Stereoselective Annulation Research Articles

Annulation of 1-methylisoquinoline with pyrrolylacetylenic ketones: catalyst-free stereoselective synthesis of (E)-acylethenylpyrrolo[1’,2’:3,4]imidazo[2,1-a]isoquinolines

1-Methylisoquinoline undergoes stereoselective annulation with pyrrolylacetylenic ketones (MeCN, 80–82 °C) to provide (E)-acylethenylpyrrolo[1’,2’:3,4]imidazo[2,1-a]isoquinolines in up to 92% yield. In the case of 5-arylpyrrolylacetylenic ketones, instead of the above cyclization, the dimerization of the starting ketones to give dipyrrolopyrazines in 38 and 39% yields occurs.

Annulations involving p-benzoquinones: stereoselective synthesis of fused, spiro and bridged molecules

The present review summarizes the recent advances (2018–2023) in stereoselective annulation involving p-benzoquinones for the construction of fused, spiro and bridged/cage frameworks.

Synthesis of sulfonyl 2-aryl-5-methylenyltetrahydropyrans.

In this study, the present research describes a high-yield method for the synthesis of sulfonyl 2-aryl-5-methylenetetrahydropyrans by one-pot straightforward DABCO-promoted intramolecular Michael addition of β-sulfonyl styrene with 2-chloromethyl-1-propenol followed by intramolecular alkylation. This Baylis-Hillman-type pathway provides a highly effective stereoselective annulation by forming one carbon-oxygen bond and one carbon-carbon bond.

Chemoselective Annulation of 2‐Benzothiazolimines Enabled by Bifunctional Phosphonium Salt: Highly Enantioselective Synthesis of Indole‐fused Cyclic Thiourea Scaffolds

AbstractA highly efficient chemoselective and stereoselective annulation utilizing 2‐benzothiazolimines as unusual C2‐synthons by thiourea‐based bifunctional phosphonium salt catalysis has been developed. This asymmetric protocol provides a rapid access to highly functionalized and indole‐fused cyclic thiourea scaffolds that bear benzothiazole cores in high yields with excellent both diastereo‐ and enatioselectivities. This transformation proceeds under mild reaction conditions and expands the catalytic potential of phosphonium salt catalysts.

Organocatalyst Design for the Stereoselective Annulation towards Bicyclic Diketones and Analogues

The Wieland–Miescher ketone, Hajos–Parrish–Eder–Sauer–Wiechert ketone, and their analogues are bicyclic diketones essential as building blocks for the synthesis of several natural and bioactive molecules. For this reason, since 1971, when Hajos and Parrish and Eder, Sauer, and Wiechert reported the stereoselective synthesis of these compounds promoted by L-proline, numerous methodologies and organocatalysts have been studied over the years with the aim of identifying increasingly efficient asymmetrical syntheses of these bicyclic ketones. This review will outline the methodological and stereochemical features of the organocatalytic stereoselective synthesis of these bicyclic scaffolds based on the different organocatalysts employed from 1971 until today. Particular emphasis will be given to the structural features of the catalysts and to the reaction conditions.

Construction of pyrazole fused spiroketals by a (3 + 2) annulation reaction

A stereoselective (3 + 2) annulation process between 4-bromo pyrazolones and benzofuran-derived azadienes was developed. A series of novel pyrazole fused spiroketals were synthesized in the presence of triethylamine.

Palladium-catalyzed stereoselective (3 + 2) cycloaddition of vinylethylene carbonates with cyclic N-sulfonyl ketimines.

A diastereoselective (3 + 2) cycloaddition of N-sulfonyl ketimines with vinylethylene carbonates (VECs) in the presence of Pd2dba3·CHCl3 and PPh3 has been developed. The reaction of various substituted VECs and diverse cyclic N-sulfonyl ketimines proceeded smoothly under mild conditions, giving highly functionalized oxazolidine frameworks in good to excellent yields with moderate to good diastereoselectivities. With the use of spiroketal-based diphosphine SKP as a chiral ligand, an asymmetric version of the current (3 + 2) cycloaddition was achieved, and chiral products were obtained in >99% ee in most cases.

