An efficient copper(II) N-heterocyclic carbene (NHC) complex catalyzing the Chan–Evans-Lam cross-coupling reaction of N-heterocyclic nucleophiles with arylboronic acid has been explored. This air-stable copper catalyst shows practical robustness that tolerates a diverse array of functional groups on both the N-nucleophile and arylboronic acid coupling partners in C−N bond forming reactions through the CEL reaction.

Abstract

An efficient copper(II) N-heterocyclic carbene (NHC) complex with an NCN coordination mode was optimized to catalyze the Chan–Evans-Lam (CEL) cross-coupling reaction of imidazole and other N-heterocyclic nucleophiles with arylboronic acid. This air-stable copper catalyst shows robust catalytic performance and tolerates a diverse array of functional groups on both the N-nucleophile and arylboronic acid coupling partners in C−N bond forming reactions with up to 95 % yield. Formation of the Cu−NHC complex in situ generated similar catalytic performance for CEL coupling. Alternative metal ions (Mn²⁺, Fe²⁺, Co²⁺, Ni²⁺, Zn²⁺, Ru²⁺, and Pd²⁺) were also screened in the presence of the NHC precursor as CEL catalysts.

The stereoselective syntheses of three 2,6-dioxabicyclo[3.3.1]nonan-3-one styryllactones, goniopypyrone, goniochelienlactone and 7-acetylgoniochelienlactone, has been accomplished based on chiron approach. In particular, (+)-goniochelienlactone and (+)-7-acetylgoniochelienlactone, which are the first total syntheses so far, were achieved in 5 steps (longest linear sequence) with a 28.3 % overall yield and in 8 steps (longest linear sequence) with a 22.2 % overall yield, respectively. The feature of this work involved a sequential reaction of Bernet-Vasella-type reductive elimination and nucleophilic addition by a one-pot sequence, sequential crossing metathesis (CM)/intramolecular oxa-Michael addition, and one-pot tandem deprotection/lactonization.

Abstract

Stereoselective total syntheses of (+)-goniochelienlactone, (+)-7-acetylgoniochelienlactone and (−)-goniopypyrone were accomplished by divergent strategies starting from readily available chiral pool methyl α-D-mannopyranoside. The present work provided an efficient strategy for the stereoselective construction of highly functionalized dioxabicyclo[3.3.1]nonan-3-one ring system through a sequential Bernet-Vasella-type reductive elimination/nucleophilic addition and a sequential cross-metathesis/intramolecular oxa-Michael addition in a one-pot process.

A series of benzofuro-fused 7-deazapurine (6H-furo[2,3-e]pyrimido[4,5-b]indole) 2’-deoxyribo- and ribonucleosides was designed and synthesized. The synthesis of key 10-chloro-6H-furo[2,3-e]pyrimido[4,5-b]indole was based on the Negishi cross-coupling of iodobenzofurane with zincated 4,6-dichloropyrimidine followed by azidation and photochemical cyclization. Glycosylation of the heterocycle with either Hoffer’s chlorodeoxyribose or protected ribose followed by cross-coupling or substitution reactions at position 10 gave the desired two sets of final nucleosides that showed moderate to weak cytostatic activity and interesting fluorescence properties.

β-Silyl ketones reacted with aldehydes by treatment with KMMDS in the presence of 18-crown-6 to give β,γ-unsaturated ketones accompanied with a skeletal rearrangement. The reactions proceeded by aldol reaction of β-silyl ketones with aldehydes followed by  [1,4]-Brook rearrangement and intramolecular 1,2-addition to form cyclopropanol derivatives, in which carbon-carbon bond cleavage took place to afford β,γ-unsaturated ketones. The β,γ-unsaturated ketones were prepared in a one-pot manner by conjugate addition of silyl anions to α,β-unsaturated ketones followed by reactions with aldehydes. The Brook rearrangement proceeded with complete inversion of configuration at the carbon center.

An efficient two-step no purification protocol for the synthesis of enolizable α-subtituted β,γ-unsaturated aldehydes is reported. The developed strategy involves two steps, epoxidation and Meinwald rearrangement, to result in a formal one-carbon homologation of α,β-unsaturated aldehydes enabling the insertion of a CHR unit.

Abstract

An efficient protocol for the synthesis of enolizable α-substituted β,γ-unsaturated aldehydes is reported. The developed strategy involves two steps, epoxidation and Meinwald rearrangement, to result in a one-carbon homologation of α,β-unsaturated aldehydes enabling the insertion of a CHR unit.

