Transition Metal‐Catalysed Intramolecular Carbenoid C−H Insertion for Pyrrolidine Formation by Decomposition of α‐Diazoesters

Abstract

The use of Pd-, Rh(II)-and Ru(II)-based catalysts has been explored in the transition metalcatalysed intramolecular carbenoid CÀH insertion of a-diazoesters leading to pyrrolidines. Although the outcome of the reaction was highly substrate-dependent, in general, it was possible to control the chemoselectivity of the process towards pyrrolidines by adequate catalyst selection. The Pd(0)-catalysts were as efficient as [Rh(Ph 3 CCO 2 ) 2 ] 2 in promoting the C(sp 3 )ÀH insertion of ortho-substituted anilines. In contrast, for anilines bearing meta-and para-substituents, the Rh(II)-catalyst provided the best chemoselectivities and reaction yields. On the other hand, [Ru(p-cymene)Cl 2 ] 2 was the most efficient catalyst for the insertion reaction of the N-benzyl-N-phenyl and N,N-dibenzyl a-diazoesters, while the C(sp 3 )ÀH insertion of the N-benzylsulfonamide substrate was only promoted by [Rh(Ph 3 CCO 2 ) 2 ] 2 . According to density functional theory (DFT) calculations, the mechanism involved in the Pd(0)-and Ru(II)catalysed C(sp 3 )ÀH insertions differs considerably from that typically proposed for the Rh(II)-catalysed transformation. Whereas the Pd(0)-catalysed reaction involves a Pd-mediated 1,5-H migration from the C(sp 3 )ÀH bond to the carbenoid carbon atom leading to the formal oxidation of the transition metal, a Ru(II)-promoted Mannich type reaction involving a zwitterionic intermediate seems to be operative in the Ru(II)-catalysed transformation.

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

“…Interestingly, similar to the reaction of 1 j , tetrahydroquinoline formation was enhanced by the use of the Pd 0 catalyst, which afforded a 1:1 mixture of 2 k and 3 k . The high tendency of ortho ‐substituted aniline 1 k to undergo sp 3 ‐C−H functionalization, which is in line with our previously reported results, can be mainly ascribed to steric factors.…”

“…In our studies on the TM‐catalyzed reactions of γ‐amino‐α‐diazoesters, we found that the use of either [Pd 2 (dba) 3 ] (dba=dibenzylideneacetone) or [{Pd(IMes)(NQ)} 2 ] (IMes=1,3‐dimesitylimidazol‐2‐ylidene, NQ=1,4‐naphthoquinone) as catalysts to promote the decomposition of N ‐isopropyl α‐diazoester 1 a resulted in chemoselective functionalization at the arylic sp 2 ‐C−H bond to give tetrahydroquinoline 2 a (Table , entries 1 and 2). With these data in hand, we began by testing the use of Grubbs catalysts Ru‐1 , Ru‐2 , and Ru‐3 (Figure ) to promote the annulation reaction from 1 a .…”

“…[b] Catalyst (5 mol %) in DCE at reflux for 24 h. [c] Catalyst (2.5 mol %) in CHCl 3 at reflux for 24 h. [d] Catalyst (3 mol %) in CH 2 Cl 2 at reflux for 24 h. [e] See ref. for more information and Figure for structures.…”

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

“…Continuing our search for methodologies to enhance the synthetic potential of organopalladium chemistry, we have also investigated the versatility of palladium as a catalyst for the carbene C–H insertion. In this context, we reported that palladium catalysts are able to promote Csp 3 –H insertion of carbenes derived from α-diazoesters to form pyrrolidines through intramolecular Csp 3 –Csp 3 bond formation [53,54].…”

Asymmetric Synthesis of a 5,7-Fused Ring System Enabled by an Intramolecular Buchner Reaction with Chiral Rhodium Catalyst

“…7 Meanwhile, Buchner reaction of α-alkyl-αdiazoesters predominantly results in β-hydrogen migration to give α,β-unsaturated esters. 5,8 Despite extensive research on the intramolecular Buchner reaction, only one example demonstrated 5,7-fused ring formation with high chemoselectivity over β-hydride migration. 9,10 Moreover, its enantioselective variant has not been reported to our knowledge.…”