Organic Letters

Herein, we report a silver-catalyzed protocol for decarboxylative cross-coupling between carboxylic acids and isocyanides, leading to linear amide products through a free-radical mechanism. The disclosed approach provides a general entry to a variety of decorated amides, accommodating a diverse array of radical precursors, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl carboxylic acids. Notably, the protocol proved to be efficient for decarboxylative late-stage functionalization of several elaborate pharmaceuticals, demonstrating its potential applications...

The reaction of 2,5-cyclohexadienones with methylene-tethered allenylsilane in the presence of Lewis or Brønsted acids leads to a cascade of intramolecular cyclization, yielding stereoselective tricyclic fused 6-5-4 carbocycles featuring a silyl-methylenecyclobutane ring. This transformation is notable for the diastereoselective asymmetric desymmetrization of prochiral dienones, attributed to the axial chirality of allene.

Bisboronic esters are critical compounds in various research fields, including drug discovery, chemical biology, and material sciences. Currently, the bisboronic esters with reactive functional groups are difficult to synthesize; this is partially due to the lack of a robust method to produce these products with diverse structures and various functional groups at specific locations. To overcome this issue, this study introduced a Ni-catalysis approach to produce bisboronic esters efficiently via cross-coupling and homocoupling using readily available halogenated boronic esters as the starting material under mild reaction conditions...

Here, we report a novel strategy for the direct construction of polycyclic fused ortho -quinone scaffolds through palladium(II)-catalyzed tandem γ-C(sp2 )-H arylation and cyclization of arylglyoxals with aryl iodides. This transformation features unique tandem transient directing of γ-C(sp2 )-H arylation and cyclization reaction mode, broad substrate scope, especially for the aromatic substrates containing oxygen and sulfur atoms, and avoiding the common issue of aromatization due to the construction of the hexatomic ring...

The asymmetric desymmetrizing [3+2] annulation reaction of p -quinamines and arylalkylketenes to synthesize hydroindoles was realized. Catalyzed by chiral bisguanidinium hemisalt via multiple hydrogen bond interactions, enantiomerically enriched products with reversal of diastereoselectivity in comparison with the racemic version were afforded in good yields under mild reaction conditions. Diaryl-substituted hydroindoles could also perform the Friedel-Crafts type of addition to give more complicated multicycles...

A two-step protocol for the conversion of alkyl-substituted alkynes to 1,3-enynes is reported. In this α-methenylation process, an iron-catalyzed propargylic C-H functionalization delivers tetramethylpiperidine-derived homopropargylic amines which undergo facile Cope elimination upon N-oxidation to afford the enyne products. A range of aryl alkyl and dialkyl acetylenes were found to be suitable substrates for this process, which constitutes an alkyne analogue for the Eschenmoser methenylation of carbonyl derivatives...

A Brønsted acid catalyzed cyclization of o -alkenyl- o' -alkynylbiaryls for the synthesis of biologically relevant dibenzo-fused medium-sized rings has been developed. The outcome of the cyclization is determined by the nature of the substituent at the alkyne, with arenes favoring seven-membered rings and alkyl substituents producing eight-membered rings. These reactions proceed via a vinyl cation, which is captured by water and, notably, by C-nucleophiles, such as electron-rich (hetero)arenes.

A Pd-catalyzed relatively general Michaelis-Arbuzov reaction of triaryl phosphites and aryl iodides for preparing useful aryl phosphonates was developed. Interestingly, water can greatly facilitate the reaction through a water-participating phosphonium intermediate rearrangement process, which also makes the reaction conditions rather mild. In comparison with the known methods, this reaction is milder and more general, as it exhibits excellent functional group tolerance, can be applied to various triaryl phosphites and aryl iodides, and can be extended to aryl phosphonites and phosphinites...

A selective three-component 1,2-sulfonyl etherification of aryl 1,3-dienes enabled by copper catalysis to afford biologically interesting alkenyl 1,2-sulfone ether derivatives through C-S and C-O bond formation is described. The protocol proceeds with the sulfonyl chloride and alcohols under simple, mild, and base-free conditions, providing a straightforward route to sulfonylated allyl ether compounds with broad functional group tolerance and excellent chemo- and regioselectivity. Mechanistic studies indicate that the selective alkene difunctionalization includes a key copper-mediated single-electron transfer process...

A series of nitrogen-bridged BODIPY oligomers were synthesized via nucleophilic aromatic substitution (SN Ar) as a convenient approach. Further transformations achieved novel α,α-aryl BODIPY dimers as well as a BODIPY hexamer efficiently. These BODIPY oligomers showed good photophysical properties, such as apparent absorption and emission both in visible and near-infrared regions. Interestingly, the high air and photothermal stability, strong NIR absorption, and high photothermal conversion rates of hexamer B6 suggest potential applications in photothermal therapy...

