Palladium-catalysed intramolecular carbenoid insertion of α-diazo-α-(methoxycarbonyl)acetanilides for oxindole synthesis

Abstract

A novel, selective palladium-catalysed carbenoid C(aryl)-H insertion of α-diazo-α-(methoxycarbonyl)acetanilides leading to oxindoles is described.

Palladium Catalysis in the Intramolecular Carbene C–H Insertion of α‐Diazo‐α‐(methoxycarbonyl)acetamides to Form β‐Lactams

“…We also explored the palladium‐catalyzed carbene C–H insertion of α‐diazo‐α‐(methoxycarbonyl)acetanilides. We found that when using palladium catalysts the C–H insertion of such amides occurs selectively into the arylic Csp 2 –H to give the oxindole …”

Palladium‐ and Ruthenium‐Catalyzed Intramolecular Carbene CAr−H Functionalization of γ‐Amino‐α‐diazoesters for the Synthesis of Tetrahydroquinolines

“…To this end, we first explored the process involving 1 a , which, in the presence of [{Pd(IMes)(NQ)} 2 ], led to the formation of tetrahydroquinoline 2 a (Table , entry 2). Similar to related Pd 0 ‐mediated C−H insertions of α‐diazocarbonyl compounds, our calculations started from the corresponding pallada(0)–carbene intermediate INT0 , formed by the reaction of diazo compound 1 a and a model Pd 0 catalyst in which the bulky mesyl groups in the N‐heterocyclic carbene (NHC) ligand were replaced by phenyl groups. This species evolves into the seven‐membered palladacycle INT1 via transition state TS1 in a highly exergonic transformation (Δ G R =−25.3 kcal mol −1 ).…”

“…The examples in Ta bles1and 2, below,c onfirm the generality and functional group tolerance of these reactions. As observed in Ta ble 1, no competition from sp 3 -CÀHi nsertion was observed upon startingf rom para-a nd meta-substituted N-isopropylanilines ( meta-Substituted anilines 1e-i also underwent chemoselective sp 2 -C Ar ÀHf unctionalization to give the corresponding tetrahydroquinolines with either the Pd 0 or Ru-1 catalysts;t he latter once again afforded the highest reaction yields ( Table 1, entries [15][16][17][18][19][20][21][22][23][24][25]. With these substrates, the regioselectivity of insertion( 5-X/7-X ratio) seems to be controlled by ac ombination of steric and electronic effects.…”

“…In recent years, we have been exploring the use of different TM catalysts as alternatives to the widely used Rh II complexes for carbene C−H insertion of α‐diazocarbonyl compounds . In this context, we have reported that palladium catalysts efficiently promote carbene sp 2 ‐C Ar −H functionalization of α‐diazo‐β‐(methoxycarbonyl)acetanilides to form oxindoles through a sequential insertion/alkylation process (Scheme a) …”

“…[15] In this context, we have reported that palladium catalysts efficiently promote carbene sp 2 -C Ar ÀHf unctionalization of a-diazo-b-(methoxycarbonyl)acetanilidest of orm oxindoles throughasequential insertion/alkylation process (Scheme 1a). [16] Mechanistically,t his palladium-catalyzed insertion is clearly different from that of sp 2 -C Ar ÀHf unctionalization based on other TMs andi nvolves ap alladium-mediated 1,5-H migration followed by reductive elimination.…”