Correction to "Iterative Dual-Metal and Energy Transfer Catalysis Enables Stereodivergence in Alkyne Difunctionalization: Carboboration as Case Study".

[This corrects the article DOI: 10.1021/acscatal.3c03570.

Iterative Dual-Metal and Energy Transfer Catalysis Enables Stereodivergence in Alkyne Difunctionalization: Carboboration as Case Study.

Stereochemically defined tetrasubstituted olefins are widespread structural elements of organic molecules and key intermediates in organic synthesis. However, flexible methods enabling stereodivergent access to and isomers of fully substituted alkenes from a common precursor represent a significant challenge and are actively sought after in catalysis, especially those amenable to complex multifunctional molecules. Herein, we demonstrate that iterative dual-metal and energy transfer catalysis constitutes a unique platform for achieving stereodivergence in the difunctionalization of internal alkynes.

Design of New Dispersants Using Machine Learning and Visual Analytics.

Artificial intelligence (AI) is an emerging technology that is revolutionizing the discovery of new materials. One key application of AI is virtual screening of chemical libraries, which enables the accelerated discovery of materials with desired properties. In this study, we developed computational models to predict the dispersancy efficiency of oil and lubricant additives, a critical property in their design that can be estimated through a quantity named blotter spot.

Palladium-Catalyzed PIDA-Mediated δ-C(sp )-H Acetoxylation of Amino Acid Derivatives: Overriding Competitive Intramolecular Amination.

The selective δ-C(sp )-H acetoxylation of N-(SO Py)-protected amino acid derivatives has been accomplished by using palladium-catalysis and PhI(OAc) (PIDA) as both terminal oxidant and acetoxy source. The distinct structural and electronic features of the SO Py compared to more traditional carbonyl-based directing groups is essential to override the otherwise more favourable competitive intramolecular C-H amination. The δ-site selectivity predominates over traditionally more favorable 5-membered cyclopalladation at competitive γ-CH .

Beyond classical sulfone chemistry: metal- and photocatalytic approaches for C-S bond functionalization of sulfones.

The exceptional versatility of sulfones has been extensively exploited in organic synthesis across several decades. Since the first demonstration in 2005 that sulfones can participate in Pd-catalysed Suzuki-Miyaura type reactions, tremendous advances in catalytic desulfitative functionalizations have opened a new area of research with burgeoning activity in recent years. This emerging field is displaying sulfone derivatives as a new class of substrates enabling catalytic C-C and C-X bond construction.

One-Metal/Two-Ligand for Dual Activation Tandem Catalysis: Photoinduced Cu-Catalyzed Anti-hydroboration of Alkynes.

A dual catalyst system based on ligand exchange of two diphosphine ligands possessing different properties in a copper complex has been devised to merge metal- and photocatalytic activation modes. This strategy has been applied to the formal anti-hydroboration of activated internal alkynes via a tandem sequence in which Cu/Xantphos catalyzes the Bpin--hydroboration of the alkyne whereas Cu/BINAP serves as a photocatalyst for visible light-mediated isomerization of the resulting alkenyl boronic ester. Photochemical studies by means of UV-vis absorption, steady-state and time-resolved fluorescence, and transient absorption spectroscopy have allowed characterizing the photoactive Cu/BINAP species in the isomerization reaction and its interaction with the intermediate -alkenyl boronic ester through energy transfer from the triplet excited state of the copper catalyst.

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed -Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes.

The cooperative action of the acetate ligand, the 2-pyridyl sulfonyl (SOPy) directing group on the alkyne substrate, and the palladium catalyst has been shown to be crucial for controlling reactivity, regioselectivity, and stereoselectivity in the acetoxylation of unsymmetrical internal alkynes under mild reaction conditions. The corresponding alkenyl acetates were obtained in good yields with complete levels of β-regioselectivity and -acetoxypalladation stereocontrol. Experimental and computational analyses provide insight into the reasons behind this delicate interplay between the ligand, directing group, and the metal in the reaction mechanism.

Remote -C-H functionalization medium-sized cyclopalladation.

Compared to the tremendous progress made in directed -C-H functionalization five- or six-membered cyclopalladation, protocols with the ability to selectively activate more remote C-H bonds through the intermediacy of larger, less favorable, seven- or eight-membered metalacycles are particularly challenging and remain rare. However, such a strategy would provide new retrosynthetic opportunities for generating structural diversity and complexity. Intense recent research based on the use of either mono-anionic bidentate or monodentate directing groups is characterizing this approach as an increasingly viable tool for selective C-C and C-X bond-forming reactions.

