Cationic palladium(II) complex-catalyzed [2 + 2] cycloaddition and tandem cycloaddition-allylic rearrangement of ketene with aldehydes: An improved synthesis of sorbic acid

Article abstract of DOI:10.1039/a908709e

Cationic palladium(II) complexes [PdL₂(PhCN)₂](BF₄)₂ efficiently catalyze the [2 + 2] cycloaddition of ketene with aldehydes to give the corresponding oxetan-2-ones, among which 4-vinyl-substituted ones are further isomerized under the conditions to give 3,6-dihydro-2H-pyran-2-ones in good yields.

Full text of DOI:10.1039/a908709e

Cationic palladium(II) complex-catalyzed [2 + 2] cycloaddition and tandem
cycloaddition–allylic rearrangement of ketene with aldehydes: an improved
synthesis of sorbic acid
Tetsutaro Hattori,* Yutaka Suzuki, Osamu Uesugi, Shuichi Oi and Sotaro Miyano*
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Aramaki-Aoba 07,
Aoba-ku, Sendai 980-8579, Japan. E-mail: hattori@orgsynth.che.tohoku.ac.jp
Received (in Cambridge, UK) 2nd November 1999, Accepted 24th November 1999
Cationic palladium(II) complexes [PdL2(PhCN)2](BF4)2 effi-
ciently catalyze the [2 + 2] cycloaddition of ketene with
aldehydes to give the corresponding oxetan-2-ones, among
which 4-vinyl-substituted ones are further isomerized under
the conditions to give 3,6-dihydro-2H-pyran-2-ones in good
yields.
After usual work-up, the crude product was subjected to GC
analysis to determine the yield of lactone 3.
The results are listed in Table 1. The reaction of cyclohex-
anecarbaldehyde 1a with ketene in the presence of 5 mol% of a
palladium complex 2a–e proceeded even at 278 °C to give the
lactone 3a (entries 1–5). The catalytic activity of the palladium
complexes 2a–e varied depending on the coordinating phos-
phine ligands, among which dppb (2d) was the most effective.
Addition of powdered molecular sieves (3 Å) did not improve
the yield of lactone 3a (entry 6). An irregular temperature
dependence of the product yield was found in the reaction
conducted at 240 °C (entry 7, as compared with entries 4, 8 and
9). This may be ascribed to the balance between an increase in
the rate constant with the rise in the reaction temperature and a
significant decrease in the concentration of ketene around its
boiling point (241 °C). Lactone 3a was obtained in quantitative
yield at room temperature, even if the quantity of the catalyst
was reduced to 1 mol% (entry 10). Judging from the high
catalytic activity and the lack of apparent effect of the
dehydrating agent (entry 6), the catalyst seems to be compatible
with the trace amounts of water in the system. The reaction of
several other aldehydes 1b–f with ketene afforded the corre-
sponding lactones 3b–f in good to excellent yields (entries
11–15).
There has been much current interest in the preparation of
oxetan-2-ones (b-lactones) because they are not only structural
units in biologically active natural products but also versatile
synthetic intermediates.1 Among various synthetic routes to this
class of compounds, the most efficient and concise is the Lewis
acid-catalyzed [2 + 2] cycloaddition of ketenes with aldehydes.1
Recently, we have reported the first asymmetric version of the
cycloaddition mediated by a catalytic amount of Corey’s
aluminium-based bissulfonamides.2 However, the reaction
requires the use of at least 10 mol% of the catalyst to obtain the
lactones in practical yields, as has been revealed in the related
reactions catalyzed by typical metal-based Lewis acids. This
may be ascribed to the highly oxophilic nature of the acid,
which causes competitive ligation between the reactants and the
product to the catalyst to reduce the catalytic efficiency.
Deactivation of the catalyst by a trace amount of incidental
water in the reaction system is another plausible problem.
On the other hand, it has been recognized in the last decade
that certain transition metal complexes have considerable Lewis
acid character and can displace conventional Lewis acids in a
variety of the so-called Lewis acid-catalyzed reactions.3
Furthermore, some of the transition metal-based Lewis acids are
reported to be effective even in the presence of water.4 These
facts prompted us to examine whether this class of Lewis acids
can effect the cycloaddition reaction. Herein, we report a highly
efficient [2 + 2] cycloaddition of ketene with aldehydes 1 using
cationic palladium(II) complexes [PdL2(PhCN)2](BF4)2 25 as
the catalyst (Scheme 1).
Next, our interest was directed toward the possibility of using
the palladium complex 2d as the catalyst for the cycloaddition
of ketene with a,b-unsaturated aldehydes 1g–k (Scheme 2). The
reaction of ketene with crotonaldehyde 1g under the standard
conditions (Method A, vide supra) afforded not the b-lactone 3g
but a d-lactone, 3,6-dihydro-6-methyl-2H-pyran-2-one (iso-
parasorbic acid) 4g,6 though only in poor yield, along with an
unidentifiable polymer (vide infra) (Table 2, entry 1).7 Low-
Table 1 Cycloaddition of ketene with aldehydes 1a–f catalyzed by
palladium complexes 2a–e
The general procedure for the [2 + 2] cycloaddition is as
follows (Method A): to a solution of complex 2 (50.0 mmol) in
dry CH2Cl2 (20 cm3) was added aldehyde 1 (1.00 mmol) under
nitrogen at an appropriate temperature. Gaseous ketene (ca. 2.5
mmol) was bubbled into the mixture over a period of 5 min and
the resulting mixture was stirred at this temperature for 1 h.
Entry
1
2
T/°C
3
Yield (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2d
2d
2d
2d
2dc
2d
2d
2d
2d
2d
278
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
33
46
55
66
56
63b
52
97
98
99
99
97
99
63
61d
278
278
278
278
278
240
0
room temp.
room temp.
room temp.
room temp.
room temp.
room temp.
room temp.
a Determined by GC analysis on ASTEC Chiraldex G-TA column (0.25 mm
i.d. 3 20 m) by the internal standard method. b Powdered molecular sieves
(3 Å) (100 mg) were added. c 1.0 mol%. d Isolated yield of the 1,3-diol
derived from compound 3f.
Scheme 1 Reagents and conditions: i, 2, CH2Cl2. dppp = 1,3-bis(diphenyl-
phosphino)propane, dppf = 1,1A-bis(diphenylphosphino)ferrocene.
Chem. Commun., 2000, 73–74
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73

