Lewis base catalyzed [4+2] annulation of electron-deficient chromone-derived heterodienes and acetylenes

Lewis base catalyzed [4+2] annulation reactions between electron-deficient chromone oxa- and azadienes and acetylene carboxylates provide tricyclic benzopyrones inspired by natural products. An asymmetric synthesis of the tricyclic benzopyrones was developed by using modified cinchona alkaloids as enantiodifferentiating Lewis base catalysts.     

Platinum- and gold-catalyzed hydrative carbocyclization of oxo diynes for one-pot synthesis of benzopyrones and bicyclic spiro ketones

We report a one-pot synthesis of benzopyrones and tricyclic spiroketones from hydrative carbocyclization of oxodiyne substrates catalyzed by PtCl2 and PPh3AuCl/AgOTf, respectively. The distinct carbocyclizations with Pt and Au catalysts stem from their altered regioselectivity in the oxo-assisted hydration of the neighboring alkyne carbons.     

Synthesis of Benzothiophene-Fused Oxa[6.6.5]tricyclic Skeletons through a Cinchonidine- or NaOH-Promoted Quadruple Domino Sequence

Two base-promoted quadruple domino reactions between thioaurones and allylic phosphonium salts have been developed to synthesize benzothiophene-fused oxa[6.6.5]tricyclic skeletons in moderate to good yields with excellent stereoselectivity and broad functional-group tolerance. This is a simple and useful protocol for the rapid construction of the umbrella-like oxa[6.6.5]tricyclic skeleton.     

Synthesis of Isoindolinones by Palladium-Catalyzed Carbonylative Cyclization of 2-Bromobenzaldehyde with Diamines

2-Bromobenzaldehyde reacts with diamines under carbon monoxide in the presence of a catalytic amount of a palladium complex to afford the corresponding tricyclic isoindolinones in fair to good yields.     

Synthesis of 2,4-diaminoquinazolines and tricyclic quinazolines by cascade reductive cyclization of methyl N-cyano-2-nitrobenzimidates

An efficient route to N(4)-substituted 2,4-diaminoquinazolines has been developed by employing tandem condensation of cyanoimidate-amine and reductive cyclization in iron-HCl system. This method is tolerant of a following intramolecular N-alkylation and produces two fused heterocycles in a one-pot procedure. This protocol is a facile two-step synthesis of tricyclic quinazolines, which is effected by potent cyanoimidation and tandem reductive cyclization from 2-nitrobenzaldehydes. Moreover, the forming process of tricyclic quinazolines has been investigated from the ring-opening/ring-closing cascade point of view. It is found that the preparation of tricyclic quinazolinones in good yields relies on the selective hydrolysis of tricyclic quinazolines in base or acid system.     

Asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids by diastereoselective alkylation of camphor-based tricyclic iminolactone

A novel and convenient route for the preparation of chiral tricyclic iminolactones 9 and 10 from camphorquinone has been developed. Alkylation of iminolactones 9 and 10 provided iminolactones 16 and 17 in high yields which were, in turn, alkylated again to afford the alpha,alpha-disubstituted products in good yields (70-90%) and excellent diastereoselectivities (>98%). Hydrolysis of the alkylated iminolactones furnished the desired alpha,alpha-disubstituted alpha-amino acids in good yields and high enantiomeric excesses with good recovery yields of the chiral auxiliary 12 and 13. The extremely high endo-face selectivity for alkylation is discussed using semiempirical (MOPAC 93) calculations.     

Rhodium-catalyzed tandem vinylcyclopropanation of strained alkenes

This communication reports an unusual rhodium-catalyzed 1,6-addition of a dienylboronate ester to highly strained alkenes. The resulting vinylcyclopropane-fused tricyclic products were produced in moderate to good yields. Preliminary mechanistic studies are also presented.     

Asymmetric synthesis of 2H-azirine 3-carboxylates

[reaction: see text] Dehydrochlorination of methyl 2-chloroaziridine 2-carboxylates generates the first examples of enantiopure 2-substituted 2H-azirine 3-carboxylates which undergo the aza Diels-Alder reaction with dienes to give bicyclic and tricyclic aziridines in good yields.     

