1
526
Synlett
Q. Wang, B. List
Letter
Table 1 Substrate Scope of the Mukaiyama–Claisen Reaction
O
O
OTMS
O
O
90 °C
KHF2
OTBS
+
Ph toluene
MeOH
O
Ph
OMe
O
O
O
9
0 °C
KHF2
O
O
2a
2c
4, 59% yield
+
O
or
OTMS toluene MeOH R1
OMe
R1
R2 R2
O
O
Ph
1
OMe
3
O
2b
Scheme 1 Intramolecular cyclization observed using silyl enol ether 2c
Entrya
1
Product
Yield (%)
85
as nucleophile
BocHN
O
O
O
O
O
O
3a
Ph
OMe
OMe
BocHN
Acknowledgment
2
3b
3c
3d
3e
3f
78
85
84
61
73
73
75
Ph
Generous support by the Max-Planck-Society and the European
Research Council (Advanced Grant ‘High Performance Lewis Acid
Organocatalysis, HIPOCAT’) is gratefully acknowledged.
TBSO
O
O
O
3
Ph
OMe
OMe
Supporting Information
TBSO
O
O
O
4
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380145.
Ph
Ph
S
u
p
p
o
nrtIo
i
g
f
rm oaitn
S
u
p
p
ortioIgnfmr oaitn
O
O
O
O
O
O
5b
6b
7
References and Notes
OMe
OMe
(
1) (a) Koskinen, A. M. P.; Karisalmi, K. Chem. Soc. Rev. 2005, 34,
77. (b) Aginagalde, M.; Bello, T.; Masdeu, C.; Vara, Y.; Arrieta,
6
A.; Cossío, F. P. J. Org. Chem. 2010, 75, 7435. (c) Shimada, N.;
Stawart, C.; Bow, W. F.; Jolit, A.; Wong, K.; Zhou, Z.; Tius, M. A.
Angew. Chem. Int. Ed. 2012, 51, 5727. (d) Pandit, R. P.; Lee, Y. R.
Org. Biomol. Chem. 2014, 12, 4407.
Ph
O
O
O
O
O
3g
3h
(
2) (a) Himmelsbach, M.; Lintvedt, R. L.; Zehetmair, J. K.; Nanny, M.;
Heeg, M. J. J. Am. Chem. Soc. 1987, 109, 8003. (b) Chizhov, D. L.;
Sevenard, D. V.; Lork, E.; Pashkevich, K. I.; Roschenthaler, G.-V.
J. Fluorine Chem. 2004, 125, 1137. (c) Miyatake-Ondozabal, H.;
Barrett, A. G. M. Org. Lett. 2010, 12, 5573. (d) Jiang, J.-A.; Huang,
W.-B.; Zhai, J.-J.; Liu, H.-W.; Cai, Q.; Xu, L.-X.; Wang, W.; Ji, Y.-F.
Tetrahedron 2013, 69, 627.
OMe
O
8
OMe
a
Reactions were carried out with 1 (0.1 mmol) and 2 (0.4 mmol) in toluene
(
1 mL) for 4–5 h at 90 °C.
Reactions were carried out at 110 °C.
(3) (a) Work, S. T.; Hauser, C. R. J. Org. Chem. 1963, 28, 725.
b
(b) Bartoli, G.; Bosco, M.; Cimarelli, C.; Dalpozzo, R.; Guercio, G.;
Palmieri, G. J. Chem. Soc., Perkin. Trans. 1993, 2081.
1
Interestingly, when a silyl enol ether (2c) was explored
(c) Sánchez-Larios, E.; Thai, K.; Bilodeau, F.; Gravel, M. Org. Lett.
2011, 13, 4942. (d) Kalaitzis, J. A.; Cheng, Q.; Thomas, P. M.;
Kelleher, N. L.; Moore, B. S. J. Nat. Prod. 2009, 72, 469.
as the nucleophile, an intramolecular cyclization was ob-
served and 2-methyl-6-phenyl-4H-pyran-4-one (4) was
isolated in 59% yield (Scheme 1). Presumably, under these
conditions, a triketone is initially formed and subsequently
(
4) (a) Rahn, T.; Nguyen, V. T. N.; Dang, T. H. T.; Ahmed, Z.;
Methling, K.; Lalk, M.; Fischer, C.; Spannenberg, A.; Langer, P.
J. Org. Chem. 2007, 72, 1957. (b) Rahn, T.; Dang, T. H. T.;
Spannenberg, A.; Fischer, C.; Langer, P. Org. Biomol. Chem. 2008,
6, 3366. (c) Rahn, T.; Appel, B.; Baumann, W.; Jiao, H.; Börner,
A.; Fischer, C.; Langer, P. Org. Biomol. Chem. 2009, 7, 1931.
7
undergoes cyclization to heterocycle 4.
In summary, a thermally promoted synthesis of 3,5-
diketo esters via a Mukaiyama–Claisen reaction of 4H-1,3-
dioxin-4-one derivatives with silylated enolate nucleophiles
(d) Büttner, S.; Desens, W.; Michalik, D.; Langer, T. Eur. J. Org.
8
Chem. 2011, 6663. (e) Ilida, A.; Takai, K.; Okabayashi, T.; Misaki,
T.; Tanabe, Y. Chem. Commun. 2005, 3171. (f) Ilida, A.; Osada, J.;
Nagase, R.; Misaki, T.; Tanabe, Y. Org. Lett. 2007, 9, 1859.
has been developed. The desired oligocarbonyl compounds
were obtained in good yields. This methodology may find
applications in the synthesis of bioactive polyketides or
polyols.
(g) Raynolds, P. W.; Deloach, J. A. J. Am. Chem. Soc. 1984, 106,
4566.
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Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1525–1527