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may be a possible intermediate for the present reaction. We
found, however, that BF3·OEt2 also catalyzed the rearrange-
ment to give lactone 4g, though only in 13% yield, when
aldehyde 1g was treated with ketene (method B) in Et2O (200
cm3) at room temperature in the presence of 1.5 equiv. of the
acid.10 This observation, along with the result that lactone 3h
did not isomerize to lactone 4h, may suggest another possibility,
that coordination of the carbonyl oxygen of 4-vinyl lactones 3g,
i–k to Lewis acid 2d promoted the heterolytic cleavage of the
C(4)–O bond of the lactones to form a zwitterion, recombina-
tion of which at the other allylic terminus afforded lactones 4.
Further treatment of lactone 4g with EtOH in the presence of
HCl followed by saponification of the resulting ethyl sorbate,
gave hexa-2,4-dienoic acid (sorbic acid) 5 in 90% yield
(Scheme 2). Therefore, the present method provides an easy
access to the acid 5. It should be noted that sorbic acid 5 is
important as a mould and yeast inhibitor, the first step of an
industrial synthesis of which relies on the cycloaddition of
ketene with crotonaldehyde 1g catalyzed by a zinc carbox-
ylate.11 However, the product obtained from the reaction is not
the b-lactone 3g but its ring-opening polymer, poly(3-hydroxy-
hex-4-enoic acid), the viscosity of which causes a great deal of
trouble during the subsequent destructive distillation of the
polyester to the acid 5. Further studies on the scope and
limitations of the allylic rearrangement, as well as the [2 + 2]
cycloaddition, are in progress.
Scheme 2 Reagents and conditions: i, 2d, CH2Cl2; ii, EtOH, conc. HCl,
reflux; iii, KOH, aqueous EtOH, reflux.
Table 2 Tandem cycloaddition–allylic rearrangement of ketene with a,b-
unsaturated aldehydes 1g–k catalyzed by palladium complex 2d
Entry
1
Methoda CH2Cl2/cm3
4
Yield (%)b
1
2
3
4
5
6
7
8
9
1g
1g
1g
1g
1g
1gd
1h
1i
A
A
B
B
B
B
B
B
B
B
20
200
200
200
500
200
200
200
200
200
4g
4g
4g
4g
4g
4g
4h
4i
13
55
70
50c
81
65
0e
This work was supported in part by grants from the Center of
Interdisciplinary Research (Tohoku University), the Takasago
International Corporation and the Chisso Corporation.
77c
58c
66c
1j
1k
4j
4k
10
a See text. b Determined by GC analysis on Quadrex MPS-10 column (0.32
mm i.d. 3 25 m) by the internal standard method. c Isolated yield after
column chromatography on silica gel with hexane–EtOAc (1+1) as the
eluent. d 2.00 mmol. e Lactone 3h was obtained in 96% yield.
Notes and references
† Method B: To a solution of complex 2d (50.0 mmol) in CH2Cl2 (200 or
500 cm3) was added aldehyde 1 (200 mmol). Ketene (ca. 250 mmol) was
bubbled into the mixture over a period of 1 min and the mixture was stirred
for 5 min. This series of operations was repeated until added aldehyde 1
reached the total amount of 1.00 mmol. To the mixture was added an
additional amount of ketene (ca. 1.0 mmol) and the resulting mixture was
stirred for 1 h before work-up.
ering the reaction temperature and changing the molar ratios of
