Enantioselective palladium(0)-catalyzed C-H arylation strategy for chiral heterocycles

Transition-metal-catalyzed C-H functionalizations have emerged as complementary and powerful tools to access molecular complexity from widely available starting materials. Herein, we present a strategy for asymmetric intramolecular Pd(0)-catalyzed C-H functionalizations. The outlined reactivity is based on the cooperative effect between a chiral phosphorous ligand and a carboxylate base acting as a relay of chirality during the enantio-discriminating concerted metalation deprotonation step. This approach allows the enantioselective construction of a range of important semi-saturated chiral nitrogen-containing heterocycles such as indolines, tetrahydroquinolines, and dibenzazepinone

Photocatalytic Synthesis of Polycyclic Indolones

In this work, a photocatalytic strategy for a rapid and modular access to polycyclic indolones starting from readily available indoles is reported. This strategy relies on the use of redox-active esters in combination with an iridium-based photocatalyst under visible-light irradiation. The generation of alkyl radicals through decarboxylative single electron reductions enables intramolecular homolytic aromatic substitutions with a pending indole moiety to afford pyrrolo- and pyridoindolone derivatives under mild conditions. Furthermore, it was demonstrated that these radicals could also be engaged into cascades consisting of an intermolecular Giese-type addition followed by an intramolecular homolytic aromatic substitution to rapidly assemble valuable azepinoindolones

Enantioselective palladium(0)-catalyzed C-H arylation strategy for chiral heterocycles

Transition-metal-catalyzed C-H functionalizations have emerged as complementary and powerful tools to access molecular complexity from widely available starting materials. Herein, we present a strategy for asymmetric intramolecular Pd(0)-catalyzed C-H functionalizations. The outlined reactivity is based on the cooperative effect between a chiral phosphorous ligand and a carboxylate base acting as a relay of chirality during the enantio-discriminating concerted metalation deprotonation step. This approach allows the enantioselective construction of a range of important semi-saturated chiral nitrogen-containing heterocycles such as indolines, tetrahydroquinolines, and dibenzazepinones

Formal Homo-Nazarov and Other Cyclization Reactions of Activated Cyclopropanes

The Nazarov cyclization of divinyl ketones gives access to cyclopentenones. Replacing one of the vinyl groups by a cyclopropane leads to a formal homo-Nazarov process for the synthesis of cyclohexenones. In contrast to the Nazarov reaction, the cyclization of vinyl-cyclopropyl ketones is a stepwise process, often requiring harsh conditions. Herein, we describe two different approaches for further polarization of the three-membered ring of vinyl-cyclopropyl ketones to allow the formal homo-Nazarov reaction under mild catalytic conditions. In the first approach, the introduction of an ester group α to the carbonyl on the cyclopropane gave a more than tenfold increase in reaction rate, allowing us to extend the scope of the reaction to non-electron-rich aryl donor substituents in the β position to the carbonyl on the cyclopropane. In this case, a proof of principle for asymmetric induction could be achieved using chiral Lewis acid catalysts. In the second approach, heteroatoms, especially nitrogen, were introduced β to the carbonyl on the cyclopropane. In this case, the reaction was especially successful when the vinyl group was replaced by an indole heterocycle. With a free indole, the formal homo-Nazarov cyclization on the C3 position of indole was observed using a copper catalyst. In contrast, a new cyclization reaction on the N1 position was observed with Brønsted acid catalysts. Both reactions were applied to the synthesis of natural alkaloids. Preliminary investigations on the rationalization of the observed regioselectivity are also reported

Convenient Preparation of Tri-tert-butylphosphonium Tetrafluoroborate

The versatile tri-tert-butylphosphonium tetrafluoroborate ligand is prepared in a convenient, simple, and high-yielding procedure without the isolation of sensitive intermediates

Heteroatom Nucleophile Induced C-C Fragmentations to Access Functionalized Allenes

The rich structural and reactivity profile of allenes render them versatile synthetic intermediates. However, application of allenes in organic chemistry is often attenuated by inconvenient methods of preparation. Herein we present an operationally simple route to functionalized allenes from vinyl triflate precursors through a Grob-type fragmentation induced by heteroatom nucleophiles such as water, alcohols, thiols or amines. The fragmentation occurs under mild conditions and is well suited for one-pot or domino processes allowing access to a range of synthetically useful intermediates

Synthesis of Functionalized Spiroindolines via Palladium-Catalyzed Methine C-H Arylation

The synthesis of cyclopropyl spiroindolines is described using an intramolecular palladium(0)-catalyzed C-H functionalization of a methine C(sp(3))-H bond. This transformation can be coupled with intermolecular Suzuki couplings or direct arylations of heteroaromatics to access functionalized indoline scaffolds in a single step