Diastereoselective synthesis of oxazolo[3,4-b]tetrahydroisoquinolin-3-ones via Lewis acid TMSOTf-mediated Pictet–Spengler reaction

An alternative and efficient method to stereoselectively synthesize oxazolo[3,4-b]tetrahydroisoquinolin-3-ones via a Pictet–Spengler reaction promoted by Lewis acid TMSOTf from readily available (S)-4-benzyl-2-oxazolidinone with various aromatic, aliphatic, and cyclic aldehydes under room temperature is described.     

Efficient synthesis of polycyclic dispirooxindoles via domino Diels–Alder cyclodimerization reaction

Three-component reactions of 4-cyanopyridine or ethyl isonicotinate with electron-deficient alkynes and isatins in dimethoxyethane at room temperature afforded spiro[3H-indole-3,2′-[2H,9aH-pyrido[2,1-b][1,3]oxazine] derivatives. Alternately, the similar three-component reaction at elevated temperature resulted in polycyclic dispirooxindole derivatives. The reaction mechanism is believed to involve sequential generation and cycloaddition of Huisgen's 1,4-dipole, and Diels–Alder cyclodimerization reaction. The similar three-component reactions containing acenaphthenequinone and phenanthrenequinone also afforded corresponding polyheterocyclic derivatives.     

Stereoselective synthesis of α-methylenecyclopentenones via a Diels–Alder/retro-Diels–Alder protocol

A new procedure for the stereoselective synthesis of cross-conjugated dienones is reported. This method makes use of the Diels–Alder adduct of anthracene and dimethyl fumarate, a precursor to a spirocyclopent-2-enone anthracene adduct as the key intermediate. The addition of propyllithium or octyllithium to the key intermediate followed by a retro-Diels–Alder reaction furnished α-methylenecyclopentenones bearing a γ-propyl or γ-octyl side chain, respectively, in moderate yields and as single geometric isomers.     

Ene reaction of Diels–Alder adducts of levoglucosenone and 1,3-dienes with acetaldehyde

Diels–Alder adducts of levoglucosenone with isoprene, butadiene and piperylene in the presence of AlCl₃ smoothly react with acetaldehyde or benzaldehyde to give products of the ene reaction, the hydroxy group of the primary intermediates participating in the formation of semiketal moiety. The yields of the reaction products depend both on the Lewis acid used (AlCl , BF ·Et O, ZnBr , SnCl or EtAlCl₂) and on the nature of the substrate.     

Asymmetric synthesis of N-phenylethyl-2-phenyldecahydroquinolin-4-ones via Lewis acid catalyzed imino-Diels–Alder reaction

The asymmetric synthesis of N-phenylethyl-2-phenyldecahydroquinolin-4-ones was performed via a Lewis acid catalyzed imino-Diels–Alder reaction between the enantiopure (R)-N-phenylethylbenzylideneimine and the trimethylsilyl enol ether of acetylcyclohexene. The regio- and stereoselective formation of intermediary bicyclic enoxysilanes, followed by their stereoselective protonation was evidenced. The initial stereoselectivity was kept only if the reaction mixture was treated using controlled basic conditions. Three enantiopure title compounds were isolated with a 5–15% yield.     

Diastereoselective synthesis of a highly functionalized cyclohexene embedded with a quaternary stereogenic centre by self Diels–Alder dimerization of a [3]dendralene attached to a (−)-menthol auxiliary

A novel route to a chiral functionalized [3]dendralene attached to a (−)-menthol auxiliary has been developed, which involves a dimethylsulfonium methylide mediated olefination of a substituted ethenylidene phosphonoacetate (−)-menthyl ester, followed by a Horner–Wordsworth–Emmons reaction with 4-bromobenzaldehyde. The chiral [3]dendralene was reactive enough to undergo intermolecular Diels–Alder cyclodimerization to give the highly substituted cyclohexene with very high regio- and diastereoselectivity.     

