Lactone formation by rhodium-catalyzed C-C bond cleavage of cyclobutanone

Article abstract of DOI:10.1002/1521-3773(20000717)39:14<2484::AID-ANIE2484>3.0.CO;2-1

As a coordinating ligand, the phenol group in appropriately substituted cyclobutanones facilitates the Rh¹-catalyzed activation of the C-C bond between the carbonyl group and the α-carbon atom. This novel reaction leads, depending on the position of the phenol group on the cyclobutanone ring, to lactones of varying ring size (for example, as shown for a seven-membered-ring lactone).

Full text of DOI:10.1002/1521-3773(20000717)39:14<2484::AID-ANIE2484>3.0.CO;2-1

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The following mechanism explains the formation of the six-
membered-ring lactones from 1a. Rhodium initially under-
goes insertion between the carbonyl carbon and the a-carbon
atom to afford the five-membered (acyl)rhodium intermedi-
ate 2. The phenolic hydroxy group then reacts with the acyl
group on rhodium to form the six-membered-ring lactone 3.[8]
Direct reductive elimination produces the saturated lactone
4a. The other product, unsaturated lactone 5a, is formed from
3 through b-hydride elimination and subsequent isomeriza-
tion to an a,b-unsaturated system.
Lactone Formation by Rhodium-Catalyzed
À
C C Bond Cleavage of Cyclobutanone**
Masahiro Murakami,* Takuo Tsuruta, and
Yoshihiko Ito*
Of the variety of synthetic transformations mediated by
transition metals, catalytic processes involving cleavage of
[1]
À
C C single bonds are among the most difficult to achieve.
Hence, their development remains an important challenge in
organic chemistry. We recently found that the bond between
the carbonyl carbon and the a-carbon atom of a cyclobutanone
can be catalytically cleaved by a rhodium(i) complex.[2]
Phenolic hydroxy groups have also been reported to direct
Other examples of the rhodium-catalyzed six-membered
ring lactone formation are listed in Table 1. Both substrates
having methyl (entry 1; Table 1) and chloro (entry 2; Table 1)
intramolecular functionalization of unreactive bonds such as
[3]
Table 1. Rhodium-catalyzed six-membered-ring lactone formation.
À
À
C H bonds. Thus we anticipated that C C bond cleavage
would be facilitated by appropriate placement of a phenol
group in the substrate molecule. Here we report new lactone-
Entry
1
Time [h]
4:5
Yield of 4 ‡ 5 [%]
Me
À
forming reactions by the rhodium-catalyzed C C bond
1
9
81:19
68
cleavage of a cyclobutanone having a pendant phenol group.
Cyclobutanone 1a, which has an o-substituted phenol
group at the 3-position,[4] was heated to 1408C in m-xylene
in the presence of a rhodium complex prepared in situ from
[Rh(cod)2]BF4 (5 mol%, cod ˆ 1,5-cyclooctadiene) and cyclo-
hexyldiphenylphosphane (PCyPh2, 12 mol%)[5] under an argon
atmosphere. The substrate 1a was consumed after 210 min.
Chromatographic purification afforded a mixture of saturated
and unsaturated six-membered-ring lactones (4a and 5a,
68:32) in 76% combined yield (Scheme 1).[6] The reaction
occurred at 1408C even under an atmosphere of carbon
monoxide to give an analogous result.[7]
OH
Cl
1b
O
2
3
4
85:15
100:0
82
57
OH
OH
1c
1d
O
O
Me
24
groups as the phenol substituent afforded the corresponding
six-membered-ring lactones as a mixture of saturated 4 and
unsaturated 5 in good combined yield. In the case of 1d, which
is equipped with an additional methyl group at the 3-position,
b-hydride elimination is inaccessible in the intermediate
corresponding to 3, and hence the saturated lactone was the
sole product (entry 3; Table 1).
A cyclobutanone possessing an o-substituted phenol group
at the 2-position (6a)[9] was also examined. The reaction of 6a
proceeded under milder conditions (1008C), and more
interestingly, a mixture of the seven-membered-ring lactones
7a and 8 was obtained together with the cyclopropane 9
(Scheme 2). When an analogous reaction was carried out under
Scheme 1. Reaction of 1a to give six-membered-ring lactones and the
postulated mechanism for this reaction.