ketene and catalyst 2d to aldehyde 1g did not improve the
product yield, while dilution of the reaction solution was found
to be highly effective (entry 2). Eventually, lactone 4g could be
obtained in good yields by adding aldehyde 1g and ketene
portionwise to a dilute solution of catalyst 2d (Method B†)
(entries 3 and 5). Under these conditions, 2.5 mol% of the
catalyst 2d was sufficient to complete the reaction (compare
entry 6 with entry 3). Similar d-lactones 4i–k were also
obtained in the reaction of a,b-unsaturated aldehydes 1i–k,
while acrolein 1h afforded b-lactone 3h under the same
conditions (entries 7–10).
The formation of lactone 4 can be rationalized by the initial
[2 + 2] cycloaddition of aldehyde 1 with ketene to give the allyl
ester 3, followed by its allylic rearrangement to form lactone 4.
It is known that this type of 1,3-rearrangement of allylic esters
is promoted by Pd0 and PdII complexes.8 It should be noted,
however, that the palladium(II)-catalyzed reaction is reportedly
a [3,3]-sigmatropic rearrangement of allyl esters, which is
impossible for the said lactones 3g–k due to steric reasons. On
the other hand, the palladium(0)-catalyzed rearrangement is
believed to involve a p-allylpalladium(II) intermediate. It is also
reported that palladium(II) salts promote the ring opening of
4-vinyl- (3h), and 4-isopropenyl-oxetan-2-one to afford the
corresponding penta-2,4-dienoic acids.9 A metallacyclic s-
allylpalladium intermediate generated by oxidative addition of
the C(4)–O bond of the oxetan-2-ones to a palladium(0) species
is proposed for the reaction. Thus, an allylpalladium species
1 Review: A. Pommier and J.-M. Pons, Synthesis, 1993, 441.
2 Y. Tamai, H. Yoshiwara, M. Someya, J. Fukumoto and S. Miyano,
J. Chem. Soc., Chem. Commun., 1994, 2281.
3 Review: B. Bosnich, Aldrichim. Acta, 1998, 31, 76.
4 W. Odenkirk, A. L. Rheingold and B. Bosnich, J. Am. Chem. Soc., 1992,
114, 6392; S. Kanemasa, Y. Oderaotoshi, S. Sakaguchi, H. Yamamoto,
J. Tanaka, E. Wada and D. P. Curran, J. Am. Chem. Soc., 1998, 120,
3074.
5 J. A. Davies, F. R. Hartley and S. G. Murray, J. Chem. Soc., Dalton
Trans., 1980, 2246; S. Oi, K. Kashiwagi, E. Terada, K. Ohuchi and Y.
Inoue, Tetrahedron Lett., 1996, 37, 6351.
6 R. Stevenson and J. V. Weber, J. Nat. Prod., 1988, 51, 1215.
7 Only one report was found in literature, which described a formation of
similar d-lactones in the cycloaddition of ketene with ketones: F. G.
Young, J. Am. Chem. Soc., 1949, 71, 1346.
8 Reviews: R. P. Lutz, Chem. Rev., 1984, 84, 205; L. E. Overman, Angew.
Chem., Int. Ed. Engl., 1984, 23, 579.
9 A. F. Noels, J. J. Herman and P. Teyssie´, J. Org. Chem., 1976, 41,
2527.
10 Hagemeyer reported that the boron trifluoride-catalyzed reaction of
ketene with crotonaldehyde 1g gave lactone 3g: H. J. Hagemeyer, Jr.,
US 2,478,388/1949 (Chem. Abstr., 1950, 44, 1132). See also: J. H.
McCain and E. Marcus, J. Org. Chem., 1970, 35, 2414.
11 H. J. Hagemeyer Jr., Ind. Eng. Chem., 1949, 41, 765.
Communication a908709e
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Chem. Commun., 2000, 73–74