Rh(I)-catalyzed CO gas-free cyclohydrocarbonylation of alkynes with formaldehyde to α,β-butenolides

Article abstract of DOI:10.1039/b503816b

The rhodium(I)-catalyzed reaction of alkynes with formaldehyde proceeds via the double incorporation of a carbonyl moiety from formaldehyde, resulting in a CO gas-free cyclohydrocarbonylation leading to α,β-butenolides. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b503816b

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Rh(I)-catalyzed CO gas-free cyclohydrocarbonylation of alkynes with
formaldehyde to a,b-butenolides{
Koji Fuji, Tsumoru Morimoto,* Ken Tsutsumi and Kiyomi Kakiuchi
Received (in Cambridge, UK) 17th March 2005, Accepted 4th May 2005
First published as an Advance Article on the web 1st June 2005
DOI: 10.1039/b503816b
catalyst in a sealed tube, leading to the quantitative formation of
a,b-butenolide 2 (Table 1, entry 1). Apparently, two units of
formaldehyde carbonyl group participate in the construction of the
butenolide ring; one of which is incorporated as a carbonyl group
of 2, and the other as a CH2O unit in the butenolide ring. Similar
catalytic transformations of alkynes with highly pressurized carbon
monoxide or synthesis gas (CO–H2) have been reported to date.5
Thus, the present reaction is available as an accessible alternative
to them. The use of dppp or TPPTS as a ligand resulted in a sharp
decrease in the yield (42%) or no formation of 2, respectively. A
lower catalyst loading (2.5 mol% of [RhCl(cod)]2, 5 mol% of dppp,
The rhodium(I)-catalyzed reaction of alkynes with formalde-
hyde proceeds via the double incorporation of a carbonyl
moiety from formaldehyde, resulting in
a CO gas-free
cyclohydrocarbonylation leading to a,b-butenolides.
Methods for incorporating carbon monoxide into simple organic
substrates for the construction of value-added chemicals can take
advantage of the availability of a wide variety of transition metal
catalysts.1 However, the methods suffer from one major
disadvantage, namely the difficulty of handling toxic, gaseous
carbon monoxide. Considerable attention has been paid to
developing catalytic CO gas-free carbonylation reactions, because
of their experimental simplicity and ease of use. Consequently, the
use of various organic and inorganic carbonyl compounds as a
substitute for carbon monoxide would be highly desirable, since it
would eliminate the direct use of carbon monoxide, in reactions
such as the hydroesterification, hydroamidation and hydrocarbox-
ylation of alkenes and alkynes, the hydroformylation of alkenes,
the alkoxy-, amino- and hydroxycarbonylation of aromatic and
alkenyl halides, and the Pauson–Khand reaction.2 All of the above
reactions are mono carbonylations, in which one organic substrate
incorporates only one carbonyl moiety from the substitutes.
Our recent studies have demonstrated that a combination of
aldehydes with a rhodium(I) catalyst affords an alternative
protocol for CO gas-free carbonylation.3 The methodology utilizes
a compatible synergy of two catalytic processes, the decarbonyla-
tion of aldehydes by the transition-metal catalyst and the
successive carbonylation of organic substrates by carbonyl transfer
from the metal carbonyl that is formed. During the course of our
studies of this methodology, we discovered a new type of catalytic
CO gas-free carbonylation reaction, which proceeds via the double
incorporation of a carbonyl moiety from formaldehyde. Herein we
report on the rhodium(I)-catalyzed CO gas-free cyclohydrocarbo-
nylation of alkynes with formaldehyde leading to the production
of a,b-butenolides [eqn (1)].
Table 1 Rh(I)-catalyzed cyclohydrocarbonylation of 1 using various
carbonyl source
Entry Conditionsa Carbonyl source
Yield of 2 (%)b
1
2
3
4
5
a
A
A
A
B
B
Formalin (3 equiv.) 98
Benzaldehyde (5 equiv.) 0 (79)
CO (1 atm)
(CH2O)n (5 equiv.)c
CO–H2 5 1 : 1 (1 atm)
0 (84)
72
6 (68)
Condition A: [RhCl(cod)]2 (5 mol%), dppp (10 mol%), TPPTS
(10 mol%), and SDS (2 equiv.) in H2O at 100 uC; condition B:
[RhCl(cod)]2 (5 mol%) and dppp (10 mol%) in xylene at 100 uC.
