Synthesis of a tetracyclic lactam system of Nuevamine by four-component reaction and free radical cyclization

Synthesis of Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via a One-Pot (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2) Process. A Suitable Alternative towards Novel Aza-Analogues of Falipamil

“…Thus, it can be found in the literature of our own reports [10,11,12,13,14,15], which are previous works to the present one, and in the above-mentioned methodology from the Couture’s group [7], which is a close work to the present one, in which Falipamil ( 1 ) and some of its analogues ( 2 – 3 ) are synthesized efficiently, but via a stepwise strategy, resulting in larger times and generally using harsh conditions. Moreover, pioneering works from Bienaymé and Zhu [16,17] allowed the synthesis of pyrrolo[3,4- b ]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/ N -acylation/aromatization) in good yields, short reaction times, and under relatively milder conditions with respect to stepwise methods.…”

“…The synthesis of the desired pyrrolo[3,4- b ]pyridin-5-ones 11a – i was performed using our previously optimized conditions [10]: scandium(III) triflate as the Lewis-acid catalyst (3% mol) [19], microwaves (MW) as heat source to reduce reaction times [20], and benzene as the solvent. Thus, 1.0 equiv.…”

“…In this context, we have reported some one-pot syntheses on a series of novel, fused, polyheterocyclic pyrrolo[3,4- b ]pyridin-5-one-based compounds via an Ugi-3CR/aza Diels-Alder/ N -acylation/aromatization cascade sequence combined with further cyclization processes like free-radical mediated [10], Pummerer [11], Pictet-Spengler [12], and Pomeranz-Fritsch [13]. In the same way, we developed an oxidative [14] and a repetitive version [15] of this robust one-pot cascade process (Ugi-3CR/aza Diels-Alder/ N -acylation/aromatization).…”

One-Pot Synthesis of Nuevamine Aza-Analogues by Combined Use of an Oxidative Ugi Type Reaction and Aza-Diels–Alder Cycloaddition

“…Several post-transformations of Ugi products have been reported, including cyclocondensa- 16 radical cyclization, 17 S N Ar 18 and S N 2 reactions, 19 cycloaddition, 20 and metathesis reactions. 21 In this way, we recently focused on the preparation of libraries of synthetically nitrogenated analogues of important natural products by using I-MCR processes, such as Ugi type reactions combined with other post-functionalization techniques involving free-radicals, 22 Pummerer, 23 and PictetSpengler cyclizations. 24 Zhu and co-workers 25 reported an efficient 2-iodoxybenzoic acid (IBX) mediated Ugi type reaction.…”

MW-Assisted Synthesis of Eight New 6-Nitrilmethyl Pyrrolo[3,4-b]pyridin-5-Ones via a Domino Process: aza Diels–Alder/N-Acylation/Aromatization

“…Most of the reported methods to assemble pyrrolo [3,4-b]pyridin-5one based architectures involve multistep strategies as well as the use of harsh conditions-see for example the synthetic methodology reported by Devasthale et al [2]. However, various multicomponent reaction (MCR)-based synthetic strategies toward series of novel pyrrolo [3,4b]pyridin-5-one-containing polyheterocycles have been reported in the last decade by us [7][8][9][10][11][12][13][14] as an integral part of our ongoing research program. It is important to note that MCRs are highly convergent one-pot processes in which three or more reagents are combined sequentially to assemble complex products [15] like polyheterocycles [16], eventually in good yields, obeying most of the green chemistry principles [17].…”