Remote Enantioselective [4 + 1] Annulation with Copper-Vinylvinylidene Intermediates.

The first copper-catalyzed enantioselective [4 + 1] annulation of yne-allylic esters with 1,3-dicarbonyl compounds was realized through an elegant remote stereocontrol strategy. The very remote ε regioselective nucleophilic substitution was developed by employing a novel chiral copper-vinylvinylidene species from the new C4 synthon yne-allylic esters. Thus, greatly diverse spirocycles were obtained with ample scope and excellent levels of chemo-, regio-, and enantioselectivities. Moreover, detailed mechanistic studies suggest an yne-allylic substitution and Conia-ene cascade pathway on the remote stereochemical induction progress.

Catalytic Asymmetric Vinylogous and Bisvinylogous Propargylic Substitution.

Distinct regio- and enantioselectivity control in copper-catalyzed vinylogous and bisvinylogous propargylic substitution has been accomplished by using a novel chiral N,N,P ligand. The developed method provides an efficient and selective approach to an array of highly enantioenriched alkynyl unsaturated carbonyl compounds. Salient features include excellent functional group tolerance and broad substrate scope. The synthetic utility of the developed method is further demonstrated by a gram-scale synthesis and by application to a range of transformations including enantioselective synthesis of unique challenging compounds.

Ynamide-Mediated Thionoester and Dithioester Syntheses.

A novel ynamide-mediated synthesis of thionoesters and dithioesters is described. The selective addition reactions of various monothiocarboxylic acids with ynamide furnish α-thioacyloxyenamides, which undergo transesterification with nucleophilic -OH or -SH species to afford thionoesters and dithioesters, respectively. The broad substrate scope, mild reaction conditions, and excellent yields make this method an attractive synthetic approach to thionoesters and dithioesters.

Site-Specific Incorporation of Multiple Thioamide Substitutions into a Peptide Backbone via Solid Phase Peptide Synthesis.

Among various peptide modification strategies, thioamide substitution by replacing the carbonyl oxygen atom of an amide bond with a sulfur atom constitutes an invaluable tool for chemical biology, for use in peptide drug discovery and protein structure-function studies. However, the thioamide substitution effect has not been well studied because of the lack of synthetic methods for site-specifically incorporating a thioamide bond into a peptide backbone, particularly introducing multiple thioamide substitutions into peptide on a solid support. Herein, we report a highly efficient method for incorporating a thioamide bond into the peptide backbone in a site-specific manner by employing α-thioacyloxyenamides, which are formed from the addition of N-protected monothioamino acids and ynamides, as novel thioacylating reagents in solid phase peptide synthesis. This method is amenable for 19 of 20 proteinogenic amino acids, His being the exception. One to multiple thioamide substitutions could be incorporated into a growing peptide with no epimerization or a low level of epimerization. By using this method, a fully thioamide-substituted hexapeptide containing up to five continuous thioamide bonds could be synthesized smoothly. This synthetic methodology will spur the application of the thioamide substitution tool for protein engineering and peptide drug discovery.

High energy flexible supercapacitors formed via bottom-up infilling of gel electrolytes into thick porous electrodes.

Formation of thick, high energy density, flexible solid supercapacitors is challenging because of difficulties infilling gel electrolytes into porous electrodes. Incomplete infilling results in a low capacitance and poor mechanical properties. Here we report a bottom-up infilling method to overcome these challenges. Electrodes up to 500 µm thick, formed from multi-walled carbon nanotubes and a composite of poly(3,4-ethylenedioxythiophene), polystyrene sulfonate and multi-walled carbon nanotubes are successfully infilled with a polyvinyl alcohol/phosphoric acid gel electrolyte. The exceptional mechanical properties of the multi-walled carbon nanotube-based electrode enable it to be rolled into a radius of curvature as small as 0.5 mm without cracking and retain 95% of its initial capacitance after 5000 bending cycles. The areal capacitance of our 500 µm thick poly(3,4-ethylenedioxythiophene), polystyrene sulfonate, multi-walled carbon nanotube-based flexible solid supercapacitor is 2662 mF cm-2 at 2 mV s-1, at least five times greater than current flexible supercapacitors.

Enantioselective Polyene Cyclization Catalyzed by a Chiral Brønsted Acid.

The first enantioselective polyene cyclization initiated by a BINOL-derived chiral N-phosphoramide (NPA) catalyzed protonation of an imine is described. The ion-pair formed between the iminium ion and chiral counter anion of the NPA plays an important role for controlling the stereochemistry of the overall transformation. This strategy offers a highly efficient approach to fused tricyclic frameworks containing three contiguous stereocenters, which are widely found in natural products. In addition, the first catalytic asymmetric total synthesis of (-)-ferruginol was accomplished with an NPA catalyzed enantioselective polyene cyclization, as the key step for the construction of the tricyclic core, with excellent yield and enantioselectivity.

Synthesis of Pyrido-Fused Quinazolinone Derivatives via Copper-Catalyzed Domino Reaction.

A simple and efficient synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones by Cu(OAc)2·H2O-catalyzed reaction of easily available substituted isatins and 2-bromopyridine derivatives has been developed. The reaction involves C-N/C-C bond cleavage and two C-N bond formations in a one-pot operation. This methodology is complementary to previously reported synthetic procedures, and two plausible reaction mechanisms are discussed.