A study of Heck cyclization reactions to form phenanthridine ring systems

A survey of conditions for the palladium catalyzed intramolecular Heck cyclization of protected amines has shown that the Herrmann-Beller palladacycle can be exploited under ‘cationic’ conditions to provide a robust and rapid route (<2 h) to the synthesis of single double bond isomer phenanthridines in excellent yield (76-99%). In addition, the same cyclization can be performed under ‘neutral’ conditions to provide phenanthridines with a double bond isomer profile suitable for exploitation in diversity-based applications. We have also shown that the highly reactive (^tBu₃P)₂Pd catalyst can induce cyclization at low temperatures (≤50 °C), giving similar results to the ‘neutral’ conditions, and offering an alternative pathway for sensitive substrates.     

An oxidative entry into the amido trioxadecalin ring system

The amido trioxadecalin ring system is a key structural component of the architecturally interesting anticancer and immunosuppressive agents of the mycalamide, theopederin, and onnamide families of natural products. We report a new entry into this structure in which a mixed acetal serves as a surrogate for a formaldehyde hemiacetal in an addition to an oxidatively generated acyliminium ion. The stereochemical outcome of this process can be explained by the conformational preferences of the product ring system. [reaction: see text]     

A new entry to the isogeissoschizoid skeleton

[reaction: see text] The tetracyclic isogeissoschizoid skeleton has been prepared by a novel route that involves the ozonolysis and double reductive amination of a cyclopentene, a nickel-catalyzed cyclization, and a late-stage Fischer indole synthesis.     

A new type of angular phenothiazine ring system

The first synthesis of monoaza- and diaza-analogues of benzo[a]phenothiazine ring system is achieved under anhydrous conditions by base-catalysed reaction of o-aminoheterocyclic thiones with 2,3-dichloronaphtho-1,4-quinone. If the reactions were carried out in methanol, 2-chloro-3-methoxynaphtho-1,4-quinone was also isolated. The ease of air oxidation of the Na₂S₂O₄ reduced compounds makes them suitable for consideration as vat dyes.     

A synthetic entry into the quino[2,1-b][1,3]benzoxazine ring system

The double ring closure of N-(2-hydroxybenzyl)anthranilic acids 1 with acetic anhydride or its acyclic analogous (RCH₂CO)₂O 2b and 2e lead to the formation of novel 12H-quino[2,1-b][1,3]benzoxazin-5-ones. The structure of the obtained compounds was proved with the use of their ir, mass, ¹H and ¹³C nmr spectra. Homo- and heteronuclear two-dimensional nmr experiments were performed to unambiguously assign all proton and carbon chemical shifts.     

A new tandem route to angular tetraquinanes. Synthesis of the Waihoensene ring system

[formula: see text] This paper describes a new tandem reaction sequence leading to angularly fused polyquinanes from squaric acid-derived bicyclo[6.3.0]-undecadienediones. Such compounds undergo a dual Michael addition. The enolate form in the first intermolecular addition undergoes the second intramolecular transannular addition to give the angular polyquinanes. A particularly interesting example is a catalytic transformation of cis-13-methylyricyclo[10.3.0.0]pentadeca-4(5),12(13)-diene-3 ,14-dione to (3R*,3aS*,5aR*,9aR*,11aR*)-3-methyl-1,2,3,5,5a,6 ,7,10,11,11a-decahydro-4H- pentaleno[6a,1-c]indene-2,10-dione, a compound having the tetracyclic ring system found in the natural product waihoensene. The mechanism and synthetic scope of these reactions are discussed.     

Radical and palladium-catalyzed cyclizations to cyclobutenes: an entry to the BCD ring system of penitrem D

A novel approach toward the synthesis of the BCD ring system of penitrem D is described. The strategy capitalizes on the fast cyclization rates of aryl radicals into cyclobutenes and allows access to a variety of fused tricyclic structures. Radical/polar crossover reactions of precursors 24-29 promoted by samarium diiodide in the presence of HMPA and acetone allow access to the fully functionalized BCD ring system of penitrem D. The stereochemical implications of these processes are evaluated, and a Pd-mediated cyclization approach toward the penitrems is also introduced.     

A photochemical approach to the Galanthan ring system

A five-step, atom-efficient synthesis of the Galanthan tetracyclic skeleton has been developed. The key step is an unusual intramolecular de Mayo reaction using an isocarbostyril substrate with a functionalized tether on nitrogen. The target molecule is produced in 35% overall yield from isocarbostyril.     

A convergent approach to the mitomycin ring system

[structure: see text]. A novel stereoselective approach to the ring system of the mitomycins is described. The synthesis was based on a convergent strategy involving a stereocontrolled addition of a beta-phenyl silyl enol ether to a pyrroline N-acyliminium ion followed by an intramolecular palladium-catalyzed aryl triflate amination to afford the (9R*,9aR*)-tetrahydropyrrolo[1,2-a]indole ring system.     

