Rh(I)-Catalyzed Asymmetric Synthesis of 3-Substituted Isoindolinones through CO Gas-Free Aminocarbonylation

Abstract

A highly efficient and accessible synthesis of chiral 3-substituted isoindolinone frameworks is described. The synthesis involved the Rh(I)-catalyzed asymmetric arylation of boronic acids to 2-halobenzaldimines and the subsequent Rh(I)-catalyzed intramolecular aminocarbonylation of the resulting 2-halobenzylamines using an aldehyde as the carbonyl source. The method tolerates a variety of functional groups, yielding isoindolinone derivatives in moderate to high yields with high ee-values. In addition, two Rh(I)-catalyzed transformations could be efficiently accomplished in a one-pot sequence to give chiral isoindolinones by the simple addition of a ligand and an aldehyde after the Rh(I)-catalyzed asymmetric arylation.

Rh-Catalyzed Domino Addition–Enolate Arylation: Generation of 3-Substituted Oxindoles via a Rh(lll) Intermediate

“…This would allow efficient and catalytic access to diverse oxindole derivatives that exhibit numerous biological activities. 6 Although oxidative addition of Rh(I) is well documented, 7 only a limited number of examples involve oxidative addition into a carbon−halogen bond under mild conditions. In recent years, Chatani 8 and Cramer 9 have demonstrated the utility of Rh-catalyzed cascade processes involving oxidative addition of Rh(I) species to access diverse building blocks.…”

The Applications of (Para)formaldehyde in Metal‐Catalyzed Organic Synthesis

“…In 2007, Kakiuchi’s group gave an example of the Rh‐catalyzed carbonylative cyclization of N ‐tosyl(2‐bromobenzylamine) to form 2‐tosylisoindolin‐1‐one by using 10 equivalents of paraformaldehyde as the CO source (Scheme ) 76. In 2012, the same group reported the Rh(I)‐catalyzed asymmetric synthesis of 3‐substituted isoindolinones by using the same strategy (Scheme ) 77. Pentafluorobenzaldehyde was a superior aldehyde with respect to the higher yield, but paraformaldehyde was obviously more practical because it is much cheaper and more readily available.…”

<span>Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue.</span><span></span>

“…First, diastereoselective reactions implying the use of a chiral auxiliary resulted effectively in various optically pure compounds [10,[18][19][20]. Second, enantioselective syntheses of these bicylic lactams were performed by using chiral transition metal-or organo-catalysts which control the configuration of the trisubstituted carbon stereocenter alpha to the nitrogen [10,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Though various metal or organic catalysts were used to promote the aza-Michael reaction in different syntheses for the creation of nitrogen-carbon bonds, phase-transfer catalysts were less studied [see reviews [35][36][37][38] in intermolecular [39][40][41][42][43] and intramolecular [44][45][46] sequences.…”