Exclusive Regioselectivity Research Articles

Rh(I)–Diene-Catalyzed Addition of (Hetero)aryl Functionality to 1,3-Dienylsulfonyl Fluorides Achieving Exclusive Regioselectivity and High Enantioselectivity: Generality and Mechanism

Exclusively regioselective addition of (hetero)aromatic groups to 1,3-dienylsulfonyl fluorides using the Rh(I)/diene catalyst produces a class of (E)-2-aryl-4-(aryl or alkyl)but-3-ene-1-sulfonyl fl...

Cp*Co(III)-Catalyzed Dearomative [3 + 2] Spiroannulation of 2-Alkenylphenols with Ynamides via C-H Activation.

An oxidative [3 + 2] C-H spiroannulation reaction of 2-alkenylphenols with ynamides has been developed toward the synthesis of spiro[4,5]decane derivatives. This dearomative reaction employs earth-abundant cobalt as the metal catalyst and occurs under rather mild reaction conditions (room temperature). The use of ynamides confers unique reactivity and exclusive regioselectivity. The products bearing an all-carbon quaternary stereogenic center were constructed in generally good yields with good functional group tolerance being observed. Experimental mechanistic studies were conducted, and a possible reaction mechanism is proposed.

Regioselective Cp*Ir(III)-Catalyzed Allylic C-H Sulfamidation of Allylbenzene Derivatives.

In this study we report the development of the regioselective Cp*Ir(III)-catalyzed allylic C-H sulfamidation of allylbenzene derivatives, using azides as the nitrogen source. The reaction putatively proceeds through a Cp*Ir(III)-π-allyl intermediate and demonstrates exclusive regioselectivity for the branched position of the π-allyl. The reaction performs well on electron-rich and electron-deficient allylbenzene derivatives and is tolerant of a wide range of functional groups, including carbamates, esters, and ketones. The proposed mechanism for this reaction proceeds via C-N reductive elimination from a Cp*Ir(V) nitrenoid complex at the branched position of the π-allyl.

Visible Light-Mediated Direct C-H Aroylation and Alkylation of Heteroarenes.

Herein, we describe the photocatalytic generation of nucleophilic aroyl radicals from simple aroyl chlorides as a universal and efficient cross-coupling strategy for the direct aroylation of heteroarenes. Furthermore, visible light-mediated direct alkylation of heteroarenes has also been achieved using unactivated bromoalkanes as radical precursors. These two strategies feature high functional group tolerance, exclusive regioselectivity for reaction at the more electrophilic position of heteroarenes, easily accessible substrates, and mild reaction conditions. Moreover, mechanism studies of two reactions are carried out to support our hypotheses.

Visible‐Light‐Mediated Regioselective Allylation, Benzylation, and Silylation of Methylene‐Malononitriles via Photoredox‐Induced Radical Cation Fragmentation

Visible‐light‐mediated regioselective allylation, benzylation, and silylation of methylene‐malononitriles using allylic/benzylic silane and disilane reagents have been developed, delivering the corresponding allylated, benzylated, and silylated products in moderate to excellent yields. These reactions proceed smoothly with exclusive regioselectivity by employing only an organo‐photoredox catalyst under very mild conditions. A photoredox‐induced radical cation fragmentation is proposed for the generation of the key allylic, benzylic, and silyl radicals.

Regioselective Radical Alkene Amination Strategies by Using Phosphite-Mediated Deoxygenation

Nitrogen-containing compounds are an essential motif in all disciplines of chemistry and the efficient synthesis of these frameworks is a highly sought-after goal. Presented here is a summary of recent efforts conducted by our group to develop radical-mediated amination strategies for the formal synthesis of primary amines from alkenes with exclusive anti-Markovnikov regioselectivity. We have found that N-hydroxyphthalimide is an effective reagent capable of supplying both the N and H atoms for alkene hydroamination in a group transfer radical addition-type mechanism. Furthermore, allyl-oxyphthalimide derivatives are similarly capable of radical group transfers and allow for the aminoallylation of an external alkene.

Chemoselective Cobalt(I)-Catalyzed Cyclotrimerization of (Un)Symmetrical 1,3-Butadiynes for the Synthesis of 1,2,4-Regioisomers.

