Organic acid induced olefination reaction of lactones

Article abstract of DOI:10.1039/c2cc33606e

(Z)-Selective olefination of several lactones with ketene silyl acetals was achieved by the catalysis of carbon acids (C-H acids) having a bis(triflyl)methyl group as an acidic functionality; in particular, the triple carbon acid having three bis(triflyl)methyl groups in phloroglucinol shows an excellent catalytic performance.

Full text of DOI:10.1039/c2cc33606e

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Organic acid induced olefination reaction of lactonesw
Hikaru Yanai* and Takeo Taguchi*
Received 18th May 2012, Accepted 18th July 2012
DOI: 10.1039/c2cc33606e
(Z)-Selective olefination of several lactones with ketene silyl acetals
was achieved by the catalysis of carbon acids (C–H acids) having a
bis(triflyl)methyl group as an acidic functionality; in particular,
the triple carbon acid having three bis(triflyl)methyl groups in
phloroglucinol shows an excellent catalytic performance.
The mixed Claisen condensation reaction is one of the most
effective C–C bond forming reactions.1 As it is documented in
several textbooks of organic chemistry, nucleophilic attack of
enolate on an ester substrate gives the tetrahedral intermediate
Fig. 1 Electrophilic activation of carbonyl compounds by in situ-generated
(eqn (1)). As shown in path A, subsequent elimination of an
alkoxide ion leads to the formation of the normal product. In
contrast, if elimination of a hydroxide ion from the tetrahedral
intermediate occurs, a b-alkoxy-a,b-unsaturated ester will be
obtained (path B). In classical enolate chemistry, the latter reaction
pathway has been reported in only limited substrates. For example,
a b-alkoxy-a,b-unsaturated ester was obtained by treating an
isochroman-1-one derivative with a large excess of a lithium
enolate.2,3 As synthetically useful reactions, the olefination of esters
or lactones giving rise to vinyl ethers was usually achieved by using
Schrock carbene precursors such as the Tebbe reagent4 and the
Petasis reagent.5 To realize effective olefination of carboxylic acid
derivatives via path B, we thought that the use of ketene silyl acetals
(KSAs) as nucleophiles would be a reasonable approach.6 Actually,
Onaka and Izumi reported that, in the presence of ferric ion-
exchanged montmorillonite, the reaction of a propiolic acid ester
with KSA slowly gives the corresponding vinyl ether in moderate
yield along with the formation of the Claisen condensation
product.7 Nucleophilic addition reactions of KSAs to lactone
and ester substrates have also been reported.8
silyl methide.
Recently, we reported that 1,1,3,3-tetrakis(triflyl)propane 1a
(Tf2CHCH2CHTf2; Tf = CF3SO2) works as one of the most
effective Brønsted acid pre-catalysts for the C–C bond forming
reactions between sterically hindered carbonyls and silylated
nucleophiles.9,10 It is known that organic compounds having the
bis(triflyl)methyl (Tf2CH) group act as notably strong carbon acids
(C–H acids) in both gas-phase11 and solution-phase.12 As shown in
Fig. 1, in the carbon acid-mediated reaction system, highly Lewis
acidic silyl methide A initially forms by the reaction of carbon acid
1 with KSA. This species acts as a ‘‘R3Si+’’ equivalent13 due to its
high silylating activity through steric repulsion between a sterically
bulky methide moiety and an R3Si moiety. That is, the carbonyl
substrate is activated via I-strain induced silylation giving rise to
carboxonium ion B.14 Since electrophilic activation of carbonyl
compounds by the ‘‘R3Si+’’ equivalent is significantly stronger
than that by usual Lewis acids such as BF3 and TiCl4,15 we tried to
apply the in situ-generation of this type of silyl methide to an ester
olefination system. Herein we describe that, by using carbon acids,
formal organocatalytic olefination reaction of lactones smoothly
proceeds under mild conditions to give the corresponding vinyl
ethers in a Z selective manner.