C-glycosides to fused polycyclic ethers. An efficient entry into the A-D ring system of gambierol

[reaction: see text]. This Letter describes our use of C-glycosides to synthesize the A-D ring system of the marine ladder toxin gambierol in 20 steps.     

A new synthetic approach to the bicyclo[5.3.1]undecane ring system in taxanes

The bicyclo[5.3.1]undecane derivative 19, which was referred to the A,b ring system of taxane diterpenes, was synthesized by a base-induced fragmentation reaction of the tricyclic diol monomesylate 18 derived highly stereoselectively from 5-methyl-1,3-cyclohexadione.     

Studies on SRN1 reactions-9 : A new access to the isoquinoline ring system

The S_RN1 reaction between o-halogeno-benzylamines and enolates derived from a series of ketones and aldehydes affords 1, 2 dihydro-isoquinolines from which are obtained (i)the isoquinoline derivatives, either spontaneously or by treatment on Pd-C and (ii) the 1,2,3,4 tetrahydro-isoquinoline derivatives after sodium borohydride reduction.     

A new entry to the synthesis of 2,3-disubstituted indoles

[reaction: see text] The Stille coupling of N-acyl-2-iodoanilines with the 1-(tributylstannyl)-1-substituted allenes affected the successive one-step formation of the 2-methyl-3-substituted indoles. Alternatively, the other type of 2-alkyl-3-substituted indoles could be synthesized in a one-pot operation, which consists of the Stille coupling reaction with the 1-(tributylstannyl)-1,3-disubstituted allenes, followed by TBAF treatment. This procedure could be applied to the synthesis of indomethacin.     

A new simple approach to the [6] (2,5)pyridinophane ring system

Upon treatment with [Mo(CO)₆], 3-phenyl-4,5-hexamethyleneisoxazole undergoes an inclusion of acetylenic ester across the C₄-C₅ bond and elimination of an oxygen atom leading to [6](2,5)pyridinophane derivative.     

A convergent rgiospecific route to the aklavinone ring system

A convergent regiospecific route to the aklavinone (II) ring system is described.     

A synthetic entry to 2,3-fused ring indole derivatives by ring-closing metathesis reactions

Six to eight-membered carbocycles and eight-membered azacycles fused to the 2,3-position of the indole ring, representing tricyclic substructures of several indole alkaloids, can be synthesized by RCM reactions from easily accessible dienic precursors.     

Expedient entry to the piperazinohydroisoquinoline ring system using a sequential Ugi/Pictet-Spengler/reductive methylation reaction protocol

An expedient entry to the piperazinohydroisoquinoline ring system present in the tetrahydroisoquinoline antitumor alkaloids family is described. The synthetic sequence involves: a sequential Ugi reaction followed by an N-Boc-deprotection process and iminium formation with a spontaneous Pictet-Spengler cyclization and reductive N-methylation, with all these processes performed in a two-operation protocol in the same reaction flask.     

A new approach to the nazarov reaction via sequential electrocyclic ring opening and ring closure

Regioselective dichlorocyclopropanation of 2-silyloxydienes furnishes vinylcyclopropanol silyl ethers in good yield. Treatment with silver(I) at room temperature effects disrotatory electrocyclic opening to a 2-chloro-3-silyloxypentadienyl cation, which then undergoes conrotatory (Nazarov) electrocyclization to provide chlorocyclopentenones. This two-step sequence offers a convenient and mild alternative to the standard Nazarov cyclization protocol via a formal 4+1 construction and furnishes products containing useful halogen functionality. In one case possessing a pendant phenyl group, interrupted Nazarov reaction to give a benzohydrindenone was observed.     

The synthesis of two novel pyridazines; A new ring system

The Diels-Alder reaction of 4,5-dimethylene-2,2-diphenyldioxolane with diethyl azodicar-boxylate and 4-phenyl-1,2,4-triazoline-3,5-dione was investigated. Reduction of the resultant adducts followed by hydrolysis provided hexahydro-4,5-dihydroxy-1,2-pyridazine dicarboxylic acid diethylester and 1,3,5,6,7,8-hexahydro-6,7-dihydroxy-2-pheny 1-2H-s-triazolo[1,2-α ]pyrida-zine-1,3-dione.     

A new entry to carbocycles: synthesis of cyclopentene and cyclohexene derivatives through endo-mode ring closure of allenyl sulfones

Treatment of dimethyl 4-(phenylsulfonyl)-4,5-hexadiene-1,1-dicarboxylate with potassium tert-butoxide in tert-butanol at room temperature effected successive endo-mode ring closure at the sp-hybridized carbon center and demethoxycarbonylation of the resulting malonate derivative leading to the exclusive formation of methyl 2-methyl-3-(phenylsulfonyl)-1-cyclopentenecarboxylate. An additional seven allenyl sulfones having a 1,3-dicarbonyl functionality gave the corresponding cyclopentene or cyclohexene derivatives in high yields.