Cross-Dehydrogenative Couplings between Indoles and β-Keto Esters : Ligand-Assisted Ligand Tautomerization and Dehydrogenation via a Proton-Assisted Electron Transfer to Pd(II)

Cross-dehydrogenative coupling reactions between -ketoesters and electron-rich arenes, such as indoles, proceed with high regiochemical fidelity with a range of -ketoesters and indoles. The mechanism of the reaction between a prototypical -ketoester, ethyl 2-oxocyclopentanonecarboxylate and N-methylindole, has been studied experimentally by monitoring the temporal course of the reaction by 1H NMR, kinetic isotope effect studies, and control experiments. DFT calculations have been carried out using a dispersion-corrected range-separated hybrid functional (B97X-D) to explore the basic elementary steps of the catalytic cycle. The experimental results indicate that the reaction proceeds via two catalytic cycles. Cycle A, the dehydrogenation cycle, produces an enone intermediate. The dehydrogenation is assisted by N-methylindole, which acts as a ligand for Pd(II). The compu-tational studies agree with this conclusion, and identify the turnover-limiting step of the dehydrogenation step, which involves a change in the coordination mode of the -keto ester ligand from an O,O’-chelate to an C-bound Pd enolate. This ligand tautom-erization event is assisted by the -bound indole ligand. Subsequent scission of the ’-C–H bond takes place via a proton-assisted electron transfer mechanism, where Pd(II) acts as an electron sink and the trifluoroacetate ligand acts as a proton acceptor, to pro-duce the Pd(0) complex of the enone intermediate. The coupling is completed in cycle B, where the enone is coupled with indole. Pd(TFA)2 and TFA-catalyzed pathways were examined experimentally and computationally for this cycle, and both were found to be viable routes for the coupling step

Hydrogen bonding in organic synthesis

This first comprehensive overview of the rapidly growing field emphasizes the use of hydrogen bonding as a tool for organic synthesis, especially catalysis. As such, it covers such topics as enzyme chemistry, organocatalysis and total synthesis, all unified by the unique advantages of hydrogen bonding in the construction of complex molecules from simple precursors.Providing everything you need to know, this is a definite must for every synthetic chemist in academia and industry

Carboxylate-Catalyzed C-Silylation of Terminal Alkynes

A carboxylate-catalyzed, metal-free C-silylation protocol for terminal alkynes is reported using a quaternary ammonium pivalate as the catalyst and commercially available N,O-bis(silyl)acetamides as silylating agents. The reaction proceeds under mild conditions, tolerates a range of functionalities, and enables concomitant O- or N-silylation of acidic OH or NH groups. A Hammett ρ value of +1.4 ± 0.1 obtained for para-substituted 2-arylalkynes is consistent with the proposed catalytic cycle involving a turnover-determining deprotonation step.peerReviewe

Carboxylate Catalysis : A Catalytic O-Silylative Aldol Reaction of Aldehydes and Ethyl Diazoacetate

A mild catalytic variant of the aldol reaction between ethyl diazoacetate and aldehydes is described using a combination of N,O-bis(trimethylsilyl)acetamide and catalytic tetramethylammonium pivalate as catalyst. The reaction proceeds rapidly at ambient temperature to afford the O-silylated aldol products in good to excellent yield, and the acetamide byproducts can be removed by simple filtration.peerReviewe

Catalytic Enantioselective Total Synthesis of (+)–Lycoperdic Acid

A concise enantio- and stereocontrolled synthesis of (+)-lycoperdic acid is presented. The stereochemical control is based on iminium-catalyzed Mukaiyama–Michael reaction and enamine-catalyzed organocatalytic α-chlorination steps. The amino group was introduced by azide displacement, affording the final stereochemistry of (+)-lycoperdic acid. Penultimate hydrogenation and hydrolysis afforded pure (+)-lycoperdic acid in seven steps from a known silyloxyfuran.peerReviewe

Palladium on Charcoal as a Catalyst for Stoichiometric Chemo- and Stereoselective Hydrosilylations and Hydrogenations with Triethylsilane

Stoichiometric quantities of triethylsilane in the presence of activated Pd/C as the catalyst can be used to effect chemo-, regio-, and stereoselective hydrosilylation and transfer hydrogenation reactions. α,β-Unsaturated aldehydes and ketones are selectively hydrosilylated to give the corresponding enol silanes or transfer hydrogenated to give the saturated carbonyl compounds in the presence of other reducible functional groups

Correction to Mild Organocatalytic α‑Methylenation of Aldehydes

Correction to Mild Organocatalytic α‑Methylenation of Aldehyde

Enantioselective Mannich Reaction of β‑Keto Esters with Aromatic and Aliphatic Imines Using a Cooperatively Assisted Bifunctional Catalyst

An efficient urea-enhanced thiourea catalyst enables the enantioselective Mannich reaction between β-keto esters and <i>N</i>-Boc-protected imines under mild conditions and minimal catalyst loading (1–3 mol %). Aliphatic and aromatic substituents are tolerated on both reaction partners, affording the products in good enantiomeric purity. The corresponding β-amino ketones can readily be accessed via decarboxylation without loss of enantiomeric purity

Carboxylate Catalysis: A Catalytic <i>O</i>‑Silylative Aldol Reaction of Aldehydes and Ethyl Diazoacetate

A mild catalytic variant of the aldol reaction between ethyl diazoacetate and aldehydes is described using a combination of N,O-bis(trimethylsilyl)acetamide and catalytic tetramethylammonium pivalate as catalyst. The reaction proceeds rapidly at ambient temperature to afford the O-silylated aldol products in good to excellent yield, and the acetamide byproducts can be removed by simple filtration