One-pot Reaction Sequence Research Articles

A short approach to cytogenin and first total synthesis of aspergisocoumarin A and fusarimarin C

A novel, efficient route to the first total synthesis of the bioactive isocoumarins aspergisocoumarin A, fusarimarin C and cytogenin is demonstrated. This approach features a groundbreaking single-step synthesis of isocoumarins utilizing a challenging cross-ester coupling of ethyl dimethoxy orsellinate and ethyl glycolate in the presence of a LiBr-LiTMP complex. The process leverages bromide ion-induced aggregation to facilitate a one-pot tandem reaction sequence: lateral lithiation, acylation, enolization, and lactonization. This innovative method directly produces the isocoumarin moiety with high efficiency. Subsequent transformations include selective BBr3-mediated demethylation, oxidation, and Wittig reactions. The streamlined synthetic routes demonstrated: a two-step pathway to cytogenin and a four-step sequence to aspergisocoumarin A and fusarimarin C, achieving overall yields of 37 %, 27 %, and 27 % respectively.

Nitrogen-doped mesoporous carbon as metal-free catalysts for the aerobic oxidation of alcohols

The selective oxidation of alcohols to carbonyl compounds is a crucial reaction in organic chemistry. In this study, we report the synthesis of nitrogen-doped mesoporous carbon material by hard template method using biomass derivative sucrose and melamine as carbon and nitrogen sources and silica sol as template agent. Using molecular oxygen as the oxidant, the obtained NC-900 exhibits excellent selectivity in the oxidation of primary alcohols to the corresponding aldehydes without generating over-oxidized acid. For example, under optimal reaction conditions, 4-methoxybenzyl alcohol is almost quantitatively converted to 4-methoxybenzaldehyde. The catalytic system showed robust tolerance to sensitive functional groups and demonstrated favorable reaction effects in gram-scale experiments and multi-step, one-pot reaction sequences. The catalyst was reused for 5 times, and its catalytic activity did not decrease significantly. Hammett correlation studies indicated that the reaction favored substrates with electron-donating substituents. Characterization and experimental results indicate that the synergistic effect of graphitic N and mesoporous structure plays a pivotal role in enhancing the catalytic activity of NC-900 in this transformation. The mechanism study shows that the reaction involves free radical process.

Modular Synthesis of Tetrasubstituted Vinyl Sulfides via One-Pot Sequential Carbene Transfer Reaction from Thiols with α-Diazo Carbonyl Compounds.

We present a one-pot reaction that offers an efficient approach to synthesizing tetrasubstituted vinyl sulfides with high stereoselectivity. This method involves the sequential Wolff rearrangement, ylide formation, and [1,4]-aryl transfer by utilizing aryl and alkyl thiols and α-diazo carbonyl compounds as substrates. Notably, this reaction features commercially available materials, straightforward operation, atom economy, and broad substrate scope. Moreover, the primary photophysical properties (aggregation-induced emission effect) of the products were also investigated, which might be useful in functional materials via structural modification.

Synthesis of Fluorine-Containing Multisubstituted Oxa-Spiro[4,5]cyclohexadienones via a Fluorinated Alcohol-Catalyzed One-Pot Sequential Cascade Strategy.

In recent years, the application of fluorinated alcohols as solvents, cosolvents, or additives has become important in modern organic synthesis. However, their potential as efficient catalysts in organic synthesis has not been well-explored. In this article, we report on the development of a one-pot sequential cascade reaction of p-quinone methides with difluoroenoxysilanes using hexafluoroisopropanol as catalyst. This reaction allows for the preparation of fluorinated multisubstituted oxa-spiro[4,5]cyclohexadienones. By using 50 mol % 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP), the reaction proceeds smoothly to yield 1,6-conjugated products, which are then subjected to oxidative dearomatization/hemiacetalization using PhI(OAc)2. The overall process affords moderate to high yields and excellent diastereoselectivities.

One-Pot Reaction Sequence: N-Acylation/Pictet-Spengler Reaction/Intramolecular [4 + 2] Cycloaddition/Aromatization in the Synthesis of β-Carboline Alkaloid Analogues.

