Media‐Driven Pd‐Catalyzed Reaction Cascades with 1,3‐Diynamides Leading Selectively to Either Indoles or Quinolines

Abstract

Divergent Pd-catalyzed reaction cascades with various 1,3-diynamides yielding either 2-amino-3-alkynylindoles or 2-amino-4-alkenylquinolines were established. Omitting or adding TBAF (tetrabutylammonium fluoride) to the reaction of N,N-(2-iodophenyl)(4-toluenesulfonyl)-1,3diynamides with secondary or primary amines in the presence of KOH in THF and catalytic amounts of Pd(PPh 3 ) 4 completely changed the outcome of the reaction. In the absence of TBAF, 2-amino-3-alkynylindoles were the sole products, while the presence of TBAF switched the product formation to 2-amino-4-alkenylquinolines. Deuterium labeling proceeded selectively at the C3 and C11 positions of the 2-amino-4alkenylquinoline products and this suggests the unprecedented formation of [4]cumulenimines from 1,3-diynamides as reactive key intermediates.

1,3-Butadiynamides the Ethynylogous Ynamides: Synthesis, Properties and Applications in Heterocyclic Chemistry

“…Recently, divergent palladium-catalyzed reaction cascades for the selective synthesis of either 2-amino-3-alkynyl-indoles 145a-d or 2-amino-4-alkenylquinolines 146a-f from 1,3-butadiynamides 144 and primary or secondary amines were established (Scheme 43) [70]. Starting from identical or similar substrates, the outcome of the reaction giving either indole or quinoline motifs is switchable, respectively, by the absence of presence of TBAF.…”

Gold‐Catalyzed Annulation of Ynamides with Aminocarbonyls as a Route to 2‐Aminoquinolines Diversely Substituted at the 4th‐Position

“…[13,14] It is not surprising, therefore, that preparative approaches to construct 2-aminoquinolines are in high demand, and a number of impressive synthetic reports on this topic have recently been published. [15][16][17][18][19][20][21][22] In this study, we developed a modular and practical approach to 2-aminoquinolines, which is based on annulation of ynamides. Ynamides, i. e. amido-functionalized alkynes [23,24] have been commonly recognized as easily available and handy building blocks for a facile construction of complex molecules, [24][25][26][27] including diverse carbo-and heterocycles.…”

“…Furthermore, 2‐aminoquinolines are currently studied as antidepressants (quipazine [10] and its 4‐derivatives [11] ) or drugs against Sickle cell disease [12] and certain cancers [13,14] . It is not surprising, therefore, that preparative approaches to construct 2‐aminoquinolines are in high demand, and a number of impressive synthetic reports on this topic have recently been published [15–22] …”

Leveraging Zn(II) Catalyst: Synthesis of Amidoquinolines via (3 + 3) Heteroannulation of Aromatic Amines and Ynamides

“…However, harsh reaction conditions and limited substituent variation at the periphery of the quinoline ring have engineered to develop metal-catalyzed protocols . In particular, 2,4-diaminoquinolines or 2,4-diamidoquinolines have tremendous existence in biologically active ingredients and marketed drug molecules. , Therefore, a number of protocols are known in the literature to install amide functionality separately at the 2- and 4-position of quinolines via an aromatic substitution reaction or to direct access of amidoquinolines via a cascade reaction . Interestingly, straightforward installation of amide and amidomethyl units into the quinoline core seems extremely challenging and is also rarely explored.…”