N-propargyl aza-Claisen rearrangement in the synthesis of heterocycles

Divergent and Nucleophile‐Assisted Rearrangement in the Construction of Pyrrolo[2,1‐b][3]benzazepine and Pyrido[2,1‐a]isoquinoline Scaffolds

“…It has been found that the Npropargyl version of the rearrangement is effective for the formation of pyrrole and pyridine rings thus making Npropargylvinylamines interesting starting materials. [11] The partially hydrated pyrrolo[2,1-b][3]benzazepine core is found in a large family of Cephalotaxus [12][13][14][15][16] alkaloids, DLhexahydroapoerysopine and in a number of other compounds exhibiting useful biological properties (Figure 1). For instance, esters of Cephalotaxine have been demonstrated to be effective for the treatment of myeloid leukemia, [16] synthetic pyrrolo[2,1b] [3]benzazepine derivatives show a muscle relaxant, antihypertensive and antipsychotic activity.…”

Modular Divergent Synthesis of Functionalized Indoles via TFA-Promoted Amino-Claisen Rearrangement at Room Temperature

“…The variation of the substituents on amine and alkynyl fragments proved to be feasible to afford the corresponding 2-substituted (2−12, 15, 21, 22), 1,2-substituted (13, 14), 2,3-substituted (16, 17), or 1,2,3-substituted (18, 19) indole derivatives in moderate to excellent yields. The equipment different functionalities on the aryl substituent of the propargylic amine substrates resulted in the formation of the corresponding indole derivatives with functionality on 4-(11, 15), 5-(2−8, 10, 15, 21, 22), 6-( 10), or 7- (9,11,12) positions. These fruitful results demonstrated the adjustable character of the current methodology.…”

“…11 The molecular structure of indole 1 was unambiguously further confirmed by the single-crystal X-ray diffraction analysis, in addition to spectrographic analysis. 12 Afterward, we focused on the investigation of the substrate scope in terms of aromatic We then tested the synthetic potential of this user-friendly protocol. As such, the gram-scale reaction was successfully carried out under the standard reaction conditions without the loss of the productivity (Figure 3a).…”

“…The reaction with the use of CF 3 COOD in deuterated dichloromethane resulted in deuterated product 44 , which indicated the involvement of acid-induced cyclization of allene intermediate T3 (Figure e). On the basis of these results and previous related reports, − we proposed the reaction mechanism as depicted in Figure f. First, a salt form of the amine trifluororoacetate intermediate T1 is formed in the presence of TFA and propargyl amine substrate S1 .…”

Base Metal-Controlled Chemodivergent Cyclization of Propargylamines for the Atom-Economic Synthesis of Nitrogen Heterocycles

“…Then, the cascade aromatization, protodecopperization, and oxidation take place to afford 2 . On the contrary, with Fe­(OTf) 3 as a stronger Lewis acid, the reaction may proceed through an amino Claisen rearrangement process via initial activation of the amino and carbonyl group by the iron catalyst ( B1 ) to give B2 , followed by the aromatization to generate B3 . Then an intramolecular aza Michael addition would take place to afford target indole heterocycles 3a .…”