Synthesis of 7-Oxabicyclo[2.2.1]heptane
and Derivatives
Antonio J. Moreno-Vargas and Pierre Vogel
Contents
1 Introduction . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . 142
2 Preparation of 7-Oxabicyclo[2.2.1]heptane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
3 Natural 7-Oxabicyclo[2.2.1]heptanes and Bioactive Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . 144
3.1 Cantharidin and Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
3.2 Monoterpenoid 7-Oxabicyclo[2.2.1]heptanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
3.3 Sesquiterpenoid 7-Oxabicyclo[2.2.1]heptanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
3.4 Diterpenoid 7-Oxabicyclo[2.2.1]heptanes and Prostaglandin Analogues . . . . . . . . . . . 150
3.5 Triterpenoid 7-Oxabicyclo[2.2.1]heptanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
3.6 Carotenoids with 7-Oxabicyclo[2.2.1]heptyl End Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
4 Preparation of 7-Oxabicyclo[2.2.1]heptane Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
4.1 Non-Diels–Alder Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
4.2 Diels–Alder Reaction of Furans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
5 Reactions of 7-Oxabicylo[2.2.1]heptanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
5.1 Acid-Induced Ethereal Bridge Nucleophilic Displacements . . . . . . . . . . . . . . . . . . . . . . . . 167
5.2 Base-Induced Ethereal Bridge Opening of 7-Oxabicyclo[2.2.1]heptanes . . . . . . . . . . 170
5.3 Reductive Ethereal Ring Opening of 7-Oxabicyclo[2.2.1]heptanones . . . . . . . . . . . . . . 172
5.4 Chalconide and Halide/Metal Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
5.5 Cleavage of Carbon–Carbon Bonds of 7-Oxabicyclo[2.2.1]heptan-2-ones . . . . . . . . . 177
6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
Abstract Nature provides a number of 7-oxanorbornanes (7-oxabicyclo[2.2.1]
heptanes), many of them with interesting biological activity. There are several
routes to their synthesis; the most common remains the Diels–Alder reaction of
furans with olefinic or acetylenic dienophiles. Several 7-oxanorbornane derivatives
A.J. Moreno-Vargas
Facultad de Quı ´mica, Departamento de Quı ´mica Orga ´nica, Universidad de Sevilla,
C/Prof. Garcı ´a Gonza ´lez, 1, 41012 Sevilla, Spain
P. Vogel (*)
LGSA, EPFL, 1015 Lausanne, Switzerland
e-mail: pierre.vogel@epfl.ch
J. Cossy (ed.), Synthesis of Saturated Oxygenated Heterocycles I, Topics in
Heterocyclic Chemistry 35, DOI 10.1007/978-3-642-41473-2_4,
© Springer-Verlag Berlin Heidelberg 2014
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