Direct one-pot synthesis of phenanthrenes via Suzuki-Miyaura coupling/aldol condensation cascade reaction

We have developed an efficient cascade reaction, a Suzuki-Miyaura coupling followed by an aldol condensation, for the construction of phenanthrene derivatives using microwave irradiation. For example, the reaction of methyl 2-bromophenylacetamide with 2-formylphenylboronic acid in the presence of a palladium catalyst and a base provided a biaryl intermediate, which underwent in situ cyclization to afford the corresponding phenanthrene in high yield.     

Total synthesis of aristolactams via a one-pot suzuki-miyaura coupling/aldol condensation cascade reaction

A direct one-pot synthesis of phenanthrene lactams, which employs a Suzuki-Miyaura coupling/aldol condensation cascade reaction of isoindolin-1-one with 2-formylphenylboronic acid, has been developed. The approach is used to efficiently produce a number of natural aristolactams, such as aristolactam BII (cepharanone B), aristolactam BIII, aristolactam FI (piperolactam A), N-methyl piperolactam A, and sauristolactam.     

Asymmetric synthesis of 3-substituted indole derivatives containing tetrahydrothiophene via cascade sulfa-Michael/Michael additions catalyzed by a chiral squaramide catalyst

The organocatalyzed enantioselective cascade sulfa-Michael/Michael addition reaction of (E)-3-mercapto-2-butenoic acid esters to (E)-3-aryl-2-(indol-3-ylcarbonyl)acrylonitriles has been developed. This process was promoted by a chiral squaramide catalyst to afford chiral 3-substituted indole derivatives containing tetrahydrothiophene with three contiguous stereocenters in excellent diastereoselectivities (up to >20:1 dr) with moderate to good yields and enantioselectivities (up to 93%, 89% ee).     

NHC-catalysed retro-aldol/aldol cascade reaction enabling solvent-controlled stereodivergent synthesis of spirooxindoles

An N-heterocyclic carbene (NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-based β-hydroxyaldehyde has been developed. The ring opening-closure process enables the diastereodivergent synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters by simply changing the reaction solvents (THF or DCE). The Michael/aldol/retro-aldol/aldol sequential protocol allows the diastereodivergent synthesis of spirocyclopentaneoxindoles from 3-substituted oxindole and α,β-unsaturated aldehyde under the relay catalysis of a chiral secondary amine and an NHC catalyst. Moreover, four stereoisomers of the product can be selectively provided by using different combinations of a chiral secondary amine and a solvent.     

Facile synthesis of thiochromanyl-spirooxindoles via K2CO3 catalyzed tandem sulfa-Michael/Aldol reaction

A facile method for the synthesis of thiochromanyl-spirooxindoles via sulfa-Michael/Aldol reaction of 3-ylideneoxindoles with thiosalicylaldehydes has been developed. This tandem reaction, which tolerates a wide variety of functional groups, furnished diverse substituted functional thiochromanyl-spirooxindoles in up to 90% yields with good diastereoselectivities. Furthermore, the reaction system could be promoted to gram-scale efficiently under the mild conditions.     

A convenient synthesis of quinazoline derivatives via cascade imino-Diels-Alder and oxidation reaction

<正>Quinazoline derivatives were synthesized fromα-iminoesters via a cascade imino-Diels-Alder and then oxidation reaction catalyzed with CuBr_2.This method provided a new strategy for preparing quinazoline derivatives which may be useful in the synthesis of heterocyclic intermediates.     

Construction of polycyclic spiro-indolines via an intramolecular oxidative coupling/cyclization cascade reaction process

An efficient protocol for assembling a polycyclic spiroindoline scaffold is developed, which involves an intramolecular oxidative coupling of dianions derived from indole-embodied β-ketoamides using iodine as the oxidant, and subsequent attack of oxygen anion to the resultant imine moiety. A number of tetracyclic spiroindolines are prepared with moderate to good yields.     

Total synthesis of ent-calystegine B4 via nitro-Michael/aldol reaction

Optically active ent-calystegine B4 was prepared in 13 steps from commercially available chiral L-dimethyl tartrate. The synthesis was achieved by the Michael addition and the aldol reaction of nitromethane to form cycloheptanone in a stereoselective manner. Reduction of the nitro group in the presence of Boc(2)O accomplished an efficient conversion to amino cycloheptanone, which readily afforded the desired ent-calystegine B4.     

Proline-mediated enantioselective construction of tetrahydropyrans via a domino aldol/acetalization reaction

Highly enantioselective synthesis of tetrahydropyrans was accomplished via a domino proline-mediated aldol reaction/intramolecular acetal formation from an aldehyde and inexpensive aqueous tetrahydro-2H-pyran-2,6-diol as a five-carbon unit.     

Direct synthesis of fluorescent 1,3a,6a-triazapentalene derivatives via click-cyclization-aromatization cascade reaction

An efficient and versatile method was established for the preparation of 1,3a,6a-triazapentalenes. The 1,3a,6a-triazapentalene skeleton without an additional fused ring system was discovered to be a compact and highly fluorescent chromophore, which exhibited various interesting fluorescent properties such as a noteworthy correlation of luminescent wavelength with the Hammett σ(p) value and a strongly positive solvatofluorochromism.     