Scaffold-directed traceless synthesis of tetrahydro-beta-carbolinehydantoins

Pharmacologically interesting tetrahydro-beta-carbolinehydantoins have been prepared through four-step traceless synthesis by a combinatorial approach. Two-arm PEG 1 (MW approximately 4000) was used as a soluble polymer support and reacted with Fmoc-protected L-tryptophane 2 to form bis-ester 3. The resulting polymer-supported amino ester 3 was deprotected, and amino ester 4 underwent Pictet-Spengler reaction with varoius ketones to form tricyclic indoles 5. The nucleophilic piperidine in the tricyclic indole reacted with isocyanate to generate the urea intermediates and simultaneously intramolecular cyclization to release the target compounds 7 from the support in good yields.     

Nucleophilic trifluoromethylation of cyclic imides using (trifluoromethyl)trimethylsilane CF3SiMe3

A variety of cyclic five-membered imides was trifluoromethylated in good to excellent chemical yields using (trifluoromethyl)trimethylsilane CF3SiMe3 under fluoride ion catalysis. The method was successfully applied to the stereoselective synthesis of trifluoromethylated bi- and tricyclic lactams which could serve as precursors for designed thrombin inhibitors.     

Intramolecular photoreactions of thiohomophthalimides with an alkenyl group in their N‐Side chain. Regioselective synthesis of heterocycle‐fused isoquinoline derivatives through [2+2] photocycloaddition

Upon irradiation, thiohomophthalimides with an alkenyl group in their N‐side chain or at the benzylic position give tricyclic isoquinoline derivatives through regioselective intramolecular [2+2] cycloaddition or Norrish type II reaction, respectively, in good yields.     

A novel one-pot two-component synthesis of tricyclic pyrano[2,3-b]quinoxalines

A one-pot two-component synthesis of tricyclic pyrano[2,3-b]quinoxalines with a pendant hydroxymethyl fuction at the 2-position relevant to molybtopterin is described by the reaction of o-phenylenediamine and phenylhydrazone derivatives of sugars in good yields.     

An Ugi-intramolecular Diels-Alder route to highly substituted tetrahydroepoxyisoindole carboxamides

The four component Ugi reaction of 2-furaldehyde, an alkenoic acid (three examples), an isonitrile (eight examples) and an amine (eight examples) affords rapid access to a family of acetylenic furan analogues, which on heating undergo an intramolecular Diels-Alder (IMDA) reaction yielding highly substituted tricyclic lactams (17 examples) in good to excellent yields (38-72% two-steps). This Ugi-IMDA reaction proved to be highly substituent tolerant across both the isonitriles and amines examined. In one instance, with N,N-dimethylaminopropylamine, a second equivalent of alkynoic acid was required to afford a good yield of the desired tricyclic lactam.     

Chiral tricyclic iminolactone derived from (1R)-(+)-camphor as a glycine equivalent for the asymmetric synthesis of alpha-amino acids

The development of a highly efficient and stereoselective methodology for the preparation of alpha-amino acids is described. The chiral template, tricyclic iminolactone 7, was synthesized from (1R)-(+)-camphor in five steps in 50% overall yield. Alkylation of iminolactone 7 afforded the alpha-monosubstituted products in good yields (74-96%) and excellent diastereoselectivities (>98%). Hydrolysis of the alkylated iminolactones furnished the desired alpha-amino acids in good yields and enantioselectivities with nearly quantitative recovery of the chiral auxiliary 4.     

A new approach to polycyclic azonia cations by ring-closing metathesis

The ring-closing metathesis (RCM) reaction of N-vinyl-alpha-(2-styryl)azinium salts, using the Hoveyda-Grubbs catalyst, leads to different tricyclic and tetracyclic azonia cations with moderate to good yields. This is the first time that a highly electron-deficient alkene such as an N-vinylpyridinium has been involved in an RCM process.     

