An alternative approach towards novel heterocycle-fused 1,4-diazepin-2-ones by an aromatic amidation protocol

Synthesis of Benzannulated Medium‐ring Lactams via a Tandem Oxidative Dearomatization‐Ring Expansion Reaction

“…Commercially available furano‐, thiopheno‐, and pyrrolocyclohexanones were transformed into the corresponding β‐hydroxy‐ N ‐methoxyamide substrates 28 , 29 , and 32 , respectively, then converted via tandem ODRE to 9‐membered ring lactam products 30 , 31 , and 33 in serviceable yields. Hypervalent iodine‐induced oxidative dearomatization reactions have been reported under the “normal” polarity reaction manifold for furans and under the umpolung reaction manifold for thiophenes and pyrroles . Further, indoles 34 and 36 proved to be reactive as nucleophiles at both the C3‐ and C2‐positions, respectively, providing the corresponding regioisomeric indole products 35 and 37 .…”

Amino acid chirons: a tool for asymmetric synthesis of heterocycles

“…142 The same group reported synthesis of heterocycle-fused 1,4-diazepin-2-ones derivatives 704 using a similar kind of strategy (Scheme 115). 143 A new type of steroid-amino acid hybrid 709 containing a nine membered D-ring with hetero atoms was reported by Panda and coworkers for the first time from estrone 706 and amino acids 383. The key intermediate 706 was synthesized from estrone, which was treated with amino acids under reductive amination conditions, followed by Yamaguchi coupling reactions affording 709 (Scheme 116).…”

Pyrrolo[3,2-e][1,4]diazepin-2-one Synthesis: A Head-to-Head Comparison of Soluble versus Insoluble Supports

“…The white solid was filtered off, washed with ice-cold Et 2 O (2 Â 5 mL), dried in vacuo to give 19 as a white powder (82 mg). R f = 0.51 (7.5% MeOH in DCM); [R] 21 D = À13.5 (c = 0.9,); 1 H NMR (CDCl 3 , 400 MHz) δ 1.80 (m, 2H), 1.99 (dt, J = 12.5, 5.5 Hz, 1H), 2.92 (dd, J = 5.4, 9.7 Hz, 1H), 3.37 (dd, J = 4.7, 9.1 Hz, 1H), 3.59 (dd, J = 5.4, 9.7 Hz, 1H), 4.55 (dt, J = 5.8, 11.6 Hz, 1H), 4.61 (d, J = 12.9 Hz, 1H), 4.81 (d, J = 12.9 Hz, 1H), 7.12 (td, J = 1.1, 7.5 Hz, 1H), 7.22 (m, 4H), 7.29 (m, 2H), 7.32 (dd, J = 1.1, 7.5 Hz, 1H), 7.36 (dt, J = 7.5, 0.7 Hz, 1H), 7.42 (td, J = 1.1, 7.5 Hz, 1H), 7.56 (m, 3H), 7.61À7.75 (m, 12H), 7.75À7.81 (m, 6H), 7.89 (ttd, J = 1.2, 2.0, 6.8 Hz, 3H), 7.97 (ddt, J = 1.9, 3.2, 8.5 Hz, 2H); 13 C NMR (75 MHz, CDCl 3 ): two conformers are observed, signals given by the second conformer are signaled with an asterisk (*), δ 39.9 (s, 1CH 2 ), 56.7 (s, 1CH 2 ), 59.5 (s, 1CH), 65.5 (s, 1CH 2 ), 70.1 (s, 1CH), 76.2 (s, 1C), 115.6 (d, J = 91.5 Hz, 1C), 117.7 (d, J = 89.5 Hz, 3C), 119.9 (s, 2CH), 120.2 (s, 2CH*), 126.7 (s, 2CH), 127.2 (s, 1CH*), 127.37 (s, 2CH), 127.41 (s, 2CH), 127.67 (s, 2CH*), 127.75 (s, 2CH*), 128.4 (s, 2CH),128.6 (s, 2CH), 128.7 (s, 4CH), 128.8 (s, 2CH*), 129.1 (s, 2CH), 129.3 (s, 2CH*), 130.8 (d, J = 12.9 Hz, 6CH), 134.5 (d, J = 10.3 Hz, 6CH), 135.1 (d, J = 10.7 Hz, 2CH), 135.8 (d, J = 3.0 Hz, 3CH), 137.1 (s, 1C), 137.9 (d, J = 1.5 Hz, 1C), 140.0 (s, 1C), 141.4 (s, 2C), 142.8 (s, 2C*), 146.1 (s, 2C), 147.5 (s, 2C*), 147.86 (s, 1C), 147.9 (s, 1C*), 175.4 (s, CdO); HRMS calcd for C 55 H 45 4-Benzylamino-1H-pyrrole-2-carboxylate TAP (25). A stirred solution of oxalyl chloride (0.42 mL, 5.01 mmol, 1.5 equiv) in DCM (6 mL) at À78 °C was treated with dry DMSO (0.47 mL, 6.68 mmol, 2 equiv) in DCM (6 mL).…”

“…11 Their notable activities and opportunity for novel structural diversity have made the development of methods for constructing and functionalizing pyrrolodiazepinone scaffolds a promising subject for medicinal chemistry research. Recent examples have key steps featuring the use of the multicomponent Ugi-type condensation, 12 phenyliodine(III)bis-(trifluoroacetate)-mediated intramolecular N-acylnitrenium ion reaction, 13 and cyclization via Schmidt thermolysis of acylazides. 14 In addition, the intramolecular PaalÀKnorr reaction has provided pyrrolo[1,2-d][1,4]diazepin-4-ones 7 (Figure 1).…”