The cobalt(I)-catalyzed cyclotrimerization of (un)symmetrical 1,4-disubstituted 1,3-butadiynes is presented. In the case of unsymmetrical 1,3-butadiynes, this reaction can generate eight 1,2,4-substituted and four 1,3,5-substituted isomers. A single 1,2,4-substituted isomer was formed in excellent yields (up to 99%) and exclusive regioselectivities (>99:1) when symmetrical or a 1,3-butadiyne with an aryl or alkyl substituent and a trimethylsilyl group were applied. A large number of products accepting a wide variety of functional groups were synthesized.

Palladium‐Catalyzed Primary Amine‐Directed Decarboxylative Annulation of α‐Oxocarboxylic Acids: Access to Indolo[1,2‐a]quinazolines

AbstractAn efficient protocol for the preparation of indolo[1,2‐a]quinazolines via palladium‐catalyzed decarboxylative annulation of indols with α‐oxocarboxylic acids has been realized by using primary amine as a directing group (DG). This transformation proceeds smoothly with exclusive regioselectivity and represents an one‐pot Domino synthesis of indo‐lo[1,2‐a]quinazolines from α‐oxocarboxylic acids.magnified image

One-pot synthesis of 2,4-disubstituted quinolines via silver-catalyzed three-component cascade annulation of amines, alkyne esters and terminal alkynes

Described herein is a new and general method for one-pot synthesis of 2,4-disubstituted quinolines via silver-catalyzed [3 + 1 + 2] annulation of simple amines, alkyne esters and terminal alkynes. The versatile transformation might initiate with the facile formation of the enamine species with the feature of good to excellent yields, exclusive regioselectivity, and excellent substrate/functional group tolerance.

A rhodium catalyzed cycloisomerization and tandem Diels-Alder reaction for facile access to diverse bicyclic and tricyclic heterocycles.

A regioselective distal cycloisomerization of 1,6-allenenes was successfully developed to afford six-membered ring exocyclic 1,3-dienes employing a rhodium/diphosphine catalyst system. Deuterium labelling experiments and DFT calculations were performed to provide insights into the reaction mechanism of this unprecedented transformation. In addition, one-pot tandem Diels-Alder reactions with various dienophiles could readily construct diverse bicyclic and tricyclic nitrogen heterocycles, which are ubiquitous core scaffolds for a variety of natural products and bioactives. High efficiency and exclusive chemo and regioselectivities for a broad substrate scope were achieved under mild conditions using a low catalyst loading of 0.5 mol%.

Rh(III)-Catalyzed meta-C-H Alkenylation with Alkynes.

Rh(III)-catalyzed meta-C-H functionalization reactions are still rare. Herein, we report the first example of Rh(III)-catalyzed meta-C-H alkenylation with disubstituted alkynes directed by a U-shaped nitrile template. Exclusive regio-selectivity has been achieved using unsymmetrical aryl and alkyl-disubstituted alkynes to afford synthetically valuable trisubstituted olefins. Propargyl alcohols are also compatible, affording complex allylic alcohols. Notably, transition metal-catalyzed meta-alkenylation with alkynes has not been successful with Pd catalysts.

Synergistic Cu/Pd Catalysis for Enantioselective Allylation of Ketimine Esters: The Direct Synthesis of α‐Substituted α‐Amino Acids and 2H‐Pyrrols

AbstractAn efficient synergistic Cu/Pd catalyzed enantioselective α‐allylation of acyclic ketimine esters has been reported, which provides an entry to nonproteinogenic α‐allyl α‐amino acids in high yield, exclusive regioselectivity, and excellent enantioselectivity. Moreover, the more challenging cyclic ketimine ester could also be employed as a nucleophile for the construction of 3,4‐dihydro‐2H‐pyrrole derivatives bearing a quaternary stereogenic center using the same catalytic system.magnified image

An Unprecedented, Lewis Acid-Mediated, Metal-Free Iodoannulation Strategy to Aromatic Iodides.

A direct transformation of ortho-alkynylated aromatic vinyl ethers to 1-iodonaphthalenes and other iodo-heterocycles under mild Lewis acidic conditions in the presence of iodide as an external nucleophile is reported. The first example of an iodoannulation strategy using a nucleophilic source of iodine, coupled with good to excellent yields, exclusive alpha regioselectivity and a broad substrate scope makes this work an attractive avenue towards the construction of aromatic iodides.

