Substrate-Dependent Regioselectivity: Pd/PTC Cooperatively Catalyzed Domino Heck/Allylation of Allenamides with α-Carbon of Carbonyl Compounds

Abstract

A Pd/phase-transfer catalyst cooperatively catalyzed domino Heck/allylation reaction is first reported, which represents interesting substrate-dependent regioselectivity. Under the same conditions, Ts-protected N-(2-iodophenyl)allenamides produced only linear allylation products, while Cbz, Ac, or Boc-protected N-(2-iodophenyl)allenamides and N-(2-iodobenzoyl)allenamides with various compounds generated branch allylation products with an exocylic CC bond and two vicinal stereocenters. Up-scale syntheses and diverse fused cyclization transformations of products were then carried out. The enantioselective version for the domino process was studied.

Synthesis of Substituted 1,2-Dihydroisoquinolines by Palladium-Catalyzed Cascade Cyclization–Coupling of Trisubstituted Allenamides with Arylboronic Acids

“…The reaction was initiated with the oxidative addition of the aryl bromide moiety of the allenamide 2 to palladium, generating arylpalladium intermediate A [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. This was followed by an intramolecular allene insertion process ( B ) to generate the π-allyl-palladium intermediate C [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. Then, ligand exchange of palladium complex C with hydroxide ion occurred, forming hydroxypalladium species D [ 39 ].…”

“…Allenamides are powerful and versatile synthetic building blocks in organic synthesis, extensively utilized as reaction substrates to produce a variety of synthetically useful organic molecules [ 23 , 24 ]. Among them, palladium-catalyzed cascade cyclization of ortho-haloaryl-substituted allenamides provides efficient approaches for the synthesis of N -heterocyclic compounds ( Scheme 1 , eq 1) [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. The key intermediate in this strategy is the π-allylpalladium species, which is generated by an oxidative addition and allene insertion sequence.…”

Synthesis of Substituted 1,2-Dihydroisoquinolines by Palladium-Catalyzed Cascade Cyclization–Coupling of Trisubstituted Allenamides With Arylboronic Acids

“…The reaction was initiated with the oxidative addition of the aryl bromide moiety of the allenamide 2 to palladium, generating arylpalladium intermediate A. This is followed by an intramolecular allene insertion process (B) to generate the π-allyl-palladium intermediate C [25][26][27][28][29][30][31][32][33][34][35][36][37]. Then ligand exchange of palladium complex C with hydroxide ion occurs, forming hydroxypalladium species D [39].…”

“…Allenamides are powerful and versatile synthetic building blocks in organic synthesis, extensively utilized as reaction substrates to produce a variety of synthetically useful organic molecules [23,24]. Among them, palladium-catalyzed cascade cyclization of ortho-haloarylsubstituted allenamides provides efficient approaches for the synthesis of N-heterocyclic compounds (Scheme 1, eq 1) [25][26][27][28][29][30][31][32][33][34][35][36][37]. The key intermediate in this strategy is the π-allylpalladium species, which is generated by an oxidative addition and allene insertion sequence.…”

Palladium-catalysed aryl/monofluoroalkylation of allenamides: access to fluoroalkyl indoles and isoquinolones

“…Diverse nucleophiles were applied to undergo the subsequent allylic substitution reaction, offering different opportunities for the difunctionalization of allenamides. 7 Representatively, dicarbofunctionalization processes were reported by Sato's, 8 Lin's, 9 Guo's, 10 Hoarau's, 11 Guo's, 12 and other groups, 13 using different carbon nucleophiles. For example, in 2018, Hoarau and co-workers reported a palladium-catalysed construction of isoquinolone-azole bisheterocyclic scaffolds through a C–H allylation reaction (Scheme 1b).…”