Intramolecular Keto Lactam Condensation: A Convenient and Straightforward Approach to Bicyclic Vinylogous Lactams

Abstract

Abstract:Although the aldol condensation is a well-known reaction, the aza-type aldol condensation, namely, the intramolecular condensation of common keto lactams leading to bicyclic vinylogous lactams, is a highly demanding transformation, with potential applications in both organic synthesis and medicinal chemistry. The known methods for this type of cyclization require several steps. In this paper, we disclose a straightforward approach that consists of the in-situ formation of silyl

Tf2O/TTBP (2,4,6-Tri-tert-butylpyrimidine): An Alternative Amide Activation System for the Direct Transformations of Both Tertiary and Secondary Amides

“…Employing the Tf 2 O (1.2 equiv)/TTBP (0.6 equiv) activation system, the additions of n -butyl and 3-phenylpropyl Grignard reagents to amide 3h produced the corresponding ketones 7a and 7b in 75 and 86% yields (Table , entries 4 and 5), respectively. Note that the yields from the Tf 2 O/DTBMP (1.2 equiv) combination were 82 and 83% (Table , entries 4 and 5), respectively.…”

“…In connection with our interest in the total synthesis of natural products, we have embarked on a program aimed at developing efficient synthetic methods for the direct transformation of amides with C–C bond formation. Our efforts have resulted in a series of valuable reactions/methods covering the reductive bis-alkylation, , and reductive alkylation of tertiary amides, the direct conversion of common tertiary and secondary amides into ketones, acylation of alkenes with secondary amides, reductive gem -cyanation-phosphonylation of secondary amides, intramolecular keto-lactam condensation, etc . In most methods that we have developed, DTBMP or 2-F-Pyr.…”

“…In most methods that we have developed, DTBMP or 2-F-Pyr. was employed as an optimal base partner of Tf 2 O for the in situ activation and transformations of tertiary, ,, or secondary amide, − respectively. In view of developing a versatile activator for the direct transformations of both tertiary and secondary amides, we were interested in exploring the Tf 2 O/2,4,6-tri- tert -butylpyrimidine (TTBP, 2 ) combination as a novel amide activation system.…”

Copper-Catalyzed Coupling of Thioamides and Donor/Acceptor-Substituted Carbenoids: Synthesis of Enamino Esters and Enaminones

“…Enamino esters and enaminones are important synthetic intermediates. − They have been used in the synthesis of a number of natural products and pharmaceutically active compounds. ,, Because of this importance, various methods are available for enamino ester and enaminone synthesis ,− and new methods are constantly pursued. − Exocyclic enamino esters and enaminones are generally prepared by the Eschenmoser sulfide contraction reaction (ESR) ,− or the imino ester (imidate) approach. ,− Both methods complement each other. In the ESR, a thioamide is the nucleophile, while in the imidate approach, an amide is converted into an electrophile.…”

Close the ring to break the cycle: tandem quinolone-alkyne-cyclisation gives access to tricyclic pyrrolo[1,2-a]quinolin-5-ones with potent anti-protozoal activity

“…Previously reported syntheses of pyrrolo[1,2-a]quinoline-5-ones were dependent on pyrrolidine or pyrrolidine-2-one precursors and therefore contained only fully saturated pyrrolo-units. [25][26][27][28] We here provide the first example of chemoselectively synthesized unsaturated pyrrolo[1,2-a]quinolin-5-ones 15 and 16 that extend the chemical space of this so far rather unexplored class of pyrrolo[1,2-a]quinolin-5-ones. To determine if these new scaffolds have biological activities similar to quinolines and quinolones, their antiparasitic activity was profiled.…”