Construction Of All-carbon Quaternary Centers Research Articles

Rhodium-Catalyzed Asymmetric Allylation of Malononitriles as Masked Acyl Cyanide with Allenes: Efficient Access to β,γ-Unsaturated Carbonyls.

A rhodium-catalyzed regio- and enantioselective intermolecular allylation of malononitriles as masked acyl cyanides (MAC) with terminal and symmetrical internal allenes is reported. A RhI /Josiphos catalytic system combined with subsequent oxidative degradation of the primary adducts enables a straightforward access to α-branched, β,γ-unsaturated carbonyl compounds. The present protocol exhibits perfect atom economy in the allylation step and is characterized by a great functional group compatibility. Furthermore, the use of α-substituted malononitriles allowed for the construction of all-carbon quaternary centers.

ChemInform Abstract: Construction of All‐Carbon Quaternary Centers Through Cu‐Catalyzed Sequential Carbene Migratory Insertion and Nucleophilic Substitution/Michael Addition.

A Cu-catalyzed three-component cross-coupling reaction of terminal alkyne, α-diazo ester, and alkyl halide has been developed. This transformation involves sequent migratory insertion of copper-carbene and nucleophilic substitution, in which a C(sp)–C(sp3) bond and a C(sp3)–C(sp3) bond are formed successively on a carbenic center. Michael addition acceptors can also be employed instead of alkyl halides that enable Michael addition to be an alternative way to build C(sp3)–C(sp3) bond. This transformation represents a highly efficient method for the construction of all-carbon quaternary centers.

Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones.

The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF3)3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee’s up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee.

Construction of All-Carbon Quaternary Centers through Cu-Catalyzed Sequential Carbene Migratory Insertion and Nucleophilic Substitution/Michael Addition.

A Cu-catalyzed three-component cross-coupling reaction of terminal alkyne, α-diazo ester, and alkyl halide has been developed. This transformation involves sequent migratory insertion of copper-carbene and nucleophilic substitution, in which a C(sp)-C(sp(3)) bond and a C(sp(3))-C(sp(3)) bond are formed successively on a carbenic center. Michael addition acceptors can also be employed instead of alkyl halides that enable Michael addition to be an alternative way to build C(sp(3))-C(sp(3)) bond. This transformation represents a highly efficient method for the construction of all-carbon quaternary centers.

Rhodium(I)-Catalyzed Sequential C(sp)-C(sp(3)) and C(sp(3))-C(sp(3)) Bond Formation through Migratory Carbene Insertion.

A Rh(I)-catalyzed three-component reaction of tert-propargyl alcohol, diazoester, and alkyl halide has been developed. This reaction can be considered as a carbene-involving sequential alkyl and alkynyl coupling, in which C(sp)-C(sp(3)) and C(sp(3))-C(sp(3)) bonds are built successively on the carbenic carbon atom. The Rh(I)-carbene migratory insertion of an alkynyl moiety and subsequent alkylation are proposed to account for the two separate C-C bond formations. This reaction provides an efficient and tunable method for the construction of all-carbon quaternary center.

The design of a spiro-pyrrolidine organocatalyst and its application to catalytic asymmetric Michael addition for the construction of all-carbon quaternary centers.

A novel chiral spiro-pyrrolidine silyl ether organocatalyst has been designed. Its catalytic asymmetric effect is demonstrated by the Michael addition reaction, which affords the desired products with an all-carbon quaternary center in up to 99% ee and 87% yield. Furthermore, the reaction process has been investigated via in situ NMR experiments.

Stereoselective construction of all-carbon quaternary center by means of chiral phosphoric acid: highly enantioselective Friedel–Crafts reaction of indoles with β,β-disubstituted nitroalkenes

Chiral phosphoric acid catalyzed Friedel–Crafts reaction of indoles with β-alkoxycarbonyl-β-disubstituted nitroalkenes was achieved.

Enantioselective construction of all-carbon quaternary centers by branch-selective Pd-catalyzed allyl-allyl cross-coupling.

The Pd-catalyzed cross-coupling of racemic tertiary allylic carbonates and allylboronates is described. This reaction generates all-carbon quaternary centers in a highly regioselective and enantioselective fashion. The outcome of these reactions is consistent with a process that proceeds by way of 3,3'-reductive elimination of bis(η(1)-allyl)palladium intermediates. Strategies for distinguishing the product alkenes and application to the synthesis of (+)-α-cuparenone are also described.

Construction of All-Carbon Quaternary Center by R2AlCl−Mediated Ring-Opening Reaction of Oxacycles

An unexpected R(2)AlCl-mediated ring-opening reaction of oxacycles for the formation of all-carbon quaternary centers was discovered, and a possible mechanism is proposed. The developed chemistry provides a concise approach to synthesize structural diverse of dolastane-type compounds.

Stereoselective Quaternary Center Construction via Atom-Transfer Radical Cyclization Using Silicon Tethers on Acyclic Precursors

A novel strategy for the stereoselective construction of all-carbon quaternary centers on acyclic molecules using a two-step tandem process is reported. The first step involves an intramolecular and stereoselective atom transfer radical cyclization reaction from an allyl or vinyl subunit attached on a silyloxy, serving as a tether, to a tertiary radical alpha to an ester. A subsequent mild acidic elimination leads stereoselectively to a quaternary center bearing an allyl or a vinyl in high yield.

Catalytic Carbon−Carbon σ Bond Activation: An Intramolecular Carbo-Acylation Reaction with Acylquinolines

Carbon-carbon sigma-bond activation is a contemporary challenge for organometallic chemistry and catalysis. Herein, we disclose a new alkene carboacylation reaction initiated by quinoline-directed, rhodium-catalyzed C-C sigma bond activation. The alkene carboacylation allows for the construction of all-carbon quaternary centers, with a broad substrate scope, providing access to carbocyclic and heterocyclic ring systems in good to excellent yields.

Synthesis of Chiral, All-Carbon Quaternary Centers via Allylic Alkylation

Asymmetric allylic alkylations have been well explored; however, the enantioselective construction of all-carbon quaternary centers still remains a challenging goal. Using γ-acetoxy-α,β-unsaturated carbonyl compounds as π-allyl precursor and cyclic β-ketoesters as nucleophile in the presence of a Pd catalyst, Zn additive and chiral diaminophosphine oxide ligand (DIAPHOX), a variety of quaternary carbon compounds were synthesized with good to excellent enantioselectivity.