Iridium-catalyzed stereoselective [3+2] annulation of α-oxocarboxylic acids with 1,3-dienes.

The stereoselective annulation of α-oxocarboxylic acids with 1,3-dienes proceeded in the presence of a hydroxoiridium catalyst to give α-hydroxy-γ-lactones in good yields with high 3,5-trans relative stereochemistry. The use of a chiral diene ligand for a cationic iridium complex enabled asymmetric annulation with high enantioselectivity.

Synthesis of benzofused cyclobutaoxepanones via intramolecular annulation of o-cinnamyl chalcones.

Intramolecular stereoselective annulation of o-cinnamyloxy chalcones provides two kinds of tricyclic benzofused cyclobutaoxepanones via the synthesized routes of DABCO/NBS (1,4-diazabicyclo[2.2.2]octane/N-bromosuccinimide)-mediated Baylis-Hillman type cyclization or low-pressure mercury (LP Hg) lamp-promoted photocontrolled [2 + 2] cycloaddition. Diversified reaction conditions have been investigated for one-pot facile, high-yield transformation.

Stereoselective Synthesis of Dihydrofuranoindoles via the Friedel-Crafts Alkylation/Annulation Cascade Process.

A stereoselective annulation protocol was developed to construct dihydrofuranoindoles from readily available starting materials. In the presence of a bifunctional squaramide, the Friedel-Crafts alkylation/annulation cascade process occurred smoothly to provide dihydrofuranoindoles in 26-95% isolated yields exclusively as trans-diastereomers (38-99% ee). This catalytic protocol was compatible with a range of structurally distinct hydroxyindoles bearing the hydroxyl group at different positions, providing four kinds of dihydrofuranoindoles. Moreover, gram-scale synthesis and further synthetic manipulation of the product were also demonstrated.

CuBr2-Mediated One-Pot Synthesis of Sulfonyl 9-Fluorenylidenes.

In this article, a high-yield method for the synthesis of sulfonyl 9-fluorenylidenes is described, which consists of a one-pot straightforward three-step synthetic route, including (i) CuBr2-mediated α-bromination of o-arylacetophenone, (ii) sequential nucleophilic substitution of the resulting α-bromo o-arylacetophenone with sodium sulfinate (RSO2Na), and (iii) the CuBr2-mediated intramolecular Friedel-Crafts cyclizative dehydration. A plausible mechanism is proposed and discussed. This protocol provides a highly effective regio- and stereoselective annulation via the formation of one carbon-carbon (C-C) bond and one carbon-sulfur (C-S) bond.

Annulations involving 2-arylidene-1,3-indanediones: stereoselective synthesis of spiro- and fused scaffolds

Stereoselective annulations of 2-arylidene-1,3-indanediones towards spiro-carbocycles as well as spiro/fused heterocycles based on various cycloadditions and tandem annulations are described.

Cooperative Tertiary Amine/Chiral Iridium Complex Catalyzed Asymmetric [4+3] and [3+3] Annulation Reactions

Asymmetric reactions merging organocatalysis and metal catalysis significantly broaden the scope of organic synthesis. Nevertheless, the accomplishment of stereoselective annulations combining two types of dipole species, independently generated from the activations of organocatalysts and metal complexes, still remains as a challenging task. Now, Morita-Baylis-Hillman carbonates from isatins and carbamate-functionalized allyl carbonates could be chemoselectively activated by achiral Lewis basic tertiary amines and chiral iridium complexes. The zwitterionic allylic ylides and 1,4-π-allyliridium dipoles formed in situ are assembled in a highly stereoselective [4+3] annulation pattern. Similar cooperative catalytic strategy could be applied for the reactions of Morita-Baylis-Hillman carbonates and vinyl aziridines, furnishing an asymmetric [3+3] annulation reaction also with excellent stereocontrol.

