Tandem Rh(III)-Catalyzed Oxidative Acylation of Secondary Benzamides with Aldehydes and Intramolecular Cyclization: The Direct Synthesis of 3-Hydroxyisoindolin-1-ones

The rhodium-catalyzed oxidative acylation between secondary benzamides and aryl aldehydes via sp² C–H bond activation followed by an intramolecular cyclization is described. This method results in the direct and efficient synthesis of 3-hydroxyisoindolin-1-one building blocks

Methylene Thiazolidinediones as Alkylation Reagents in Catalytic C–H Functionalization: Rapid Access to Glitazones

The straightforward and rapid incorporation of a thiazolidinedione scaffold into prefunctionalized (hetero)aromatic compounds is in demand for the development of antidiabetic glitazones and other pharmaceuticals. Herein, we report the unprecedented N- and O-directed C–H alkylation of various (hetero)arenes with methylene thiazolidinediones under rhodium(III) catalysis. The applicability of the developed protocol in challenging contexts is exhibited by the late-stage installation of a methylene thiazolidinedione moiety on the C–H bond of commercially available drug molecules. Combined mechanistic investigations aided the elucidation of a plausible reaction mechanism

Rh(III)-Catalyzed C8-Spiroannulation of 1‑Aminonaphthalenes with Maleimides

The rhodium(III)-catalyzed C8-spiroannulation of 1-aminonaphthalenes with maleimides is described herein. Initially formed C8-alkenylated 1-aminonaphthalenes can intercept nucleophilic 1-amino groups through the intramolecular aza-Michael reaction, resulting in the formation of spirofused tetracyclic frameworks. This protocol displayed a wide substrate scope and a broad functional group compatibility. The synthetic utility of this process is demonstrated by the gram-scale synthesis, late-stage modification, and synthetic transformations

Methylene Thiazolidinediones as Alkylation Reagents in Catalytic C–H Functionalization: Rapid Access to Glitazones

The straightforward and rapid incorporation of a thiazolidinedione scaffold into prefunctionalized (hetero)aromatic compounds is in demand for the development of antidiabetic glitazones and other pharmaceuticals. Herein, we report the unprecedented N- and O-directed C–H alkylation of various (hetero)arenes with methylene thiazolidinediones under rhodium(III) catalysis. The applicability of the developed protocol in challenging contexts is exhibited by the late-stage installation of a methylene thiazolidinedione moiety on the C–H bond of commercially available drug molecules. Combined mechanistic investigations aided the elucidation of a plausible reaction mechanism

Disparate Downstream Reactions Mediated by an Ionically Controlled Supramolecular Tristate Switch

The use of chemical messengers to control multiple and often disparate downstream events is a hallmark of biological signaling. Here, we report a synthetic supramolecular construct that gives rise to bifurcated downstream events mediated by different stimulus-induced chemical messengers. The system in question consists of a supramolecular redox-ensemble made up of a tetrathiafulvalene (TTF)-based macrocycle, benzo-TTF-calix[4]­pyrrole, and an electron deficient partner, 7,7,8,8-tetracyanoquinodimethane (TCNQ). Different tetraalkylammonium halide salts are used to trigger the reversible switching between neutral (No-ET), charge transfer (CT), and electron transfer (ET) states. The result is an effective tristate switch that provides chemical access to three different forms of TCNQ, namely, a released neutral, radical anionic (TCNQ^•–), or bound CT forms. The ionically induced switching chemistry is linked separately through the neutral and radical anion TCNQ forms to two distinct follow-on reactions. These reactions consist, respectively, of styrene polymerization, which is triggered only in the “1” (TCNQ radical anion ET) state, and a cycloaddition–retroelectrocyclization (CA–RE) reaction, which is mediated only by the neutral TCNQ “0” (No-ET) state. Neither downstream reaction is promoted by the CT form, wherein the TCNQ is receptor bound. The three states that characterize this system, their interconversion, and the downstream reactions promoted by TCNQ^•– and free TCNQ, respectively, have been characterized by single-crystal X-ray diffraction analyses and various solution phase spectroscopies

Rh(III)-Catalyzed C8-Spiroannulation of 1‑Aminonaphthalenes with Maleimides

The rhodium(III)-catalyzed C8-spiroannulation of 1-aminonaphthalenes with maleimides is described herein. Initially formed C8-alkenylated 1-aminonaphthalenes can intercept nucleophilic 1-amino groups through the intramolecular aza-Michael reaction, resulting in the formation of spirofused tetracyclic frameworks. This protocol displayed a wide substrate scope and a broad functional group compatibility. The synthetic utility of this process is demonstrated by the gram-scale synthesis, late-stage modification, and synthetic transformations

Methylene Thiazolidinediones as Alkylation Reagents in Catalytic C–H Functionalization: Rapid Access to Glitazones

