Iron‐Catalyzed Friedel–Crafts Benzylation with Benzyl TMS Ethers at Room Temperature

Abstract

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.

Nickel-Catalyzed Asymmetric Hydroarylation of Vinylarenes: Direct Enantioselective Synthesis of Chiral 1,1-Diarylethanes

“…(R)-2-Fluoro-4-methoxy-1-(1-phenylethyl)benzene (3ap). 34 Prepared according to the general procedure from styrene 1a (26.0 mg, 0.25 mmol) and 3,4-methylenedioxyphenylboronic acid 2p (85.0 mg, 0.5 mmol). 3ap was isolated in high purity without further purification as a colorless oil in 85% yield (48.9 mg, 0.21 mmol).…”

Site‐Selective Iron(III) Chloride‐Catalyzed Arylation of 4‐Aryl‐4‐methoxy‐2,5‐cyclohexadienones for the Synthesis of Polyarylated Phenols

“…Reactions using inexpensive and versatile iron catalysts are accompanied by the generation of neutral waste materials, such as methanol, and are therefore regarded as clean. Recently, we revealed that FeCl 3 efficiently activates various benzylic positions, and several FeCl 3 ‐catalyzed transformations including Friedel–Crafts reactions,,, were reported. Methyl ethers derived from secondary and tertiary benzylic alcohols were also effectively activated by FeCl 3 to generate benzylic cation intermediates, via elimination of the methoxy group, which were coupled with nucleophiles, such as an azide ion, allylic moiety, or cyanide ion .…”

Gold-Catalyzed Benzylic Azidation of Phthalans and Isochromans and Subsequent FeCl₃-Catalyzed Nucleophilic Substitutions

“…[9][10][11][12][13] We have continuously investigated the iron [14][15][16][17][18][19][20] -or gold [21][22][23] -catalyzed activation at the benzylic position of various skeletons accompanied by the benzylic C-O bond cleavage. During these investigations, the benzylic position of phthalan (1; n=1) as a benzene fused cyclic ether was found to be directly azidated in the presence of a gold catalyst and trimethylsilylazide (TMSN 3 ) without the C-O bond cleavage to give the 1-azido phthalan (2) (Chart 1).…”