Palladium-catalyzed carboxamidation reaction and aldol condensation reaction cascade: a facile approach to ring-fused isoquinolinones

Palladium-catalyzed carboxamidation reaction and aldol condensation reaction cascade are very useful for the synthesis of various ABC ring substituted fused isoquinolinones.     

Visible-light-activated selective synthesis of sulfoxides via thiol-ene/oxidation reaction cascade

A convenient, highly selective and metal-free synthesis of sulfoxides from alkenes and thiols using NHPI as an inexpensive and reusable organophotoredox catalyst is reported. The protocol involves radical thiol-ene/oxidation reaction cascade and utilizes visible light and air (O₂) as inexpensive, readily available, non-toxic and eco-sustainable reagents to afford up to 96% yields of the product at room temperature.     

Synthesis of indolequinones via a Sonogashira coupling/cyclization cascade reaction

A mild strategy for constructing indolequinone motifs is described on the basis of the Sonogashira reaction and a copper-catalyzed intramolecular cyclization cascade reaction. The first step involves the palladium- and copper-catalyzed reaction between halogenated naphthoquinone and terminal acetylene to generate a coupling product, which then reacts in a copper-catalyzed intramolecular cyclization with the nitrogen functional group adjacent to the carbon-carbon triple bond.     

A formal synthesis of ezetimibe via cycloaddition/rearrangement cascade reaction

A formal synthesis of a powerful cholesterol inhibitor, ezetymibe 1, is described. The crucial step of the synthesis is based on Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade reaction between terminal acetylene derived from acetonide of L-glyceraldehyde and suitable C,N-diarylnitrone. The adduct with (3R,4S) configuration at the azetidinone ring, obtained with high stereoselectivity, was subsequently subjected to deprotection of the diol side chain followed by glycolic cleavage and base-induced isomerization at the C3 carbon atom to afford the (3S,4S) aldehyde, which has been already transformed into ezetimibe by the Schering-Plough group.     

Enantioselective sulfa-Michael addition reaction of methyl thioglycolate to chalcones derivatives with sterically encumbered quinine squaramide organocatalyst

Asymmetric organocatalytic sulfa-Michael reactions give access to enantiomerically enriched sulfur containing adducts that can be used as valuable chiral building blocks. A variety of chalcone derivatives were allowed to react with methyl thioglycolate under optimized conditions, in the presence of a bifunctional quinine derived sterically encumbered squaramide organocatalyst, giving rise to excellent stereoselectivities, up to 99%?ee. The designed catalyst system proved to be efficient even at gram scale and under milder reaction conditions.     

Highly chemo- and enantioselective vinylogous aldol/cyclization cascade reaction to construct chiral 5,6-dihydropyran-2-ones

An organocatalytic chemo- and enantioselective vinylogous aldol/cyclization cascade reaction between β,γ-unsaturated amides and β,γ-unsaturated α-keto esters was developed. With 5?mol% of chiral tertiary amine-thiourea catalyst C3, highly functionalized 5,6-dihydropyran-2-ones with a quaternary stereocenter were constructed in a straightforward manner with high yields (up to 99%) and excellent enantioselectivities (up to 98% ee).     

Organocatalyzed stereoselective construction of N-formylpiperidines via a Michael-aza-Henry-hemiaminalization reaction cascade

An efficient asymmetric synthesis of N-formylpiperidines via an organocatalytic Michael-aza-Henry-hemiaminalization reaction cascade of an aldehyde, a nitroalkene, and an N-arylideneformamide is reported. The reaction is triggered by diphenylprolinol trimethylsilyl ether and creates two C-C and one C-N bonds leading to the formation of highly enantio-enriched N-formylpiperidines with five contiguous chiral centers in a one-pot operation.     

Synthesis of benzoxazine and 1,3-oxazine derivatives via ligand-free copper(I)-catalyzed one-pot cascade addition/cyclization reaction

A novel and efficient synthesis of benzoxazine and 1,3-oxazine derivatives via ligand-free copper(I)-catalyzed one-pot cascade addition/cyclization reaction has been developed. A variety of carbodiimides coupled with o-halophenylmethanols and/or substituted (Z)-3-iodoprop-2-en-1-ols to give the corresponding products in moderate to excellent yields under the mild condition.     

Synthesis of highly functionalized furanones via aldol reaction of 3-silyloxyfurans

[reaction: see text] The stereoselective aldol reaction of 3-silyloxyfurans with aldehydes in the presence of a Lewis acid is described. N-Bromosuccinimide (NBS)-mediated cyclization of the aldol product leads to the formation of the 2,7-dioxa-bicyclo[2.2.1]heptan-3-one ring system, which represents the formal product of hetero Diels-Alder reaction of the furan with the aldehyde.     

Facile synthesis of oxaspirobicyclic butenolides via a domino Michael addition/aldol reaction/γ-lactonization sequence

A three-component domino reaction approach between a primary amine, a dialkyl acetylenedicarboxylate, and 1,3-dimethylalloxan that affords novel oxaspirobicyclic γ-butenolidobarbiturate derivatives is reported. The reaction sequence consists of an initial Michael-addition of primary amines to dialkyl acetylenedicarboxylates, followed by aldol-like reaction with 1,3-dimethylalloxan, and then γ-lactonization to afford the products. This cascade reaction sequence represents a rapid and unprecedented route to the described biologically interesting molecules.