One-pot synthesis of tetrahydro-β-carbolines, fused with an isoindole core, was proposed starting from maleic anhydride and azomethines easily available from tryptamines and 3-(hetaryl)acroleins. This sequence includes four key steps: an acylation of the aldimine with maleic anhydride, a Pictet-Spengler cyclization, an intramolecular Diels-Alder reaction, and a concluding [1,3]-H shift. As a result, six- or seven-nuclear alkaloid-like heterocyclic systems, containing a benzo[1,2]indolizino[8,7-b]indole fragment annulated with furan, thiophene, or pyrrole, are formed in a diastereoselective manner.

Facile synthesis of tetrahydroquinoline containing dithiocarbamate derivatives via one-pot sequential multicomponent reaction.

An efficient sequential multi-component method for the synthesis of tetrahydroquinoline containing dithiocarbamates has been developed. This reaction involved a boronic acid-catalysed reduction of quinolines to tertrahydroquinolines, followed by nucleophilic addition reaction with carbon disulphide to form dithiocarbamic acids and subsequent S-arylation via external base-free Chan-Evans-Lam coupling in a one-pot operation. The methodology is compatible with a wide variety of functional groups and also useful in the late-stage functionalization of pharmaceuticals. The dual role of the boronic acid as a catalyst (in the reduction of quinolines) and as a reagent (in the S-arylation) has been demonstrated for the first time herein.

Stereospecific Synthesis of Unprotected, α,β-Disubstituted Tryptamines and Phenethylamines from 1,2-Disubstituted Alkenes via a One-Pot Reaction Sequence.

Unprotected, α,β-disubstituted tryptamines and phenethylamines are obtained by a one-pot, metal-free sequence that proceeds by the in situ formation of aziridinium salts followed by Friedel-Crafts reaction with electron-rich (hetero)arenes. Both steps are facilitated by hexafluoroisopropanol as the solvent. The one-pot sequence was effective for diversely substituted indoles and 1,3,5-trimethoxybenzene, for cyclic and acyclic alkenes, and proceeded in a stereospecific fashion for both (E)- and (Z)-1,2-disubstituted alkenes. Moreover, one-pot morpholine addition to an aziridinium salt provided a diamine.

Diastereoselective Synthesis of cis-2,6-Disubstituted Dihydropyrane Derivatives through a Competitive Silyl-Prins Cyclization versus Alternative Reaction Pathways

A convenient regioselective synthesis of allyl- and vinylsilyl alcohols, from a common precursor, was described, by selecting the appropriate reaction conditions. Allyl- and vinylsilyl alcohols were tested in silyl-Prins cyclizations for the preparation of disubstituted oxygenated heterocycles in a one-pot sequential reaction. The methodology was sensitive to the structure of the starting alkenylsilyl alcohol and reaction conditions, with competitive pathways observed (particularly for allylsilyl alcohols), such as Peterson elimination and oxonia-Cope reactions. However, the use of vinylsilyl alcohols allowed the preparation of differently disubstituted cis-2,6-dihydropyrans in moderate to good yields. Computational studies support the proposed mechanism.

Brønsted Acid Catalyzed Friedel-Crafts Alkylation of Naphthols with In Situ Generated Naphthol-Derived ortho-Quinone Methides: Synthesis of Chiral and Achiral Xanthene Derivatives.

We disclose herein an enantioselective protocol for the Brønsted acid catalyzed addition of naphthols to in situ generated naphthol-derived ortho-quinone methides (o-QMs) followed by intramolecular cyclization, which delivers substituted chiral xanthene derivatives, in a one-pot reaction sequence under mild conditions. This process serves to convert naphthol-derived ortho-hydroxyl benzylic alcohols into reactive naphthol-derived o-QMs using a chiral phosphoric acid (CPA) catalyst. Moreover, it is helpful in controlling the enantioselectivity of the carbon-carbon bond-forming event via hydrogen-bonding followed by intramolecular cyclization. Additionally, for the first time, we observe a Brønsted acid catalyzed C(sp2)-C(sp3) bond cleavage of naphthol-derived ortho-hydroxyl benzylic alcohols for the synthesis of achiral xanthene (sigma plane containing) derivatives in good to excellent yields.

Swapping Copper-Catalytic Process: Selective Access to Pyrazoles and Conjugated Ketimines from Oxime Acetates and Cyclic Sulfamidate Imines.

