Copper-Catalyzed Regioselective Imidation of 2-Pyridones.

We demonstrate a ligand- and glovebox-free regioselective direct C(3)-H imidation of 2-pyridones and also benzylic-type imidation of 2-pyridones bearing a methyl substituent employing Cu(OAc)·HO as the catalyst and -fluorobenzenesulfonimide (NFSI) as an imidating reagent. A broad range of imidated 2-pyridone derivatives is made up to excellent yields. The present strategy operates well on a gram scale, and the ensuing product can be readily subjected to - and -desulfonylation reactions.

Direct Trideuteromethylation of Sulfenate Anions Generated In Situ from β-Sulfinyl Esters: An Access to Trideuteromethyl Sulfoxides.

Deuterated organic molecules have immense value in the pharmaceutical industry. Here, we present a synthetic strategy for direct trideuteromethylation of sulfenate ions derived in situ from β-sulfinyl esters in the presence of a base utilizing inexpensive and abundant CDOTs as the electrophilic trideuteromethylating agent. This protocol provides straightforward access to an array of trideuteromethyl sulfoxides in yields of 75-92% with a high degree of deuteration.

Palladium-Catalyzed Regioselective C3-Allylic Alkylation of 2-Aryl Imidazopyridines with MBH Carbonates.

Imidazopyridine is an important framework that constitutes several pharmaceutical drugs and biologically active molecules. Herein, we present the palladium-catalyzed regioselective C3-allylic alkylation of 2-aryl imidazopyridines with MBH carbonates. This strategy furnishes a broad spectrum of C3-allylated imidazopyridines, and their structures have been unequivocally established using X-ray analysis.

Heteroarylation of Sulfenate Ions In Situ Generated from β-Sulfinyl Esters under Transition-Metal-Free Conditions.

Heteroaryl sulfoxides are an integral part of several bioactive molecules and pharmaceuticals. We have described a transition-metal-free route for the direct sulfinylation of 2-halobenzothiazoles and 2-halobenzimidazoles using β-sulfinyl esters as the source of the sulfenate ion in the presence of a Brønsted base such as LiOBu, and the corresponding heteroaryl sulfoxides were isolated in yields of 30 to 94%. Moreover, we hypothesized a plausible concerted nucleophilic aromatic substitution (cSAr) pathway for the direct incorporation of sulfinyl functionality into the 2-haloheteroarenes.

Regioselective allenylation and propargylation of various -quinone methides using alkynyl azaarenes as pronucleophiles.

We have developed Brønsted base-mediated regioselective allenylation and propargylation of various -quinone methides using unfunctionalized 2-alkynyl azaarenes as pronucleophiles. The appropriate choice of a base provides an opportunity to achieve either an allenylated product or the propargylated product. The use of KOBu as a Brønsted base promotes the formation of allenylated products, whereas NaN(SiMe) furnishes the propargylated products.

Palladium-Catalyzed Direct C2-Biarylation of Indoles.

Biaryl and indole units are important structural motifs in several bioactive molecules and functional materials. We have accomplished straightforward access to C2-biarylated indole derivatives through palladium-catalyzed C-H activation strategy with a broad range of substrate scope in yields of 24 to 92%. Besides, the UV/visible absorption and fluorescence properties of the ensuing products were explored.

Base-promoted 1,6-conjugate addition of alkylazaarenes to para-quinone methides.

1,1,2-Triarylethanes embedded with an azaarene unit were prepared in a single step at ambient temperature via the sodium hexamethyldisilazide mediated 1,6-conjugate addition of unactivated alkylazaarenes on para-quinone methides (p-QMs). The extent of this methodology was investigated with a wide range of p-QMs and alkylazaarenes, and the respective products were obtained in moderate to excellent yields. The regioselective 1,6-conjugate addition of the trialkylazaarene precursor on para-quinone methide was also presented.

Direct Catalytic Asymmetric Mannich-Type Reaction of α- and β-Fluorinated Amides.

The last two decades have witnessed the emergence of direct enolization protocols providing atom-economical and operationally simple methods to use enolates for stereoselective C-C bond-forming reactions, eliminating the inherent drawback of the preformation of enolates using stoichiometric amounts of reagents. In its infancy, direct enolization relied heavily on the intrinsic acidity of the latent enolates, and the reaction scope was limited to readily enolizable ketones and aldehydes. Recent advances in this field enabled the exploitation of carboxylic acid derivatives for direct enolization, offering expeditious access to synthetically versatile chiral building blocks.

Iterative direct aldol strategy for polypropionates: enantioselective total synthesis of (-)-membrenone A and B.

An iterative direct aldol reaction using a C3 propionate unit as an aldol donor offers expeditious access to polyketide assembly in a highly diastereo- and enantioselective manner. An all-syn polyketide array with four consecutive stereogenic centers was efficiently constructed by an aldol reaction of thiopropionamide via soft Lewis acid/hard Brønsted base cooperative catalysis. This iterative aldol strategy led to an enantioselective synthesis of (-)-membrenone A and B.

Two approaches toward the formal total synthesis of oseltamivir phosphate (Tamiflu): catalytic enantioselective three-component reaction strategy and L-glutamic acid strategy.

Two independent formal total syntheses of oseltamivir phosphate were successfully achieved: the first utilized a copper-catalyzed asymmetric three-component reaction strategy, and the second utilized L-glutamic acid γ-ester as a chiral source to install the correct stereochemistry. Both strategies used Dieckmann condensation to construct a six-membered ring core, after which manipulation of the functional groups and protecting groups accessed Corey's intermediate for the synthesis of oseltamivir phosphate. While the first synthesis was accomplished via four purification steps in 25.

A versatile C-H functionalization of tetrahydroisoquinolines catalyzed by iodine at aerobic conditions.

A versatile aerobic catalytic system (I(2) and O(2)/TBHP) for C-H functionalization is reported. This CDC (cross-dehydrogentive coupling) reaction is compatible with a large number of nucleophiles and is performed under ambient reaction conditions. The scope of the metal-free CDC is illustrated by synthesizing a variety of functionalized tetrahydroisoquinolines and N,N-dimethylaniline.

C-H functionalization of tertiary amines by cross dehydrogenative coupling reactions: solvent-free synthesis of α-aminonitriles and β-nitroamines under aerobic condition.

A solvent-free synthesis of α-aminonitriles and β-nitroamines by oxidative cross-dehydrogenative coupling under aerobic condition is reported. A catalytic amount of molybdenum(vi) acetylacetonoate was found to catalyze cyanation of tertiary amines to form α-aminonitriles, whereas vanadium pentoxide was found to promote aza-Henry reaction to furnish β-nitroamines. Both of these environmentally benign reactions are performed in the absence of solvents using molecular oxygen as an oxidant.

An oxidative cross-dehydrogenative-coupling reaction in water using molecular oxygen as the oxidant: vanadium catalyzed indolation of tetrahydroisoquinolines.

An aerobic oxidative cross-dehydrogenative coupling reaction between sp(3) C-H and sp(2) C-H bonds is developed by employing a vanadium catalyst (10 mol%) in an aqueous medium using molecular oxygen as the oxidant. This environmentally benign strategy exhibits larger substrate scope and shows high regioselectivity.