ð1Þ
Initially, we investigated the reaction of isochroman-1-one 2a
with KSA derived from ethyl acetate in the presence of several
carbon acids. Selected results are shown in Table 1. As shown in
entry 1, to a solution of 2a and 4 mol% of Tf2CHCH2CHTf2 1a
in CH2Cl2, 1.2 equiv. of KSA was added over 1 h at 0 1C. When
the mixture was stirred for further 1 h (total 2 h) at the same
temperature, clean formation of adduct 3aa was observed in
TLC analysis of the reaction mixture. Desired olefin formation
was also achieved by increasing reaction temperature. That is,
the resulting mixture was additionally stirred for 3 h at room
temperature to give olefin product 4aa in 53% yield. In this
case, complete consumption of 2a was not observed and it was
School of Pharmacy, Tokyo University of Pharmacy and Life
Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
E-mail: yanai@toyaku.ac.jp, taguchi@toyaku.ac.jp;
Fax: +81 676 3257; Tel: +81 676 3257
w Electronic supplementary information (ESI) available: Details of
experiments, NMR data of all new compounds, and crystal structures
of 4ha and 4ia. CCDC 881214 and 881215. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/
c2cc33606e
c
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Table 1 Survey of effective carbon acid catalysts
the corresponding vinyl ethers 4ba and 4bc in excellent yields,
respectively. In the reaction of 7-nitroisochroman-1-one 2c,
the use of KSA derived from ethyl acetate resulted in only
moderate product yield due to the competitive addition of
KSA to the generated vinyl ether 4ca. In contrast, we found
that KSA derived from isopropyl acetate instead of ethyl
acetate is effective for the clean formation of 4cc. That is,
the nucleophilic addition of isopropylated KSA to 2c completed
within 2 h at 0 1C, then, the product 4cc was obtained in 83% yield
by subsequent stirring for 5 h at room temperature. Likewise,
7-bromoisochroman-1-one 2d and 7-acetamidoisochroman-1-one
2e could be converted to vinyl ethers 4dc and 4ea in 84% and 87%
yields, respectively. Remarkably, vinyl ether 4fa was isolated
in 85% yield by the reaction of benzo[c]chromenone 2f despite its
low stability in acidic media.19 Compared to isochroman-1-ones,
brominated phthalides 2g and 2h showed a slow reaction rate at the
olefination step. For example, although the nucleophilic addition of
ethylated KSA to 2g completed within 2 h at 0 1C, for the
completion of the following olefination giving rise to 4ga it took
9 h at room temperature. During the present olefination,
alkynylated and alkylated lactones smoothly formed the
corresponding vinyl ethers in good to excellent yields. Notably,
1H-isochromen-1-one 2n, which has vinyl ester functionality, gave
the desired vinyl ether 4nb in 81% yield. On the other hand, by
the Reformatsky reaction of isochromen-1-one derivatives,
1-naphthol derivatives as major products are formed.20 Therefore,
this finding supports that lactone ring-opening in the tetrahedral
intermediate hardly occurs during the present olefination.
Heterocycle-fused lactones are also suitable substrates. For instance,
the reactions of indole- and furan-fused substrates 2o and 2p gave
the vinyl ethers 4oa and 4pa in excellent yields, respectively.
In addition, as direct evidence of the reaction pathway, we
successfully isolated a Mukaiyama aldol adduct. By the reaction of
2d with isopropylated KSA at ꢀ10 1C in the presence of carbon
acid 1c, aldol adduct 3dc was obtained in 86% yield along with
the formation of a small amount of vinyl ether 4dc (Scheme 1).
By treating with a catalytic amount of 1c, 3dc could be rapidly
converted to 4dc in 98% yield.
Entry
Organic acid/mol%
KSA/equiv.
Yielda (%)
1
2
3
4
5
6
7
Tf2CHCH2CHTf2 1a (4.0)
Tf2CHC6F5 1b (4.0)
TfOH (4.0)
1.2
1.2
1.2
1.2
1.2
1.2
2.0
53
30b
3b
25
51
72
85
Tf2NH (4.0)
Triple carbon acid 1c (1.0)
Triple carbon acid 1c (1.0)
Triple carbon acid 1c (2.0)
a
b
Isolated yield. Based on H NMR analysis of a crude mixture.
1
recovered in 41% yield. Under the same conditions, the use of
Tf2CHC6F5 1b16 instead of 1a resulted in poor yield of 4aa
(entry 2). Likewise, the reactions in the presence of a catalytic
amount of TfOH or Tf2NH did not give 4aa in reasonable
yields (entries 3 and 4). In contrast, triple carbon acid 1c17,18
showed an excellent catalytic performance in this transformation.
Thus, comparable yield of 4aa was achieved by using only 1 mol%
of 1c compared to the reaction using 1a (entry 5). Furthermore, the
product yield was significantly improved by increasing the loading
of 1c and KSA. In the presence of 2 mol% of 1c, the reaction with
2 equiv. of KSA gives 4aa in 85% yield with complete consumption
of 2a (entry 7). It should be noted that only a vinyl ether product
having the Z configuration was formed in all cases. On the other
hand, acyclic esters such as methyl benzoate did not react with
KSA under similar conditions because the electrophilicity of acyclic
ester functionality is generally lower than that of lactone
functionality. The reaction of d-valerolactone with KSA also
gave the corresponding adduct in good yield and its conversion
to vinyl ether in a one-pot manner was not achieved (see ESIw).