The straightforward and rapid incorporation of a thiazolidinedione scaffold into prefunctionalized (hetero)aromatic compounds is in demand for the development of antidiabetic glitazones and other pharmaceuticals. Herein, we report the unprecedented N- and O-directed C–H alkylation of various (hetero)arenes with methylene thiazolidinediones under rhodium(III) catalysis. The applicability of the developed protocol in challenging contexts is exhibited by the late-stage installation of a methylene thiazolidinedione moiety on the C–H bond of commercially available drug molecules. Combined mechanistic investigations aided the elucidation of a plausible reaction mechanism

Disparate Downstream Reactions Mediated by an Ionically Controlled Supramolecular Tristate Switch

The use of chemical messengers to control multiple and often disparate downstream events is a hallmark of biological signaling. Here, we report a synthetic supramolecular construct that gives rise to bifurcated downstream events mediated by different stimulus-induced chemical messengers. The system in question consists of a supramolecular redox-ensemble made up of a tetrathiafulvalene (TTF)-based macrocycle, benzo-TTF-calix[4]­pyrrole, and an electron deficient partner, 7,7,8,8-tetracyanoquinodimethane (TCNQ). Different tetraalkylammonium halide salts are used to trigger the reversible switching between neutral (No-ET), charge transfer (CT), and electron transfer (ET) states. The result is an effective tristate switch that provides chemical access to three different forms of TCNQ, namely, a released neutral, radical anionic (TCNQ^•–), or bound CT forms. The ionically induced switching chemistry is linked separately through the neutral and radical anion TCNQ forms to two distinct follow-on reactions. These reactions consist, respectively, of styrene polymerization, which is triggered only in the “1” (TCNQ radical anion ET) state, and a cycloaddition–retroelectrocyclization (CA–RE) reaction, which is mediated only by the neutral TCNQ “0” (No-ET) state. Neither downstream reaction is promoted by the CT form, wherein the TCNQ is receptor bound. The three states that characterize this system, their interconversion, and the downstream reactions promoted by TCNQ^•– and free TCNQ, respectively, have been characterized by single-crystal X-ray diffraction analyses and various solution phase spectroscopies

Disparate Downstream Reactions Mediated by an Ionically Controlled Supramolecular Tristate Switch

The use of chemical messengers to control multiple and often disparate downstream events is a hallmark of biological signaling. Here, we report a synthetic supramolecular construct that gives rise to bifurcated downstream events mediated by different stimulus-induced chemical messengers. The system in question consists of a supramolecular redox-ensemble made up of a tetrathiafulvalene (TTF)-based macrocycle, benzo-TTF-calix[4]­pyrrole, and an electron deficient partner, 7,7,8,8-tetracyanoquinodimethane (TCNQ). Different tetraalkylammonium halide salts are used to trigger the reversible switching between neutral (No-ET), charge transfer (CT), and electron transfer (ET) states. The result is an effective tristate switch that provides chemical access to three different forms of TCNQ, namely, a released neutral, radical anionic (TCNQ^•–), or bound CT forms. The ionically induced switching chemistry is linked separately through the neutral and radical anion TCNQ forms to two distinct follow-on reactions. These reactions consist, respectively, of styrene polymerization, which is triggered only in the “1” (TCNQ radical anion ET) state, and a cycloaddition–retroelectrocyclization (CA–RE) reaction, which is mediated only by the neutral TCNQ “0” (No-ET) state. Neither downstream reaction is promoted by the CT form, wherein the TCNQ is receptor bound. The three states that characterize this system, their interconversion, and the downstream reactions promoted by TCNQ^•– and free TCNQ, respectively, have been characterized by single-crystal X-ray diffraction analyses and various solution phase spectroscopies

Disparate Downstream Reactions Mediated by an Ionically Controlled Supramolecular Tristate Switch

The use of chemical messengers to control multiple and often disparate downstream events is a hallmark of biological signaling. Here, we report a synthetic supramolecular construct that gives rise to bifurcated downstream events mediated by different stimulus-induced chemical messengers. The system in question consists of a supramolecular redox-ensemble made up of a tetrathiafulvalene (TTF)-based macrocycle, benzo-TTF-calix[4]­pyrrole, and an electron deficient partner, 7,7,8,8-tetracyanoquinodimethane (TCNQ). Different tetraalkylammonium halide salts are used to trigger the reversible switching between neutral (No-ET), charge transfer (CT), and electron transfer (ET) states. The result is an effective tristate switch that provides chemical access to three different forms of TCNQ, namely, a released neutral, radical anionic (TCNQ^•–), or bound CT forms. The ionically induced switching chemistry is linked separately through the neutral and radical anion TCNQ forms to two distinct follow-on reactions. These reactions consist, respectively, of styrene polymerization, which is triggered only in the “1” (TCNQ radical anion ET) state, and a cycloaddition–retroelectrocyclization (CA–RE) reaction, which is mediated only by the neutral TCNQ “0” (No-ET) state. Neither downstream reaction is promoted by the CT form, wherein the TCNQ is receptor bound. The three states that characterize this system, their interconversion, and the downstream reactions promoted by TCNQ^•– and free TCNQ, respectively, have been characterized by single-crystal X-ray diffraction analyses and various solution phase spectroscopies