-Hydroarylation of Activated Internal Alkynes: Merging Pd and Energy Transfer Catalysis.

A general catalytic -hydroarylation of electron-deficient internal alkynes compatible with both electron-poor and electron-rich aryl reagents is reported. This selectivity is achieved through a sequential -carbopalladation of the alkyne by an Ar-Pd species, followed by a tandem, Ir-photocatalyzed, counter-thermodynamic → isomerization. The use of -substituted boronic acids enables direct access to pharmaceutically relevant heterocyclic cores via a cascade process.

Access to Benzazepinones by Pd-Catalyzed Remote C-H Carbonylation of γ-Arylpropylamine Derivatives.

A general method for the construction of seven-membered rings through Pd-catalyzed C(sp)-H carbonylation at the remote ε-position of γ-arylpropylamine derivatives, including chiral α-amino acids, has been developed using Mo(CO) as the CO source, furnishing richly functionalized benzo[ c]azepin-1-one derivatives. The readily removable N-SOPy protecting/directing group provides high levels of chemo-, regio- and diastereoselectivity. Furthermore, this method is amenable to the postsynthetic modification of complex molecules such as small peptides.

Rhodium-Catalyzed Copper-Assisted Intermolecular Domino C-H Annulation of 1,3-Diynes with Picolinamides: Access to Pentacyclic π-Extended Systems.

A new mode of reactivity of 1,3-diynes in rhodium-catalyzed oxidative annulation reactions has enabled the rapid assembly of extended π systems from readily available picolinamide derivatives. The process involves a double C-H bond activation and the iterative annulation of two 1,3-diyne units, with each alkyne moiety engaged in an orchestrated insertion sequence with high regiocontrol, leading to the formation of five new C-C bonds and the construction of four fused rings in a single operation. Either isoquinoline-1-carboxamides or fused polycyclic systems can be accessed by a switch in the regioselectivity of the second diyne insertion depending on the reaction conditions.

Cobalt-Catalyzed ortho-C-H Functionalization/Alkyne Annulation of Benzylamine Derivatives: Access to Dihydroisoquinolines.

A practical picolinamide-directed C-H functionalization/alkyne annulation of benzylamine derivatives enabling access to the previously elusive 1,4-dihydroisoquinoline skeleton was developed using molecular O as the sole oxidant and Co(OAc) as precatalyst. The method is compatible with both internal and terminal alkynes and shows high versatility and functional-group tolerance. Furthermore, full preservation of enantiopurity is observed when using non-racemic α-substituted benzylamine derivatives.

Hybridizing Feature Selection and Feature Learning Approaches in QSAR Modeling for Drug Discovery.

Quantitative structure-activity relationship modeling using machine learning techniques constitutes a complex computational problem, where the identification of the most informative molecular descriptors for predicting a specific target property plays a critical role. Two main general approaches can be used for this modeling procedure: feature selection and feature learning. In this paper, a performance comparative study of two state-of-art methods related to these two approaches is carried out.

Rh/Rh catalyst-controlled divergent aryl/heteroaryl C-H bond functionalization of picolinamides with alkynes.

The ability to establish switchable site-selectivity through catalyst control in the direct functionalization of molecules that contain distinct C-H bonds remains a demanding challenge that would enable the construction of diverse scaffolds from the same starting materials. Herein we describe the realization of this goal, namely a divergent heteroaryl/aryl C-H functionalization of aromatic picolinamide derivatives, targeting two distinct C-H sites, either at the pyridine ring or at the arene unit, to afford isoquinoline or -olefinated benzylamine (or phenethylamine) derivatives. This complementary reactivity has been achieved on the basis of a Rh/Rh switch in the catalyst, resulting in different mechanistic outcomes.

Cu-catalyzed silylation of alkynes: a traceless 2-pyridylsulfonyl controller allows access to either regioisomer on demand.

The Cu-catalyzed silylation of terminal and internal alkynes bearing a 2-pyridyl sulfonyl group (SO2Py) at the propargylic position affords a breadth of vinyl silanes in good yields and with excellent regio- and stereocontrol under mild conditions. The directing SO2Py group is essential in terms of reaction efficiency and chemoselectivity. Importantly, this group also provides the ability to reverse the regiochemical outcome of the reaction, opening the access to either regioisomer without modification of the starting substrate by virtue of an in situ base-promoted alkyne to allene equilibration which takes place prior to the silylcupration process.

Pd-catalyzed directed ortho-C-H alkenylation of phenylalanine derivatives.