A powerful CuCl-catalyzed sequential one-pot reaction of aryl methyl ketoxime acetates with cyclic N-sulfonyl imines followed by elimination in the presence of base is reported. This hydrazine-free method conveniently makes C-C and N-N bonds via a radical cleavage of the N-O bond, delivering a special class of C3-hydroxyarylated pyrazoles in good yields. Surprisingly, while employing CuI as a catalyst instead of CuCl, the reaction proceeds through a non-radical pathway which embodies a new tactic for the high-yielding access to value-added conjugated N-unsubstituted ketimines. Moreover, additive-free approach to sulfamidate-fused-pyrazoles was achieved by successfully catalyzing addition and oxidative N-N bond-making reactions by CuI and CuCl, respectively. Significantly, our novel technique could convert the prepared ketimines into the pharmacologically recognized 6H-benzo[c]chromene frameworks.

One-pot two-step cross-dehydrogenative-coupling polycondensation for synthesis of tetrafluorobenzene-based conjugated polymer

Polycondensation of 1,2,4,5-tetrafluorobenzene (1) with 3,3′-dihexyl-2,2′-bithiophene via Pd/Ag dual-catalyzed cross-dehydrogenative coupling was examined. In situ deprotonation-metalation of 1 with Ag salt proceeded smoothly at 25 °C, and the subsequent transmetalation with a Pd catalyst provided a cross-coupling product. The sequential one-pot two-step reaction method effectively suppressed undesired homo-coupling defects during polymerization. The obtained highly regioregular polymer had a packing structure and exhibited strong fluorescence in the film state, which was also evaluated for use as an emitting material in organic light-emitting diodes.

Robust Construction of Supersmall Zwitterionic Micelles Based on Hyperbranched Polycarbonates Mediates High Tumor Accumulation

Despite the numerous advantages of nanomedicines, their therapeutic efficacy is hampered by biological barriers, including fast in vivo clearance, poor tumor accumulation, inefficient penetration, and cellular uptake. Herein, cross-linked supersmall micelles based on zwitterionic hyperbranched polycarbonates can overcome these challenges for efficiently targeted drug delivery. Biodegradable acryloyl/zwitterion-functionalized hyperbranched polycarbonates are synthesized by a one-pot sequential reaction of Michael-type addition and ring-opening polymerization, followed by controlled modification with carboxybetaine thiol. Cross-linked supersmall zwitterionic micelles (X-CBMs) are readily prepared by straightforward self-assembly and UV cross-linking. X-CBMs exhibit prolonged blood circulation because of their cross-linked structure and zwitterion decoration, which resist protein corona formation and facilitate escaping RES recognition. Combined with the advantage of supersmall size (7.0 nm), X-CBMs mediate high tumor accumulation and deep penetration, which significantly enhance the targeted antitumor outcome against the 4T1 tumor model by administration of the paclitaxel (PTX) formulation (X-CBM@PTX).

One-pot sequential cascade reaction for selective gluconic acid production from cellulose photobiorefining.

We demonstrate the feasibility of cellulose photobiocatalytic conversion with >75% cellulose conversion and >75% gluconic acid selectivity from converted glucose. This process is realized via a one-pot sequential cascade reaction by cellulase enzymes and a carbon nitride photocatalyst that can realize selective glucose photoreforming into gluconic acid. Cellulase enzymes breakdown cellulose into glucose, which will subsequently be converted into gluconic acid by essential oxidative species (˙O2- and ˙OH) via a selective photocatalysis process with simultaneous H2O2 formation. This work demonstrates a good example to realize direct cellulose photobiorefining into value-added chemicals via the photo-bio hybrid system.

Synthesis of fused bis-indazoles/indazoles via a one-pot sequential strategy.

We report here an efficient synthesis of fused bis-indazoles/indazoles via a one-pot sequential strategy starting from o-azido aldehydes and amines. This novel method involves the sequential formation of 2H-indazole followed by a Pd-catalyzed intramolecular cross-dehydrogenative coupling reaction. Overall, this one-pot sequential reaction involved the formation of new five bonds, resulting in the formation of three heterocyclic rings.

Metal-free and atom-efficient protocol for diarylation of selenocyanate by diaryliodonium salts.

We developed an atom- and reaction mass efficient strategy for the preparation of diarylselenides using iodonium salts as reactants. The developed approach allows the obtaining of diarylselenides from the corresponding trimethoxyphenyl-substituted iodonium salts via a two-step one-pot reaction sequence. The proposed metal-free methodology is based on the involvement of both iodonium aryl groups for diarylation.

