Synthesis of 1‐Aminoindenes through Aza‐Prins‐Type Cyclization

Abstract

An acid-catalyzed aza-Prins-type endo cyclization of 2-alkenylbenzaldehydes with BocNH or aniline derivatives through in situ generation of iminium intermediates has been developed, and various 1-aminoindene derivatives were readily obtained. The first catalytic asymmetric variant of the present reaction has also been demonstrated.

Access to Chiral 1-Aminoindene Derivatives by Asymmetric Brønsted Acid Catalysis

“…1C) reported the first asymmetric Brønsted acid-catalyzed aza-Prins type endo cyclization of 2-alkenylbenzaldehydes with BocNH2 or anilines through in situ generation of iminium intermediates to generate chiral 1-aminoindenes, however, only five examples have been demonstrated and moderate to good ee values were obtained. 11 Recently, our research group reported a BINOLderived chiral N-triflyl phosphoramide (NTPA) catalyzed enantioselective intramolecular iminium ion cyclization reaction Click here to insert a dedication.…”

“…the generation of iminium intermediates in situ to give chiral 1-aminoindenes (Figure 1C); however, only five examples were examined, and moderate to good ee values were obtained. 11 We recently reported an enantioselective intramolecular iminium-ion cyclization reaction of 2-alkenylbenzaldimines catalyzed by a BINOL-derived chiral N-triflylphosphoramide (NTPA) for the synthesis of chiral 1-aminoindenes and tetracyclic 1-aminoindanes. 12 We commenced our reaction-condition screening by investigating a variety of chiral Brønsted acid catalysts PA1-8 for cyclization of the model substrate 1a in toluene at 60 °C (Scheme 1).…”

“…10 Moreover, Kano, Maruoka, and co-workers reported the first asymmetric Brønsted acid-catalyzed aza-Prins-type endo -cyclization of 2-alkenylbenzaldehydes with BocNH 2 or anilines through the generation of iminium intermediates in situ to give chiral 1-aminoindenes (Figure 1 C); however, only five examples were examined, and moderate to good ee values were obtained. 11 We recently reported an enantioselective intramolecular iminium-ion cyclization reaction of 2-alkenylbenzaldimines catalyzed by a BINOL-derived chiral N -triflylphosphoramide (NTPA) for the synthesis of chiral 1-aminoindenes and tetracyclic 1-aminoindanes. 12…”

“…Loss of a proton from intermediate Int-2 gives the final chiral 1-aminoindene products 2 . 11 Alternatively, we postulate that an imino-Nazarov cyclization is also a possible pathway. In this, intermediate Int-1 is transformed into its resonance structure Int-3 , which undergoes an electrocyclic reaction to give Int-2 , which undergoes further conversion to product 2 , as above.…”

The Aza-Prins Reaction of 1,2-Dicarbonyl Compounds with 3-Vinyltetrahydroquinolines: Application to the Synthesis of Polycyclic Spirooxindole Derivatives

“…The control of the stereochemistry in the aza-Prins reaction has been recently studied by several groups. Maruoka and Kano reported the asymmetric aza-Prins-type cyclization in the presence of chiral phosphoric acid, 5 and Dobbs reported the stereoselective aza-Prins reaction by introducing a chiral auxiliary to the homoallylamine. 2c , 6 The enantiopure nitrogen heterocycles synthesized by these studies are expected to be important intermediates for the synthesis of biologically active molecules.…”