1,2-Bis(diphenylphosphino)ethanes (DPPEs) are versatile and immensely important ligands in transition metal catalysts. Here we report the dithiophosphinylation of readily available allenyl acetates to give DPPEs in high yields and regioselectivity. This protocol features a broad substrate scope and mild conditions, avoiding the use of transition metals and air-sensitive sources of phosphorus. Mechanism studies indicate that the reaction was accomplished via an SN 2'-type addition-elimination followed by a 1,4-addition step...

Pd(OAc)2 /Nixantphos or CoI2 /Nixantphos catalyzed allylic substitutions with weakly acidic C(sp)3 -H bonds of azaarylmethylamines are described. This method facilitates access to various kinds of heteroaryl rings containing homoallylamines (39 examples, 30-98% yields) with excellent functional group tolerance and diastereoselectivity. Compared with the Pd/Nixantphos complex, the Co/Nixantphos catalysis could obtain the cyclic products with good to excellent diastereoselectivities. Importantly, the CoI2 /( R,R )-Me-Duphos catalyzed reactions exhibit moderate enantioselectivity...

The synthesis of diaryl alkanes and tertiary organoboronates via Barluenga coupling at room temperature occurred via photoactivated conversion of aryl sulfonyl hydrazones to diazo compounds in the presence of soluble bases. The combination of arylsulfonyl hydrazone and a soluble base is necessary to provide a near-UV chromophore. Using aromatic hydrazones and aromatic boronic acids resulted in rapid deboronation because of the instability of dibenzylic boron intermediates. Alkyl hydrazones allowed the isolation of derivatives of the tertiary boronate...

A method was developed for the enantioselective formal 1,2-diamination of disubstituted ketenes using iminosulfinamides as nitrogen sources. The protocol involves the addition of lithium iminosulfinamides to ketenes to form N -iminosulfinyl amide metalloenolates. These metalloenolates then undergo a [2,3]-sigmatropic rearrangement to yield unnatural α,α-disubstituted α-amino acid derivatives with high enantiopurity. The chirality present at the sulfur atom in the iminosulfinamides is effectively transferred to α carbon of the resulting products, facilitating the highly enantioselective amination of ketenes...

The ability of α-amanitin to potently inhibit RNA polymerase II (RNAP II) has elicited further research into its use as a novel payload for antibody-drug conjugates. Despite this promise, the de novo synthesis of α-amanitin is still a major challenge as it possesses an unusual bicyclic octapeptide structure that contains several oxidized amino acids, most notably 4,5-dihydroxy-l-isoleucine. Here, we report a concise chemoenzymatic synthesis of this key amino acid residue, which features two regioselective and diastereoselective enzymatic C-H oxidations on l-isoleucine...

An unprecedented palladium-catalyzed and visible-light-driven relay reaction of allenylphosphine oxide with in situ generated nitrile imines is presented for the direct synthesis of highly valuable polyarylbipyrazole skeletons. This one-pot strategy involves double 1,3-dipolar cycloaddition and C(sp3 )-P(V) bond cleavage under photocatalyst-free and mild reaction conditions. The approach features simple operation, a high step economy, and a broad substrate scope, affording the corresponding products in moderate to excellent yields...

Operationally simple and generally applicable arene nitration with cheap and easily accessible chemicals has been a long-sought transformation in the synthetic organic community. In this work, we realized this goal with nontoxic and inexpensive Fe(NO3 )3 ·9H2 O as the nitro source and easily recyclable solvent hexafluoroisopropanol as the promotor via a network of hydrogen-bonding interactions. As a result of the relative mildness and high reliability of this protocol, late-stage nitration of various highly functionalized natural products and commercially available drugs was realized...

Asymmetric sulfonylation from a reaction of cyclopropan-1-ol, sulfur dioxide, and 1-(alkynyl)naphthalen-2-ol in the presence of a catalytic amount of organocatalyst at room temperature is developed. Axially chiral ( S )-( E )-1-(1-(alkylsulfonyl)-2-arylvinyl)naphthalen-2-ols are generated in moderate to good yields with excellent enantioselectivity and regioselectivity under mild conditions. During this transformation, γ-keto sulfinate generated in situ from cyclopropan-1-ol and sulfur dioxide acts as the key intermediate...

Herein, we report a catalyst-free reaction of cyclobutanone oximes with chlorophosphines (R2 PCl), which forms a fragile C═N-O-PR2 species that undergoes N-O homolysis, fragmentation, and radical-radical coupling, leading to the formation of cyano-containing phosphine oxides in good yields. The reaction features an in situ activation of cyclobutanone oximes for radical generation, in which R2 PCl plays a dual role as both an activator and a reactant.

The ruthenium/O2 -catalyzed oxidative annulation reaction of imidazo[1,5- a ]quinolin-2-ium salts with alkynes via N -heterocyclic carbene-directed C-H activation to obtain π-conjugated fused imidazo[1,5- a ]quinolin-2-ium derivatives is reported. Molecular oxygen has been explored as an economic and clean oxidant and an alternative to metal oxidants. The current protocol exhibits a wide range of substrate scope including bioactive (±)-α-tocopherol derivatives. Moreover, most of the annulated products show strong fluorescence properties, indicating their potential for making new light-emitting materials...