Ethynyl Benzoxazinanones Research Articles

Doubly Stereoconvergent Propargylic Alkylation of α-Cyanocarbonyls: Enantioselective Construction of Vicinal Stereocenters.

An asymmetric propargylic alkylation of α-cyanocarbonyls is developed for the first time under cooperative Cu(I) and organocatalysis. With ethynyl benzoxazinanones as the propargylic electrophile, this decarboxylative doubly stereoconvergent reaction evades alkyne hydroamination to furnish acyclic α-propargylic cyanocarbonyls, bearing vicinal tertiary and quaternary stereocenters, with high diastereo- and enantioselectivity (up to >20:1 dr and 99.5:0.5 er).

Mild Base-Promoted Tandem Nucleophilic Substitution/Decarboxylation/Hydroamination: Access to 3-Sulfonylindoles and 2-Methyleneindophenols.

We have developed an efficient construction of 3-sulfonylindoles and 2-methyleneindophenols via decarboxylative propargylation/hydroamination of ethynyl benzoxazinanones using sodium sulfonates and phenols as the nucleophiles. The reaction featured mild conditions (K2CO3), simple operation, and high chemoselectivity and was transition-metal-free. Our protocol could also be extended to other nucleophiles, including malonates, alcohols, and indoles. The broad substrate scope and scalability made this protocol practical for the synthesis of indole derivatives.

Base‐Mediated Decarboxylative [3+2] Annulation of Ethynyl Benzoxazinanones and Benzimidamides: Synthesis of Imidazole Derivatives

AbstractA base‐mediated decarboxylative [3+2] annulation of trimethylsilylethynyl benzoxazinanones and benzimidamides hydrochloride was achieved under mild reaction conditions to give various imidazole derivatives in high yields. Notably, it demonstrated a new reaction mode of alkynyl benzoxazinanones.magnified image

Synthesis of Heterobiaryl 4-Aryl Furans through a Base-Promoted Decarboxylative Propargylation/Cycloisomerization Annulation

A transition-metal-free synthesis of heterobiaryl 4-aryl furans through a base-promoted decarboxylative propargylation/cycloisomerization annulation of ethynyl benzoxazinanones and readily accessible β-keto esters or 1,3-diketones has been developed. A series of novel heterobiaryl 4-aryl furans were accessed efficiently in the presence of base under mild reaction conditions. This protocol is significant for probing the reaction mechanism of ethynyl benzoxazinanones and even other propargylic compounds.

Formal [3+2] Annulation of Copper‐Allenylidenes with 3‐Oxo‐3‐Arylpropanenitriles: Synthesis of Tetrasubstituted Furans

AbstractThe copper‐catalyzed decarboxylative [3+2] annulation of ethynyl benzoxazinanones with 3‐oxo‐3‐arylpropanenitriles has been developed, producing tetrasubstituted furan derivatives in moderate to high yield. This reaction was generally compatible with a wide range of substrates. Notably, the intermediate copper‐allenylidenes worked as a C2 synthon in the cycloaddition reaction.magnified image

Highly Diastereoselective Synthesis of Polycyclic Indolines through Formal [4+2] Propargylic Cycloaddition of Indoles with Ethynyl Benzoxazinanones.

A formal [4+2] propargylic annulation of indoles and pyrrole with ethynyl benzoxazinanones was described. This protocol provides a concise synthesis of tetrahydro-5H-indolo[2,3-b]quinolines and tetrahydro-3H-pyrrolo[3,2-b]quinoline, the core structures of alkaloid frameworks, featuring excellent yields, high diastereoselectivity, mild conditions and wide substrate scope.

N‐Heterocyclic Carbene/Copper Cooperative Catalysis for the Asymmetric Synthesis of Spirooxindoles

AbstractHighly enantioselective [3+3] and [3+4] annulations of isatin‐derived enals with ethynylethylene carbonates and ethynyl benzoxazinanones are enabled by NHC/cooper cooperative catalysis, leading to a big library of spirooxindole derivatives in high structural diversity and enantioselectivity (up to 99 % ee). Both reactions represent a nicely synergistic integration of NHC and copper catalysis, in which both catalysts activate the substrates and the chiral NHC perfectly controls the stereochemistry.

N-Heterocyclic Carbene/Copper Cooperative Catalysis for the Asymmetric Synthesis of Spirooxindoles.

Highly enantioselective [3+3] and [3+4] annulations of isatin-derived enals with ethynylethylene carbonates and ethynyl benzoxazinanones are enabled by NHC/cooper cooperative catalysis, leading to a big library of spirooxindole derivatives in high structural diversity and enantioselectivity (up to 99 % ee). Both reactions represent a nicely synergistic integration of NHC and copper catalysis, in which both catalysts activate the substrates and the chiral NHC perfectly controls the stereochemistry.

Asymmetric [4+2] cycloaddition of azlactones with dipolar copper–allenylidene intermediates for chiral 3,4-dhydroquinolin-2-one derivatives

In this paper, a pybox-copper catalyzed enantioselective decarboxylative [4+2] cycloaddition reaction of ethynyl benzoxazinanones with azlactones has been developed, which provides optically active 3,4-dihydroquinolin-2-ones in high yields with good enantioselectivities and diastereoselectivities. In this transformation, the chiral dipolar copper–allenylidene intermediates are kinetically generated via decarboxylative ethynyl benzoxazinanones, followed by the attack of the enolate azlactones to form enantiomerically enriched 3,4-dihydroquinolin-2-one structures.

