Regioselective Mercury(I)/Palladium(II)-Catalyzed Single-Step Approach for the Synthesis of Imines and 2-Substituted Indoles

Abstract

An efficient synthesis of ketimines was achieved through a regioselective Hg(I)-catalyzed hydroamination of terminal acetylenes in the presence of anilines. The Pd(II)-catalyzed cyclization of these imines into the 2-substituted indoles was satisfactorily carried out by a C-H activation. In a single-step approach, a variety of 2-substituted indoles were also generated via a Hg(I)/Pd(II)-catalyzed, one-pot, two-step process, starting from anilines and terminal acetylenes. The arylacetylenes proved to be more effective than the alkyl derivatives.

Pd‐Catalyzed Switchable Access to Imines and Amines from Secondary Alcohols

“…It is well known that imines are valuable scaffolds for indole synthesis [22–25] . Motivated by the selectivity of our protocol for imine formation, we performed the synthesis of a variety of indoles starting from the corresponding amines and secondary alcohols by transformation of the in situ formed imines to the corresponding indoles (Table 2).…”

Divergent Pd-catalyzed Functionalization of 4-Oxazolin-2-ones and 4-Methylene-2-oxazolidinones and Synthesis of Heterocyclic-Fused Indoles

“…First, a Pd­(II)-catalyzed (Pd­(OAc) 2 , 0.2 mol %) biselectrophilic substitution leads to the σ-Pd­(II)-(C 5 ) 2 complex IV , which undergoes the homocoupling process to generate dienes 13a–13e (Scheme ). Since reductive elimination gives rise to the Pd(0)­L n species, the latter is reoxidized to Pd­(II)­L n with Cu­(OAc) 2 to restart the catalytic cycle. , …”

“…For the construction of aza-heterocycles in general, and indoles in particular, transition metal complexes play a key role. The Pd­(II)-catalyzed approach for the synthesis of indoles is probably the most appropriate strategy for the preparation of these important target molecules. , Consequently, 4-methylene-2-oxazolidinones 14a–14k were presently explored as the precursors of oxazolo­[3,4- a ]­indol-3-ones 15a–15k through a Pd­(II)-catalyzed oxidative cyclization (Table ).…”

“…Once having the compounds of series 14a–14k on hand, their Pd­(II)-catalyzed conversion into oxazolo­[3,4- a ]­indol-3-ones 15a–15k was explored via oxidative cyclization by modifying the reaction conditions. , The optimal conditions included Pd­(OAc) 2 as the catalyst, Cu­(OAc) 2 as the oxidant agent, and pivalic acid as the additive in DMSO, allowing for the production of 15a–15k in low to high yields (Table ). When the N -aryl ring of the 4-methylene-2-oxazolidinone 14 was substituted at the ortho position, it was necessary to increase the reaction temperature, leading to lower yields (entries 10 and 11).…”

“…Numerous methods exist for the construction of indoles. , However, particularly relevant as short, versatile, and efficient approaches are the protocols involving a palladium­(II)-catalyzed C–H activation of N -vinyl anilines (i.e., enamines, enamides, and enecarbamates) to form the C3–C3b bond of the heterocycle through dehydrogenative cross-coupling. , …”