Geometry-dependent divergence in the gold-catalyzed redox cascade cyclization of o-alkynylaryl ketoximes and nitrones leading to isoindoles

Abstract

We report geometry-dependent cyclizations of o-alkynylaryl ketoximes and nitrones catalyzed by gold complexes. (E)-Ketoximes undergo N-attack to give isoquinoline-N-oxides. In sharp contrast, (Z)-ketoximes undergo unprecedented O-nucleophilic attack, followed by a redox cascade leading to a novel catalytic entry to isoindoles of diverse scope. The structure of an isoindole was unambiguously supported by X-ray crystallography. We demonstrated the generality of the isoindole synthesis from either (Z)-oximes or nitrones, and presented a mechanistic model of this redox cascade based on the reaction profiles of various substrates.

Isolation of Azomethine Ylides and Their Complexes: Iridium(III)‐Mediated Cyclization of Nitrone Substrates Containing Alkynes

“…Two distinct types of products have been reported in the redox cyclization of nitrone alkynes (Scheme ). Gold(I)‐catalyzed cyclization of nitrone alkynes 1 afforded isoindoles with the intermediacy of both an oxo carbenoid (type B ) and a five‐membered azomethine gold species (type C ) 3a. In contrast, TpRu II ‐catalyzed (Tp=tris(1‐pyrazolyl)borate) cyclization of such terminal alkynes yielded 3‐isoquinolones without forming intermedieate α‐oxo carbenoid species 4.…”

Stereoselective One‐Pot Synthesis of 1‐Aminoindanes and 5,6‐Fused Azacycles Using a Gold‐Catalyzed Redox‐Pinacol‐Mannich‐Michael Cascade

“…Using the current protocol, we were able to introduce various alkyl, alkenyl, alkynyl, and aryl groups at the quaternary center. Furthermore, the mechanistic uncertainty regarding the nature of the gold‐catalyzed redox chemistry of the nitrone became clear from the unambiguous involvement of the carbenoid and the imine 6b. 19 Further efforts in our laboratory are aimed at the target‐oriented synthesis of biologically active natural products utilizing this atom‐efficient, step‐, and redox‐economical approach 1d…”

Neue Ansätze für die Synthese von Metallcarbenen

“…Ebenso können Ketoxime zur Synthese der Isoindole 496 über die α‐Oxogoldcarben‐Intermediate 497 eingesetzt werden, deren Bildung eine N‐H‐Insertion und eine Eliminierung von Gold folgen (Schema a) . Shin et al.…”