Enantioselective [4 + 2]-Annulation of Azlactones with Copper-Allenylidenes under Cooperative Catalysis: Synthesis of α-Quaternary α-Acylaminoamides

The first enantioselective decarboxylative [4 + 2]-annulation of ethynyl benzoxazinanones with azlactones has been developed under cooperative copper and bifunctional tertiary aminourea catalysis. This direct and modular approach combines dipolar copper-allenylidene intermediates with azlactone enolates and allows for the synthesis of α-quaternary α-acylaminoamides as a single diastereomer generally in high yields with good to excellent enantioselectivities (up to 99:1 er).

Asymmetric [3 + 3] Annulation of Copper-Allenylidenes with Pyrazolones: Synthesis of Chiral 1,4-Dihydropyrano[2,3- c]pyrazoles.

The copper-catalyzed asymmetric [3 + 3] annulation of ethynyl benzoxazinanones with pyrazolones has been achieved, providing simple access to 1,4-dihydropyrano[2,3- c]pyrazole derivatives in moderate to excellent yields with excellent enantioselectivities (up to 99% ee). Compared with previous annulation reactions of copper-allenylidenes from ethynyl benzoxazinanones, the current reaction fused the three carbon atoms of the propargyl moiety into a heterocyclic framework.

Synthesis of 3,3'-Biindoles through a Copper-Catalyzed Friedel-Crafts Propargylation/Hydroamination/Aromatization Sequence.

A copper-catalyzed Friedel-Crafts propargylation/hydroamination/aromatization sequence is described. In the presence of a catalytic amount of CuI, this sequential reaction can convert ethynyl benzoxazinanones and indoles into a diverse set of 3,3'-biindoles with high efficiency and selectivity. Moreover, the synthesis of other indole-heteroaryl molecules and the catalytic asymmetric formation of axially chiral 3,3'-biindoles are demonstrated.

Enantioselective Decarboxylative Propargylation/Hydroamination Enabled by Organo/Metal Cooperative Catalysis.

The first catalytic enantioselective decarboxylative propargylation/hydroamination reaction of ethynyl benzoxazinanones with malononitriles enabled by organo/copper cooperative catalysis was established. Various 3-indolin-malononitrile derivatives, displaying a high tolerance for functional groups, could be obtained in good yields with high levels of enantioselectivity (up to 85% yield, 96:4 er). More importantly, this organo/metal cooperative catalytic system will provide a powerful synthetic strategy for new reaction development.

Asymmetric Catalytic [4 + 2] Cycloaddition via Cu-Allenylidene Intermediate: Stereoselective Synthesis of Tetrahydroquinolines Fused with a γ-Lactone Moiety.

A decarboxylative formal [4 + 2] cycloaddition reaction between ethynyl benzoxazinanones and 5-substituted 2-silyloxyfurans catalyzed by chiral Cu-Pybox complex is described. This method allows the formation of intriguing tetrahydroquinolines fused with a butyrolactone moiety featuring three contiguous chiral centers in high yields with excellent diastereo- and enantioselectivities in most cases. The utility of this method was exemplified by the removal of the N-protecting groups and derivatization on the terminal alkyne functionality of the cyclization products.

Copper-catalyzed decarboxylative cyclization via tandem C–P and C–N bond formation: access to 2-phosphorylmethyl indoles

A novel copper-catalyzed decarboxylative cyclization of ethynyl benzoxazinanones with P(O)H compounds has been developed. This protocol leads to a series of 2-phosphorylmethyl indoles with high efficiency and selectivity (up to 99% yield) through tandem C-P/C-N bond formation under mild conditions.

Copper-catalyzed decarboxylative propargylation/hydroamination reactions: access to C3 β-ketoester-functionalized indoles.

A copper-catalyzed reaction of ethynyl benzoxazinanones with readily accessible β-ketoesters via a decarboxylative propargylation/hydroamination sequence has been developed. This protocol furnished a diverse range of C3 β-ketoester-functionalized indoles in good to excellent yields.

Enantioselective Cascade Reaction for Synthesis of Quinolinones through Synergistic Catalysis Using Cu-Pybox and Chiral Benzotetramisole as Catalysts.

In contrast to the well-studied asymmetric catalyzed synthesis of tetrahydroquinolines, the asymmetric methodologies toward 3,4-dihydroquinolin-2-ones are quite rare. Herein, the first asymmetric cascade reaction is reported between ethynyl benzoxazinanones and mixed-anhydrides generated from aryl acetic acids and pivaloyl chloride, based on synergistic catalysis. This allowed the formation of attractive 3,4-dihydroquinolin-2-ones bearing two vicinal chiral centers at C3 and C4 in high yields with excellent diastereo- and enantioselectivities. A plausible chiral induction model for this reaction was proposed. The utility of this methodology was exemplified by further elaboration of the cyclization products by removal of the N-protecting groups.