An efficient synthesis of fused tricycles with a benzene core via intramolecular double ring-closing enyne metathesis

A double enyne metathesis reaction has been developed for the efficient synthesis of tricyclic products with a benzene core in good yields. By this protocol, bisannulated benzenes with different ring sizes may be simultaneously constructed from the corresponding precursors in just ‘one shot’.     

Stereoselective synthesis of conformationally constrained tropane analogues: 6‐Chloro‐2,5‐diazatetracyclo[8.5.0.02,13.04,9]pentadeca‐4,6,8‐triene‐11‐one and 6‐chloro‐2,7‐diazatetracyclo‐[8.5.0.02,13.04,9]pentadeca‐4,6,8‐triene‐11‐one

Two conformationally constrained tropane derivatives were prepared as rigid nicotinic acetylcholine receptor ligands. A palladium catalyzed intramolecular α‐arylation reaction was employed to generate the tricyclic compounds in good yields from N‐(bromo‐chloropyridylmethyl)‐8‐azabicyclo[3.2.1]octan‐3‐ones.     

A green and convenient protocol for the synthesis of novel pyrazolopyranopyrimidines via a one-pot,four-component reaction in water

Novel tricyclic fused pyrazolopyranopyrimidines containing both biologically active pyranopyrazole and pyranopyrimidine templates are synthesized using a one-pot, four-component reaction involving ethyl acetoacetate, hydrazine hydrate, benzaldehydes, and barbituric acid catalyzed by DABCO in water. Pure target compounds are obtained in very good to excellent yields over short reaction times and with a straightforward work-up procedure.     

A Chiron-based Approach for the Synthesis of Tricyclic Tyrosine Analogue

A chiron approach-based enantioselective synthesis of designed tricyclic tyrosine analogue D-2 was developed. A SmI2-mediated free radical cyclization, an intramolecular Friedel-Crafts reaction and an intramolecular Mannich reaction served as key steps. These key steps were optimized and repeated in good yields. All the stereochemistries in the synthesis were established and confirmed.     

Diverse reactions of 1,4-dilithio-1,3-dienes with nitriles: facile access to tricyclic Delta1-bipyrrolines, multiply substituted pyridines, siloles, and (Z,Z)-dienylsilanes by tuning of substituents on the butadienyl skeleton

Addition cyclization of 1,2,3,4-tetrasubstituted 1,4-dilithio-1,3-dienes (Type I) with four equivalents of various aromatic nitriles in the presence of hexamethylphosphoramide (HMPA) gives exclusively fully substituted pyridines in moderate to good yields. Similarly, trisubstituted pyridines can be prepared by the reaction of 2,3-dialkyl- or diaryl-substituted 1,4-dilithio-1,3-dienes (Type II) with nitriles. However, five- or six-membered-ring fused 2,3-disubstituted 1,4-dilithio-1,3-dienes (Type III) reacted with various aromatic and aliphatic nitriles without alpha-hydrogen atoms to afford tricyclic Delta1-bipyrrolines in high yields. The reaction of six-membered-ring fused 2,3-disubstituted 1,4-dilithio-1,3-diene (Type III) with 2-cyanopyridine afforded the corresponding pyridine, and no tricyclic Delta1-bipyrroline was observed. Seven-membered-ring fused dilithiodienes reacted with PhCN or trimethylacetonitrile to afford the corresponding pyridines in good yield. When 1,2,3,4-tetrasubstituted dilithio reagents (Type I) were treated with Me3SiCN, a tandem silylation/intramolecular substitution process readily occurred to yield siloles, whereas the reaction of 2,3-disubstituted dilithio reagents (Types II and III) with Me3SiCN gave rise to (Z,Z)-dienylsilanes with high stereoselectivity. These results revealed that the formation of tricyclic Delta1-bipyrrolines, pyridines, siloles, and (Z,Z)-dienylsilanes are strongly dependent on the substitution patterns of the dilithio butadienes and the nature of the nitriles employed.