Palladium‐Catalyzed Imidoylative Cyclization of α‐Isocyanoacetamides: Efficient Access to C2‐Diversified Oxazoles

Abstract

A novel procedure for the synthesis of C2-diversified oxazoles, through palladium-catalyzed imidoylative cyclization of α-isocyanoacetamides with aryl, vinyl, alkynyl halides, or triflates, was developed. Migratory insertion of isocyanide into a Csp3-palladium(II) intermediate in a cascade process was also realized, generating alkyl-substituted oxazoles. Therefore, oxazoles functionalized at the C2 position with sp, sp(2), and sp(3) hybridized carbon atoms are accessible by applying this method.

Synthesis of Diversely Functionalized Oxindoles Enabled by Migratory Insertion of Isocyanide to a Transient σ‐Alkylpalladium(II) Complex

“…Reactions involving migratory insertion of isocyanide to C(sp 3 )ÀPd II complexes remain unexploited. [6] In contrast, while the coordinating ability of isocyanide to transition metals has been well appreciated in organometallic chemistry, [7] this property also renders the development of isocyanide-based enantioselective transformations difficult. To the best of our knowledge,o nly one single example has been reported from the group of Hayashi.…”

“…[8] In connection with our interest in palladium-catalyzed domino processes [9] and isocyanide chemistry, [10] we envisaged that an intramolecular carbopalladation of alkenes followed by migratory insertion of the resulting isocyanide-coordinated C(sp 3 )ÀPd II complex A might be an attractive way to form an alkylimidoyl-Pd II species which could be converted into ad iversely functionalized oxindoles (Scheme 1b). [11] We report herein that palladium-catalyzed reactions of N-arylacrylamides (1)w ith isocyanides (2)t ook place smoothly to afford ad iverse set of 3,3-disubstituted oxindoles (3)(4)(5)(6) incorporating an amide,anester, aketone,and abenzoxazole unit. We also document an unprecedented asymmetric carbopalladation/isocyanide insertion/methoxylation process for the synthesis of enantioenriched imidates (7).…”

Silver‐Catalyzed Chemoselective [4+2] Annulation of Two Isocyanides: A General Route to Pyridone‐Fused Carbo‐ and Heterocycles

“…Generally, in the reported [3+2] cycloaddition reactions of two isocyanides, an aryl isocyanide acts as the two‐atom component and the aryl groups of the isocyanides remain intact during the transformation . Meanwhile, isocyanoacetamides are mainly known for the carbene‐like reactivity of the isocyano group when used as a five‐atom component in multicomponent reactions or palladium‐catalyzed imidoylative cyclization reactions, and the α‐carbon atom of isocyanoacetamides has only been shown to serve as a nucleophile in formal [3+2] cycloaddition and alkylation reactions . Therefore, broader exploration of the reactivity profiles of both aryl isocyanides and isocyanoacetamides remains highly desirable.…”

Silver‐Catalyzed Chemoselective [4+2] Annulation of Two Isocyanides: A General Route to Pyridone‐Fused Carbo‐ and Heterocycles

“…[8] Among these transformations,t he [3+ +2] cycloaddition of activated methylene isocyanides with aryl isocyanides has emerged as an efficient protocol for the catalytic synthesis of imidazoles [Scheme 1, Eq. [10][11][12] Meanwhile, isocyanoacetamides are mainly known for the carbene-like reactivity of the isocyano group when used as af ive-atom component in multicomponent reactions [1,13] or palladiumcatalyzed imidoylative cyclization reactions, [14] and the acarbon atom of isocyanoacetamides has only been shown to serve as anucleophile in formal [3+ +2] cycloaddition [1,10,15] and alkylation reactions. [9][10][11][12] Generally,i nt he reported [3+ +2] cycloaddition reactions of two isocyanides,a na ryl isocyanide acts as the two-atom component and the aryl groups of the isocyanides remain intact during the transformation.…”

“…[9][10][11][12] Generally,i nt he reported [3+ +2] cycloaddition reactions of two isocyanides,a na ryl isocyanide acts as the two-atom component and the aryl groups of the isocyanides remain intact during the transformation. [10][11][12] Meanwhile, isocyanoacetamides are mainly known for the carbene-like reactivity of the isocyano group when used as af ive-atom component in multicomponent reactions [1,13] or palladiumcatalyzed imidoylative cyclization reactions, [14] and the acarbon atom of isocyanoacetamides has only been shown to serve as anucleophile in formal [3+ +2] cycloaddition [1,10,15] and alkylation reactions. [1,16] Therefore,b roader exploration of the reactivity profiles of both aryl isocyanides and isocyanoacetamides remains highly desirable.In continuation of our studies on isocyanide-based annulation reactions, [17] we report herein an unprecedented [4+ +2] annulation of aryl and heteroaryl isocyanides with asubstituted isocyanoacetamides [Scheme 1, Eq.…”