Carlos Roque Duarte Correia

• PhD
• Professor (Full) at State University of Campinas (UNICAMP)

We report herein a novel, efficient, and expeditious approach for enantioselective intramolecular carbonylative Heck–Matsuda reaction, employing highly accessible, stable, and cost-effective nitroarenes as masked electrophiles.

A new class of amino acids, so-called fatty amino acids, which integrate the typical structural motif of another important type of natural products, fatty acids, is presented. Applying the palladium-catalyzed...

Novel phosphine ligands based on (benzo)furylphosphines, enable the efficient palladium-catalyzed telomerization of 1,3 butadiene with methanol. The synthesis of industrially relevant 1-methoxy-2,7-octadiene (1-MODE) occurs in quantitative yields and excellent productivity...

Increasing emissions of carbon dioxide into the atmosphere due to the use of fossil fuels and ongoing deforestation are affecting the global climate. To reach the Paris climate agreement, in the coming decades low emission technologies must be developed, which allow for carbon removal on a Gt per year‐scale. In this regard, we propose the electroch...

A theoretical mechanistic study for a Heck-Matsuda reaction mediated by nickel complexes was performed using DFT calculations considering 3-cyclopenten-1-ol as the initial olefin. Two pathways were identified: a closed shell singlet Ni(0)/Ni(II) and an open shell doublet Ni(I)/Ni(III). Analysis of kinetic energy profiles through span analysis revea...

A one‐pot tandem process was developed aiming at the concise and expeditious enantioselective synthesis of dihydrobenzofuran, dihydrobenzosulfone, and dihydroindole scaffolds under mild, and open‐flask conditions. This process combines the in situ generation of aryldiazonium salt directly from the anilines in methanol telescoped to an intramolecula...

We report herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N -protected 2,5-dihydro-1 H -pyrroles with aryldiazonium salts, using the chiral N , N -ligand ( S )-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation followed by a sequential Jone...

Carboxymethyl C5-functionalized pyridine-oxazoline (PyOx) ligands were immobilized onto Merrifield and Wang resins utilizing three distinct strategies. The immobilized PyOx ligands were employed in the Pd-catalyzed heterogeneous Heck-Matsuda reaction for the desymmetrization of 3-cyclopenten-1-ol, resulting in the production of 20 examples of aryl-...

Circularly polarized luminescence (CPL) from lanthanide (Ln III ) complexes has aroused extensive attention in the last decade owing to its potential use in displays or as anti-counterfeiting devices, for instance. However,...

We report herein an enantioselective palladium-catalyzed Heck-Matsuda reaction for the desymmetrization of N -protected 2,5-dihydro-1- H -pyrroles with aryldiazonium salts, using the chiral N - N -ligand ( S )-PyraBOx. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation followed by a sequential Jon...

This work describes an effective method to obtain chiral vinyl cyclopentenols with a high degree of enantioselectivity and diastereoselectivity through Heck desymmetrization of cyclopent‐3‐en‐1‐ylmethanol using vinyl triflates as coupling agents and chiral N,N ligands. This Heck vinylation protocol allowed the synthesis of several structurally comp...

The enantioselective synthesis of isoindolones via Heck‐Mizoroki reactions of endocyclic enamides using a palladium‐bis(oxazoline) catalyst system is described. The N,N‐ligands, which are under‐represented in palladium‐catalyzed reactions involving aryl halides, proved to be an effective and low‐cost alternative to their phosphine‐based chiral liga...

A new enantioselective intramolecular strategy for the synthesis of enantioenriched bridged benzoxacines, unsaturated spirobenzofurans, 2,3‐dihydrobenzofuran and 2,3‐indoline acetate scaffolds in a tandem‐like diazotization/Heck‐Matsuda process directly from anilines has been developed. The process combines the in situ diazotization of the aniline,...

Arenediazonium salts represent an important class of aromatic organic compounds widely used as building blocks in academia and industry. Due to the high energy associated with the diazonium group, many of these salts are reported as thermally unstable and/or unsafe to work with. However, most of the tetrafluoroborate arenediazonium salts, are fairl...

