Organic chemistry frontiers : an international journal of organic chemistry最新文献

A nickel-catalysed reductive cross-coupling reaction between 2-bromo cycloalkenyl carboxylic acids and alkyl bromides has been developed, affording all-carbon tetrasubstituted cycloalkenes in moderate to excellent yields up to 92%. Mechanistic studies indicated that the carboxylic acid group plays an important assisting role in this sterically demanding coupling reaction.

N-Fluoroalkylated 1,2,3-triazoles underwent a microwave-heating-assisted ring opening, nitrogen molecule elimination and concomitant group rearrangement to form isolable N-fluoroalkylketenimines. This reagent-free process is characterized by a wide scope and high efficiency and provides a new route to unexplored N-fluoroalkyl compounds. The reaction mechanism was investigated by a combination of mechanistic and computational studies. [2 + 2] cycloaddition of ketenimines with alkynes or alkenes afforded novel cyclobutenimines and cyclobutanimines, respectively. Addition of oxygen-, sulfur- and nitrogen nucleophiles to ketenimines gave new N-fluoroalkyl imidates, thioimidates and amidines.

Iodine(iii)-mediated dehydroaromatization of cyclohexanones with primary amines and CD₃SSO₃Na has been developed, providing direct access to ortho-SCD₃ anilines with the formation of C–N and C–S bonds. Detailed mechanism studies indicate that hypervalent iodine(iii) plays dual roles as an efficient mediator and an oxidant, and the continuously generated α-acetoxylated ketones and α-SCD₃ ketones are the key intermediates in the current three-component reactions. The present transformations demonstrate excellent chemo-selectivity, and only employ an iodine(iii) reagent as a stoichiometric mediator, making the strategy applicable for late-stage modification of numerous pharmaceuticals.

5- and 6-membered heteroarenes, both azoles and azines, were directly alkylated by alkanes, ethers and carbamates using t-butyl peroxybenzoate under LED irradiation. As a serendipitous finding, an organic photosensitizer, 9,10-dichloroanthracene, significantly increased overall efficiency of radical couplings via energy transfer of exciplexes and allowed many examples of oxidative couplings to proceed in good yields, even when 1.5 equivalents of alkanes were used.

Historically, deuteration reactions have been primarily utilized for mechanistic studies, but recently, their pharmacological importance has been recognized. Many efforts have been made to fulfill the urgent need for deuteration tools since the FDA's approval of the first deuterated drug used to treat chorea-associated Huntington's disease. Current deuteration strategies prevailingly involve reversible H/D exchange at the target C–H bond and suffer from low functional group tolerance and deuterium content. Herein, a ruthenium-catalyzed deoxygenative deuteration of ketones is developed with 20 examples under mild conditions. The reaction proceeds via HOME chemistry (hydrazone as organometallic equivalent) followed by in situ deuteration, thereby enabling regiospecific deuteration at the methylene site with 91% to 96% deuterium content.

Enantioselective tandem cycloisomerization/addition reactions of 2-alkynyl enones with 1- and 2-naphthols have been investigated using gold(i) catalysts featuring hybrid phosphine–phosphoric acid chiral ligands, according to the tethered counterion-directed catalysis (TCDC) strategy. The reactions occur at low catalyst loading (0.2–1 mol%) without silver additives, and the naphthols act as both O- and C-nucleophiles, leading to the corresponding addition products with high enantioselectivity. DFT calculations enlighten these processes.

Organocatalytic enantioselective construction of chiral spiro N,N-acetal carbon stereocenters and axially chiral 3-arylindoles has been achieved via a chiral phosphoric acid (CPA)-catalyzed (3 + 2) annulation of α-(3-isoindolinonyl) propargylic alcohols with 1-(3-indolyl)naphthalen-2-ols, affording a broad scope of pyrrolo[1,2-a]indoles bearing both enantioenriched spiro isoindolinone-indoline and atropisomeric naphthalenol frameworks. Based on control experiments and our previous work, a possible mechanism was proposed accordingly.

Hypervalent iodine compounds have evolved from structural curiosities into useful reagents owing to their unique polar and radical reactivity. In the last decade, many reactions based on their direct excitation have been reported as strong visible light sources became more available. In this review, we present different synthetic examples of the diverse reactivity of five different structural classes of hypervalent iodine compounds and their complexes.

Herein, we report a novel and highly efficient strategy for the construction of alkenyl sulfoxides via transition metal-free C–S cross-coupling of sulfenate anions with alkenylsulfonium salts. This procedure features the capture of in situ generated sulfenate anions from β-sulfinyl esters under mild conditions, which provides an efficient strategy for the synthesis of diverse alkenyl sulfoxides in moderate to good yields.

The one-electron oxidation of alkynes and the subsequent nucleophilic addition represent a straightforward way to value-added α-keto ketals, especially the less-known oxo-spiroketals, which are promising structural scaffolds in natural products and pharmaceuticals. However, this strategy remains to be developed due to the high oxidation potential of electron-deficient CC bonds and the challenge of controlling regioselectivity in the nucleophilic addition step. In particular, oxo-spiroketals have yet to be synthesized via the oxyfunctionalization of alkynes. Herein, we report the photocatalytic oxyfunctionalization of alkynes with electron-withdrawing groups to afford α-keto ketals with alcohols and molecular oxygen using riboflavin tetraacetate (RFT) as a powerful photoredox catalyst by binding to two scandium ions ([RFT-2Sc³⁺]). For unsymmetrical di-aryl acetylenes and phenyl alkyl acetylenes, excellent regioselectivity is perhaps achieved due to the stability of the final ketal products, as well as the negative charge distribution on the adjacent carbon of the CC bond induced by electron withdrawing groups at the para- or meta-position. Di-aryl acetylenes with ortho-substitutions tend to have poor site-selectivity, which may be due to unfavorable steric hindrance. Additionally, the synthesis of benzannulated oxo-5,6- and oxo-6,6-spiroketal and unprecedented oxo-6,7-spiroketal in nature has been achieved for the first time using alkynediol substrates. Mechanistic studies, including control experiments, and Hammett and spectroscopy analyses, have revealed that the electron transfer from alkynes to the excited [RFT-2Sc³⁺]* complex is the key step in the oxyfunctionalization of alkynes. Such a flavin–metal ion photocatalytic system provides a green approach to valuable multioxygen-containing motifs.