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Utilizing already existing DNA-encoded libraries (DELs) for the generation of a distinct DEL represents an expedited strategy for expanding the chemical space. Herein, we leverage the unique photoreactivity of tetrazoles to synthesize diacylhydrazines on DNA. Widely available carboxylic acids serving as building blocks were employed under the mild photomediated reaction conditions, affording diverse DNA-conjugated diacylhydrazines. This methodology also demonstrates robustness in DEL-compatible synthesis and facilitates the preparation of oligonucleotide-based chemical probes.

This study presents a Pd(II)-catalyzed method for the β-C(sp 3 )-H arylation of N -Cbz- or N -Fmoc-protected N -methyl alanines, providing ready access to building blocks for N -methylated peptide synthesis. For this transformation, the native carboxylate was exploited as the directing group, attributing its success to the use of a monoprotected amino-pyridine ligand. Its synthetic utility was demonstrated by facile generation of nine analogues of the naturally occurring N -methylated cyclic peptide cycloaspeptide A.

Photoenzymatic decarboxylation of bulky secondary and tertiary carboxylic acids catalyzed by engineered Chlorella variabilis fatty acid photodecarboxylase ( Cv FAP) is reported. Rational design and directed evolution of wild-type Cv FAP are used to improve the reactivity and expand potential applications. Moreover, engineered Cv FAP can catalyze light-driven kinetic resolution of α-substituted carboxylic acid. Our work sheds light on the production of chiral building blocks and bioactive molecules from bulky carboxylic acids via the photoenzymatic way.

A visible-light mediated deoxygenative radical addition of carboxylic acids to dehydroalanines has been disclosed. The method can be used in β-acyl alanine derivative synthesis, including those chiral and deuterated variants, and late-stage peptide modification with various functional groups, both in the homogeneous phase and on the resin in SPPS. It provides a new tool kit for rapid construction of bioactive peptide analogues, which has been demonstrated by modification of the antimicrobial peptide Feleucin-K3.

A multicomponent synthesis of tetrahydroisoquinolines from carboxylic acids, alkynyl ethers, and dihydroisoquinolines is described. This process features readily available starting materials, simple experimental procedures for achievement of molecule complexity, and structural diversity. The preliminary control experiment and crossover reaction provide important insight into the reaction mechanism. The formed tetrahydroisoquinolines could be transformed to an array of compounds. [ABSTRACT FROM AUTHOR]

The first aryl carboxyl radical generation by the donor–acceptor complex with N-acyloxyphthalimides and Hantzsch esters is reported. Regio- and chemoselective C(sp3)–H bond allylation is enabled by aryl carboxyl radicals with visible light irradiation under mild and metal-free conditions. [ABSTRACT FROM AUTHOR]

The combination of a Pd(0) complex with benzoic acid converts propargylic tryptamines to the corresponding tetrahydro-β-carbolines. The method uses unprotected indoles and affords the desired products with ample functional group tolerance. Detailed modeling studies reveal a close synergy between the organic and metal catalysts, which enables sequential alkyne isomerization, indole C–H activation, and eventual C–C reductive elimination to afford the target heterocycles. [ABSTRACT FROM AUTHOR]

An iridium photoredox catalyst in combination with phenanthroline-supported palladium catalyst catalyzes decarboxylative alkenylation of tertiary and secondary aliphatic carboxylic acids with vinyl arenes to deliver β-alkylated styrenes with Z-selectivity. A broad scope of aliphatic carboxylic acids, including amino acids, exhibit as amenable substrates, and external oxidant is not required. The reaction proceeds by synergistic utilization of both energy-transfer and electron-transfer reactivity of iridium photoredox catalyst merging with palladium-catalyzed hydride elimination and insertion. [ABSTRACT FROM AUTHOR]

A new method for chlorination of alcohols and carboxylic acids, using α,α-dichlorodiphenylmethane as the chlorinating agent and FeCl3 as the catalyst, was developed. The method enables conversions of various alcohols and carboxylic acids to their corresponding alkyl and acyl chlorides in high yields under mild conditions. Particulary interesting is the observation that the respective alkyl bromides and iodides can be generated from alcohols when either LiBr or LiI are present in the reaction mixtures. [ABSTRACT FROM AUTHOR]