A new enantioselective intramolecular strategy for the synthesis of enantioenriched bridged benzoxacines, unsaturated spirobenzofurans, methyl-2,3-dihydrobenzofuran acetates, and methyl-2,3-indoline acetate scaffolds in a tandem-like diazotization/Heck Matsuda process directly from anilines has been developed. The process combines the in situ diazo...

The chiral aryl lactam nucleus is a common motif present in many bioactive natural products and the development of effective enantioselective methodologies for its preparation is of great interest. In this work, we report the synthesis of several enantioenriched aryl lactams in good yields and enantiomeric ratios using a combined strategy employing...

(E)-Cinnamaldehyde is very active against Meloidogyne incognita but has low persistence in soil. To circumvent this problem, esters of cinnamic acid were evaluated as a substitute for (E)-cinnamaldehyde. The best results under assays with M. incognita second-stage juveniles (J2) were obtained for the methyl esters of (E)-p-fluoro- (13), (E)-p-chlor...

A dynamic kinetic asymmetric Pd-catalyzed cross-coupling reaction of heterobiaryl bromides with ketone N-tosylhydrazones for the synthesis of heterobiaryl styrenes is described. The combination of Pd(dba)2 as a precatalyst with a TADDOL-derived phosphoramidite ligand provides the corresponding coupling products in good yields and high enantioselect...

The catalytic synthesis of isoprenol by hydrogenation of 3-methylbut-3-en-1-yl acetate on heterogeneous bimetallic Cu-Pt catalysts was carried out for the first time. The best selectivity of isoprenol (76%) was obtained on the 5%Cu–1%Pt/SiO2 catalyst with a full ester conversion in 6 h of the reaction.

An in tandem enantioselective Heck‐Matsuda (HM) reaction of cyclic and acyclic olefins directly from anilines is described. The method relies on a process involving the progressive in situ diazotization of the starting anilines followed by a palladium‐catalyzed Heck‐Matsuda arylation using chiral N,N‐ligands. This intermolecular enantioselective HM...

The catalytic cycles proposed for a Heck--Matsuda reaction mediated by nickel complexes occurring via a closed shell singlet Ni(0)/Ni(II) or via an open shell doublet Ni(I)/Ni(III) were obtained, as well as a thermodynamic analysis of its pre-catalysis. The energy span analysis from the kinetic energy profile for the singlet Ni(0)/Ni(II) cycle indi...

N-Arylation of n-octylamine and adamantane-containing amines with iodobenzene and its deriva­tives has been performed in DMSO using copper(I) iodide and copper nanoparticles in the presence of various ligands as catalysts. In all cases, 2-isobutyrylcyclohexanone turned out to be the most efficient ligand, and higher yields of the arylation products...

The therapeutic potential of 3H-pyrrolo[2,3-c]quinolines—the main core of Marinoquinoline natural products—has been explored for the development of new anti-TB agents. The chemical modification of various positions in this scaffold has led to the discovery of two pyrroloquinolines (compounds 50 and 54) with good in vitro activity against virulent s...

The N-heteroarylation of n-octylamine and adamantane-containing amines with 2-iodopyridine and 2-bromopyridine and its fluorinated derivatives under the catalysis of CuI and copper nanoparticles in DMSO in the presence of various ligands was studied. 2-Isobutyrylcyclohexanone was found to be the most efficient ligand in the reactions catalyzed by C...

Comparison of the homogeneous and heterogeneous copper-catalyzed arylation of model primary amines with (hetero)-aryl iodides in DMSO revealed a comparable efficiency of CuI and commercially available unsupported copper nanoparticles (25 nm size) in the presence of 2-isobutyryl-cyclohexanone or L-proline.

Marine halophytes are an outstanding reservoir of natural products and several species have anti-infectious traditional uses. However, reports about their potential use against neglected tropical ailments, such as Chagas disease, are scarce. This work evaluated for the first time the in vitro anti-Trypanosoma cruzi activity of extracts from the aro...

Two reactive phenanthrene derivatives, 4-(1H phenanthrol [9,10-d] imidazole-2-yl) benzaldehyde (PIB) and 6,9-dimethoxyphenanthro[9,10-c]furan-1,3-dione (PA) with high fluorescent quantum yields were prepared and used as fluorescent marker in fluorescence microscopy. In particular, silane modified μmZeolite-L containing amino group (-NH2) in the sur...

