Since the isolation of yuzurimine in 1966, nearly fifty members of the yuzurimine-type alkaloids have been identified, making this group one of the largest subfamilies within the Daphniphyllum alkaloids, accounting for approximately one-sixth of all known congeners. Despite extensive synthetic efforts directed toward this structurally challenging and biologically intriguing family, only a few syntheses of yuzurimine-type alkaloids have been accomplished to date. Here, we wish to report the detailed story of our enantioselective total synthesis of (+)-caldaphnidine J, a highly complex representative of this subfamily. Our strategy features a facile ring-expansion sequence, a palladium-catalyzed regioselective hydroformylation, a samarium(II)-mediated pinacol coupling to construct the key 7/5 bicyclic system, and a novel one-pot Swern oxidation/ketene dithioacetal Prins reaction. In addition, we have extended our synthetic investigations toward the related alkaloid Daphcalycine, further demonstrating the potential of our approach for accessing other members of this previously unexplored family.
We describe a metal-free visible-light method for the C-alkylation of thiophenols using Redox-Active Esters (RAEs) as alkyl radical precursors. A simple L-proline/EDA complex enables efficient radical generation and selective coupling under mild conditions. The protocol provides functionalized thioethers in moderate to good yields and requires no external photocatalyst. Importantly, the successful use of chiral L-proline under visible-light–driven conditions suggests that related reaction designs may enable future asymmetric variants of radical alkylation chemistry.
A series of novel oxazoline-functionalized chiral diene ligands were developed for rhodium-catalyzed asymmetric 1,4-addition reactions of arylboronic acids to α,β-unsaturated compounds. The catalysts with these ligands showed remarkable catalytic performance to achieve high chemical yields (up to 99%) and outstanding enantioselectivities (90-99% ee) for both cyclic and linear enones, alkenoates and enamides under mild reaction conditions (using weak base at room temperature). This strategy proved effective for synthesizing key pharmaceutical intermediates. Remarkably, enantiomeric purity remained high even in gram scale reactions, highlighting its potential for practical applications. Furthermore, density functional theory (DFT) calculations provided further insight into the pivotal role of the modified diene ligand in inducing chirality during the catalytic process.
The pre-preparation process of homogeneous transition metal complex catalysts is crucial for ensuring the structure and reproducibility of the active species and achieving controllable catalytic performance, yet its systematic investigation is often overlooked. In this study, by rationally designing the catalyst pre-preparation process, the selective regulation of the nickel-catalyzed hydrocyanation of 1,3-butadiene was achieved. By systematically optimizing pre-coordination variables—including component addition sequence, temperature, aging time, and olefin pre-contact—the formation pathway of the catalytic complex critically influencing both activity and product distribution is demonstrated. Under mild conditions (80°C, ambient pressure), this approach enables total pentenenitrile yields exceeding 95%. Notably, the same catalytic system achieves integrated hydrocyanation-isomerization functionality: linear selectivity can be precisely modulated either during the hydrocyanation step (79% 3-PN yield at elevated catalyst loading) or through subsequent isomerization of branched 2M3BN (94% conversion at 90°C). This work provides a versatile strategy for selectivity control in homogeneous catalysis that complements traditional ligand design and advances sustainable routes to adiponitrile precursors.
The catalytic construction of carbon–carbon (C-C) bonds via cross-electrophile coupling (XEC) has emerged as a powerful alternative to traditional nucleophile-electrophile strategies, offering operational simplicity and avoiding the need for sensitive organometallic reagents. In this work, we report the first nickel-catalyzed cross-electrophile coupling between aryl alkyl tellurides and aryl bromides, using Ni(COD)2/BINAP as the catalytic system and magnesium as a reductant. This protocol exploits the inherently weak C-Te bond and enables efficient C-C bond formation under mild, reductive conditions. The reaction proceeds with broad substrate scope and functional group tolerance, delivering biaryl products in moderate to excellent yields. Control experiments and mechanistic investigations support a dual activation pathway involving in situ formation of aryl Grignard species and a Ni(II) telluride complex. This work establishes organotellurium compounds as competent pseudohalides in nickel-catalyzed XEC, thus expanding the electrophile repertoire for sustainable C–C bond-forming strategies.