The decarboxylative alkynylation of (hetero)aryl carboxylic acids with terminal alkynes has been achieved by using a Pd(PPh3)4/PCy3 catalyst. This Pd-catalyzed method exhibits good functional group tolerance for both coupling partners and enables chemical modification of complex molecules. The establishment of this decarboxylative alkynylation reaction is attributed to the discovery of a highly selective decarboxylative bromination of (hetero)aryl carboxylic acids with NBS (N-bromosuccinimide). [ABSTRACT FROM AUTHOR]

The first palladium-catalyzed esterification of carboxylic acids with aryl iodides is described. A palladium-based catalytic system consisting of IBnF (1,3-bis((pentafluorophenyl)methyl)imidazole-2-ylidene) ligand was found to significantly accelerate the aryl-O bond-forming esterification reaction. A series of aryl iodides and carboxylic acids undergoes a palladium-catalyzed coupling reaction to provide the corresponding aryl esters in moderate to good yields. In addition, sterically hindered aryl iodides and carboxylic acids were well-tolerated yielding the corresponding aryl esters. [ABSTRACT FROM AUTHOR]

This work describes three new red-photocleavable dyes. The best-performing dye exhibits a quantum yield of 5.7% in 30:70 v/v water/acetonitrile and approximately 80% release of benzoic acid using a 626 nm LED. Photo-orthogonality between this dye and a UV-activated photouncaging group was demonstrated. Additionally, a qualitative comparison between the same pair of dyes in a gel was performed, highlighting the superior penetration depth that can be achieved using the newly reported dye. [ABSTRACT FROM AUTHOR]

Visible-light-driven enantiodifferentiating photodimerization of 2-anthracenecarboxylic acid (AC) sensitized by Schiff base Pt(II) complex-grafted γ-cyclodextrins leads the first triplet-triplet annihilation-based catalytic photochirogenesis. The syn-head-to-tail (HT) photodimer 2 was achieved in up to 31.4% ee at 61.0% conversion in the presence of 0.5% equiv of the photocatalyst. [ABSTRACT FROM AUTHOR]

A two-step straightforward method for the preparation of ortho-alkylated vinylarenes from readily available benzoic acids is described. The synthetic route involves the dearomatization of benzoic acids by Birch reduction providing alkylated cyclohexa-2,5-dienyl-1-carboxylic acids. The diene subsequently undergoes a decarboxylative C-H olefination followed by rearomatization to deliver ortho-alkylated vinylarene. Mechanistic studies suggest that a Pd/Ag bimetallic catalytic system is important in the tandem decarboxylative C-H olefination/rearomatization step. [ABSTRACT FROM AUTHOR]

An operationally simple protocol is disclosed to facilitate entry to benzo-3,4-coumarins directly from biaryl carboxylic acids without the need for substrate prefunctionalization. Complementary to classic lactonization strategies, this disconnection relies on the oxidation competence of photoactivated (-)-riboflavin (vitamin B2) to generate the heterocyclic core via photoinduced single electron transfer. Collectively, the inexpensive nature of the catalyst, ease of execution, and absence of external metal additives are a convincing endorsement for the incorporation of simple vitamins in contemporary catalysis. [ABSTRACT FROM AUTHOR]

The cobalt(II)-catalyzed acyloxylation of C-H bonds in aromatic amides containing an 8-aminoquinoline moiety as the directing group with carboxylic acids is reported. Various carboxylic acids including aromatic and aliphatic carboxylic acids are applicable to the reaction. The reaction displays a broad substrate scope and high functional group tolerance. The reaction is carried out under air. [ABSTRACT FROM AUTHOR]

Tetramethyl orthosilicate (TMOS) is shown to be an effective reagent for direct amidation of aliphatic and aromatic carboxylic acids with amines and anilines. The amide products are obtained in good to quantitative yields in pure form directly after workup without the need for any further purification. A silyl ester as the putative activated intermediate is observed by NMR methods. Amidations on a 1 mol scale are demonstrated with a favorable process mass intensity. [ABSTRACT FROM AUTHOR]

The addition of tertiary carbon radicals generated by an Ir-catalyzed visible-light photocatalyst to electron-deficient 1,3-dienes proceeds in good yields to append a δ-substituted β,γ-unsaturated carbonyl fragment to a tertiary alcohol or carboxylic acid precursor and construct a new quaternary carbon center. [ABSTRACT FROM AUTHOR]

A straightforward synthesis of 2-styrylbenzoic acids from aryl carboxylic acids is disclosed through a carboxylate-assisted coupling under Ru(II) catalysis. This protocol is simple and exhibits broad scope with high tolerance of common organic functional groups, providing good to excellent yields of diverse olefinated products. The efficacy of this protocol has been showcased through sequential syntheses of isochromanone, isocoumarin, and formal synthesis of anacardic acid derivative in good yields. [ABSTRACT FROM AUTHOR]