The heterocyclic 3H‐pyrrolo[2,3‐c]quinoline system and its closely related natural products, the marinoquinolines, have been attracting considerable attention in recent years in view of its interesting chemistry and diverse biological activities. Known since 1924, only in 2006 were the 3H‐pyrrolo[2,3‐c]quinolines associated with the first marinoqui...

The enantioselective palladium‐catalyzed Heck arylation of olefins using arenediazonium salts is one of the last features in the evolution of a synthetic method known as the Heck‐Matsuda reaction. This personal account highlights the development of the enantioselective Heck‐Matsuda reaction in its initial stages, the challenges faced along the way,...

The title pyrrolidine compound, C18H23NO7, is a tetra-substituted species in which the five-membered ring has a twisted conformation with the twist occurring in the C—C bond bearing the adjacent acet­yloxy substituents; the Cm—Ca—Ca—Cp torsion angle is −40.76 (18)° [m = methyl­ene, a = acet­yloxy and p = phen­yl]. The N atom, which is sp²-hybridize...

C 17 H 23 NO 5 , monoclinic, P 2 1 (no. 4), a = 6.0479(9) Å, b = 9.7032(10) Å, c = 14.711(2) Å, β = 94.174(9)°, V = 861.0(2) Å ³ , Z = 2, R gt ( F ) = 0.0440, wR ref ( F ² ) = 0.1436, T = 293(2) K.

C 18 H 24 N 2 O 5 , monoclinic, P 2 1 / c (no. 14), a = 11.4784(7) Å, b = 9.0180(8) Å, c = 17.9483(17) Å, β = 92.823(7)°, V = 1855.6(3) Å ³ , Z = 4, R gt ( F ) = 0.0505, wR ref ( F ² ) = 0.1611, T = 293 K.

C 19 H 24 N 2 O 6 , monoclinic, P 2 1 (no. 4), a = 8.3611(7) Å, b = 9.0521(8) Å, c = 13.8988(8) Å, β = 106.710(5)°, V = 1007.52(14) Å ³ , Z = 2, R gt ( F ) = 0.0428, wR ref ( F ² ) = 0.1174, T = 293(2) K.

A highly efficient Heck‐Matsuda desymmetrization of unsaturated spirohydantoins directed by non‐covalent interactions, which allows the construction of two simultaneous stereogenic centers, including a trisubstituted quaternary one, is described. This Heck arylation permitted a novel enantioselective total synthesis of the S1PR1 agonist (also an S1...

The title compound, C23H24N2O9, is a tetra-substituted pyrrolidine derivative with a twisted conformation, with the twist evident in the C—C bond bearing the adjacent acet­yloxy substituents. These are flanked on one side by a C-bound 4-meth­oxy­phen­yl group and on the other by a methyl­ene group. The almost sp²-N atom [sum of angles = 357°] bears...

The title compound, C13H19NO8, is based on a tetra-substituted pyrrolidine ring, which has a twisted conformation about the central C—C bond; the Cm—Ca—Ca—Cme torsion angle is 38.26 (15)° [m = methyl­carboxyl­ate, a = acet­yloxy and me = methyl­ene]. While the N-bound ethyl­carboxyl­ate group occupies an equatorial position, the remaining substitue...

The palladium-catalyzed Heck arylation of olefins using arenediazonium salts, known as the Heck-Matsuda reaction, constitutes an effective, green, and sustainable way to synthesize functionalized aryl intermediates for organic synthesis. The present review highlights this strategy focusing on some selected examples from our laboratory. The examples...

A quantum-chemical study based on the Kohn–Sham density functional theory (DFT) has been performed in order to investigate the asymmetric Heck–Matsuda (HM) reactions involving a chiral N,N ligand pyrimidine-oxazoline. The oxidative addition (OA) of arenediazonium cation was analyzed to provide further insights in the unexpected high reactivity of N...