To reveal the scope of the present olefination, next, we
conducted the reactions of several lactones with KSAs (Fig. 2).
The reaction of 2a with KSA derived from methyl acetate gave
(Z)-vinyl ether 4ab in 82% yield. Phthalide 2b, which has
5-membered lactone structure, also reacted with both KSAs
derived from ethyl acetate and from isopropyl acetate to give
Regarding the reaction mechanism, we propose the formal
catalysis by ‘‘R3Si+’’ equivalents. As shown in Fig. 3, silylated
carboxonium B smoothly reacts with KSA to give intermediate C.
This intermediate also works as an ‘‘R3Si+’’ equivalent.
Indeed, silyl group transfer from C to unreacted lactone 2
results in the formation of aldol adduct 3 along with regeneration
of intermediate B. Since intermediate C is reversibly generated
from produced adduct 3 and ‘‘R3Si+’’ equivalents existing in
Fig. 2 Carbon acid-induced olefination of lactones. In all cases, only (Z)-vinyl ether products were formed.
c
This journal is The Royal Society of Chemistry 2012
8968 Chem. Commun., 2012, 48, 8967–8969

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Transformations by Organocatalysts’’ from MEXT. We also
thank the Asahi Glass Foundation.
Notes and references
1 For reviews, see: (a) B. P. Davis and P. J. Garratt, in Comprehensive
Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon,
Oxford, 1991, vol. 2, p. 795; (b) S. Benetti, R. Romagnoli, C. De Rosi,
G. Spalluto and V. Zanirato, Chem. Rev., 1995, 95, 1065.
2 M. Yamaguchi, S. Nakamura, T. Okuma and T. Minami, Tetrahedron
Lett., 1990, 31, 3913.
Scheme 1 Formation of Mukaiyama aldol adduct 3dc and its conversion
to vinyl ether 4dc.
3 Stereoselective olefination of esters with lithium enolates was also
reported. See: M. Shindo, T. Kita, T. Kumagai, K. Matsumoto
and K. Shishido, J. Am. Chem. Soc., 2006, 128, 1062.
4 (a) S. H. Pine, Org. React., 1993, 43, 1; (b) F. N. Tebbe, G. W. Parshall
and G. S. Reddy, J. Am. Chem. Soc., 1978, 100, 3611.
5 N. A. Petasis and E. J. Bzowej, J. Am. Chem. Soc., 1990, 112, 6392.
6 For the Claisen condensation of carboxylic acid derivatives with
KSAs, see: (a) A. Iida, K. Takai, T. Okabayashi, T. Misaki and
Y. Tanabe, Chem. Commun., 2005, 3171; (b) H. Tamagaki,
Y. Nawate, R. Nagase and Y. Tanabe, Chem. Commun., 2010,
46, 5930; (c) Y. Nishimoto, A. Okita, M. Yasuda and A. Baba,
Angew. Chem., Int. Ed., 2011, 50, 8623.
7 M. Onaka, T. Mimura, R. Ohno and Y. Izumi, Tetrahedron Lett.,
1989, 30, 6341.
8 (a) K. Homma, H. Takenoshita and T. Mukaiyama, Bull. Chem.
Soc. Jpn., 1990, 63, 1898; (b) R. Csuk and M. Schaade, Tetrahedron
Lett., 1993, 34, 7907; (c) S. Iwata, T. Hamura, T. Matsumoto and
K. Suzuki, Chem. Lett., 2007, 538.
Fig. 3 Catalytic cycles in the present reaction system.
9 (a) H. Yanai, A. Takahashi and T. Taguchi, Chem. Commun.,
2010, 46, 8728; (b) H. Yanai, Y. Yoshino, A. Takahashi and
T. Taguchi, J. Org. Chem., 2010, 75, 5375; (c) A. Takahashi,
H. Yanai, M. Zhang, T. Sonoda, M. Mishima and T. Taguchi,
J. Org. Chem., 2010, 75, 1259; (d) A. Takahashi, H. Yanai and
T. Taguchi, Chem. Commun., 2008, 2385.
the reaction system, this intermediate would yield oxonium D
via proton exchange. If the reaction temperature is low enough
to inhibit elimination of R3SiOH, aldol adduct 3 can be
isolated. In contrast, at higher reaction temperature (usually, room
temperature), silylated vinyl ether E, which can also be depicted as
E0, would be formed through the E1 mechanism. We attribute the
perfect Z selectivity observed in all reactions to this E1 reaction.