Stable Pd-nanoparticles catalyzed domino C[sbnd]H activation/C[sbnd]N bond formation strategy: An access to phenanthridinones

Binaphthyl stabilized palladium nanoparticles (Pd-BNP) catalyzed synthesis of biologically active phenanthridinones via domino CH activation followed by CC and CN bond formation strategy in open air conditions is disclosed. This method works well with a broad range of N-methoxybenzamides and aryliodides substrates with different functional groups. The reaction is catalyzed by 1.5 mol% of heterogeneous Pd-BNP catalyst and afforded the phenanthridinones up to 87% yield with exclusive regioselectivity. Hot centrifuge test, UV spectroscopy analysis and Hg poisoning test are proved the heterogeneous nature of Pd-BNP catalyst.

A General Strategy for Site-Selective Incorporation of Deuterium and Tritium into Pyridines, Diazines, and Pharmaceuticals.

Methods to incorporate deuterium and tritium atoms into organic molecules are valuable for medicinal chemistry. The prevalence of pyridines and diazines in pharmaceuticals means that new ways to label these heterocycles will present opportunities in drug design and facilitate absorption, distribution, metabolism, and excretion (ADME) studies. A broadly applicable protocol is presented wherein pyridines, diazines, and pharmaceuticals are converted into heterocyclic phosphonium salts and then isotopically labeled. The isotopes are incorporated in high yields and, in general, with exclusive regioselectivity.

Abnormal NHC supported palladacycles: Regioselective arylation of heteroarenes via decarboxylation

We report synthesis of two new palladium(II) complexes of abnormal N-heterocyclic carbene ligands. The catalytic activity of these palladium(II) complexes was examined for the decarboxylative arylation of N-methylindole-carboxylic acids. An exclusive regioselectivity and very good yields were obtained with a variety of aryl halide partners.

Rhodium-Catalyzed Highly Regio- and Enantioselective Reductive Cyclization of Alkyne-Tethered Cyclohexadienones

Rhodium-catalyzed asymmetric hydrogenation of alkyne-tethered cyclohexadienones enables highly regio- and enantioselective reductive cyclization to afford cis-hydrobenzofurans and cis-hydroindoles in high yields. Desymmetrization of 1,3-diyne-tethered cyclohexadienones was also explored, wherein the intramolecular coordination of a Rh complex with the cyclohexadienone ring induces exclusive regioselectivity. Mechanistic studies including hydrogen–deuterium crossover experiments suggested that hydrogen activation is the rate-determining step for tandem reductive cyclization. Moreover, this highly practical and atom-economical transformation has tolerance to many functional groups with a broad range of substrate scope, allowing further transformations to expand the structural complexity of the bicyclic scaffolds.

Direct Synthesis of Quinolines via Co(III)-Catalyzed and DMSO-Involved C-H Activation/Cyclization of Anilines with Alkynes.

A unique Co(III)-catalyzed and DMSO-involved C-H activation/cyclization of simple, cheap, and easily available anilines with alkynes for direct and highly efficient synthesis of privileged quinolines with exclusive regioselectivity and broad substrate/functional group tolerance and in good to excellent yields, where DMSO was employed as both the solvent and the C1 building block of quinoline products, is reported. Mechanistic experiments revealed that the versatile reaction might employ the 2-vinylbenzenamine species as the active intermediate.

Dual Photoredox/Nickel-Catalyzed Regioselective Cross-Coupling of 2-Arylaziridines and Potassium Benzyltrifluoroborates: Synthesis of β-Substitued Amines.

A dual visible light photoredox and nickel-catalyzed cross-coupling reaction of 2-arylaziridines and potassium benzyltrifluoroborates is described for the first time. This strategy features high functional group tolerance, exclusive regioselectivity for reaction at the more hindered C-N bond, easily accessible substrates, and mild redox-neutral reaction conditions. A variety of diversely substituted β-substituted amines are obtained in generally good yields.

Catalytic asymmetric inverse electron demand Diels-Alder reaction of fulvenes with azoalkenes.

An unprecedented copper(i)-catalyzed asymmetric inverse electron demand Diels-Alder reaction of azoalkenes with fulvenes is reported. This methodology offers a directed entry to synthesize bicyclic tetrapyridazine derivatives in good yield with exclusive regioselectivity and excellent stereoselectivity.