Two-Step Substitution Reaction of Phosphonates Carrying a Binaphthyl Group with Grignard Reagents Leading to the Formation of P-Chirogenic Phosphine Oxides

AbstractThe reaction of phosphonates carrying a binaphthyl group with a range of Grignard reagents was complete within two hours at 0 °C to give phosphinates carrying a hydroxybinaphthyl group with high ­efficiency and diastereoselectivity. The resulting phosphinates were further subjected to a substitution reaction with MeMgBr. The reaction at reflux temperature in THF or toluene permitted the formation of P-chirogenic tertiary phosphine oxides with a high enantiomeric ratio. Rare examples of P-chirogenic alkynyl phosphine oxides were also obtained. The sequential one-pot substitution reaction of phosphonates bearing a binaphthyl group with two different Grignard reagents successfully gave the corresponding P-chirogenic phosphine oxides with enantiomeric ratios nearly equal to those of oxides derived from two-step reactions.

Chemoenzymatic Synthesis of Sterically Hindered Biaryls by Suzuki Coupling and Vanadium Chloroperoxidase Catalyzed Halogenations.

Halogenated biaryls are vital structural skeletons in bioactive products. In this study, an effective chemoenzymatic halogenation by vanadium-dependent chloroperoxidase from Camponotus inaequalis (CiVCPO) enabled the transformation of freely rotating biaryl bonds to sterically hindered axis. The yields were up to 84 % for the tribrominated biaryl products and up to 65 % when isolated. Furthermore, a one-pot, two-step chemoenzymatic strategy by incorporating transition metal catalyzed Suzuki coupling and the chemoenzymatic halogenation in aqueous phase were described. This strategy demonstrates a simplified one-pot reaction sequence with organometallic and biocatalytic procedures under economical and environmentally beneficial conditions that may inspire further research on synthesis of sterically hindered biaryls.

Synthesis of trialkyl semithioglycolurils from alkylthiourea-glyoxal cyclic adducts and dialkylureas

Condensation of 1-alkyl-4,5-dihydroxyimidazolidine-2-thiones (monoalkylthiourea-glyoxal cyclic adducts) with 1,3-dialkylureas affords novel 1,4,6-trialkylsemithio- glycolurils having non-substituted NH group linked to C=S function. Such compounds can be accessed in two-stage one-pot reaction sequence from alkylthioureas and glyoxal followed by treatment of the resulting adduct with 1,3-dialkylureas

One-Pot Sequential Synthesis of 3,3'- or 2,3'-Bis(indolyl)methanes by Using 1,3-Dithiane as the Methylene Source.

A simple and efficient method for structurally diverse symmetrical and unsymmetrical 3,3'- and 2,3'-bisindolylmethanes has been developed through a one-pot sequential reaction using 1,3-dithiane as the methylene source. The important AhR agonists ICZ and malassezin were synthesized with excellent efficiency by this straightforward approach.

Preparation of polyamides containing tetraphenyl-imidazolyl units from 1,2-bis(4-iodophenyl)-4,5-diphenyl-1H-imidazole via C–N coupling reaction and their characterization

A new aromatic diiodide compound, 1,2-bis(4-iodophenyl)-4,5-diphenyl-1H -imidazole was synthesized by a one-pot sequential diazotization-iodination reaction using 1,2-bis(4-aminophenyl)-4,5-diphenyl-1H -imidazole as the starting material in a KI/NaNO2/p -TsOH/CH3CN system at room temperature. A series of aromatic polyamides (PAs) containing tetraphenyl-imidazolyl units were prepared in good yields via a Pd(PPh3)2Cl2 catalyzed carbonylation polymerization of this diiodide, diamines and carbon monoxide in DMAc in the presence of PPh3 and 1,8-diazabicyclo[5,4,0]-7-undecene. These new PAs with inherent viscosities of 0.63–0.72 dL/g were amorphous and easily soluble in amide type aprotic solvents such as N -methyl-2-pyrrolidone (NMP), N,N’-dimethylacetamide (DMAc), N,N′-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and pyridine at room temperature. Thermal analyses data of the resulting PAs up to 800 °C in nitrogen showed their high thermal behavior with 5% weight loss temperature of 425–517 °C and char yield of 43–58%. The present PAs could be classified as “self-extinguishing polymers” based on the limiting oxygen index in the 34.7–40.7 range. Such attractive properties make these PAs promising as a new type of processable heat-resistant polymer materials.