The asymmetric synthesis of natural products and related bioactive molecules requires reliable introduction, preservation and transfer of stereochemical information. Lipases are practical tools for this purpose because they combine high stereorecognition with mild conditions, broad solvent tolerance and operational simplicity. In complex-molecule synthesis, however, lipases should not be regarded merely as general resolution catalysts. Their value depends on route stage, substrate cost, material economy and the downstream use of the enzymatically generated stereocenter. This review discusses lipase-mediated kinetic resolution, dynamic kinetic resolution, desymmetrization and chemoenzymatic stereochemical relay in representative syntheses. The emphasis is placed on substrate structural features, enzyme choice, strategic placement of the enzymatic step, scalability and limitations. A concise decision framework is proposed to help synthetic chemists decide when a lipase step is strategically useful and when alternative asymmetric methods may be preferable.
The visible-light-induced electron donor-acceptor (EDA) complex strategy offers a new avenue for photocatalyst-free and mild organic synthesis. This review systematically summarizes the recent advances in the involvement of phosphorus species (both organic phosphines and inorganic phosphates) in the formation of EDA complexes and their applications in visible-light-driven transformations. Organic phosphines can form EDA complexes with iodide salts/redox-active esters or fluorinated halo-substrates, efficiently generating alkyl, fluoroalkyl, and acyl radicals to achieve diverse bond constructions. Inorganic phosphates, as emerging electron donors, have been successfully applied in [4 + 2] cycloaddition reactions. Three distinct phosphorus-mediated radical generation pathways are categorized based on two families of phosphorus electron donors. Mechanistic features and synthetic applications are discussed, along with an outlook on future directions in this field.
A novel and efficient transformation for the regioselective synthesis of functionalized 3-aroylimidazo[1,2-a]pyridines has been developed by using an I2/KI-mediated oxidative coupling reaction. This method employs readily available starting materials, proceeds under mild and metal-free conditions, and affords the desired products in moderate to good yields. Notably, the reaction temperature enables selective formation of either 3-aroylimidazo[1,2-a]pyridines or their 2-(dimethylamino) analogues, providing a flexible and practical approach to these privileged heterocycles.
It has been shown that the oxidative transformation of 4H-pyrans into pyrylium salts is accompanied by a structural rearrangement of the resulting pyrylium cations. The reaction of 4-substituted 3-formyl-2,6-diphenyl-4H-pyrans with trityl perchlorate in 1,2-dichloroethane affords either the expected 3-formylpyrylium salts or isomeric 5-benzoylpyrylium cations. The reaction pathway depends on the temperature and the steric bulk of the substituent at position 4 of the pyran ring. DFT calculations that account for solvation effects (PCM model, 1,2-dichloroethane) and the Grimme dispersion correction (D3) suggested that, in the presence of catalytic amounts of HClO4, the isomerization of 3-formylpyrylium cations proceeds through a multistep ANRORC-type mechanism initiated by nucleophilic attack of a water molecule. Thus, a simple change in oxidation conditions reveals a previously unknown rearrangement channel of pyrylium cations during oxidative dehydrogenation and allows the selective preparation of two series of structurally distinct pyrylium salts from the same 4H-pyran precursor.
The double lithiation of 2,6-dimethylpyridine (lutidine) has been optimised for efficient P-C bond formation by reaction with easily accessible chlorophosphines (R2PCl) to access a range of symmetrically and unsymmetrically substituted pyridine-based PNP pincer ligands. In-situ transmetalation to magnesium prior to R2PCl addition allows the utilisation of base-sensitive chlorophosphines that are incompatible with the di-lithiated intermediate. Protection of the crude PNPs with elemental selenium permits facile isolation, purification, and storage of the pro-ligands, while allowing quantification of their donor properties by NMR and XRD analysis. Six novel (R)2PNP(R)2 selenides with a range of diverse substituents (R = tBu, iPr, Cy, Me, Ph, Fur) have been synthesised and fully characterised, and their deprotection with (TMS)3SiH is demonstrated. Omission of selenium oxidation and air-free aqueous workup gives straightforward access to free PNPs in high purity and yield.
Electrochemical dearomative spirocyclization has recently been developed as an effective approach toward the conversion of widely accessible aromatic building blocks into complicated spirocyclic structures of great biological interest. This review provides an overview of the recent progress made in the last five years in the synthesis of spirocyclic derivatives via electrochemically assisted dearomative spirocyclization. The presented spirocyclizations can be divided into two major groups, namely (i) spirocyclization processes triggered by the direct electrochemical oxidation/reduction of the aromatic starting materials and (ii) spirocyclization processes triggered by the electro-oxidation/reduction of other radical precursors. Besides the described synthetic examples, some mechanistic aspects and limitations of the described approaches are presented here.