Isolated yields. Values in parentheses are the yields of recovered 1.
b
c
Paraformaldehyde was used.
ð1Þ
Using the same conditions as described in a previous report,3c
which consist of 5 mol% of [RhCl(cod)]2, 10 mol% of dppp, and
10 mol% of TPPTS as a catalyst system, and 2 equiv. of SDS as a
surfactant in water at 100 uC,4 a mixture of diphenylacetylene (1)
and formaldehyde was reacted in the presence of the rhodium
{ Electronic supplementary information (ESI) available: Experimental
details. See http://www.rsc.org/suppdata/cc/b5/b503816b/
*morimoto@ms.naist.jp
Scheme 1 Proposed pathway for Rh(I)-catalyzed cyclohydrocarbonyl-
ation of 1 using formaldehyde.
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Chem. Commun., 2005, 3295–3297 | 3295

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and 5 mol% of TPPTS) resulted in no significant decrease in the
yield of 2 (95%).
Although details of the reaction mechanism are unclear, a
probable pathway that rationalizes the results obtained in Table 1
is shown in Scheme 1. Initially, the decarbonylation of formalde-
hyde by the rhodium would proceed to yield Rh–CO and H2. The
carbonylative cyclization of the alkyne 1 with two carbonyl
moieties on the rhodium would give a maleoylrhodium A,
analogues of which have been frequently proposed as a key
intermediate in the catalytic transformation of alkynes with CO or
CO–H2 to butenolides.5a,d,f The subsequent isomerization of A
affords a (g4-bisketene)rhodium C.9 The oxidative addition of H2,
followed by the 1,4-addition of a Rh-H in C, produces the
b-formyl-acylrhodium intermediate D. Finally, the addition of the
Rh-acyl bond to the formyl group in D followed by reductive
elimination gives the a,b-butenolide 2.10
The present cyclohydrocarbonylation reaction was found to be
unique to formaldehyde. Under the same conditions as entry 1, the
reaction of 1 with benzaldehyde, instead of formaldehyde, afforded
no trace of the butenolide 2, and the unreacted alkyne was
recovered in 79% yield (Table 1, entry 2). Moreover, under
atmospheric gaseous carbon monoxide conditions, no formation
of 1 was observed (entry 3). Interestingly, the use of paraformal-
dehyde in a non-aqueous system (in dry xylene as a solvent) led to
the formation of 2 in 72% yield (entry 4). The results from entries
1–3 show clearly that the hydrogens on the c-carbon of 2 formed
in the reaction of entry 1 are derived not from H2O, but from the
aldehydic hydrogen of formaldehyde.6 Moreover, the reaction with
1 atm of CO–H2 (1 : 1) afforded 2 although in low yield (6%)
(entry 5).7 This would mean that the use of (para)formaldehyde in
the presence of the rhodium catalyst yields the hydroformylation
conditions.8
The possibility of a lactonization process via D was demon-
strated by the following reaction in which the corresponding
intermediate D9 is presumed to be generated. Thus, upon the
exposure of o-phthalaldehyde (3) to conditions B in Table 1, the
Table 2 Rh(I)-catalyzed cyclohydrocarbonylation of alkynes using formaldehyde
Entry
1
Conditionsa
A
Product
Yield (%)b,c
93
Entry
8
Conditionsa
A
Product
Yield (%)b,c
74 (74/26)
n 5 2
R1 5 R2 5 C3H7
2
3
4
5
6
A
A
A
A
A
R1 5 Ph, R2 5 H
R1 5 Ph, R2 5 SiMe3
R1 5 Ph, R2 5 CH3
0
0
92 (66/34)
9
A
A
B
B
n 5 3
n 5 4
n 5 3
n 5 4
94 (81/19)
95 (56/44)
71 (63/37)
69 (54/46)
10
11
12
R1 5 p-C6H4CN, R2 5 Ph 76 (96/4)
R1 5 Ph, R2 5 p-C6H4OCH3 76 (52/48)
7
B
91 (52/48)
13
B
65 (99/1)
14
B
80 (57/43)
a
Condition A: formalin, [RhCl(cod)]2 (5 mol%), dppp (10 mol%), TPPTS (10 mol%), and SDS (2 equiv.) in H2O at 100 uC; condition B:
b
c
paraformaldehyde as a precursor of formaldehyde, [RhCl(cod)]2 (5 mol%) and dppp (10 mol%) in xylene at 100 uC. Isolated yields. Major
regioisomers are depicted. Ratios are the regioselectivities with respect to substituents on the termini of alkynes. The ratios of major isomers
are shown at the left of the values in parentheses.
