Stereo- and Regiospecific SN2' Reaction of MBH Adducts with Isocyanoacetates: en Route to Transition-Metal-Free α-Allylation of Isocyanoacetates.

Herein, we report that under mild and transition-metal-free conditions an unprecedented and practical SN2' reaction of Morita-Baylis-Hillman adducts with isocyanoacetates takes place in a stereo- and regiospecific manner. This reaction which tolerates a wide variety of functionalities delivers transformable α-allylated isocyanoacetates in high efficiencies. Preliminary studies on the asymmetric version of this reaction indicate that ZnEt2/chiral amino alcohol combinations are an asymmetric catalytic system for this transformation, giving an enantioenriched α-allylated isocyanoacetate with a chiral quaternary carbon in a high yield.

Regulation of Chiral Phosphoric Acid Catalyzed Asymmetric Reaction through Crown Ether Based Host-Guest Chemistry.

Supramolecular asymmetric catalysis has arisen from the in-depth intersection of supramolecular chemistry and asymmetric catalysis due to its unique advantages in building chiral catalyst libraries and regulating performance of catalysts. Herein, we combine crown ether based host-guest chemistry with chiral phosphoric acid mediated asymmetric catalysis to actualize the supramolecular regulation of catalytic asymmetric two-component tandem acetalization reactions. By comparison with the catalytic reaction without host-guest interaction, improvement of up to 72% in yield and increases of up to 13% in enantioselectivity were acquired after addition of the alkali metal guests, which demonstrated the great advantages of this supramolecular regulation strategy.

Crown Ether-Derived Chiral BINOL: Enantioselective Michael Addition of Alkenyl Boronic Acids to α,ß-Unsaturated Ketones.

A new class of aza-crown ether-derived chiral BINOL catalysts were designed, synthesized, and applied in the asymmetric Michael addition of alkenylboronic acids to α,ß-unsaturated ketones. It was found that introducing aza-crown ethers to the BINOL catalyst could achieve apparently higher enantioselectivity than a similar BINOL catalyst without aza-crown ethers did, although the host-guest complexation of alkali ions by the aza-crown ethers could not further improve the catalysis effectiveness. Under mediation of the aza-crown ether-derived chiral BINOL and in the presence of a magnesium salt, an array of chiral γ,δ-unsaturated ketones were furnished in good enantioselectivities (81-95% ees).

Aerobic Cu-catalyzed oxidative 1 : 2 coupling of benzynes with terminal alkynes.

Cu-Catalyzed oxidative 1 : 2 couplings of arynes with nucleophilic terminal alkynes under aerobic conditions are described herein. A mechanistic investigation revealed a plausible involvement of an aryl-Cu(iii)-generating pathway. By this method, ubiquitous arenediynes can be efficiently assembled in a single step under mild conditions.

Chiral Metallacycles as Catalysts for Asymmetric Conjugate Addition of Styrylboronic Acids to α,ß-Enones.

Introducing self-assembly strategies into the construction of catalysts has been proven to have great advantages in asymmetric catalysis. We constructed two chiral metalla-triangles by highly efficient coordination-driven self-assembly from a chiral 3,3'-dipyridyl-substituted BINOL donor. They were successfully applied in asymmetric conjugate addition of a series of α,ß-unsaturated ketones with trans-styrylboronic acids. The use of these metalla-triangles as supramolecular catalysts is obviously conducive to the enhancement of catalytic activity and stereoselectivity in the presented addition reactions. Under induction of the chiral metalla-triangles, an array of α,ß-enones were converted to chiral γ,δ-unsaturated ketones in medium to quantitative yields (40-98%) with high enantioselectivities (87-96% ee).

Potassium tert-Butoxide-Mediated Condensation Cascade Reaction: Transition Metal-Free Synthesis of Multisubstituted Aryl Indoles and Benzofurans.

An efficient and facile method to synthesize valuable disubstituted 2-aryl indoles and benzofurans in good yields has been demonstrated, based on a tert-butoxide-mediated condensation reaction involving a vinyl sulfoxide intermediate. Products are obtained from N- or O-benzyl benzaldehydes using dimethyl sulfoxide as a carbon source. The methodology features a wide functional group tolerance and transition metal-free environment. Preliminary mechanistic studies suggest that the reaction involves a tandem aldol reaction/Michael addition/dehydrosulfenylation/isomerization sequence through an ionic protocol.

