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Iron‐Catalyzed Friedel–Crafts Benzylation with Benzyl TMS Ethers at Room Temperature
Author(s) -
Sawama Yoshinari,
Shishido Yuko,
Kawajiri Takahiro,
Goto Ryota,
Monguchi Yasunari,
Sajiki Hironao
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201302862
Subject(s) - friedel–crafts reaction , benzyl alcohol , chemistry , ether , catalysis , organic chemistry , nucleophilic substitution , williamson ether synthesis , nucleophile , alcohol , benzyl chloride , medicinal chemistry
Friedel–Crafts benzylations between unactivated arenes and benzyl alcohol derivatives are clean and straightforward processes to construct biologically useful di‐ and tri‐arylmethanes. We have established an efficient iron‐catalyzed Friedel–Crafts benzylation method at room temperature that uses benzyl TMS ethers as substrates, which are poorly reactive under common nucleophilic substitution conditions. The reaction seems to progress through iron‐catalyzed self‐condensation of the benzyl TMS ether to the corresponding dibenzylic ether. The use of excess arene relative to benzyl TMS ether produced mono‐benzylated arene (di‐ and tri‐arylmethane products), whereas the use of excess benzyl TMS ether versus arene provided bis‐benzylated arene (polyarylated products) in high yields and regioselectivities. In previous methods, the latter double Friedel–Crafts benzylations hardly proceed.