Diazenes are valuable compounds that have found broad applicability because of their optical and biological properties. We report the synthesis of alkylaryldiazenes via formal, photoredox catalyzed, deformylative C-N bond formation. The procedure employs dihydropyridines for the generation of alkyl radicals, which are then trapped by diazonium salt...

Herein we report the enantioselective Heck‐Matsuda arylation of acyclic E and Z‐alkenyl aryl ethers. The reactions were carried out under mild conditions affording the enantioenriched benzyl ethers in a regioselective manner, moderate to good yields (up to 73%), and in good to excellent enantiomeric ratios (up to 97:3). The enantioselective Heck‐Ma...

O presente projeto visa o aprimoramento da potência e das propriedades físico-químicas do composto líder desenvolvido por nosso grupo. Este aprimoramento será realizado através de modificações estruturais realizadas por meio da adição de um espaçador do tipo metileno e modificações no grupo carbamato, trocando-o por outros carbamatos e uréias.

The arylative oxygenation of the electron-rich olefins styrene, α-methylstyrene, vinyl pyrrolidinone, and vinyl oxazolidinone was accomplished using arenediazonium salts and catalytic amounts of FeSO4 in an effective single electron transfer radical process. A broad range of aryldiazonium salts was tolerated using water, methanol, or their combinat...

A density functional theory (DFT) study has been carried out with respect to the cationic and neutral mechanism of ligand-free Heck-Matsuda cross-coupling reaction involving allylic esters and arenediazonium salts. Full Heck-Matsuda (HM) catalytic cycles were explored in the presence of different possible combinations of ligands based on previous m...

With the progress on the enantioselective arylation of 3-cyclopentenol obtained by our group, the present project was motivated to explore new possible substrates for the enantioselective Heck-Matsuda reactions (EHM) and try to propose new synthetic routes for tricyclic skeletons, found in tromboxan inhibitors and other related pharmaceuticals. In...

In this communication, we describe the enantioselective synthesis of phthalides and isochromanones through a new palladium‐catalyzed Heck–Matsuda arylation/NaBH4‐reduction/lactonization sequence of 2,3‐ and 2,5‐dihydrofurans in good overall yields and excellent enantioselectivities (up to 98:2 er). This expeditious synthesis of chiral Heck lactol i...

Unprecedented enantioselective intramolecular Heck carbonylation reactions of arenediazonium salts were enabled by a chiral N,N ligand. This reaction constitutes the first enantioselective Heck carbonylation that proceeds through migratory insertion followed by CO insertion. The enantioenriched functionalized dihydrobenzofurans were obtained in goo...

Unprecedented enantioselective intramolecular Heck carbonylation reactions of arenediazonium salts were enabled by a chiral N,N ligand. This reaction constitutes the first enantioselective Heck carbonylation that proceeds through migratory insertion followed by CO insertion. The enantioenriched functionalized dihydrobenzofurans were obtained in goo...

Enantioselective substrate directed Heck reactions are desirable for the stereoselective synthesis of complex molecules. However, due to the coordination requirements of both chiral ligands and directing groups, such methodologies are underdeveloped. We report herein the desymmetrization of meso (1 R ,2 S )‐cyclohex‐4‐ene‐1,2‐diol in an enantiosele...

We report the discovery of marinoquinoline (3H-pyrrolo[2,3-c]quinoline) derivatives as new chemotypes with antiplasmodial activity. We evaluated their inhibitory activities against P. falciparum and conducted a structure-activity relationship study, focusing on improving their potency and maintaining low cytotoxicity. Next, we devised quantitative...

Highly diastereo and enantioselective non‐covalent substrate directable Heck desymmetrizations of cyclopentenyl olefins bearing hydroxymethyl and carboxylate functional groups are presented. These conformationally unbiased cyclic olefins underwent effective arylations in yields of up to 97%, diastereoselectivity up to >20:1, and enantiomeric excess...

Cross-linking/Mass spectrometry (XLMS) is a consolidated technique for structural characterization of proteins and protein complexes. Despite its success, the cross-linking chemistry currently used is mostly based on N-hydroxysuccinimed (NHS) esters, which react primarily with lysine residues. One way to expand the current applicability of XLMS int...

