Organic Chemistry Frontiers最新文献

A highly efficient copper-catalyzed coupling reaction of diynylic acetates with hydrophosphoryl compounds is developed based on the concept of site-selective nucleophilic interception of copper-cumulenylidene-type intermediates. This reaction enables an expeditious synthesis of a novel class of conjugated allenynylphosphoryl compounds in good to high yields from readily available materials under mild conditions.

The high strain energy of cyclobutanes has been utilized for selective ring-opening, enabling the synthesis of valuable linear aliphatic compounds. Although significant progress has been observed recently, most of the approaches appear to be limited to two major manifolds, namely, transition metal-catalyzed carbon–carbon (C–C) oxidative addition or cyclobutyloxy radical-initiated ring opening. In sharp contrast, we describe photoinduced C–C activation using a cyclobutylcarbinyl radical to access γ,δ-unsaturated ketones obtained from cyclobutyl tertiary alcohols and sulfonyl chlorides through a strain release strategy associated with the formation of a stabilized radical. Furthermore, the ketocarbonyl group also enables diverse post-synthetic modifications. Overall, our approach is characterized by broad functional group tolerance, ample substrate scope, and scalability. Our findings represent an alternative method to the aforementioned methods for remote 1,4-difunctionalizations, accompanied by a synthetically useful C–C double bond persisting in the obtained products.

An efficient asymmetric Friedel–Crafts-type alkylation/cyclization of 5-aminopyrazoles with α,β-unsaturated 2-acyl imidazoles has been developed, affording corresponding pyrazolo[3,4-b]pyridine analogues in 81–98% yield with 85–99% enantioselectivity. Remarkably, this protocol exhibits extraordinary advantages in terms of reactivity and enantioselectivity, given the fact that chiral Rh(III) complex at an amount as low as 0.05 mol% can promote the title reaction on the gram scale to afford the desired product, with excellent enantioselectivity (96% ee). Application of the methodology in the efficient synthesis of pyrazolo[3,4-b]pyridine via dehydrogenation is reported.

The first total synthesis of the monoterpene indole alkaloid (–)-deglycocadambine is achieved in 12 steps with (+)-genipin as the chiral starting material. The reported synthetic approach is characterized by an orchestrated cascade annulation between tryptamine and the highly functionalized dialdehyde precursor, rapidly introducing the unique 6/5/6/7/6-fused pentacyclic skeleton and the ketone functional group at C19 in a convergent manner. The successful implementation of transannular oxidative cyclization at C3 for bridged oxazolidine formation in the late-stage synthetic campaign ensured the final total synthesis of this molecule.

The incorporation of a difluoromethyl group within an aromatic ring is highly desirable. However, studies on direct C–H difluoromethylation reactions of arenes have been sparsely reported in the literature. Therefore, in this work, a light-induced Mn-enabled DavePhos-promoted direct C–H difluoromethylation reaction of general arenes has been explored in detail using ArSO₂CF₂Br with variable characteristics as the coupling partner under mild conditions. Various arenes and bioactive molecules were all well tolerated, producing the resultant products in moderate to high yields. Preliminary mechanistic studies suggested that Mn₂(CO)₁₀ could not only mediate the halogen-atom transfer process (XAT) to provide active ArSO₂CF₂˙ radicals but also coordinate with the arenes through π-complexation to activate the aromatic ring. This facilitated the reaction between the aromatic ring and the ArSO₂CF₂˙ radical.

We report the synthesis of a novel squaramide-based cryptand incorporating both anion and cation binding domains, and a fluorescent reporter designed to monitor the complexation process. The preorganization of the binding domains in the cryptand structure favored stronger binding of anions as compared with the open chain counterpart. X-ray structural analysis of the cryptand complex with ion pairs confirmed the interaction of ions with binding sites in the solid state. Employing a ball milling technique resolved solubility issues, facilitating the study of interactions between the cryptand and salts. We found that the cryptand exhibits stronger binding affinity for carboxylates than for chloride anions. This property, coupled with the closed structure of the cryptand, was utilized for the selective recognition of zwitterions differing in chain length. Mechanochemical methods allow for qualitative binding of amino acids within the receptor cavity. Fluorescence studies revealed the behavior of cryptand 1 as a sensor enabling the selective recognition of zwitterions, a capability not observed in the sensors with an open structure.

C(sp³) hybridized fragments have been widely explored for the formation of crucial Ni-alkyl intermediates in the field of nickel-catalyzed C(sp²)–C(sp³) coupling reactions. Traditional alkyl metal reagents and diverse C(sp³) radical precursors developed with the renascence of photocatalysis are effective coupling partners. However, though Ni-alkyl intermediates can be readily obtained to activate carbon–carbon bonds, cyclopropane derivatives have rarely been employed as partners to couple with aryl halides. Herein, we disclose a Ni/photoredox protocol for coupling methylenecyclopropanes with aryl bromides via selective distal bond cleavage. A range of 1,1-dibenzylethylene derivatives has been obtained in moderate-to-good yields under mild conditions with excellent functional group tolerance. Mechanistic studies demonstrate the unique ratio of the nickel catalyst to bidentate ligand (Ni/Ligand = 2/1) utilized in this reaction, which was derived from two distinct roles of nickel played in the oxidative addition step with MCP substrates and aryl bromides. This context presents an unusual catalytic mode in transition-metal-catalyzed transformations of methylenecyclopropanes.

Ring-opening of vinyl epoxides is an important reaction for organic synthesis and can involve various potential mechanisms. When using a transition metal complex with both π-activity and Lewis acidity as the catalyst, the transformation modes become complicated. This mechanistic study on the Cu-catalyzed ring-opening of vinyl epoxides serves as a typical case study from a theoretical perspective. The results indicate that the ring-opening is enabled by alkene insertion, in which copper exhibits the π-activity property. The alkene insertion process plays a key role in directing the reaction pathway and determining the chemoselectivity of the overall reaction. The reaction pathways involving initial 1,3-epoxide insertion and 1,5-vinyl epoxide insertion are less energetically favorable than that triggered by alkene insertion. The atomic charges on the copper centers in each case were computed to reveal the insertion process and origins of the energy differences.

A highly enantioselective aza-Friedel–Crafts arylation of biphenyl-bridged seven-membered cyclic N-sulfonylimines with indolizines was developed, affording a wide range of chiral indolizine modified biphenyl-bridged ε-sultams in excellent yields (up to 99% yield) and enantioselectivities (up to 99% ee) by utilizing chiral phosphoric acid organocatalysis. Furthermore, scale-up reactions and diversified synthetic transformations of the desired ε-sultams without the loss of stereochemical purity substantiated their potential utility values.

A catalytic asymmetric formal (2 + 3) cycloaddition of methyl-substituted 2-indolylmethanols with 3-substituted-2-indolylmethanols was conducted in the presence of chiral phosphoric acids, which delivered a series of chiral pyrrolo[1,2-α]indoles in overall high yields (up to 98%) with excellent diastereoselectivities (all >95 : 5 dr) and good enantioselectivities (up to 94% ee). Moreover, theoretical calculations provided an in-depth understanding of the reaction pathways. This work not only establishes the first catalytic asymmetric cycloaddition of methyl-substituted 2-indolylmethanols, but also realizes the first catalytic asymmetric formal (2 + 3) cycloaddition between different 2-indolylmethanols, which will enrich the chemistry of indolylmethanols.