Sequential Knoevenagel Condensation/Cyclization for the Synthesis of Indene and Benzofulvene Derivatives

Sequential Knoevenagel
condensation/cyclization leading to indene
and benzofulvene derivatives has been developed. The reaction of 2-(1-phenylvinyl)­benzaldehyde
with malonates gave benzylidene malonates, cyclized indenes, and dehydrogenated
benzofulvenes. The product selectivity depends on the reaction conditions.
The reaction with piperidine, AcOH in benzene at 80 °C for 1.5
h gave a benzylidene malonate in 75% yield as a major product. The
reactions with piperidine, AcOH in benzene at 80 °C for 17 h
and with TiCl4-pyridine at room temperature gave an indene
derivative in 56 and 79% yields, respectively, as a major product.
The reaction with TiCl4-Et3N gave a benzofulvene
in 40% yield selectively. Indene was transformed to a benzofulvene
derivative using the reagents TiCl4-Et3N and
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The reaction of variously
substituted aryl derivatives with dimethyl malonate gave indene and
benzofulvene derivatives. The reactions of 2-(1-phenylvinyl)­benzaldehyde
with Meldrum’s acid or malononitrile also gave cyclized compounds
in the suitable sequential or stepwise conditions. Furthermore, the
reaction of 2-arylbenzaldehydes has been investigated. The limitation
and scope have been described. The reaction mechanism of the cyclization
steps has been examined by DFT calculations.