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

Abstract

The intramolecular carbene C–H insertion of α‐diazo‐α‐(methoxycarbonyl)acetamides leading to β‐lactams is effectively catalyzed by palladium complexes. It is found that although Pd0 catalysts typically produce mixtures of β‐lactams together with Buchner‐type reaction products, the use of PdII catalysts results in highly chemoselective transformations. According to DFT calculations, this insertion reaction occurs stepwise and involves an unprecedented PdII‐promoted Mannich‐type reaction through a metallacarbene‐induced zwitterionic intermediate.

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

“…With these substrates, the regioselectivity of insertion( 5-X/7-X ratio) seems to be controlled by ac ombination of steric and electronic effects. Thus, similar moderate regioselectivities were obtained in the reactions of anilines 1e and 1f, which had m-methoxy and m-chloros ubstituents, respectively, with either [{Pd(IMes)(NQ)} 2 ]o rRu-1 ( Table 1, entries [15][16][17][18][19]. However,w ith m-iodo-substituted aniline 1g,t he Pd 0 catalyst afforded betterr egioselectivity than that of Ru-1 ( Table 1, entries 20 and 21).…”

“…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) …”

“…[13] In recent years, we have been exploring the use of different TM catalysts as alternatives to the widely used Rh II complexes [14] for carbene CÀHi nsertion of a-diazocarbonyl compounds. [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.…”

Site Selectivity in Pd-Catalyzed Reactions of α-Diazo-α-(methoxycarbonyl)acetamides: Effects of Catalysts and Substrate Substitution in the Synthesis of Oxindoles and β-Lactams

“…This allowed us to develop a one-pot methodology to prepare 3-(chloroethyl)oxindoles by means of a sequential C–H insertion/alkylation process (Equation (a) in Scheme 2). More recently, we have described the synthesis of β-lactams by Pd(II)-catalyzed carbene Csp 3 –H insertion of α-diazo-α-(methoxycarbonyl)acetamides (Equation (b) in Scheme 2) [56].…”