Reaction pathways for ambident aryloxide O- and C-nucleophiles in SNAr displacement versus Meisenheimer complex formation with picryl halides. Stereoelectronic effects on regioselectivity

Article abstract of DOI:10.1002/(SICI)1099-1395(199608)9:8<515::AID-POC816>3.0.CO;2-5

To probe regioselectivity in Meisenheimer complexation, the reaction of two picryl halides (PiX where X = F, Cl) with a series of aryloxide nucleophiles (phenoxide, 2,4,6-trimethylphenoxide and 2,6-di-t-butylphenoxide) were monitored by ₁H NMR spectroscopy in dimethyl sulphoxide at ambient temperature and in acetonitrile-dimethoxyethane(MeCN-DME) at low temperature (-40°C). The reactions of both picryl halides with the ambident (oxygen versus carbon) nucleophile, phenoxide ion (PhO^-), and 2,4,6-trimethylphenoxide (mesitoxide, MesO^-) leads to clean S_NAr displacement of X via the oxygen site of the nucleophile to form the respective aryl picryl ethers, i.e. phenyl picryl ether (3a) and mesityl picryl ether (3b). Meisenheimer complex formation at C-1 or C-3 was not detected in these systems. With 2,6-di-t-butylphenoxide (2,6-DTBPhO^-), where oxygen attachment of the aryloxide is precluded by the bulky ortho t-butyl groups, para-carbon attachment was found to occur at C-1 to give picryl 2,6-di-t-butylphenol (3d) in competition with C-attack at C-3 to give the respective carbon-bonded Meisenheimer complexes [X = Cl (4) and X = F (5)]. For both picryl halides, the ratio of 3d, the product of C-1 attack, to the product of C-3 attack, 4 or 5, was roughly 7:1. These findings are considered with regard to the nucleofugality of the halide, X, steric hindrance (F-strain) to attack by the aryloxides at the various positions and stereoelectronic stabilization of C-1 adducts afforded by n → σ* donation.