3296 | Chem. Commun., 2005, 3295–3297
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Koji Fuji, Tsumoru Morimoto,* Ken Tsutsumi and Kiyomi Kakiuchi
Graduate School of Materials Science, Nara Institute of Science and
Technology (NAIST), Takayama, Ikoma, Nara 630-0192, Japan.
E-mail: morimoto@ms.naist.jp; Fax: +81 743 72 6089;
Tel: +81 743 72 6084
highly efficient formation of benzolactone 4 occurred [eqn (2)],
probably via the similar transformation from D9 to that from D to
butenolide 2 in Scheme 1.11
Notes and references
1 (a) H. M. Colquhoun, D. J. Thompson and M. V. Twigg,
Carbonylation: Direct Synthesis of Carbonyl Compounds, Plenum
Press, New York, 1991; (b) C. D. Frohning, C. W. Kohlpaintner and
H. -W. Bohnen, Applied Homogeneous Catalysis with Organometallic
Compounds, Vol. 1, ed. B. Cornils and W. A. Herrmann, Wiley-VCH,
Weinheim, 2002, pp. 31–194.
ð2Þ
2 For a review, see: T. Morimoto and K. Kakiuchi, Angew. Chem., Int.
Ed., 2004, 43, 5580–5588.
The scope of the reaction with respect to substitution of alkynes
and compatibility of functional groups was investigated next
(Table 2). The use of analogues of 1, in which two propyl groups
replace the two phenyl groups on the termini of 1, also resulted in
the formation of the corresponding butenolide (entry 1).
Unfortunately, the reaction of phenylsilylacetylene or phenyl-
acetylene gave none of the desired products, probably because of
the polymerization of the desilylated alkyne or phenylacetylene
itself, respectively (entries 2 and 3). When an unsymmetrically
substituted alkyne contains phenyl and methyl groups, a moderate
regioselectivity with respect to the substituents on the a- and
b-carbon was observed (entry 4). Diarylacetylene, having an
electron-withdrawing group (CN) on the aromatic ring, reacted
with formaldehyde to yield the corresponding butenolide with high
regioselectivity, while the introduction of an electron-donating
group showed almost no regioselectivity (entries 5 and 6).
Although an alkyne substituted with a heteroaromatic ring, such
as a furyl group, did not react under aqueous conditions
(conditions A), the reaction proceeded smoothly to give the
butenolide when non-aqueous conditions were used (conditions B)
(entry 7). Benzyl-protected alkynols were carbonylated under
aqueous conditions to yield the corresponding butenolides in high
yields with moderate selectivities (entries 8–10), while, for non-
protected alkynols, non-aqueous conditions were needed (entries
11 and 12). Nitrogen-functionalities, such as morpholino and
phthalimide groups, were also tolerated, but only for non-aqueous
reactions (entries 13 and 14).
3 (a) T. Morimoto, K. Fuji, K. Tsutsumi and K. Kakiuchi, J. Am. Chem.
Soc., 2002, 124, 3806–3807; (b) T. Morimoto, M. Fujioka, K. Fuji,
K. Tsutsumi and K. Kakiuchi, Chem. Lett., 2003, 32, 154–155; (c)
K. Fuji, T. Morimoto, K. Tsutsumi and K. Kakiuchi, Angew. Chem.,
Int. Ed., 2003, 42, 2409–2411; (d) K. Fuji, T. Morimoto, K. Tsutsumi
and K. Kakiuchi, Tetrahedron Lett., 2004, 45, 9163–9166.
4 Abbreviation: dppp
5 1,3-bis(diphenylphosphino)propane;
TPPTS 5 triphenylphosphine-3,39,30-trisulfonic acid trisodium salt;
SDS 5 sodium dodecylsulfate.