Palladium-catalyzed C-H alkenylation of arenes using thioethers as directing groups.

Thioethers have been proven to be reliable directing groups for palladium catalyzed alkenylation of arenes via C-H activation. Mechanistic investigation reveals that the C-H cleavage of arenes is the turnover-limiting step, and an acetate-bridged dinuclear cyclopalladation intermediate is involved. The alkenylated thioethers can be easily removed and transformed into a variety of useful groups.

Synthesis of functionalized indolizines via copper-catalyzed annulation of 2-alkylazaarenes with α,ß-unsaturated carboxylic acids.

A novel copper-catalyzed annulation of 2-alkylazaarenes with α,ß-unsaturated carboxylic acids has been accomplished. This reaction featuring C-H olefination and decarboxylative amination processes provides a concise access to C-2 arylated indolizines from simple and readily available starting materials.

Adenylate-forming enzymes of rubradirin biosynthesis: RubC1 is a bifunctional enzyme with aminocoumarin acyl ligase and tyrosine-activating domains.

The biosynthesis of aminocoumarin antibiotics requires two acyladenylate-forming enzymes: one for the activation of L-tyrosine as a precursor of the aminocoumarin moiety and another for the linkage of an acyl moiety to the aminocoumarin moiety. Unexpectedly, the biosynthetic gene cluster of the aminocoumarin antibiotic rubradirin was found to contain three genes for putative acyladenylate-forming enzymes of aminocoumarin biosynthesis and conjugation. We expressed, purified, and investigated these three proteins. Orf4 (55 kDa) was shown to be an active aminocoumarin acyl ligase. RubF6 (56 kDa) was inactive, but could be converted into an active enzyme by site-directed mutagenesis. RubC1 (138 kDa) was shown to be a unique bifunctional enzyme, comprising an aminocoumarin acyl ligase, and tyrosine-adenylation and peptidyl-carrier domains. This natural hybrid enzyme is unique among known proteins. A hypothesis is proposed as to how such an enzyme could offer a particularly effective machinery for aminocoumarin antibiotic biosynthesis.

Copper-catalyzed synthesis of α-amino imides from tertiary amines: Ugi-type three-component assemblies involving direct functionalization of sp3 C-Hs adjacent to nitrogen atoms.

α-Amino imides can be accessed straightforwardly from tertiary amines through copper-catalyzed three-component reactions involving the direct functionalization of sp(3) C-Hs adjacent to nitrogen atoms. This reaction has demonstrated a tolerance to a wide range of functionalizations and can be performed under very mild conditions. A plausible mechanism has been proposed in which an Ugi-type cascade assembly has been included.

Gold-catalyzed efficient tandem assembly of terminal alkynes and arynes: synthesis of alkynylated biphenyl derivatives.

Gold catalysts have been found to catalyze the tandem assembly of arynes and terminal alkynes efficiently in the presence of CuI under mild reaction conditions to provide useful alkynylated biphenyl derivatives.

Copper-catalyzed alkyne-aryne and alkyne-alkene-aryne coupling reactions.

The efficient copper-catalyzed two-component coupling reaction of alkynes with arynes and the three-component coupling reaction of alkynes with allylic chlorides and arynes have been developed. Copper acetylide was postulated as a transient intermediate for the initiation of the coupling reactions.

Synthesis of indolo[1,2-f]phenanthridines from palladium-catalyzed reactions of arynes.

A novel convenient approach for the construction of indolo[1,2-f]phenanthridine was developed from the reaction of arynes with 1-(2-bromophenyl)-1H-indole in the presence of palladium catalyst.

A new tandem reaction of benzyne: one-pot synthesis of aryl amines containing anthracene.

[reaction: see text] The reaction of benzyne with N-substituted imidazoles affords a novel way to prepare arylamines containing anthracene under very mild conditions. This transformation is assumed to proceed via a tandem reaction involving a Diels-Alder reaction and an intermolecular nucleophilic coupling reaction.