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2‐, 3‐, and 4‐(Trifluoromethoxy)phenyllithiums: Versatile Intermediates Offering Access to a Variety of New Organofluorine Compounds
Author(s) -
Castagnetti Eva,
Schlosser Manfred
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200102)2001:4<691::aid-ejoc691>3.0.co;2-a
Subject(s) - phenyllithium , chemistry , electrophile , nucleophile , butyllithium , halogen , lithium (medication) , metalation , medicinal chemistry , organic chemistry , stereochemistry , catalysis , medicine , alkyl , endocrinology
Consecutive treatment of (trifluoromethoxy)benzene with sec ‐butyllithium and electrophilic reagents affords previously inaccessible ortho ‐substituted derivatives in generally excellent yields. 2‐(Trifluoromethoxy)phenyllithium acts as the key intermediate. The 3‐ and 4‐isomers can readily be generated from the corresponding 3‐ and 4‐bromo precursors by halogen‐metal interconversion with butyllithium or tert ‐butyllithium. Upon trapping of the 2‐, 3‐ and 4‐(trifluoromethoxy)phenyllithiums with 11 different electrophiles the expected products were formed in generally high yields. Only the attempted nucleophilic addition of 2‐(trifluoromethoxy)phenyllithium to oxirane did not succeed. This failure is tentatively attributed to a lowering of the nucleophilicity by fluorine‐lithium interactions. Conformationally restricted analogs — i.e., 2,2‐difluoro‐1,3‐benzodioxol‐4‐phenyllithium and its 5‐fluoro‐ and 5‐bromo‐substituted congeners — did indeed react smoothly with oxirane, affording the adducts in ordinary yields.