A practical Pd-catalyzed ortho-olefination of enantioenriched N-(SO2Py)-protected aryl-alanine and norephedrine derivatives with electron-deficient alkenes has been developed using N-fluoro-2,4,6-trimethylpyridinium triflate as the terminal oxidant. The reaction occurs efficiently with excellent monosubstitution selectivity and without loss of enantiopurity. This cross-coupling proved to be broad in scope, tolerating a variety of steric and electronic changes to both coupling partners.

Copper-catalyzed mild nitration of protected anilines.

A practical copper-catalyzed direct nitration of protected anilines, by using one equivalent of nitric acid as the nitrating agent, has been developed. This procedure features mild reaction conditions, wide structural scope (with regard to both N-protecting group and arene substitution), and high functional-group tolerance. Dinitration with two equivalents of nitric acid is also feasible.

Synthesis of alkylidene pyrrolo[3,4-b]pyridin-7-one derivatives via Rh(III)-catalyzed cascade oxidative alkenylation/annulation of picolinamides.

A practical Rh(III)-catalyzed cascade olefination/annulation of picolinamides leading to pyrrolo[3,4-b]pyridines has been developed. The reaction shows wide scope, complete regiocontrol and excellent stereoselectivity.

Copper-catalyzed ortho-C-H amination of protected anilines with secondary amines.

A practical Cu-catalyzed picolinamide-directed o-amination of anilines showing excellent mono-substitution selectivity and high functional group tolerance has been developed.

Copper-catalyzed ortho-halogenation of protected anilines.

A practical Cu-catalyzed direct ortho-halogenation of anilines under aerobic conditions has been developed. The reaction shows typically excellent mono-substitution selectivity, high ortho-regiocontrol and large functional group tolerance.

Formal regiocontrolled hydroboration of unbiased internal alkynes via borylation/allylic alkylation of terminal alkynes.

In accessing trisubstituted vinyl boronates from terminal alkynes, a propargyl directing (2-pyridyl)sulfonyl group allows terminal alkynes to undergo Cu-catalyzed B2(pin)2-borylation and subsequent Cu-catalyzed allylic alkylation with Grignard reagents without affecting the pinacolboronate moiety, thereby formally enabling a highly stereo- and regiocontrolled access to hydroboration products of unbiased dialkyl internal alkynes.

Pd(II)-catalyzed di-o-olefination of carbazoles directed by the protecting N-(2-pyridyl)sulfonyl group.

Despite the significance of carbazole in pharmacy and material science, examples of the direct C-H functionalization of this privileged unit are quite rare. The N-(2-pyridyl)sulfonyl group enables the Pd(II)-catalyzed ortho-olefination of carbazoles and related systems, acting as both a directing and readily removable protecting group. This method features ample structural versatility, affording typically the double ortho-olefination products (at C1 and C8) in satisfactory yields and complete regiocontrol.

Catalytic asymmetric Mannich reaction of glycine Schiff bases with α-amido sulfones as precursors of aliphatic imines.

A general and practical Cu(I)-Fesulphos-catalyzed Mannich reaction of glycinate Schiff bases with aliphatic imines generated in situ from α-amido sulfones is described. Imines with linear and branched alkyl chains, including substrates bearing functional groups, can be efficiently applied. The resulting syn-configured orthogonally protected β-alkyl-α,β-diamino acid derivatives are produced with excellent levels of diastereo- (typically syn/anti >90 : <10) and enantioselectivity (generally ≥90% ee).

Regiocontrolled Cu(I)-catalyzed borylation of propargylic-functionalized internal alkynes.

Good to excellent reactivity and regiocontrol have been achieved in the Cu(I)-catalyzed borylation of dialkyl internal alkynes with bis(pinacolato)diboron. The presence of a propargylic polar group (OH, OR, SAr, SO(2)Ar, or NHTs), in combination with PCy(3) as ligand, allowed maximizing the reactivity and site-selectivity (β to the propargylic function). DFT calculations suggest a subtle orbitalic influence from the propargylic group, matched with ligand and substrate size effects, as key factors involved in the high β-selectivity.

Palladium-catalyzed coupling of arene C-H bonds with methyl- and arylboron reagents assisted by the removable 2-pyridylsulfinyl group.

The Pd(II)-catalyzed direct coupling of arene C-H bonds with organoboron reagents assisted by the 2-pyridylsulfinyl group is reported. Methylboronic acid and arylboronic acid neopentyl esters proved to be efficient coupling partners, furnishing methylated arenes and biaryl products in moderate to good yields. The 2-pyridylsulfinyl group can be easily removed to provide the free biaryls.