Due to their structural rigidity, spirocyclic compounds have attracted considerable attention from chemists. Among them, five-membered lactam-based spirocyclohexadiene belongs to an important spiro-skeleton, which is found in many bioactive molecules. However, the strategy to construct this class of spiro-skeletons is very limited. Meanwhile, it is challenging to achieve good control over the diastereoselectivity when constructing spirocyclic frameworks with adjacent stereocenters. To solve these challenging issues, in this work, a Pd-catalyzed regioselective [2+3] annulation of o-quinone methides with vinyloxazolidines was established, constructing five-membered lactam-based spirocyclohexadiene skeletons with adjacent quaternary carbon centers in moderate to good yields (48% to 98%) with excellent diastereoselectivities (all >95:5 dr). After establishing the optimal reaction condition, we evaluated the substrate scope of vinyloxazolidine and o-quinone methides in the [2+3] annulation. In general, all tested substrates exhibit good reaction efficiency to generate lactam-based spirocyclohexadienes in moderate to excellent yields with excellent diastereoselectivities. The successful one-mmol-scale reaction and downstream transformation demonstrated the potential synthetic applications of this transformation. Furthermore, preliminary studies on the catalytic asymmetric [2+3] cyclization reaction demonstrate that the catalytic system of Pd-chiral phosphine ligand could achieve some extent of enantiocontrol of the transformation. This transformation not only expands the application of o-quinone methides as two-atom synthons in annulation reactions but also provides a novel strategy for the efficient and highly diastereoselective construction of five-membered lactam-based spirocyclohexadiene architectures. The general procedure of the [2+3] annulation is as follows: To an oven-dried Schlenk-tube, vinyloxazolidine (30.9 mg, 0.1 mmol), o-quinone methide (30.7 mg, 0.12 mmol), Pd₂(dba)₃ (9.1 mg, 0.01 mmol), PPh₃ (2.6 mg, 0.01 mmol) and DCE (1.0 mL) were added under N₂ atmosphere. The reaction mixture was stirred at 50 ^oC for 16 h. After completion of the reaction, the reaction mixture was concentrated by vacuum, purified by silica gel chromatography (petroleum ether/ethyl acetate) to yield pure products.

Key words: annulation, o-quinone methides, chemoselectivity, diastereoselectivity, spiro-compound