Facile and Efficient Synthesis of 3‐Pyrimidinyl Oxindoles by Phase‐Transfer‐Catalyzed Regioselective Nucleophilic Aromatic Substitution

Abstract

Phase‐transfer‐catalyzed regioselective nucleophilic aromatic substitution of 2,4‐dichloropyrimidines with N‐Boc‐protected 3‐substituted oxindoles is reported. The reaction allows the formation of unsymmetrical all‐ carbon quaternary centers in the benzylic position of heteroaromatic scaffolds and proceeds with high chemical yield and excellent functional‐group tolerance. Various activated heteroaryl chlorides including dichloropyridazine and activated chloropyridines can also be reacted under the reaction conditions.

Domino Transformations of 3‐Fluoro‐1,2,4‐Triazine Derivatives towards Spirocyclic and Fused Pyridines

“…This sequence was extended to α‐amino acids and 3‐aryloxindoles as nucleophiles and arene chromium complexes as electrophiles by Maruoka [17] . Interestingly, Togni reported a racemic PT‐catalyzed S N Ar involving 2,4‐dichloropyrimidines as electrophiles but a single example led to the corresponding 3‐pyrimidinyl oxindole in 60% ee [18] …”

“…[17] Interestingly, Togni reported a racemic PTcatalyzed S N Ar involving 2,4-dichloropyrimidines as electrophiles but a single example led to the corresponding 3-pyrimidinyl oxindole in 60% ee. [18] Based on this background knowledge, we wondered whether an enantioselective heteroaylation step could be integrated in our domino S N Ar-ihDA/rDA reaction based on a PTC approach, highlighting thereby 1,2,4triazines electrophiles are new players in that field. Considering the challenge of this approach, cyanomalonate derivative 9 a was chosen as model substrate at first.…”

An efficient synthesis of 6‐benzyl‐2‐arylthieno[2,3‐d]pyrimidin‐4(3H)‐ones catalyzed by HCl involving a Friedel‐Crafts alkylation reaction

“…[ 1 ] A well‐known example is 5‐fluorouracil, and it is an effective drug to treat gastrointestinal, esophageal, breast, and colorectal cancers. [ 2 ] In order to acquire a better pesticide effect, lots of novel procedures have been developed to build structurally diversified pyrimidines [ 3 ] for bio‐active screening.…”