Synthesis of functionalized pyrroles and fused pyrroles through intermolecular [3 + 2] cycloaddition reaction

A facile and efficient synthesis of pyrrole and pyrrole-fused heterocyclic compounds has been demonstrated. The current protocol involves the in situ generation of azomethine ylides which undergoes intermolecular cycloaddition reaction and subsequent treatment with DDQ provides the pyrrole and fused heterocyclic compounds in good yields.     

Stereoselective synthesis of chiral hydrocarbazoles via the catalytic Diels–Alder reaction of siloxyvinylindole and cyclic Z-olefin

The catalytic Diels–Alder reaction of siloxyvinylindole and cyclic Z-olefin derived from pyroglutamic acid gave optically active substituted hydrocarbazoles. The exo/endo selectivity of this reaction could be controlled by using an appropriate Lewis acid. Scandium triflate gave high exo-selectivity and copper triflate gave moderate endo-selectivity. Subsequent stereoselective alkylation of the cycloadduct led to the synthesis of highly substituted hydrocarbazoles with five continuous chiral centers including a quaternary carbon.     

One-pot synthesis of 3-triazolyl-quinolin-2-(1H)-ones via sequential Ugi-“click”-Knoevenagel condensations

A variety of novel 3-triazolyl-quinolin-2-(1H)-ones were synthesized in a one-pot, five-component condensation. In this event, a set of α-acylamino-amides were assembled from o-acylanilines, aldehydes, isocyanides and 2-azidoacetic acid. Subsequently, a Cu(I)-catalyzed cycloaddition on these azido-decorated Ugi products generated a triazole moiety and activated the neighboring methylene group, inducing an intramolecular Knoevenagel cyclization to finish the heterocyclic scaffold.     

Design and synthesis of oxa-bowls via Diels–Alder reaction and ring-rearrangement metathesis as key steps

Ring-rearrangement metathesis of norbornene derivatives prepared by Diels–Alder reaction has been used to design various oxa-bowls. Enyne ring-rearrangement metathesis of norbornene ring systems with propargyl moiety produced diene containing oxa-bowls, suitable for further expansion by Diels–Alder strategy.     

NaHSO4–SiO2-catalyzed aza-Diels–Alder reaction of o-hydroxybenzaldimines with 2,3-dihydrofuran: Diastereoselective synthesis of furanobenzopyrans

NaHSO₄ supported on silica gel catalyzes the aza-Diels–Alder reaction of o-hydroxybenzaldimines with 2,3-dihydrofuran to provide furanobenzopyrans in reasonable yields and diastereoselectivity. The catalyst is recyclable and reusable up to two times without a significant loss of activity.     

Reactivity of 2-methylene-1,3-dicarbonyl compounds: catalytic enantioselective Diels–Alder reaction

The catalytic enantioselective Diels–Alder reaction of 1,1-dicarbonylethenes 3 with cyclopentadiene in the presence of Ti-TADDOLs, Mg–Ph-box and Mg–Ph-mox complexes was investigated. Although both exo- and enantioselectivity with Ti-TADDOL catalysts were poor, they were much improved using Mg–Ph-box or Mg–Ph-mox complexes as chiral catalysts. Thus, 3 was an efficient two-point binding dienophile and the non-C₂-symmetric Ph-mox 8 could be used as a chiral ligand.     

A tandem hetero Diels–Alder/Mannich approach for the synthesis of a versatile hexahydro-2H-pyrano[3,2-c]pyridin-4(3H)-one core

The synthesis of a highly functionalizable hexahydro-2H-pyrano[3,2-c]pyridin-4(3H)-one core is described and sequentially involves a hetero-Diels Alder (HDA) reaction and an intramolecular Mannich reaction resulting in selective formation of the trans-fused ring geometry.     