5 (a) J. Tsuji and T. Nogi, J. Am. Chem. Soc., 1966, 88, 1289–1292; (b)
K. Doyama, T. Joh, K. Onitsuka, T. Shinohara and S. Takahashi,
J. Chem. Soc., Chem. Commun., 1987, 649–650; (c) T. Joh, K. Doyama,
K. Onitsuka, T. Shinohara and S. Takahashi, Organometallics, 1991, 10,
2493–2498; (d) E. M. Campi, G. D. Fallon, W. R. Jackson and
Y. Nilsson, Aust. J. Chem., 1992, 45, 1167–1178; (e) T. Joh, H. Nagata
and S. Takahashi, Chem. Lett., 1992, 1305–1308; (f) T. Joh, H. Nagata
and S. Takahashi, Inorg. Chim. Acta, 1994, 220, 45–53; (g) K. H. Park,
S. Y. Kim and Y. K. Chung, Org. Biomol. Chem., 2005, 3, 395–398.
6 Previous reports by Takahashi’s and Chung’s groups described that two
hydrogens on the c-carbon of 2 are derived from water. See refs 5b, 5c,
and 5e–g.
7 In this reaction, 2,3,4,5-tetraphenylcyclopent-2-en-1-one was obtained in
9% yield. This by-product would be formed from the Pauson–Khand
reaction of 1 and stilbene, generated by the hydrogenation of 1, with
carbon monoxide.
8 For papers on the use of paraformaldehyde as a substitute for synthesis
gas (CO–H2), see: (a) T. Okano, T. Kobayashi, H. Konishi and J. Kiji,
Tetrahedron Lett., 1982, 23, 4967–4968; (b) H. S. Ahn, S. H. Han,
S. J. Uhm, W. K. Seok, H. N. Lee and G. A. Korneeva, J. Mol. Catal.
A: Chem., 1999, 144, 295–306.
9 (a) C. F. Jewell Jr., L. S. Liebeskind and M. Williamson, J. Am. Chem.
Soc., 1985, 107, 6715–6716; (b) T. Kondo, Y. Kaneko, Y. Taguchi,
A. Nakamura, T. Okada, M. Shiotsuki, Y. Ura, K. Wada and
T. Mitsudo, J. Am. Chem. Soc., 2002, 124, 6824–6825.
In conclusion, we describe the Rh(I)-catalyzed cyclohydrocar-
bonylation reactions of alkynes with formaldehyde. The strategy
has the potential for application to more double carbonylations as
well as mono carbonylation.12 Furthermore, the present reaction
should provide a new, readily accessible tool for the synthesis of
a,b-butenolides, which have been of continuous interest due to
their utility as synthetic intermediates and their biological
activity.13
10 For an example of the lactonization process via the intermediate
analogous to D, see: B. G. Van den Hoven, B. El Ali and H. Alper,
J. Org. Chem., 2000, 65, 4131–4137.
11 S. H. Gergens, D. P. Fairlie and B. Bosnich, Organometallics, 1990, 9,
566–571.
12 For general reviews on succesive catalytic incorporation reactions of two
molecules of carbon monoxide (so-called ‘‘double carbonylation’’), see:
(a) Y.-S. Lin and A. Yamamoto, Handbook of Organopalladium
Chemistry for Organic Synthesis, ed. E.-i. Negishi, Wiley, New York,
2002, pp. 2399–2423; (b) L. S. Liebeskind, S. L. Baysdon, M. S. South,
S. Iyer and J. P. Leeds, Tetrahedron, 1985, 41, 5839–5853 and references
therein; (c) N. Chatani, Y. Fukumoto, T. Ida and S. Murai, J. Am.
Chem. Soc., 1993, 115, 11614–11615; (d) M. Barrow, N. L. Cromhout,
A. R. Manning and J. F. Gallagher, J. Chem. Soc., Dalton Trans., 2001,
1352–1358; (e) see also ref. 10b.
This work was financially supported, in part, by a Grant-in-Aid
for Scientific Research (No. 15036247, ‘‘Reaction Control of
Dynamic Complexes’’, and No. 15750133) from MEXT, and by
The Association for the Progress of New Chemistry granted to
T.M. K.F. acknowledges JSPS Research Fellowship for Young
Scientists. We also thank Ms Yoshiko Nishikawa for assistance in
obtaining HRMS spectra.
13 For representative reviews, see: (a) Y. S. Rao, Chem. Rev., 1976, 76,
625–694; (b) E.-I. Negishi, Tetrahedron, 1997, 53, 6707–6738; (c)
I. Collins, J. Chem. Soc., Perkin Trans. 1, 1999, 1377–1396.
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Chem. Commun., 2005, 3295–3297 | 3297