A copper-catalyzed decarboxylative disulfonylation of alkynyl carboxylic acids with sulfinic acids in aqueous solution has been developed. The reaction provides a straightforward and practical access to (E)-1,2-disulfonylethenes, which are important building blocks in synthetic organic chemistry, and exhibits a good functional group tolerance and excellent stereoselectivity. A possible mechanism for the transformation is proposed. [ABSTRACT FROM AUTHOR]

An N-heterocyclic carbene-catalyzed oxidative LUMO activation of the β-cabons of saturated carboxylic esters is disclosed. This approach allows for efficient asymmetric access to lactams and lactones by directly installing functional groups to the typically inert β-sp³ carbons of saturated esters. The use of HOBt as an additive was found to significantly improve both yields and enantioselectivities of the reactions. [ABSTRACT FROM AUTHOR]

A scalable and efficient electrocatalytic dehydrogenative esterification is reported. With an indirect electrolysis strategy, both intra- and intermolecular-type reactions were amenable to this practical method. With n-Bu4NI as the catalyst, undesired decarboxylation and Baeyer-Villiger oxidation were suppressed. More importantly, this novel method provided reliable and direct access to the natural product cytosporanone A on a gram scale. [ABSTRACT FROM AUTHOR]

An efficient photoredox-catalyzed alkylation/lactonization reaction of unsaturated carboxylic acids by using alkyl N-hydroxyphthalimide esters as alkylation reagents has been developed. Varieties of redox-active esters derived from aliphatic carboxylic acids were proved viable in this method, affording alkyl substituted lactones in moderate to good yields. This redox-neutral procedure features mild conditions and operational simplicity, which provides a new strategy for the synthesis of alkyl substituted lactones. [ABSTRACT FROM AUTHOR]

A convenient, highly efficient, and selective transformation of aliphatic and aromatic carboxylic acids to acyl fluorides is reported. In contrast to established approaches that require toxic or volatile additives and base and reaction control (i.e., cooling, slow addition), this protocol allows for a straightforward access to various R-COF entities upon direct reaction with the bench-stable, solid reagent (Me4N)SCF3 at room temperature. The method is base- and additive-free, compatible with late-stage synthetic applications, high functional group tolerance, and facile target compound purification via filtration. [ABSTRACT FROM AUTHOR]

It is demonstrated that difluoromethyl diazomethane (HCF2CHN2) can react with a broad range of carboxylic acids. The reaction is convenient, operationally simple, mild, and tolerant of a variety of different functional groups. In sharp contrast, trifluoromethyl diazomethane (CF3CHN2) fails to react with carboxylic acids in most solvents, and in acetonitrile this reagent instead undergoes an interrupted esterification (a Mumm reaction) to yield N-trifluoroethyl imides. This striking example of the ability of a single F-for-H substitution to alter a reaction pathway was rationalized through a DFT study. [ABSTRACT FROM AUTHOR]

A cobalt-catalyzed decarboxylative cross-coupling reaction of (hetero)aryl carboxylic acids with benzothiazoles or benzoxazoles is reported. This represents a first example of metal-catalyzed decarboxylative C-H heteroarylation of benzo-fused heterocycles. The transformation provides a convenient route, with good yields and functional group tolerance, to various important arylheteroaryl and unsymmetrical biheteroaryl structural motifs. [ABSTRACT FROM AUTHOR]

A direct, palladium-catalyzed, carbonylative transformation of allylic alcohols for the synthesis of β,γ-unsaturated carboxylic acids has been developed. With formic acid as the CO source, various allylic alcohols were conveniently transformed into the corresponding β,γ-unsaturated carboxylic acids with excellent linear and (E)-selectivity. The reaction was performed under mild conditions; toxic CO gas manipulation and high-pressure equipment were avoided in this procedure. [ABSTRACT FROM AUTHOR]

A one-step protocol for the difluoromethylation of carboxylic acids is described. The reaction involves the interaction of intermediate acyl chlorides with in situ generated difluorinated phosphorus ylide Ph3P=CF2. Aromatic acids can be selectively transformed within one step either to bis-difluoromethylated alcohols or to difluorinated ketones depending on the particular reaction conditions. For bulky α-branched carboxylic acids, only ketones are produced. [ABSTRACT FROM AUTHOR]