Copper‐Catalyzed Intramolecular Electrophilic Carbofunctionalization of Allylic Amides

Abstract

Allylic amides and their derivatives represent a versatile class of nitrogen-containing building blocks, the bifunctional nature of which has enabled a diverse array of transformations and established them as strategically important molecules in chemical synthesis. [1,2] Particularly useful are reactions where an electrophile activates the carbon-carbon double bond towards attack of the pendant oxygen atom of the amide carbonyl group to form either a five or sixmembered ring heterocycle, depending on the mode of cyclization (Scheme 1 a). [3] Most of these reactions are triggered by heteroatom electrophiles, often activated by a catalyst, and result in the formation of a carbon-oxygen and a carbon-heteroatom bond. It is, however, surprising that the related electrophilic carbofunctionalization process is rare. One possible reason for this is the lack of suitable carbon electrophiles that can activate the carbon-carbon double bond of the allylic amide. The development of Pd-catalyzed oxyarylation and aminoarylation reactions, in particular by Wolfe and co-workers, [4] as well as related Pd, [5] Cu, [6] and Aucatalyzed [7] processes have provided an alternative approach to related alkene difunctionalization [8] and can be applied to derivatives of the generic allylic amine framework. Despite these advances, the development of novel methods that catalytically generate carbon electrophiles capable of activating alkenes to nucleophilic attack remains a challenge; the solution to this challenge would be of significant use in complex molecule synthesis.As part of an overarching program aimed at the exploitation of high oxidation state metal species we, [9] and others, [10] have established that the combination of copper catalysts and diaryliodonium salts gives rise to a high oxidation state Cu III / aryl [11] intermediate that displays reactivity of an aromatic electrophile (Scheme 1 b). We reasoned that this distinct catalytic activation strategy could be used to generate the aromatic electrophile equivalent that would be needed to affect an intramolecular oxyarylation of allylic amides, thus complementing the corresponding heteroatom electrophile triggered cyclizations that have become a mainstay in synthesis.We selected aryl-substituted allylic amides with which to test our copper-catalyzed oxyarylation strategy as the products would generate a broadly useful class of diarylated amino alcohols. Furthermore, we noted that some aryl-substituted allylic amides have been utilized in other electrophile triggered cyclization reactions. For example, treatment with acid induces an intramolecular hydration-type reaction to form the 6-membered-ring oxazine product (Scheme 1 c). [13] Similarly, treatment with bromine gives rise to a bromocyclization, again forming the oxazine product, although this is dependent on the geometry of the starting alkene and the electronic nature of the aromatic ring. [14,15] To the best of our knowledge, there are no examples of such a catalytic electrophilic carbofunctionalization of this class of ...

Diaryliodonium Salts in Organic Syntheses: A Useful Compound Class for Novel Arylation Strategies

“…In 2013, a new copper catalyzed endoselective oxyarylation and oxyvinylation of allylic amides 66 (80) was developed by Gaunt and coworkers. The procedure enables the arylation of allylic amides both with diaryl-and vinyl(aryl)iodonium triflates in the presence of CuTC (TC = thiophene-2-carboxylate) catalyst (Scheme 33).…”

“…[54][55][56][57][58][59][60][61][62][63][64][65][66][67] Utilizing this concept, several syntheses of diverse heterocyclic skeletons were developed in the last few years in our and other laboratories. The copper catalyzed synthesis of new oxazoline derivatives (89) from propargyl amides (88) and diaryliodonium salts was recently developed by our research group.…”

Organohypervalent Iodine Reagents in the Synthesis of Bioactive Heterocycles

“…Formation of an oxazine ring through sequential C-O and C-C bonds formation delivered oxazine derivatives 152 with high stereoselectivity [51]. Treatment of 151 with easily accessible diaryliodonium salts in the presence of a catalytic amount of copperthiophenecarboxylate (CuTC) furnished highly functionalized oxazines 152.…”

Atom‐Economical Applications of Diaryliodonium Salts

“…Diaryliodonium salt, as as table ande asily prepared reagent (Scheme 1), was reported by Hartmann and Meyer in 1894, [1] and it has long been one of the most efficient arylation reagents in organic synthesis. For example, cross-coupling reactions involving diaryliodonium salts with arenes, [2] alkynes, [3] alkenes, [4] carbonyl compounds, [5] andh eteroatoms [6] have been well explored. On the other hand, diaryliodonium saltsn ot only have been extensively utilized in transition-metal-catalyzed reactions, [7] splendid efforts have also been devoted to developing transition-metal-free arylation with nucleophiles by the Olofsson group andt he Kita group [8] In spite the popular application of diaryliodonium salts, this reagent is generally only applied as as ingle arylation source and the regenerated aryl iodide is aw aste of resources in traditional methods (Scheme2).…”