5 mol%
[Rh(cod)2]BF4
12 mol%
PCyPh2
+
O
m-xylene, 100 °C
[*] Prof. M. Murakami, Prof. Y. Ito, T. Tsuruta
Department of Synthetic Chemistry and Biological Chemistry
Kyoto University
HO
6a
Yoshida, Kyoto 606-8501 (Japan)
Fax : (‡81)75-753-5668
+
+
O
O
O
O
HO
E-mail: murakami@sbchem.kyoto.u.ac.jp
yoshi@sbchem.kyoto-u.ac.jp
7a
8
9
20%
0%
under Ar (4 h) 22%
under CO (15 h) 86%
31%
trace
[**] We thank Dr. T. Tanaka (Kyoto University) for GC analysis of H2, and
Dr. M. Miura (Osaka University) for helpful discussions. Support from
Monbusho (Grant-in-Aid for Scientific Research on Priority Areas,
No. 283: Innovative Synthetic Reactions) is gratefully acknowledged.
Scheme 2. Rhodium-catalyzed reaction of 6a under Ar and CO atmos-
pheres.
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Table 2. Rhodium-catalyzed seven-membered-ring lactone formation.
an atmosphere of carbon monoxide instead of an argon
atmosphere, the unsaturated lactone 7a was selectively
Entry
6
Phosphane
Time
[h]
7
Yield
[%]
[10]
obtained in 86% yield,
and only a trace of 8 was formed.
The decarbonylation to 9 was completely suppressed under
these conditions. In addition, nearly quantitative evolution of
dihydrogen from the reaction mixture was detected by GC
analysis.
A mechanistic scheme postulated to explain these results is
shown in Scheme 3. Initially, the phenolic hydroxy group of 6a
coordinates to the rhodium atom, bringing it into proximity to
Me
Me
1
P(p-MeOC6H4)3
6
91
87
O
O
O
O
O
O
7b
6b
HO
HO
2
P(p-MeOC6H4)3 24
7c
6c
Me
Me
OMe
OMe
3
4
PCyPh2
PCyPh2
24
12
92
77
O
O
O
O
O
O
7d
6d
HO
HO
Cl
Cl
7e
6e
better results than PCyPh2 in some cases. When the pendant
phenol group has an additional electron-donating substituent
such as methyl and methoxy, the corresponding seven-
membered-ring lactone was obtained in high yield (en-
tries 1 ± 3; Table 2). Substrate 6e with a p-chlorophenol group
afforded 7e in slightly lower yield (77%, entry 4; Table 2).
For comparison, an analogous reaction was carried out
using cyclobutanone 6 f which had a methyl substituent in
addition to a phenol group at the 2-position. Unlike the case
of 6a, no reaction occurred at 1008C. The reaction at an
elevated temperature (1408C) afforded the five-membered-
ring lactone 13 (Scheme 4). None of the seven-membered-
ring lactone was observed. The additional steric constraints
Scheme 3. The postulated mechanism for the formation of 7a, 8, and 9
from 6a.
À
the a-C C bond of the carbonyl group. Insertion of the
rhodium atom into this bond is thus facilitated and affords the
five-membered (acyl)rhodium intermediate 10, which can
react in two ways. Extrusion of the carbonyl group from the
rhodacycle followed by reductive elimination affords cyclo-
propane 9. It seems reasonable that this process is disfavored
in a CO atmosphere. Alternatively, the hydroxy group of 10
can react intramolecularly with the (acyl)rhodium group to
form the seven-membered-ring lactone 11. Direct reductive
elimination forms the saturated lactone 8, while b-hydride
elimination yields 7a. The resulting rhodium(iii) dihydride
complex evolves dihydrogen by reductive elimination to
regenerate the rhodium(i) catalyst. It is plausible to assume
that the b-hydride elimination from 11 is intrinsically rever-
sible and that carbon monoxide acts as a ligand for rhodium
expelling the produced 7a from the coordination sphere, and
promoting this process forward irreversibly. Thus, the reaction
under a CO atmosphere gives 7a selectively.
Scheme 4. Reaction of 6 f to give five-membered-ring lactone 13 and the
postulated mechanism for this reaction.
introduced by the extra methyl substituent at the 2-position
À
The different rates of reactions of the substrates 1a and 6a
are noteworthy. The reaction of 1a at 1008C was much slower
(6% conversion under Ar after 4 h, no conversion under CO)
than that of 6a. Although the rate-determining step of the
lactonization reaction has not been elucidated, it is assumed
that, in the case of 6a, the transition state of the rate-
determining step is stabilized more efficiently by the phenolic
hydroxy group located closer to the inserting metal, and
therefore, the reaction proceeds faster.
hampered the cleavage of the proximal a-C C bond. Instead
the initial rhodium insertion was transposed to the less sub-
À
stituted C C bond on the far side, affording rhodacycle 12.
