Grubbs catalysts in intramolecular carbene C(sp³)–H insertion reactions from α-diazoesters

Abstract

Grubbs complexes are also useful catalysts to chemoselectively promote intramolecular carbene C–H insertion from amino-tethered α-diazoesters to give pyrrolidines.

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

“…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.…”

“…The process affording the same tetrahydroquinoline (2a) from 1a meditated by the first-generation Grubbs catalyst ( Table 1, entry 3) was studied next. Similar to the above Pdmediated transformation and related sp 3 -CÀHa ctivationsp romotedb yt his Ru catalyst, [20] our calculations also startf rom the analogous ruthenacarbene INT0-Ru (in which the bulky tricyclohexylphosphine (PCy 3 )p hosphine ligand wasr eplaced by PMe 3 ;F igure 3). [25] We located as imilar Ru-assisted 1,6-H migration reaction; however,t he rather high barrier required to reach the corresponding transition state (TS1''-Ru, DG ¼ 6 = 56.4 kcal mol À1 )m akes this reaction unfeasible.…”

“…More recently, we reported the first example of an unprecedented non‐metathetic chemistry of Grubbs complexes, which were applied to promote the carbene sp 3 ‐C−H insertion of γ‐dialkylamino‐α‐diazoesters to form pyrrolidines (Scheme c) …”

“…[18] More recently,w er eported the first example of an unprecedentedn on-metathetic chemistry of Grubbs complexes, [19] which were appliedt op romote the carbene sp 3 -CÀHi nser-tion of g-dialkylamino-a-diazoesters to form pyrrolidines (Scheme 1c). [20] Continuing our program of developing efficient methodologies for the synthesis of nitrogen heterocycles, [21] we sought to explore the construction of tetrahydroquinolines by TM-catalyzed decomposition of g-anilino-a-diazoesters (Scheme 1d). The extensive bioactivity of tetrahydroquinolines, including antitumor, antiviral, antibacterial,a ntimalarial, and antifungal activity,i sw ell documented, and the development of efficient procedures for their preparation is therefore of considerable interest.…”

[Co(TPP)]‐Catalyzed Formation of Substituted Piperidines

“…Recently, the group of Zhang reported the synthesis of chiral pyrrolidines and related five‐membered ring compounds, starting from N‐tosylhydrazone derivatives and catalyzed by cobalt(II) complexes of D 2 ‐symmetric chiral amidoporphyrins (Scheme A) . Related reactions leading to five‐membered N‐heterocycles through carbene insertion into activated C−H bonds, mediated by Grubbs‐type catalysts, were recently disclosed by the group of Fernández …”