Int. Ed. 2006, 45,
1897; b) B. M. Trost, C. Jonasson, Angew. Chem. 2003, 115, 2109;
Angew. Chem. Int. Ed. 2003, 42, 2063; c) B. M. Trost, C.
Jonasson, M. Wuchrer, J. Am. Chem. Soc. 2001, 123, 12736;
d) A. W. Sromek, M. Rubina, V. Gevorgyan, J. Am. Chem. Soc.
2005, 127, 10500; e) N. Krause, A. Hoffmann-Röder, J. Canisius,
Synthesis 2002, 1759; f) S. Ma, J. Zhang, L. Lu, Chem. Eur. J.
2003, 9, 2447; g) J. Huang, R. P. Hsung, J. Am. Chem. Soc. 2005,
127, 50; h) N. Nishina, Y. Yamamoto, Angew. Chem. 2006, 118,
3392; Angew. Chem. Int. Ed. 2006, 45, 3314; i) K. Tonogaki, K.
Itami, J.-i. Yoshida, J. Am. Chem. Soc. 2006, 128, 1464; j) T.
Nishimura, S. Hirabayashi, Y. Yasuhara, T. Hayashi, J. Am.
Chem. Soc. 2006, 128, 2556.
[8] The 1,2migration of sulfanyl groups in transition-metal-cata-
lyzed reactions of allenes is known, see: a) J. T. Kim, A. V.
Kelꢀin, V. Gevorgyan, Angew. Chem. 2003, 115, 102; Angew.
Chem. Int. Ed. 2003, 42, 98; b) for a review on sulfanyl migration,
see: D. J. Fox, D. House, S. Warren, Angew. Chem. 2002, 114,
2572; Angew. Chem. Int. Ed. 2002, 41, 2462.
[9] a) G. Shi, Y. Xu, M. Xu, Tetrahedron 1991, 47, 1629; b) T. Ye,
M. A. McKervey, Chem. Rev. 1994, 94, 1091; c) M. P. Doyle,
M. A. McKervey, T. Ye, Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds, Wiley-Interscience, New
York, 1998.
[10] For selected reviews, see: a) A. Padwa, M. D. Weingarten, Chem.
Rev. 1996, 96, 223; b) D. M. Hodgson, F. Y. T. M. Pierard, P. A.
Stupple, Chem. Soc. Rev. 2001, 30, 50; c) G. Mehta, S. Muthus-
amy, Tetrahedron 2002, 58, 9477.
[11] a) A. S. K. Hashmi, M. Rudolph, J. P. Weyrauch, M. Wölfle, W.
Frey, J. W. Bats, Angew. Chem. 2005, 117, 2858; Angew. Chem.
Int. Ed. 2005, 44, 2798; b) A. S. K. Hashmi, M. C. Blanco, E.
´
Kurpejovic, W. Frey, J. W. Bats, Adv. Synth. Catal. 2006, 348, 709.
[12] B. A. B. Prasad, F. K. Yoshimoto, R. Sarpong, J. Am. Chem. Soc.
2005, 127, 12468.
[13] For selected recent reviews, see: a) C. Aubert, O. Buisine, M.
Malacria, Chem. Rev. 2002, 102, 813; b) G. C. Lloyd-Jones, Org.
Biomol. Chem. 2003, 1, 215; c) K. Miki, S. Uemura, K. Ohe,
Chem. Lett. 2005, 34, 1068; d) A. M. Echavarren, C. Nevado,
Chem. Soc. Rev. 2004, 33, 431; e) S. Ma, S. Yu, Z. Gu, Angew.
Chem. 2006, 118, 261; Angew. Chem. Int. Ed. 2006, 45, 200.
[14] F. Xu, W. Shi, J. Wang, J. Org. Chem. 2005, 70, 4191.
[15] M. H. Suhre, M. Reif, S. F. Kirsch, Org. Lett. 2005, 7, 3925.
[16] For a recent review, see: A. Ajamian, J. L. Gleason, Angew.
Chem. 2004, 116, 3842; Angew. Chem. Int. Ed. 2004, 43, 3754.
[17] RhII-catalyzed 1,3-dipolar cycloaddition of cyclic diazo-1,3-
dicarbonyl compounds with acetylenes gives furan derivatives,
see: M. C. Pirrung, J. Zhang, A. T. Morehead, Jr., Tetrahedron
Lett. 1994, 35, 6229.
[3] a) J. A. Marshall, X.-j. Wang, J. Org. Chem. 1991, 56, 960; b) J. A.
Marshall, G. S. Bartley, J. Org. Chem. 1994, 59, 7169; c) A. S. K.
Hashmi, Angew. Chem. 1995, 107, 1749; Angew. Chem. Int. Ed.
Engl. 1995, 34, 1581; d) A. S. K. Hashmi, T. L. Ruppert, T.
Knöfel, J. W. Bats, J. Org. Chem. 1997, 62, 7295; e) A. S. K.
Hashmi, L. Schwarz, J.-H. Choi, T. M. Frost, Angew. Chem. 2000,
1908 www.angewandte.org
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