Synthesis of Eight- to Ten-Membered Ring
Ethers
Elena Soriano and Jose ´ Marco-Contelles
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
2 Methods and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
2.1 Metathesis to Form Carbon–Carbon Double Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
2.2 Cyclization to Form Carbon–Carbon Single Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344
2.3 Cyclization to Form Carbon–Oxygen Single Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
2.4 Ring Expansion and Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
2.5 Ring Opening and Rearrangement of Epoxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360
3 Conclusion and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
Abstract Polyfunctionalized medium-sized cyclic ethers have attracted much
attention from synthetic and medicinal chemists due to their presence in a wide
range of biologically active natural products. Accordingly, much attention has been
focused on efficient approaches towards these systems. However, their synthesis is
generally difficult via standard cyclization methods due to the ring size. In this
chapter, we summarize the most important and successful approaches and strategies
to prepare eight- to ten-membered oxacycles, including oxocanes, oxonanes, and
oxecanes, and their applications to the synthesis of natural products containing
these structural motifs.
E. Soriano (*)
Sı ´ntesis, Estructura y Propiedades de Compuestos Orga ´nicos (SEPCO), Instituto de Quı ´mica
Orga ´nica General (CSIC), Juan de la Cierva, 3, 28006 Madrid, Spain
e-mail: esoriano@iqog.csic.es
J. Marco-Contelles
Laboratorio de Quı ´mica Me ´dica, Instituto de Quı ´mica Orga ´nica General (CSIC), Juan de la
Cierva, 3, 28006 Madrid, Spain
e-mail: iqoc21@iqog.csic.es
J. Cossy (ed.), Synthesis of Saturated Oxygenated Heterocycles II, Topics in
Heterocyclic Chemistry 36, DOI 10.1007/978-3-642-41470-1_2,
© Springer-Verlag Berlin Heidelberg 2014
321
Ethers
Elena Soriano and Jose ´ Marco-Contelles
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
2 Methods and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
2.1 Metathesis to Form Carbon–Carbon Double Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
2.2 Cyclization to Form Carbon–Carbon Single Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344
2.3 Cyclization to Form Carbon–Oxygen Single Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
2.4 Ring Expansion and Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
2.5 Ring Opening and Rearrangement of Epoxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360
3 Conclusion and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
Abstract Polyfunctionalized medium-sized cyclic ethers have attracted much
attention from synthetic and medicinal chemists due to their presence in a wide
range of biologically active natural products. Accordingly, much attention has been
focused on efficient approaches towards these systems. However, their synthesis is
generally difficult via standard cyclization methods due to the ring size. In this
chapter, we summarize the most important and successful approaches and strategies
to prepare eight- to ten-membered oxacycles, including oxocanes, oxonanes, and
oxecanes, and their applications to the synthesis of natural products containing
these structural motifs.
E. Soriano (*)
Sı ´ntesis, Estructura y Propiedades de Compuestos Orga ´nicos (SEPCO), Instituto de Quı ´mica
Orga ´nica General (CSIC), Juan de la Cierva, 3, 28006 Madrid, Spain
e-mail: esoriano@iqog.csic.es
J. Marco-Contelles
Laboratorio de Quı ´mica Me ´dica, Instituto de Quı ´mica Orga ´nica General (CSIC), Juan de la
Cierva, 3, 28006 Madrid, Spain
e-mail: iqoc21@iqog.csic.es
J. Cossy (ed.), Synthesis of Saturated Oxygenated Heterocycles II, Topics in
Heterocyclic Chemistry 36, DOI 10.1007/978-3-642-41470-1_2,
© Springer-Verlag Berlin Heidelberg 2014
321