A DNA-conjugated small molecule catalyst enzyme mimic for site-selective ester hydrolysis.

The challenge of site-selectivity must be overcome in many chemical research contexts, including selective functionalization in complex natural products and labeling of one biomolecule in a living system. Synthetic catalysts incorporating molecular recognition domains can mimic naturally-occurring enzymes to direct a chemical reaction to a particular instance of a functional group. We propose that DNA-conjugated small molecule catalysts (DCats), prepared by tethering a small molecule catalyst to a DNA aptamer, are a promising class of reagents for site-selective transformations.

Aerobic Copper-Catalyzed O-Methylation with Methylboronic Acid.

The oxidative coupling of alkylboronic acids with oxygen nucleophiles offers a strategy for replacing toxic, electrophilic alkylating reagents. Although the Chan-Lam reaction has been widely applied in the arylation of heteroatom nucleophiles, O-alkylation with boronic acids is rare. We report a Cu-catalyzed nondecarboxylative methylation of carboxylic acids with methylboronic acid that proceeds in air with no additional oxidant.

Catalytic methyl transfer from dimethylcarbonate to carboxylic acids.

Although methylation reactions are commonplace, currently used reagents are hazardous, toxic, and/or unstable. Dimethylcarbonate has been put forth as an inexpensive, nontoxic, and "green" potential methylating reagent. Herein we report a general, base-catalyzed methyl transfer from dimethylcarbonate to carboxylic acids.

Interaction-dependent PCR: identification of ligand-target pairs from libraries of ligands and libraries of targets in a single solution-phase experiment.

Interaction-dependent PCR (IDPCR) is a solution-phase method to identify binding partners from combined libraries of small-molecule ligands and targets in a single experiment. Binding between DNA-linked targets and DNA-linked ligands induces formation of an extendable duplex. Extension links codes that identify the ligand and target into one selectively amplifiable DNA molecule.

Reactivity-dependent PCR: direct, solution-phase in vitro selection for bond formation.

In vitro selection is a key component of efforts to discover functional nucleic acids and small molecules from libraries of DNA, RNA, and DNA-encoded small molecules. Such selections have been widely used to evolve RNA and DNA catalysts and, more recently, to discover new reactions from DNA-encoded libraries of potential substrates. While effective, current strategies for selections of bond-forming and bond-cleaving reactivity are generally indirect, require the synthesis of biotin-linked substrates, and involve multiple solution-phase and solid-phase manipulations.

Fluorenes and styrenes by Au(I)-catalyzed annulation of enynes and alkynes.

Intermolecular annulation of enynes and propargyl esters to selectively produce styrenes or fluorenes is reported. The divergent arene syntheses involve a Au-catalyzed, two-pot, multistep process proceeding by cis-diastereoselective cyclopropanation, cycloisomerization, and, finally, annulation or elimination.

Relativistic effects in homogeneous gold catalysis.

Transition-metal catalysts containing gold present new opportunities for chemical synthesis, and it is therefore not surprising that these complexes are beginning to capture the attention of the chemical community. Cationic phosphine-gold(i) complexes are especially versatile and selective catalysts for a growing number of synthetic transformations. The reactivity of these species can be understood in the context of theoretical studies on gold; relativistic effects are especially helpful in rationalizing the reaction manifolds available to gold catalysts.

Synthesis of benzonorcaradienes by gold(I)-catalyzed [4+3] annulation.

A formal [4 + 3]-annulation of vinyl arenes and diynyl propargyl esters is described. A mechanism involving cationic phosphinegold(I)-catalyzed tandem cyclopropanation/hydroarylation to produce the benzonorcaradiene products is proposed. In accord with this mechanism, the alkynyl cyclopropane can also be prepared with excellent regio- and diastereocontrol.

Gold(I)-catalyzed stereoselective olefin cyclopropanation.

A triphenylphosphinegold(I)-catalyzed cyclopropanation of olefins using propargyl esters as gold(I)-carbene precursors is reported. This reaction provided the basis for the use of a DTBM-SEGPHOS gold(I) complex as a catalyst in the enantioselective (up to 94% ee) preparation of vinyl cyclopropanes with high cis-selectivity.

Gold(I)-catalyzed intramolecular acetylenic Schmidt reaction.

Substituted pyrroles were prepared by a gold(I)-catalyzed acetylenic Schmidt reaction of homopropargyl azides. The reaction allows for regiospecific substitution at each position of the pyrrole ring under mild conditions. A mechanism in which azides serve as nucleophiles toward gold(I)-activated alkynes with subsequent gold(I)-aided expulsion of dinitrogen is proposed.

Synthesis of 2-cyclopentenones by gold(I)-catalyzed Rautenstrauch rearrangement.

The rearrangement of 1-ethynyl-2-propenyl pivaloates to cyclopentenones catalyzed by cationic triphenylphosphinegold(I) complexes is described. The reaction tolerates both alkyl and aryl substitution at the acetylenic and olefinic positions. Importantly, the gold(I)-catalyzed rearrangement of enantioenriched propargyl pivaloates proceeds with excellent chirality transfer, thus providing a practical method for the enantioselective synthesis of cyclopentenones.