2.2.2 Metal-Mediated Cyclization
This method has been mainly applied with success for the synthesis of eight- and
nine-membered ethers. We will describe the syntheses of both sizes of cycles in a
common subsection. On the other hand, to our knowledge, this approach has not
been applied for the construction of ten-membered ring ethers.
Palladium-catalyzed cyclization implies the addition of the carbon–palladium
bond to another carbon-based center. Provided with easily accessible starting
materials and mild reaction conditions, carbopalladation has been viewed as one
of the most important methods in organic synthesis [130]. So ¨derberg et al. [131],
Majumdar et al. [132], and Chattopadhyay et al. [133] reported the synthesis of
medium-sized oxa-heterocycles by palladium-catalyzed intramolecular Heck reaction. As shown in Scheme 32, eight-membered ethers 157 were obtained from the
corresponding aryl bromide precursors 156 in good yields. Similar reactions were
also reported by Chattopadhyay et al. who described a sequential Claisen
rearrangement and intramolecular Heck cyclization to access benzoxocine- and
benzoxonine-fused coumarin and quinolone derivatives, such as 158–160, in moderate yields (Scheme 32) [133]. Thermally induced Claisen rearrangement of
7-allyloxycoumarin 161 gave 162, which upon alkylation with 2-iodobenzyl bromide gave the Heck precursor 163. Standard Heck conditions gave the 9-endo
Scheme 32 Intramolecular Heck reaction developed by So ¨derberg et al., Majumdar et al., and
Chattopadhyay et al.
346
E. Soriano and J. Marco-Contelles
This method has been mainly applied with success for the synthesis of eight- and
nine-membered ethers. We will describe the syntheses of both sizes of cycles in a
common subsection. On the other hand, to our knowledge, this approach has not
been applied for the construction of ten-membered ring ethers.
Palladium-catalyzed cyclization implies the addition of the carbon–palladium
bond to another carbon-based center. Provided with easily accessible starting
materials and mild reaction conditions, carbopalladation has been viewed as one
of the most important methods in organic synthesis [130]. So ¨derberg et al. [131],
Majumdar et al. [132], and Chattopadhyay et al. [133] reported the synthesis of
medium-sized oxa-heterocycles by palladium-catalyzed intramolecular Heck reaction. As shown in Scheme 32, eight-membered ethers 157 were obtained from the
corresponding aryl bromide precursors 156 in good yields. Similar reactions were
also reported by Chattopadhyay et al. who described a sequential Claisen
rearrangement and intramolecular Heck cyclization to access benzoxocine- and
benzoxonine-fused coumarin and quinolone derivatives, such as 158–160, in moderate yields (Scheme 32) [133]. Thermally induced Claisen rearrangement of
7-allyloxycoumarin 161 gave 162, which upon alkylation with 2-iodobenzyl bromide gave the Heck precursor 163. Standard Heck conditions gave the 9-endo
Scheme 32 Intramolecular Heck reaction developed by So ¨derberg et al., Majumdar et al., and
Chattopadhyay et al.
346
E. Soriano and J. Marco-Contelles