The hydroxy group, and the phenol moiety in particular, is ubiquitous in several natural products, in organic synthesis and/or pharmaceutical industry. With the uprise of photoredox catalysis, many efforts worldwide focus on developing novel and sustainable protocols, providing an easy access to hydroxy-containing molecules. Boronic acids and boronic ester derivatives are considered valuable precursors for the synthesis of hydroxyl group derivatives. Herein, we report a novel, sustainable, light-driven protocol, where the impact of wavelength irradiation on boronic acid aerobic photooxidation was examined. In this work, UVA-light (370 nm) irradiation was found to promote the photocatalyst-free aerobic oxidation of boronic acids and boronic acid derivatives. Furthermore, a broad scope of substrates was tested and extensive mechanistic studies were performed, in order to probe the reaction mechanism.

Sulfur-centered radicals have a key role in a plethora of synthetic organic transformations, whose scope has been further expanded thanks to the possibility to generate such species under visible light photocatalytic conditions. The current literature overview focuses on those transformations involving isocyanides and sulfur-centered radicals with the aim to highlight the chemical space accessible, both in terms of complexity and diversity, and the mechanistic rational underpinning the current and future development of such chemical methodologies.

We studied the mechanism behind the formation of fluorescent syn-bimane. This work combines theoretical and experimental approaches. Our computational study supports Kosower's mechanism while introducing a crucial diaziridine intermediate. Our results suggest the rate-limiting step is the formation of a diazoketene. The reaction of 4,5-dimethyl-2,3-diazacyclopentadienone with diphenylcyclopropenone produced the unexpected unsymmetrical anti-(Me,Me)(Ph,Ph)bimane.

Abstract

Theoretical and experimental mixed approaches are complementary and valuable. Our DFT calculations support the mechanism suggested by Kosower, adding to it a key diaziridine intermediate that determines the relative product distribution of this reaction. Our results are consistent with the formation of the diazoketene intermediate as the rate-limiting step. Based on curve fittings, first or second-order kinetics cannot be ruled out. This may indicate that more than one mechanism is simultaneously at play in this transformation. This unexpected outcome led us to study an alternative cyclopropenone intermediate. Although cyclopropenone is not likely to be formed under thermal conditions, adding it to the reaction mixture results in bimane structures. The most staggering finding from this investigation was the unanticipated generation of the unsymmetrical anti-(Me,Me)(Ph,Ph)bimane. The optimization of this route towards unsymmetrical bimanes will require additional investigation.

Computational chemistry allows to elucidate the observed selectivity in the photochemistry of chloroanilines. A meta-ortho effect of the substituents favours the population of the prefulvenic conical intersection which leads to rapid deactivation of the m- and o-isomers of chloroaniline, while the para derivative lives long enough to emit and populate the reactive triplet state which leads to C−Cl dissociation.

Abstract

Direct excitation of aromatic compounds grants access to high-energy intermediates that can be utilised in organic synthesis. Understanding and predicting the substituent effects at the excited state for aromatic molecules remains challenging for the synthetic photochemist. In this work, we present an experimental and computational investigation of the excited state of the isomeric chloroanilines, which promptly react by losing the chloride when the amino group is in para position, but are non-reactive and non-emissive in the meta and ortho isomers. XMS-CASPT2//CASSCF computations explain this apparent contradiction of the meta-ortho selectivity rule of Zimmerman, which originates from the substituent effects lowering to a different extent the barrier to populate the prefulvenic conical intersection that deactivates non-radiatively the singlet excited state of the chloroanilines.

An efficient three-component synthesis of disubstituted 4-aryl-2-aminothiazoles was reported. The protocol features transition-metal free, short reaction time, easily available starting materials, good yields and broad substrates scope, showing potential synthetic value for the synthesis of a variety of biological or pharmaceutical active compounds.

Abstract

An efficient three-component synthesis of 4-aryl-2-aminothiazoles was reported. Phenyl-thioureas reacted with 2-bromoacetophenones to form 4-aryl-2-aminothiazoles through cyclization, and the subsequent C−N bonding with benzyl/allyl bromides gave the desired disubstituted thiazoles smoothly. The protocol features transition-metal free, short reaction time, easily available starting materials, good yields and broad substrate scope, showing potential synthetic value for the synthesis of a variety of biologically or pharmaceutically active compounds.