In the title compound, C28H34N2O5, the adjacent ester and nitro­benzene substituents are connected via an intra­molecular methyl­ene-C—H⋯π(nitrobenzene) inter­action and the mol­ecule approximates to a U-shape. The di­hydro­pyrrole ring (r.m.s. deviation = 0.003 Å) is almost co-planar with the carboxyl­ate residue [Cm—N—C1—Oc (m = methine, c = carb...

In the title compound, C12H12N2O4, the di­hydro­pyrrole ring is almost planar (r.m.s. deviation = 0.0049 Å) and is nearly coplanar with the adjacent C2O2 residue [dihedral angle = 4.56 (9)°], which links to the 4-nitro­benzene substituent [dihedral angle = 4.58 (8)°]. The mol­ecule is concave, with the outer rings lying to the same side of the cent...

The presence of surfactants in aquatic environment is a major public health concern. Recently, several methods have been developed to remove these compounds, among these are the adsorption processes. The great challenge of this technology is to achieve high removal capacities, fast adsorption and efficient adsorbent recoveries. The aim of our study...

Novel palladium-catalyzed redox-relay Heck arylation reactions of trisubstituted allylic alkenols were developed employing silyl and methyl ethers. The reactions proceeded under mild conditions in moderate to high yields in excellent anti diastereoselectivity to form α,β- disubstituted methyl ketones containing two contiguous stereocenters. The new...

Pd nanoparticles were synthesized on non-functionalized and functionalized graphene oxide with thiol and amine groups. The resulting materials were used as recyclable catalysts to study the influence of the functional groups and compare their activity and stability to non-functionalized graphene oxide and commercial catalysts in the Heck and Suzuki...

This work discloses the first examples of an effective enantioselective oxy‐Heck–Matsuda reaction using a variety of styrenic olefins to generate chiral dihydrobenzofurans. The reaction proceeds in moderate to good yields, with high trans diastereoselectivity (up to 20:1) in enantioselectivities up to 90:10 using the N,N‐ligand pyrimidine‐bisoxazol...

The title compound, C14H17NO4, features an epoxide-O atom fused to a pyrrolidyl ring, the latter having an envelope conformation with the N atom being the flap. The 4-meth­oxy­phenyl group is orthogonal to [dihedral angle = 85.02 (6)°] and lies to the opposite side of the five-membered ring to the epoxide O atom, while the N-bound ethyl ester group...

The title isoaltholactone derivative, C13H13NO3, has an NH group in place of the ether-O atom in the five-membered ring of the natural product. The five-membered ring is twisted about the N—C bond linking it to the six-membered ring, which has a half-chair conformation with the O atom connected to the ether-O atom lying above the plane defined by t...

The Fujiwara's hydroarylation of alkynes was re-investigated employing the indole addition to methyl or ethyl phenylpropiolate catalyzed by Pd(OAc)2 as a model. Reactions were monitored by both 1H-NMR, electrospray ionization mass spectrometry (ESI/MS) and via reactions performed in the gas phase using MS/MS experiments. Contrary to the original su...

Enantioselective carbonyl‐directable Heck reactions using aryldiazonium salts were developed with the aim to construct chiral quaternary spiro centers in an efficient manner. Five‐ and six‐membered spirooxindoles, spirolactones, and spirolactams (36 examples) were obtained in good to excellent isolated yields with diastereoselectivities ranging fro...

A novel, efficient and enantioselective Heck-Matsuda desymmetrization of non-activated cyclopentene-fused spiro-pyrrolidinones was developed. The reaction provided the Heck products in good to excellent yields and selectivities and tolerated a variety of functional groups in arenediazonium tetrafluoroborates (12 examples) with respect to its electr...

S- and P-stereogenic heterocycles were synthesized by a remarkably simple enantioselective Heck desymmetrization reaction based on the unprecedented non-covalent directing effect of S=O and P=O functionalities. Selected prochiral symmetric substrates were efficiently arylated using the recently disclosed chiral PyraBOx ligand under mild and open-fl...

The Heck—Matsuda desymmetrization of 3-cyclopenten-1-ol is studied by both computational and synthetic means.

