a decrease of the yield is coming from steric hindrance in the transition state.
In addition, the oxygen atoms seem not to interfere with the catalytic cycle. Eightmembered ring could be additionally attached to a sugar derivative in a spirocyclic
fashion as in 18 [45].
In order to limit the conformational freedom, appropriate positioning of the
substituents on the chain possessing the two olefinic groups can boost the cyclization. An oxygen-bearing vicinal stereocenter implies a suitable conformation of the
molecule for RCM. This conformation is also known as a gauche conformation.
Thus, Crimmins et al. reported the gauche effect of 1,2-dioxygen substituents to
facilitate the ring closure (Scheme 2). They proved the power of the RCM approach
by cyclizing chiral ethers. For instance, dienes 20, prepared by the Evans aldolization of glycolate imides with acrolein, followed by reduction and acetylation, were
cyclized to 21 with high yield by using the Grubbs catalyst 9. It was suggested that
the vicinal stereocenters in intermediate 20 induce a conformation where the
olefinic chains are positioned in a gauche conformation [46, 47].
2.1.1 Synthesis of Eight-Membered Oxacycles
The concept of the gauche effect has been applied to the synthesis of a key
precursor of (+)-laurencin by Crimmins and Choy [46]. When compounds 22 and
24 were exposed to [Ru]-catalyst 9, the corresponding RCM products 23 and 25
were obtained in good yields. The facile formation of the RCM product is due to the
two synergistic gauche effects by a pair of vicinal substituents on the dienes
(Scheme 3).
The marine red algae genus Laurencia specifically produces medium-ring ethers
as secondary metabolites, which typically possess a linear C15 carbon skeleton, one
or several halogen atoms adjacent to an ethereal oxygen atom, and an enyne or a
bromoallene side chain [48]. Since the first report of (+)-laurencin, 2, isolated from
Laurencia glandulifera by Irie et al. [3], numerous medium-ring ethers have been
isolated from Laurencia red algae. These Laurencia oxacycles have attracted the
Scheme 1 Grubbs catalyst 9 for the preparation of oxacyclene
Synthesis of Eight- to Ten-Membered Ring Ethers
325
In addition, the oxygen atoms seem not to interfere with the catalytic cycle. Eightmembered ring could be additionally attached to a sugar derivative in a spirocyclic
fashion as in 18 [45].
In order to limit the conformational freedom, appropriate positioning of the
substituents on the chain possessing the two olefinic groups can boost the cyclization. An oxygen-bearing vicinal stereocenter implies a suitable conformation of the
molecule for RCM. This conformation is also known as a gauche conformation.
Thus, Crimmins et al. reported the gauche effect of 1,2-dioxygen substituents to
facilitate the ring closure (Scheme 2). They proved the power of the RCM approach
by cyclizing chiral ethers. For instance, dienes 20, prepared by the Evans aldolization of glycolate imides with acrolein, followed by reduction and acetylation, were
cyclized to 21 with high yield by using the Grubbs catalyst 9. It was suggested that
the vicinal stereocenters in intermediate 20 induce a conformation where the
olefinic chains are positioned in a gauche conformation [46, 47].
2.1.1 Synthesis of Eight-Membered Oxacycles
The concept of the gauche effect has been applied to the synthesis of a key
precursor of (+)-laurencin by Crimmins and Choy [46]. When compounds 22 and
24 were exposed to [Ru]-catalyst 9, the corresponding RCM products 23 and 25
were obtained in good yields. The facile formation of the RCM product is due to the
two synergistic gauche effects by a pair of vicinal substituents on the dienes
(Scheme 3).
The marine red algae genus Laurencia specifically produces medium-ring ethers
as secondary metabolites, which typically possess a linear C15 carbon skeleton, one
or several halogen atoms adjacent to an ethereal oxygen atom, and an enyne or a
bromoallene side chain [48]. Since the first report of (+)-laurencin, 2, isolated from
Laurencia glandulifera by Irie et al. [3], numerous medium-ring ethers have been
isolated from Laurencia red algae. These Laurencia oxacycles have attracted the
Scheme 1 Grubbs catalyst 9 for the preparation of oxacyclene
Synthesis of Eight- to Ten-Membered Ring Ethers
325