Intermolecular C–H activation at benzylic positions: synthesis of (+)-imperanene and (−)-α-conidendrin

Catalytic asymmetric C–H insertion reactions of α-diazocarbonyl compounds

“…Lower reaction temperatures were found to favour increased enantioselectivity. 64,163,164 Improvements in both yields and enantioselectivity were noted upon changing from an electron-donating (X = OMe) to an electron-withdrawing (X = Cl) aromatic substituent for aryl diazoacetate precursors, 67,163,165,166 as had previously been noted in intramolecular C-H insertion studies. 93,107 As seen in Scheme 16, insertion is favoured at positions α to oxygen, 62,167,168 with the same preference also holding true for insertion adjacent to nitrogen, 63,65,124,164,169,170 and at benzylic 64,171 and allylic 20,[172][173][174] sites.…”

“…166 No C-H insertion is observed at the methyl group adjacent to oxygen in 1-methoxy-4-methylbenzene 123 [Scheme 18(b)], due to probable delocalisation of the electron lone pairs of oxygen into the benzene ring. 163 The p-methoxy group in this reaction serves the function of sterically protecting the ring from possible cyclopropanation, as was observed for the reaction of methyl p-bromophenyldiazoacetate and toluene. Steric protection of this kind may also be achieved with p-alkyl substituents, and, accordingly, the reaction of 120 and p-xylene 124 generates the corresponding C-H activation product 125 in 70% yield and 74% ee [Scheme 18(c)].…”

“…Steric protection of this kind may also be achieved with p-alkyl substituents, and, accordingly, the reaction of 120 and p-xylene 124 generates the corresponding C-H activation product 125 in 70% yield and 74% ee [Scheme 18(c)]. 163 This strategy of selective methyl C-H insertion has been successfully applied to the total syntheses of the natural products, (+)-imperanene, 163 and (-)-α-conidendrin, 163 and to the synthesis of the enantiomers of the antidepressant, venlafaxine. 164 Despite the electronic preferences to the contrary, 6,7 regioselective intermolecular C-H insertion into tertiary bonds is a generally difficult process.…”

Carbenoid insertions into benzylic C–H bonds with heterogeneous copper catalysts

“…As expected from the reactivity order, the primary benzylic position of toluene was completely inactive to insertion, in contrast with Rh catalysts. 20,24,25 …”

“…Davies has described the positive effect of para substitution to protect benzene ring, 20,21,24 and at the same time electron donating groups have shown to activate ethylbenzene. 20 In view of that, the effect of substitution has been studied in the case of cumene with pBrPDA using heterogeneous copper catalysts (Scheme 2).…”