Palladium-Catalyzed Carbo-Aminative Cyclization of 1,6-Enynes: Access to Napthyridinone Derivatives

Abstract

Enynes have recently stimulated enormous attention toward paving the way to unique cascade cyclizations offering complex cyclic motifs from linear substrates. We describe herein a general approach to napthyridinones via the Pd-catalyzed annulation of 1,6-enynes with 2-iodoanilines. This protocol represents a rare carbo-aminative annulative cyclization via the 6-endo-trig mode, subduing the well-documented exo-trig/dig cyclizations. The regioselective aryl palladation of alkyne followed by Heck-type intramolecular coupling before isomerization were key in realizing this cascade.

Rhodium-Catalyzed Coordination-Assisted Regioselective and Migratory Three-Point Double Annulation of o-Alkenyl Phenols with Tertiary Propargyl Alcohols

“…Interestingly, a selective concomitant aromatic ring expansion was observed in one case to form a rearranged fused adduct (Scheme c). We ,,, herein disclose a totally contrasting mode of annulation of o -alkenyl phenol with tertiary propargyl alcohols − (Scheme d). The initial annulation afforded exclusively a single regioisomer.…”

Recent Advances in Cyclization Reactions of 1,6‐Enynes

“…The Pd-catalyzed protocol, which possessed good functional group compatibility, provided access to N-heterocycles employing 1,6-enynes and 2-iodoanilines as the starting materials (Scheme 67). [54] On the basis of a series of control experiments, a conceivable mechanism is proposed in Scheme 68. The Pd(0) species is generated in situ from PdCl In 2022, an enantioselective halopalladation cyclization of 1,6-enynes was reported by the Jiang group, leading to the construction of a range of optically active α-chloromethylene-γ-butyrolactones in good to excellent yields by intramolecular chlorine transfer (Scheme 69).…”

“…The Pd‐catalyzed protocol, which possessed good functional group compatibility, provided access to N ‐heterocycles employing 1,6‐enynes and 2‐iodoanilines as the starting materials (Scheme 67). [54] …”

Photoinduced arylative formal 4-endo-dig cyclization of propargyl alcohols/amines to access strained heterocycles

“…We recently reported a method for the synthesis of fused oxetanes through Pd-catalyzed oxidative/annulative cyclization of propargyl alcohols with biphenyl amines. 12 Herein, 13 we demonstrate a totally contrasting and green approach for the synthesis of strained and small ring systems (oxetanes and azetidines) 14 via formal 4- endo-dig cyclization of propargyl alcohols/amines initiated by visible light-mediated annulation with benzoquinones. 15,16 The reaction does not require the assistance of any catalyst, reagent, or heat.…”