Subsequently, a five-membered-ring lactone linkage is formed.
The following b-hydride elimination produces the lactone 13.
It is likely that the assistance of the phenolic hydroxy group of
6 f coordinating to the inserting rhodium center is reduced for
geometrical reasons, as with the case of 1a. Thus, an elevated
temperature was required for the insertion.
À
Other examples of the rhodium-catalyzed seven-mem-
bered-ring lactone formation are shown in Table 2. The use
of tris(p-methoxyphenyl)phosphane as the ligand afforded
In summary, new catalytic C C bond cleaving reactions
were developed in which a phenol group serves as a
coordinating ligand to facilitate the catalytic activation of a
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À
C C single bond. Whereas the substrates presently employed
Ligand Electronic Effect in Enantioselective
Palladium-Catalyzed Copolymerization of
Carbon Monoxide and Propene**
benefit from relief of the structural strain,[11] the construction
of seven-membered ring lactone skeletons fused to aromatic
rings is of synthetic value because of the presence of these
subunits in biologically active compounds.
Â
Celine Gambs, Stanislav Chaloupka,
Giambattista Consiglio,* and Antonio Togni*
Experimental Section
The alternating copolymerization of olefins with carbon
monoxide (CO) catalyzed by cationic palladium(ii) complexes
modified by diphosphane ligands has attracted considerable
interest due to the potential use of the produced polyketones
as new materials.[1±7] Recently, a terpolymer derived from
ethene, propene, and CO has become commercially available
under the trade name of Carilon.
When propene is used as the substrate, control of regio- and
stereoselectivity of the olefin insertion is required to obtain
stereoregular alternating copolymers.[8, 9] Recently, a few
examples of successful, highly enantioselective CO/propene
copolymerizations have been reported, using either in situ or
preformed PdII complexes containing chiral phosphorus
ligands.[10±12] Among the catalysts studied the most active ever
reported to date (productivity of about 905 gg(Pd)À1 hÀ1)
7b: To a mixture of [Rh(cod)2]BF4 (6.0 mg, 15 mmol) and tris(p-methoxy-
phenyl)phosphane (9.6 mg, 36 mmol) in m-xylene (5 mL) under N2 at room
temperature were successively added 2-(2-hydroxy-5-methylphenyl)cyclo-
butanone (6b, 52.9 mg, 0.30 mmol) and m-xylene (5 mL). After the N2
atmosphere was replaced with CO, the mixture was heated at 1008C for 6 h.
The reaction mixture was cooled and then passed through a pad of Florisil
to remove the insoluble materials. The eluent was evaporated under
vacuum, and the residue was subjected to preparative TLC (silica gel, ethyl
acetate/hexane 1/5) to afford 7b (47.3 mg, 91%) as a colorless oil.1H NMR
(CDCl3, 300 MHz): d ˆ 2.36 (s, 3H), 3.05 (d, J ˆ 6.6 Hz, 2H), 6.03 (dt, J ˆ
9.9, 6.6 Hz, 1H), 6.83 (d, J ˆ 9.9 Hz, 1H), 7.09 ± 7.20 (m, 3H);13C{1H} NMR
(CDCl3, 75 MHz): d ˆ 20.6, 34.2, 120.9, 122.8, 126.7, 129.9, 130.1, 134.5,
148.3, 169.0; IR (neat): nÄ ˆ 1752 cmÀ1
; elemental analysis calcd for
C11H10O2: C 75.84, H 5.79; found: C 75.97, H 5.77.
Received: February 16, 2000 [Z14720]
contained
(R)(Sp)-1-[2-(diphenylphosphanyl)ferrocenyl]-
ethyldicyclohexylphosphane (Josiphos) as the modifying
ligand.[13, 14] With this system both a very high regioregularity
(>99% head-to-tail enchainments) and stereoregularity
(>96% of isotactic diads) were achieved. Thus, despite
contrasting proposals,[15] and a precedent example of a system
with low catalytic activity,[16] the best combination of donor
groups in the chelate diphosphane ligand seems to be that of
two electronically nonequivalent ligand fragments: a basic
PCy2 group to ensure high regioselective incorporation of
propene and a slightly acidic PPh2 donor.
