Regioselectivity of Meisenheimer complexation in reaction of oxygen-centred nucleophiles with picryl aryl ethers: Polar vs. SET mechanisms

Picryl alkyl ethers react with hydroxide and methoxide ions to give regioisomeric Meisenheimer (anionic σ-) adducts; the C-3 adduct is kinetically favoured and the C-1 adduct is thermodynamically favoured (K3T1 behaviour). In the current 400 MHz NMR spectroscopic study of the reactions of two picryl aryl ethers, picryl phenyl ether (PicOPh, 1) and picryl mesityl ether (PicOMes, 2), the charge localized nucleophiles OH – and MeO – displayed the same K3 regioselectivity as found with picryl alkyl ethers; attachment at C-1 leads to S N Ar displacement of the aryloxide. In contrast, phenoxide (PhO – ) and the sterically demanding 2,4,6-trimethylphenoxide (mesitoxide, MesO – ) react with 1 and 2 to form the C-1 O-adduct as the product of kinetic control (i.e., K1 behaviour). These reactions were studied at low temperature (–40°C in acetonitrile-d 3 :dimethoxyethane-d 10 1:1) and as a function of increasing temperature (–40°C to ambient). On the thermodynamic side, the C-1 PhO – O-adduct of 1 is also the more stable of the possible phenoxide O-adducts; it shows T1 regioselectivity within the manifold of O-adducts (K1T1), but the C-3 C-adduct (via para-attack of PhO – ) is the ultimate thermodynamic product. The C-1 O-adducts formed by MesO – with 1 or 2 give way with time (or temperature increase) in favour of their C-3 regioisomers or a C-1,3-O-diadduct. Mesitoxide, therefore, displays K1T3 regioselectivity. Stereoelectronic stabilization is discussed as a factor influencing T1 regioselectivity in O-adduct formation. Frontier molecular orbital (FMO) interactions between the HOMO of the nucleophile and the LUMO of the picryl ether may play a role in the K1 preference of aryloxides. An alternative argument is presented based on a single electron (radical) transfer (SET) pathway for the aryloxide nucleophiles rather than the polar (S N Ar) pathway for hydroxide and methoxide. The SET pathway also predicts a kinetic preference for C-1, as the C-1 position is of higher spin density than C-3 in the radical anion of the picryl ether and thus should be the preferred site for coupling by the aryloxide radical.Key words: anionic Meisenheimer adducts, regioselectivity, kinetic–thermodynamic control, FMO, stereoelectronic stabilization, single electron transfer (SET).

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