The Same but Different: Isostructural Polymorphs and the Case of 3‑Chloromandelic Acid

The expression “isostructural polymorphs” would appear to be an impossible combination of two mutually incompatible words. “Isostructural” implies a high degree of structural similarity; however, conversely, “polymorph” implies structural distinguishability. The structures of two newly determined polymorphs of 3-chloromandelic acid nevertheless justify the use of this expression, for they differ only in crystal symmetry and hardly at all in molecular position or conformation within the crystalline lattice. We demonstrate that parameters derived by the XPac program can be useful in establishing the limits of isostructurality

When Weaker Can Be Tougher: The Role of Oxidation State (I) in P- vs N‑Ligand-Derived Ni-Catalyzed Trifluoromethylthiolation of Aryl Halides

The direct introduction of the valuable SCF₃ moiety into organic molecules has received considerable attention. While it can be achieved successfully for aryl chlorides under catalysis with Ni⁰(cod)₂ and dppf, this report investigates the Ni-catalyzed functionalization of the seemingly more reactive aryl halides ArI and ArBr. Counterintuitively, the observed conversion triggered by dppf/Ni⁰ is ArCl > ArBr > ArI, at odds with bond strength preferences. By a combined computational and experimental approach, the origin of this was identified to be due to the formation of (dppf)­Ni^I, which favors β-F elimination as a competing pathway over the productive cross-coupling, ultimately generating the inactive complex (dppf)­Ni­(SCF₂) as a catalysis dead end. The complexes (dppf)­Ni^I–Br and (dppf)­Ni^I–I were isolated and resolved by X-ray crystallography. Their formation was found to be consistent with a ligand-exchange-induced comproportionation mechanism. In stark contrast to these phosphine-derived Ni complexes, the corresponding nitrogen-ligand-derived species were found to be likely competent catalysts in oxidation state I. Our computational studies of N-ligand derived Ni^I complexes fully support productive Ni^I/Ni^III catalysis, as the competing β-F elimination is disfavored. Moreover, N-derived Ni^I complexes are predicted to be more reactive than their Ni⁰ counterparts in catalysis. These data showcase fundamentally different roles of Ni^I in carbon–heteroatom bond formation depending on the ligand sphere

Synthesis of Oxindole-Based Bioorganometallic Kinase Inhibitors Incorporating One or More Ferrocene Groups

A series of oxindole-containing ferrocenes has been synthesized, studied in the solid state by X-ray crystallography, and tested for in vitro kinase inhibition. Many compounds show low or submicromolar activities against DYRK isoforms and VEGFR2, which in certain cases have been rationalized by molecular docking studies

Synthesis of Oxindole-Based Bioorganometallic Kinase Inhibitors Incorporating One or More Ferrocene Groups

A series of oxindole-containing ferrocenes has been synthesized, studied in the solid state by X-ray crystallography, and tested for in vitro kinase inhibition. Many compounds show low or submicromolar activities against DYRK isoforms and VEGFR2, which in certain cases have been rationalized by molecular docking studies

Synthesis of a Class of Core-Modified Aza-BODIPY Derivatives

The convenient synthesis of a new class of conjugated aza-BODIPY derivatives from readily available precursors has been achieved. The new materials bear close structural similarity to BODIPYs but differ significantly in electronic configuration from known derivatives, leading to markedly different absorption and emission properties

Stereoselective Synthesis of Densely Functionalized Pyrrolidin-2-ones by a Conjugate Addition/Nitro-Mannich/Lactamization Reaction

Copper-catalyzed conjugate addition of diorgano zinc reagents to nitroacrylate <b>1</b> followed by a subsequent nitro-Mannich reaction and <i>in situ</i> lactamization leads to an efficient one-pot synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones (<b>5</b>). The versatility of the reaction is shown for a wide range of <i>N</i>-<i>p</i>-(methoxy)­phenyl protected aldimines <b>3</b> derived from alkyl, aryl, and heteroaryl aldehydes. The densely functionalized pyrrolidin-2-ones <b>5</b> are isolated as single diastereoisomers (40 examples, 33–84% yield). An enantioselective copper-catalyzed conjugate addition of diethylzinc led to highly crystalline products that could be recrystallized to enantiopurity in high yield. A range of successful chemoselective transformations were investigated, which widens the applicability of the pyrrolidn-2-ones as stereochemically pure building blocks for further organic synthesis

Stereoselective Synthesis of Densely Functionalized Pyrrolidin-2-ones by a Conjugate Addition/Nitro-Mannich/Lactamization Reaction

Copper-catalyzed conjugate addition of diorgano zinc reagents to nitroacrylate <b>1</b> followed by a subsequent nitro-Mannich reaction and <i>in situ</i> lactamization leads to an efficient one-pot synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones (<b>5</b>). The versatility of the reaction is shown for a wide range of <i>N</i>-<i>p</i>-(methoxy)­phenyl protected aldimines <b>3</b> derived from alkyl, aryl, and heteroaryl aldehydes. The densely functionalized pyrrolidin-2-ones <b>5</b> are isolated as single diastereoisomers (40 examples, 33–84% yield). An enantioselective copper-catalyzed conjugate addition of diethylzinc led to highly crystalline products that could be recrystallized to enantiopurity in high yield. A range of successful chemoselective transformations were investigated, which widens the applicability of the pyrrolidn-2-ones as stereochemically pure building blocks for further organic synthesis

Stereoselective Synthesis of Densely Functionalized Pyrrolidin-2-ones by a Conjugate Addition/Nitro-Mannich/Lactamization Reaction

Copper-catalyzed conjugate addition of diorgano zinc reagents to nitroacrylate <b>1</b> followed by a subsequent nitro-Mannich reaction and <i>in situ</i> lactamization leads to an efficient one-pot synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones (<b>5</b>). The versatility of the reaction is shown for a wide range of <i>N</i>-<i>p</i>-(methoxy)­phenyl protected aldimines <b>3</b> derived from alkyl, aryl, and heteroaryl aldehydes. The densely functionalized pyrrolidin-2-ones <b>5</b> are isolated as single diastereoisomers (40 examples, 33–84% yield). An enantioselective copper-catalyzed conjugate addition of diethylzinc led to highly crystalline products that could be recrystallized to enantiopurity in high yield. A range of successful chemoselective transformations were investigated, which widens the applicability of the pyrrolidn-2-ones as stereochemically pure building blocks for further organic synthesis

Expanded Porphyrin-like Structures Based on Twinned Triphenylenes

Triphenylene twins are intriguing structures, and those bridged through their 3,6-positions by dipyrromethene units give a new class of macrocycles that can be viewed as rigid, expanded porphyrin derivatives in which coplanarity is enforced in a formally antiaromatic π system. Somewhat surprisingly, however, macrocyclization leads to significant overall stabilization of the dipyrromethene chromophores