Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes.
ABSTRACT: Intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes is realized using visible light photoredox catalysis, yielding a variety of cyclic allylic amines in fair to good yields. This method exhibits significant group tolerance particularly with heterocycles. It can also be used to prepare complex heterocycles such as fused indolines.
Project description:One-step synthesis of carbocycles substituted with amines from simple starting materials remains rare. We recently developed intermolecular [3+2] annulation of cyclopropylanilines with alkenes and alkynes that enable this one-step synthesis. Herein, we report our findings for a fullscale study of the annulation. Significant expansion of the substrate scope for both cyclopropylanilines and alkynes is achieved. A range of structurally diverse carbocycles substituted with amines is prepared.
Project description:The hydroamination of internal alkynes via tandem rhodium catalysis gives branched N-allylic indolines with high regio- and enantioselectivity. An acid switch provides access to the linear isomer in preference to the branched isomer by an isomerization mechanism. Mechanistic studies suggest formation of an allene intermediate, which undergoes hydroamination to generate allylic amines instead of the enamine or imine products typically observed in alkyne hydroaminations.
Project description:Compared with the reported intramolecular electro-oxidative cyclization of alkenyl amines or vinyl anilines for the preparation of pyrrolidines or indolines, the intermolecular version is less studied. Herein, this electrochemical intermolecular oxidative annulation of anilines and alkenes for the preparation of indolines proceeded under external oxidant-free conditions. The most noteworthy achievement of our work is the facile generation of indolines with quaternary centers at the 2-position. In addition, alkenes and anilines bearing various functional groups can be well tolerated. Remarkably, electrolyte-free conditions were used in an electrochemical flow cell, which shows the application potential of this method.
Project description:We herein report a visible-light-mediated heterogeneous [4+2] annulation of N-cyclobutylanilines with alkynes catalyzed by self-doped Ti3+ @TiO2 . The self-doped Ti3+ @TiO2 is stable under photooxidation conditions, easy to recycle, and can be used multiple times without appreciable loss of activity. Extensive mechanistic studies suggest that the annulation reaction is mediated by singlet oxygen, which is generated through the photosensitization of oxygen in the air by the self-doped Ti3+ @TiO2 . In contrast, the homogeneous variant catalyzed by a far more expensive iridium complex proceeds under an inert atmosphere, which indicates a different mechanism. The substrate scopes of the two processes are comparable.
Project description:An efficient construction of imidazole ring by a Cs2CO3-promoted annulation of amidoximes with terminal alkynes in DMSO has been developed. This protocol provides a simple synthetic route with high atom-utilization for the synthesis of 2,4-disubstituted imidazoles in good yields under transition-metal-free and ligand-free conditions. Internal alkynes can also undergo the annulation to give 2,4,5-trisubstituted imidazoles.
Project description:Intermolecular hydroaminoalkylation reactions of alkynes with secondary amines, which selectively give access to allylic amines with E configuration of the alkene unit, are achieved in the presence of titanium catalysts. Successful reactions of symmetrically substituted diaryl- and dialkylalkynes as well as a terminal alkyne take place with N-benzylanilines, N-alkylanilines, and N-alkylbenzylamines.
Project description:A two-step process is described for the union of aromatic imines, conjugated alkynes, and aldehydes that results in a stereoselective synthesis of highly substituted piperidines. This synthetic process has been made possible by defining a unique regioselective functionalization of conjugated alkynes that establishes a suitably functionalized substrate for subsequent heterocycle-forming cationic annulation. Given the flexibility of the coupling process, heterocycles can be accessed through a process that establishes up to four stereogenic centers and four fused rings.
Project description:We report the first example of an intermolecular [4+2] annulation of cyclobutylanilines with alkynes enabled by visible-light photocatalysis. Monocyclic and bicyclic cyclobutylanilines successfully undergo the annulation with terminal and internal alkynes to generate a wide variety of amine-substituted cyclohexenes including new hydrindan and decalin derivatives with good to excellent diastereoselectivity. The reaction is overall redox neutral with perfect atom economy.
Project description:?-Pyridones and ?-pyrones are ubiquitous structural motifs found in natural products and biologically active small molecules. Here, we report an Rh-catalyzed electrochemical vinylic C-H annulation of acrylamides with alkynes, affording cyclic products in good to excellent yield. Divergent syntheses of ?-pyridones and cyclic imidates are accomplished by employing N-phenyl acrylamides and N-tosyl acrylamides as substrates, respectively. Additionally, excellent regioselectivities are achieved when using unsymmetrical alkynes. This electrochemical process is environmentally benign compared to traditional transition metal-catalyzed C-H annulations because it avoids the use of stoichiometric metal oxidants. DFT calculations elucidated the reaction mechanism and origins of substituent-controlled chemoselectivity. The sequential C-H activation and alkyne insertion under rhodium catalysis leads to the seven-membered ring vinyl-rhodium intermediate. This intermediate undergoes either the classic neutral concerted reductive elimination to produce ?-pyridones, or the ionic stepwise pathway to produce cyclic imidates.
Project description:The development of metal-free organic reactions is one of the hotspots in the synthesis of cyclic compounds. ROTf (alkyl trifluoromethanesulfonates), due to their good electrophilicity, are powerful alkylating reagents at heteroatoms such as nitrogen, oxygen, sulfur and phosphorus to induce an electrophilic centre for carbon-carbon or carbon-heteroatom bond formation. Inspired by this chemistry, a variety of research concentrating on heterocycles synthesis has been carried out. In this review, we mainly summarize the ROTf-induced annulation of heteroatom reagents such as nitriles, carbodiimides, azobenzenes, isothiocyanates, aldehydes, isocyanates and phosphaalkene with themselves or alkynes to afford cyclic compounds.