Regio- and Diastereoselective Synthesis of Cyclohexadienylborons via an Intermolecular Diels–Alder Reaction of Alkenyl MIDA Boronates with 2-Pyrones

An efficient synthesis of highly functionalized cyclohexadienylborons via an inverse electron-demand Diels–Alder reaction/CO₂ extrusion of alkenyl MIDA boronates with 2-pyrones is outlined. By controlling the reaction temperature, the corresponding C(sp³)-rich bicyclolactones could also be readily formed. The exo-selective reactions feature good functional-group tolerance, broad substrate scope, and excellent regio- and diastereoselectivity. Oxidation of the cyclohexadienylborons in a one-pot procedure led to the construction of aromatic boronates bearing valuable functional groups. Synthetic transformations of the C−B bond were demonstrated.     

Synthesis of pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives via Aza-Diels–Alder reaction: evaluation of torsion effect of pyrazoylimines

A modified method for the synthesis of pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine was developed through an Aza-Diels–Alder reaction of pyrazoylimines with maleimides in the sealed tube. Based on the control experiment, the yields for the Aza-Diels–Alder reaction seemed proportional to the suitable torsion conformation of pyrazoylimine, which was modulated by N,N-disubstituted amidinyl moiety. The versatile sealed tube technique was also proved to promote the higher isolated yields in the Aza-Diels–Alder reaction.     

Asymmetric synthesis of isoquinuclidines by Diels–Alder reaction of 1,2-dihydropyridine utilizing a chiral Lewis acid catalyst

The chiral isoquinuclidine derivative, 2-azabicyclo[2.2.2]octane ring system, endo-(7R)-3 was obtained in good yield with excellent diastereoselectivity (up to 92% de) by Diels–Alder reaction of 1-(phenoxycarbonyl)-1,2-dihydropyridine 1 with N-acryloyl-(4S)-4-benzyloxazolidin-2-one (4S)-2 using titanium-(2R,3R)-TADDOLate 4 as a chiral Lewis acid catalyst in toluene at 0 °C. On the other hand, endo-(7S)-3 was obtained in good yield with excellent diastereoselectivity (up to 97% de) by Diels–Alder reaction of 1 with (4R)-2 using Cu(OTf)₂/(4S,4′S)-bis(oxazoline) catalyst 8 as a chiral Lewis acid catalyst in dichloromethane at 0 °C. In these reactions, the choice of solvent and the combination of titanium-(2R,3R)-TADDOLate 4 {or Cu(II)/(4S,4′S)-bis(oxazoline) 8} and dienophile (4S)-2 {or (4R)-2} are very important. The stereochemistry of endo-(7R)-3 has been established to be (1R,4S,7R) and the reaction mechanism is proposed.     

Synthesis of selenium-containing biindolyls and their Diels–Alder reaction toward the synthesis of heteroannulated [a]- and [c]-carbazoles

We reported the first syntheses of 2- and 3-(2-(benzo[b]selenophen-2-yl)-indoles and their Diels–Alder reactions to furnish six unique annulated benzoselenphene carbazoles. This facile route can be used to synthesize selenium-containing biindolyl derivatives that possessed potential pharmaceutical activities.     

Synthesis of Bicyclo[4.3.0]Non-3-ene-7,9-diones via Solventless Diels–Alder Methodology

Four novel bicyclo[4.3.0]non-3-ene-7,9-diones have been synthesized in moderate to good yields through a solventless Diels–Alder cycloaddition method and characterized. Atom economies after purification ranged from 21% to 32%, and E factors ranged from 2.7 to 3.7. All reaction products exhibited endo selectivity. Dienophiles with heteroatoms that contribute electrons to the π system exhibited faster reaction times than the carbocyclic analog. Hydrogen-bond donating ability in the diene had no noticeable effect on reaction times.

Design and synthesis of spirobiisoxazoline dibenzoquinone derivatives via [3 + 2] double 1,3-dipolar cycloaddition reaction

“A series of novel spirobiisoxazoline dibenzoquinone derivatives were synthesized starting from 2,5-dimethoxybenzaldehyde in a six-step synthetic sequence”. The key step [3?+?2] double 1,3-dipolar cycloaddition of oxime chloride with allenoate was performed under mild reaction conditions using sodium carbonate at ambient temperature. This is the first innovative synthesis of Spirobiisoxazoline Dibenzoquinone system where quinone ring is alkylated to isoxazoline moiety.