Finally, silyl group transfer from E to unreacted adduct 3 results in
the formation of 4 along with the regeneration of C. Since it is
possible to isolate adduct 3, the olefin formation via the latter
catalyst cycle would be relatively slow at 0 1C or below 0 1C.
External ‘‘R3Si+’’ species including ArCH2C(SiR3)Tf2, which is
generated from triple carbon acid 1c and KSA, would play dual
roles. Thus, the ‘‘R3Si+’’ species catalyzes not only the C–C bond
forming step but also the olefination step. Directly catalysis of the
olefin formation step by a very low amount of triple carbon acid
1c would be an alternative pathway.21
10 For synthetic applications of Tf2CH2, see: (a) H. Yanai, M. Fujita
and T. Taguchi, Chem. Commun., 2011, 47, 7245; (b) H. Yanai,
A. Takahashi and T. Taguchi, Tetrahedron Lett., 2007, 48, 2993.
11 I. Leito, E. Raamat, A. Kutt, J. Saame, K. Kipper, I. A. Koppel,
I. Koppel, M. Zhang, M. Mishima, L. M. Yagupolskii, R. Yu.
Garlyauskayte and A. A. Filatov, J. Phys. Chem. A, 2009, 113, 8421.
12 The pKa of Tf2CH2 in DMSO is 2.1. Tf2CH2 acts as the stronger
proton donor relative to PhOH (18.0), PhCO2H (11.1) and CF3CO2H
(3.45). See: F. G. Bordwell, Acc. Chem. Res., 1988, 21, 456.
13 For examples on synthetic reactions catalyzed by silylium or
silylium equivalents, see: (a) R. K. Schmidt, K. Muther,
C. Muck-Lichtenfeld, S. Grimme and M. Oestreich, J. Am. Chem.
Soc., 2012, 134, 4421; (b) K. Hara, R. Akiyama and M. Sawamura,
Org. Lett., 2005, 7, 5621; (c) C. Douvris and O. V. Ozerov, Science,
2008, 321, 1188.
14 B. Mathieu and L. Ghosez, Tetrahedron, 2002, 58, 8219.
15 (a) A. Hasegawa, K. Ishihara and H. Yamamoto, Angew. Chem.,
Int. Ed., 2003, 42, 5731; (b) R. F. Childs, D. L. Mulholland and
A. Nixon, Can. J. Chem., 1998, 60, 801.
16 (a) K. Ishihara, A. Hasegawa and H. Yamamoto, Angew. Chem., Int.
Ed., 2001, 40, 4077; (b) J. Saadi, M. Akakura and H. Yamamoto,
J. Am. Chem. Soc., 2011, 133, 14248; (c) A. Hasegawa, T. Ishikawa,
K. Ishihara and H. Yamamoto, Bull. Chem. Soc. Jpn., 2005, 78, 1401.
17 H. Yanai, H. Ogura, H. Fukaya, A. Kotani, F. Kusu and
T. Taguchi, Chem.–Eur. J., 2011, 17, 11747.
In summary, we found that triple carbon acid 1c shows
excellent catalytic activity in the olefination reaction of lactones
using KSAs. In the present reaction, the catalytic performance of
1c is remarkably higher than that of Tf2CHCH2CHTf2 1a. This
result also reflects thermal stability of 1c. That is, as we previously
pointed out,17 1a undergoes reversible decomposition in solution
phase at relatively high reaction temperature, while 1c is so stable in
solution. In addition, multiple Tf2CH functionalities in the mole-
cular structure of 1c would cooperatively contribute to its high
catalytic performance. This reaction system is not only an organo-
catalytic process for olefination, but also the Mukaiyama aldol
adduct can be obtained by controlling the reaction conditions.
This work was partially supported by a Grant-in-Aid for
Scientific Research on Innovative Areas ‘‘Advanced Molecular
18 The pKa of triple carbon acid 1c in DMSO is measured as 2.0
(ref. 18). By comparing pKa values in DMSO, Tf2CH groups in 1c
behave as better proton donating functionalities to basic species.
19 By chromatographic purification on neutral silica gel, vinyl ether
4fa partly gave the corresponding hydroxyketone. Therefore, 4fa
was isolated by chromatography on basic alumina. Similar low
stability of 4nb and 4pa on silica gel was also observed.
20 F. M. Hauser and R. Rhee, J. Am. Chem. Soc., 1977, 99, 4533.
21 Silyl methide species would react with a trace amount of water
existing in the reaction system to give a free carbon acid (Fig. 1).
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 8967–8969 8969