New computationally driven protocols for the Heck desymmetrization of 3-cyclopenten-1-ol with aryldiazonium tetrafluoroborates were developed. These new conditions furnished remarkable product selectivity originating from a resident hydroxyl group and the critical choice of the reaction solvent. Mechanistic insights gleaned from theoretical calcula...

We describe herein a highly regio- and enantioselective Pd-catalyzed Heck arylation of unactivated trisubstituted acyclic olefins to provide all-carbon quaternary stereogenic centers. Chiral N,N ligands of the pyrimidine- and pyrazino-oxazoline class were developed for that purpose, providing the desired products in good to high yields with enantio...

A new palladium‐catalyzed route to 3‐hydroxy‐4‐arylcyclopentanones and 4‐arylcyclopentenones in a diastereo‐ and enantioselective manner by a Heck–Matsuda desymmetrization was achieved from the commercially available meso cis ‐4‐cyclopentene‐1,3‐diol. This method is highly practical, mild, high yielding and is carried out under “open vessel” condit...

The boom in visible light photoredox catalysis (VLPC) research has demonstrated that this novel synthetic approach is here to stay. VLPC enables reactive radical intermediates catalytically generated at ambient temperature, a feat not generally allowed through traditional pyrolysis- or radical initiator-based methodologies. VLPC has vastly extended...

Successful Heck-Matsuda arylations of non-activated olefins applying microwave irradiation as an alternative heating mode are presented. Cleaner reactions were performed with arenediazonium tetrafluoroborates bearing electron-donating and electron-withdrawing groups in good to excellent yields with reaction times reduced from 3.5-18 h to 12-30 min.

The Heck arylation of olefins by the substrate-directed Heck–Matsuda strategy using arenediazonium salts, especially the tetrafluoroborates, constitutes an effective way to synthesize functionalized olefins, thus making them more valuable intermediates in organic synthesis. The basic principle of the method relies on the complexation of a cationic...

A new enantioselective Heck–Matsuda desymmetrization reaction was accomplished by using 3-cyclopentenol to produce chiral five-membered 4-aryl cyclopentenol scaffolds in good yields and high ee’s, together with some 3-aryl-cyclopentanones as minor products. Mechanistically, the hydroxyl group of 3-cyclopentenol acts as a directing group and is resp...

We describe herein a general method for the controlled Heck arylation of allylated malonates. Both electron-rich and electron-poor aryldiazonium salts were readily employed as the aryl-transfer agents in good yields and in high chemo-, regio-, and stereoselectivity without formation of decarboxylated byproducts. Reaction monitoring via ESI-MS was u...

Design of experiments was employed to optimize the reaction conditions used to synthesize stilbene derivatives. New Heck conditions were tested using several styrenes and aryldiazonium tetrafluoroborates, generating the desired stilbenes in good yields in all cases under very practical, economical and effective conditions. This methodology was used...

New, efficient protocols for the syntheses of the marine natural products prepolycitrin A as well as polycitrins A and B were developed by employing the Heck-Matsuda arylation of maleic anhydride or dimethyl fumarate with aryldiazonium tetrafluoroborates. Both symmetrical and unsymmetrical 3,4-diarylmaleic anhydrides were easily and effectively pre...

This patent application has as purpose the application/utilization of esters and ethers derived from xylitol, obtained by organic synthesis, as alternative emollient, moisturizing, emulsifier and co-emulsifier and preservatives for pharmaceutical, cosmetic and veterinarian products. The molecules required in this invention patent are mainly xylitol...

New synthetic routes toward the commercial drugs cinacalcet hydrochloride, alverine, and tolpropamine were developed using a Heck-Matsuda arylation as the key-step. Several reaction conditions were evaluated for the Heck-Matsuda reaction using allylamine derivatives and arenediazonium salts. For cinacalcet hydrochloride, N-formylamide provided the...

A series of bisaryl-substituted fluorescent maleimides was synthesized via the Heck arylation. The compounds showed broad fluorescence emission bands in the visible region, a large Stokes shift in polar solvents and emission quantum yields varying from 0.04 to 0.71, depending on the structure and solvent medium. The difference in dipole moments of...