Construction of Fused Polyheterocycles through Sequential [4 + 2] and [3 + 2] Cycloadditions

Abstract

A method for Pd-catalyzed aerobic oxidative reaction of quinazolinones and alkynes has been developed for sequential [4 + 2] and [3 + 2] cycloadditions to assemble a novel fused-polycyclic system containing tetrahydropyridine and dihydrofuran rings. The reaction process involves C-H and N-H bond functionalization for the formation of tetrahydropyridine and an oxygen radical cyclization for the dihydrofuran ring. This atom- and step-economical synthesis is highly efficient and has good substrate tolerance, which provides a new approach for the construction of polycyclic molecules with potential pharmaceutical interest.

Direct Construction of Diverse Polyheterocycles Bearing Pyrrolidinediones via Rh(III)‐Catalyzed Cascade C−H Activation/Spirocyclization

“…Cu (OAc) 2 in DMF were allowed to react at 90°C for 4 h, generating an unexpected product 3 a in 50% yield (entry 1). In addition, no products were obtained in the absence of either [RhCp*Cl 2 ] 2 , acetic acid, or oxidants (entries [16][17][18]. However, increasing the amount of AgSbF 6 to 20 mol% or decreasing it to 10 mol% did not improve the yield of 3 a (entries 5-6).…”

“…Further attempts to increase the yield of 3 a using different copper oxidants such as Cu(acac) 2 , CuCl 2 , CuO, and CuI were not successful (entries [12][13][14][15]. In addition, no products were obtained in the absence of either [RhCp*Cl 2 ] 2 , acetic acid, or oxidants (entries [16][17][18]. In particular, with Cu(II) as a promoter and oxidant, the desired product 3 a was not formed (entry 16).…”

“…[13] Transition-metal-catalyzed CÀ H activation has received much attention in organic synthesis in the past decades. [15] The typical methods include Pd-catalyzed sequential [4 + 2] and [3 + 2] cycloaddition reactions of quinazolinones with internal alkynes (Scheme 1a), [16] Ru(II)-catalyzed CÀ H alkenylation/ hydroamination of quinazolinones with allyl acetate (Scheme 1b), [17] and Ru(II)-catalyzed alkenylation or alkenylation/hydroamidative cyclization of quinazolinones with terminal alkynes, depending on the presence of electron-donating or electron-withdrawing substituents (Scheme 1c). [15] The typical methods include Pd-catalyzed sequential [4 + 2] and [3 + 2] cycloaddition reactions of quinazolinones with internal alkynes (Scheme 1a), [16] Ru(II)-catalyzed CÀ H alkenylation/ hydroamination of quinazolinones with allyl acetate (Scheme 1b), [17] and Ru(II)-catalyzed alkenylation or alkenylation/hydroamidative cyclization of quinazolinones with terminal alkynes, depending on the presence of electron-donating or electron-withdrawing substituents (Scheme 1c).…”

Palladium‐Catalyzed Double Cyclization Processes Leading to Polycyclic Heterocycles: Recent Advances

“…In a nice recent example, 2‐arylquinazolin‐4(3 H )‐ones and diarylacetylenes were converted into 1,2,3a,14a‐tetraaryl‐3a,14a‐dihydro‐13 H ‐furo[3′,2′:3,4]isoquinolino[1,2‐ b ]quinazolin‐13‐ones, using PdCl 2 (MeCN) 2 as catalyst in the presence of CuBr and O 2 as the reoxidizing system (Scheme ) . The process begins with nitrogen‐directed palladation at the ortho position of the aryl group.…”

Rhodium(III)‐Catalyzed Synthesis of N‐(2‐Acetoxyalkyl)isoquinolones from Oxazolines and Alkynes through C−N Bond Formation and Ring‐Opening

“…[12][13][14] We focused on introducing the functional group at the Nalkyl chain of isoquinolone derivatives. With our ongoing interest in the synthesis of heterocycles, [15] herein, we report a rhodium(III)-catalyzed synthesis of N-(2-acetoxyalkyl)isoquinolones based on oxazoline-directed aromatic CÀH activation with alkynes. Notably, the oxazoline ring system can be opened 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 during the reaction and successfully introduced as an acetoxy group at the N-alkyl chain, which can transform into potential biological groups.…”