[1] Reviews: a) R. H. Crabtree, Chem. Rev. 1985, 85, 245; b) B. Rybtch-
inski, D. Milstein, Angew. Chem. 1999, 111, 918; Angew. Chem. Int.
Ed. 1999, 38, 870; c) M. Murakami, Y. Ito in Activation of Unreactive
Bonds and Organic Synthesis (Ed.: S. Murai), Springer, Berlin, 1999,
p. 97.
[2] a) M. Murakami, H. Amii, Y. Ito, Nature 1994, 370, 540; b) M.
Murakami, H. Amii, K. Shigeto, Y. Ito, J. Am. Chem. Soc. 1996, 118,
8285; c) M. Murakami, K. Takahashi, H. Amii, Y. Ito, J. Am. Chem.
Soc. 1997, 119, 9307; d) M. Murakami, T. Itahashi, H. Amii, K.
Takahashi, Y. Ito, J. Am. Chem. Soc. 1998, 120, 9949.
[3] a) T. Satoh, J.-i. Inoh, Y. Kawamura, Y. Kawamura, M. Miura, M.
Nomura, Bull. Chem. Soc. Jpn. 1998, 71, 2239; b) K. Kokubo, K.
Matsumasa, Y. Nishinaka, M. Miura, M. Nomura, Bull. Chem. Soc.
Jpn. 1999, 72, 303; c) T. Satoh, T. Itaya, M. Miura, M. Nomura, Chem.
Lett. 1996, 823; d) M. Hirano, N. Kurata, T. Marumo, S. Komiya,
Organometallics 1998, 17, 501.
[4] The cyclobutanone 1a was prepared by [2‡2] cycloaddition of o-
(methoxymethoxy)styrene with dichloroketene and the subsequent
treatment with zinc in acetic acid.
[5] A cationic rhodium(i) complex having two PCyPh2 ligands per
rhodium atom is postulated as the catalytic species. No reaction
occurred in the absence of the rhodium catalyst.
[6] The ratio of 4a to 5a changed little (68:32 ± 75:25), when other catalyst
systems like [Rh(cod)2]BF4/PPh3, [Rh(cod)2]BF4/P(p-methoxyphen-
yl)3, and [Rh(cod)(Ph2PCH2CH2CH2PPh2)]BF4 were used.
[7] The reactions previously reported[2] normally failed to occur under a
CO atmosphere.
Since planar-chiral ferrocenyl ligands represent a system
that is synthetically easy to modify, and 1) in view of
investigating possible electronic effects on both the copoly-
mer structure and the performance of the catalyst, and 2) to
gain insight on the role of electronic differentiation of the two
binding sites in these ligands,[17, 18] we prepared a series of
related chiral diphosphanes 1a ± g (Scheme 1) according to
already published general methods.[19±22] Here we report
extremely active PdII systems bearing chiral ferrocenyl
diphosphanes 1b ± d for highly enantioselective alternating
copolymerization of propene and carbon monoxide.
Thus, in typical experiments, in situ PdII systems prepared
by reacting Pd(OAc)2 with ligands 1a ± g and BF3 ´ Et2O in
CH2Cl2 ± MeOH were investigated (Scheme 2). In fact, 31P
[8] a) M. Hidai, K. Ishimi, M. Iwase, E. Tanaka, Y. Uchida, Tetrahedron
Lett. 1973, 1189; b) R. Grigg, T. R. B. Mitchell, S. Sutthivaiyakit,
Tetrahedron 1981, 37, 4313.
[9] The cyclobutanone 6a was prepared according to the literature
procedure: B. M. Trost, M. J. Bogdanowicz, J. Am. Chem. Soc. 1973,
95, 5321.
[10] The formation of the corresponding a,b-unsaturated isomer was not
observed.
[*] Prof. G. Consiglio
Laboratorium für Technische Chemie der ETH Zürich
Universitätstrasse 6, 8092 Zürich (Switzerland)
Fax : (‡41)1-632-11-62
[11] With less strained substrates like 2-(2-hydroxyphenyl)cyclopenta-
none, an analogous reaction failed to occur.
E-mail: consiglio@tech.chem.ethz.ch
Prof. A. Togni, C. Gambs, S. Chaloupka
Laboratorium für Anorganische Chemie der ETH Zürich
Universitätstrasse 6, 8092 Zürich (Switzerland)
Fax : (‡41)1-632-10-90
E-mail: togni@inorg.chem.ethz.ch
[**] This work was supported by the ETH Zürich. We thank Novartis AG
and Solvias AG, Basel, for the donation of chemicals.
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