Dynamic stereoselective annulation via aldol-oxa-cyclization cascade reaction to afford spirooxindole pyran polycycles

Spiro polycyclic compounds bearing pyran ring systems are found in bioactive molecules, and we recently reported the construction of spirooxindole all-carbon polycycles. Here we show the development of catalytic stereoselective annulation reactions that afford spirooxindole pyran polycycles. Oxindole-derived spiro[4,5]decanes are reacted with arylglyoxal to construct a pyran ring via the formation of carbon-carbon and carbon-oxygen bonds through dynamic aldol-oxa-cyclization cascade reactions, leading to the formation of spirooxindole pyran polycycles bearing six stereogenic centers as single diastereomers. During the reaction, the starting material is isomerized to the diastereomer, and this is key to afford the product. Taking advantage of this isomerization, highly enantiomerically enriched single diastereomers of spirooxindole pyran polycycles are obtained. The reactions generating the spiro pyran polycycles show stereoselectivities distinct from those previously observed in the construction of all-carbon polycycles.

A Highly Chemo-, Regio-, and Stereoselective Metallacycle-Mediated Annulation Between a Conjugated Enyne and an Ene-Diyne.

Alkoxide-directed metal-centered intermolecular [2+2+2] annulation is shown to chemo-, regio-, and stereoselectively engage two polyunsaturated substrate in productive cyclization chemistry. This annulation process is unique in the field, revealing that it is possible to selectively engage three of five π-systems residing in the coupling partners in initial [2+2+2] reaction, and demonstrating that one of the two remaining π-systems (the TMS-alkyne) can ultimately serve to simply generate a new metallacyclopentene of great potential value in additional metallacycle-mediated coupling chemistry.

Metal-free stereoselective annulation of quinolines with trifluoroacetylacetylenes and water: an access to fluorinated oxazinoquinolines.

Metal-free reaction between quinolines, aryltrifluoroacetylacetylenes and water at -18 °C-rt in MeCN resulted in stereoselective assembly of trifluoromethylated oxazinoquinolines with up to 99% yield that was essentially in contrast to a similar reaction with pyridines. The annulation proceeded via the 1,3-dipolar adducts of quinolines with trifluoroacetylacetylenes followed by intramolecular cyclization involving the trifluoroacetyl group and a molecule of water.

Synthetic Studies of Yessotoxin: Stereoselective Annulation of the CD and JK Ring Fragments by Using Pd(II)-Catalyzed Cyclization

Synthetic Studies of Yessotoxin: Stereoselective Annulation of the CD and JK Ring Fragments by Using Pd(II)-Catalyzed Cyclization

Stereoselective annulation between an allene, an alkene, and two nitrosoarenes to access bis(isoxazoliodine) derivatives.

This work reports metal-free annulations between one allene, two nitrosoarenes and one electron-deficient alkene to afford bis(isoxazolidine) derivatives stereoselectively. This process involves an initial formation of isoxazolidin-4-imine oxides, followed by their dipolar [3 + 2]-cycloaddition with electron-deficient alkenes. To highlight the utility, the annulations of 5-alleneyl-1-enes with nitrosoarenes were also feasible to afford the desired bis(isoxazolidine) products with excellent stereocontrol. The resulting bis(isoxazolidine) products produced from two systems were reduced with Zn/MeOH to induce reductive N-O cleavages, yielding branched polyaminols stereoselectively.

Origin of Stereoselectivity in Cooperative Asymmetric Catalysis Involving N-Heterocyclic Carbenes and Lewis Acids toward the Synthesis of Spirooxindole Lactone

An increasing number of examples are now being reported that use chiral N-heterocyclic carbenes (NHCs) in conjunction with Lewis acids to enhance catalytic potential. Herein, we provide molecular insights into an NHC-catalyzed stereoselective annulation reaction between N-methylisatin and an enal leading to spirooxindole lactone in the presence of LiCl as the Lewis acid. Mechanistic features as well as the origin of enantio- and diastereoselectivities of the catalytic reaction have been unraveled using the density functional theory (B3LYP-D3) method. The key mechanistic steps of the reaction are identified to proceed through the formation of a Breslow intermediate between the chiral NHC catalyst and the enal, an enantioselective addition of the re face of this intermediate to the re face of the carbonyl group of N-methylisatin, and an intramolecular proton transfer and lactonization that eventually provide access to (2S,3R)-spirooxindole lactone as the final product. In the most preferred pathway, the Lew...

Stereoselective Annulation by Palladium/Phosphine–Thiourea Catalysis

Stereoselective Annulation by Palladium/Phosphine–Thiourea Catalysis