Palladium-Catalyzed [5 + 2] Heteroannulation of Phenethylamides with 1,3-Dienes to Dopaminergic 3-Benzazepines

Abstract

Phenethyltriflamides react with 1,3-dienes upon treatment with a catalytic amount of Pd(OAc)2 and Cu(OAc)2/O2 as oxidant to afford chemo-, regio-and diastereoselectively 2,3,4,5-tetrahydro-1H-benzo[d]azepines (3-benzazepine derivatives) in good to excellent yields. A DFT study of the [5+2] heteroannulation suggests a mechanistic pathway starting by the formation of the six-membered palladacycle

Recent Advances in Transition‐Metal‐Catalyzed Oxidative Annulations to Benzazepines and Benzodiazepines

“…Very recently, Saá and co-workers reported the Pdcatalyzed (5 + 2) heteroannulation of phenethyltriflamides 30 and 1,3-dienes 7 to yield 3-benzazepines 31 (Scheme 12). [49] The proposed mechanism for this transformation was supported by DFT calculations and involves an initial o-CÀ H activation (via CMD) with the generation of the six-membered palladacycle I (cis-PdX 2 L 2 ). Then, coordination of the less substituted olefin of the 1,3-diene followed by a 1,2-migratory insertion yields the π-allylic intermediate II.…”

“…3-Benzazepines have been synthesized under Pd catalysis using nitrogenated substrates bearing L-Type (amines) and X-Type (triflamides) DGs via (5 + 2) annulations. [48,49] In addition, they have been also synthesized under Rh catalysis in a tandem (3 + 2)/(5 + 2) annulation of vinyl iminocarbenes and alkynes, [50] and in a formal (5 + 2) annulation of yne-enoates and boronic acids ( Figure 5). [51] In 2014, Ariza and co-workers reported the Pdcatalyzed (5 + 2) annulation of α,α-disubstituted phenethylamines 28 with allenes 10 to give 3-benzazepines 29 (Scheme 11).…”

“…3‐Benzazepines have been synthesized under Pd catalysis using nitrogenated substrates bearing L‐Type (amines) and X‐Type (triflamides) DGs via (5+2) annulations [48,49] . In addition, they have been also synthesized under Rh catalysis in a tandem (3+2)/(5+2) annulation of vinyl iminocarbenes and alkynes, [50] and in a formal (5+2) annulation of yne‐enoates and boronic acids (Figure 5).…”

Enantioenriched α-Vinyl 1,4-Benzodiazepines and 1,4-Benzoxazepines via Enantioselective Rhodium-Catalyzed Hydrofunctionalizations of Alkynes and Allenes

“…20g However, only a single benzofused seven-membered azaheterocycle, 4-vinyl-tetrahydrobenzo[ b ][1,5]-benzoxazepine, could be synthesized in low chemical yield but good ee using the same protocol. 21 Herein, we report a Rh-catalyzed hydrofunctionalization of internal alkynes and allenes to benzofused seven-membered heterocycles employing substrates bearing N–Ar groups as nitrogenated nucleophiles. 21g The enantioselective hydroamination to 3-vinyl-1,4-BZDs and hydroalkoxylation to 3-vinyl-1,4-BZO is conveniently disclosed ( Scheme 1 ).…”

“…Recently, the group of Breit has developed an intensive study of the Rh-catalyzed hydrofunctionalizations to afford enantioenriched α-vinylated five- and six-membered azaheterocycles (through NTs nucleophiles) , and tetrahydropyrans (Scheme c) . However, only a single benzofused seven-membered azaheterocycle, 4-vinyl-tetrahydrobenzo­[ b ]­[1,5]-benzoxazepine, could be synthesized in low chemical yield but good ee using the same protocol . Herein, we report a Rh-catalyzed hydrofunctionalization of internal alkynes and allenes to benzofused seven-membered heterocycles employing substrates bearing N–Ar groups as nitrogenated nucleophiles .…”