2.5 Ring Opening and Rearrangement of Epoxides
The opening of epoxides and rearrangements have provided efficient ways to
construct medium-sized motifs during the total synthesis of many natural products.
The opening of epoxides with oxygen nucleophiles, with the exception of
polyepoxide-opening cascades [171], results in the oxygen of the epoxide acting
as an alcohol substituent of the formed ring. Additionally, there have been several
reported rearrangements of epoxide-containing substrates resulting in medium-ring
oxacycles in which the epoxide oxygen becomes the ethereal oxygen in the cycle.
Less commonly employed is the use of carbon nucleophiles for the opening of
epoxides, as this approach requires that the ethereal bond is prepared in a
separate step.
2.5.1 Epoxide Opening with Oxygen Nucleophiles
Despite that intramolecular cyclization of linear epoxy alcohols is a wellestablished method for the preparation of five- and six-membered rings and that
this method has been limited to the preparation of larger oxepane scaffolds, Suzuki
et al. have reported a method for the generation of a variety of medium-ring ethers
[172]. Thus, this group extensively investigated the Lewis acid-mediated opening
of epoxides and found that Eu(fod) 3 was suitable for the formation of eight- and
nine-cyclic ethers (Scheme 55). Later, they have successfully applied this strategy
to the preparation of several natural products such as (+)-(Z )-laureatin 266 [58] or
(+)-obtusenyne 6 [173], including examples of cyclization of highly functionalized
linear precursors.
Epoxide-opening processes [174] have been extensively used in the total synthesis of polycyclic ether natural product [175]. Based on the strategy of the
bromonium ion-assisted epoxide ring opening [176], Braddock et al. have shown,
with epoxide 267, the feasibility of an intramolecular bromonium ion-assisted
epoxide ring opening for the concurrent formation of seven-, eight-, and ninemembered ring ethers corresponding to halogenated medium-ring ethers of metabolites from Laurencia species (Scheme 56). This constitutes for the first time the
access to a medium ring of any of these natural products by a nonenzymatic
bromonium-induced cyclization process from a linear precursor [177].
Gagne ´ et al. have developed a method to generate polyether skeletons from
allene–epoxide cascade reaction promoted by Au(I) [178]. For instance, allenyl
epoxide 271 provided the 9-endo product 272 as a single diastereoisomer under
treatment with (PhO) 3 PAuCl and AgOTf (Scheme 57). In this example the methyl
group positioning on the epoxide is controlling the ring-opening regiochemistry.
360
E. Soriano and J. Marco-Contelles
The opening of epoxides and rearrangements have provided efficient ways to
construct medium-sized motifs during the total synthesis of many natural products.
The opening of epoxides with oxygen nucleophiles, with the exception of
polyepoxide-opening cascades [171], results in the oxygen of the epoxide acting
as an alcohol substituent of the formed ring. Additionally, there have been several
reported rearrangements of epoxide-containing substrates resulting in medium-ring
oxacycles in which the epoxide oxygen becomes the ethereal oxygen in the cycle.
Less commonly employed is the use of carbon nucleophiles for the opening of
epoxides, as this approach requires that the ethereal bond is prepared in a
separate step.
2.5.1 Epoxide Opening with Oxygen Nucleophiles
Despite that intramolecular cyclization of linear epoxy alcohols is a wellestablished method for the preparation of five- and six-membered rings and that
this method has been limited to the preparation of larger oxepane scaffolds, Suzuki
et al. have reported a method for the generation of a variety of medium-ring ethers
[172]. Thus, this group extensively investigated the Lewis acid-mediated opening
of epoxides and found that Eu(fod) 3 was suitable for the formation of eight- and
nine-cyclic ethers (Scheme 55). Later, they have successfully applied this strategy
to the preparation of several natural products such as (+)-(Z )-laureatin 266 [58] or
(+)-obtusenyne 6 [173], including examples of cyclization of highly functionalized
linear precursors.
Epoxide-opening processes [174] have been extensively used in the total synthesis of polycyclic ether natural product [175]. Based on the strategy of the
bromonium ion-assisted epoxide ring opening [176], Braddock et al. have shown,
with epoxide 267, the feasibility of an intramolecular bromonium ion-assisted
epoxide ring opening for the concurrent formation of seven-, eight-, and ninemembered ring ethers corresponding to halogenated medium-ring ethers of metabolites from Laurencia species (Scheme 56). This constitutes for the first time the
access to a medium ring of any of these natural products by a nonenzymatic
bromonium-induced cyclization process from a linear precursor [177].
Gagne ´ et al. have developed a method to generate polyether skeletons from
allene–epoxide cascade reaction promoted by Au(I) [178]. For instance, allenyl
epoxide 271 provided the 9-endo product 272 as a single diastereoisomer under
treatment with (PhO) 3 PAuCl and AgOTf (Scheme 57). In this example the methyl
group positioning on the epoxide is controlling the ring-opening regiochemistry.
360
E. Soriano and J. Marco-Contelles