Electrophile-induced Cyclization Research Articles

The synthesis and crystal structure of pH-sensitive fluorescent pyrene-based double aza- and diaza[4]helicenes.

Novel pyrene-based double aza- and diaza[4]helicenes have been prepared through a five-step synthetic sequence in overall good yields. Commercially available 2,3-dihaloazines (2,3-dibromopyridine, 2,3-dichloropyrazine and 2,3-dichloroquinoxaline) were used as starting materials. The synthesis employs electrophile-induced cyclizations of ortho-alkynyl bihetaryls as the key steps, leading to the formation of a helical skeleton. To discern the effect of merging azine and pyrene moieties within a helical skeleton, the X-ray structures, UV-vis absorption and fluorescence spectra of the helicenes were investigated and compared with those of the parent [4]helicene, aza- and diaza[4]helicenes. It was found that the emission properties of the synthesized helicenes can be modulated as a function of pH. The basicity of pyrene-based double aza[4]helicenes was estimated by the direct fluorimetric titration method; the pKa value was found to be equal to 1.4.

Triptycene-Based Ladder Polymers with One-Handed Helical Geometry.

Here we report an efficient synthesis of optically active ladder-type molecules and polymers through intramolecular cyclization of chiral triptycenes containing bis[2-(4-alkoxyphenyl)ethynyl]phenylene units. The electrophile-induced cyclization reactions are directed away from the bridgehead carbon atoms of triptycene by steric factors, thereby producing one-handed twisted ladder units without any detectable byproducts. Moreover, the quantitative and regioselective nature of this intramolecular cyclization allowed us to synthesize optically active ladder polymers with a well-defined one-handed helical geometry in which homoconjugated dibenzo[ a, h]anthracene units are helically arranged along the main chain. This synthesis route enables the construction of a variety of nanoscale helical ladder architectures and provides an entry into new chiroptical materials.

Fifty Years of (Benz)oxaphospholene Chemistry.

The first synthesis of benzoxaphospholenes dates back to the 1960s. Since then, the structural variety of reported (benz)oxaphospholenes has steadily increased. Organophosphorus compounds have caught the interest of synthetic chemists for a couple of decades now because of their interesting biological properties. Oxaphospholenes, in particular, could serve as carbohydrate mimetics, and benzoxaphospholenes have been reported to possess bactericidal, insecticidal, herbicidal, and fungistatical properties. Transesterification reactions and addition of phosphorus nucleophiles to carbonyl compounds were reaction types that led to the production of the first (benz)oxaphospholenes. When it was discovered that allenylphosphonates could easily be obtained from propargyl alcohols and dialkyl halophosphites, the electrophile-induced cyclization reaction of these allenylphosphonate precursors resulted in a huge boom in the amount of reports on oxaphospholene synthesis. To this day, this method is still frequently used. Ring-closing metathesis and Horner-Wadsworth-Emmons reactions have also proven their potential for the preparation of oxaphospholenes. In recent years, Pd, Rh and Au-catalysis have made their entry, generating (benz)oxaphospholenes from a wide variety of simple substrates. A couple of miscellaneous methods are summarized at the end of the Review.

Synthesis of the Reported Structures for Kealiinines B and C

Syntheses of the reported structures of kealiinines B and C have been executed. An intermolecular electrophile-induced cyclization of a pendant arene on an ene-guanidine affords the tetracyclic, oxidized naphthimidazole cores.

ChemInform Abstract: Synthesis of Cyclic Ethers Utilizing a Cyclization-Fragmentation Strategy.

Abstract A variety of cyclic ethers have been prepared via both solution phase and polymer-supported sequences of 3+2 cycloaddition of nitrile oxides to alkenes and dienes to give isoxazolines, followed by electrophile-induced cyclization. Library generation by alkylative elaboration of isoxazolines was unsuccessful, but both simple and substituted dienes were found suitable for polymer-supported formation of cyclic ethers of ring sizes five through seven.

Electrophile-Induced Cyclization of ortho-Azido Propynyl Benzenes to Quinolines

Electrophile-Induced Cyclization of <i>ortho-</i>Azido Propynyl Benzenes to Quinolines

Electrophile-induced generation of cyclic azomethine imines from steroidal δ-alkenyl hydrazones

Novel δ-alkenyl phenylhydrazones were synthesized in both the estrone and the 13α-estrone series. Electrophile-induced cyclizations of alkenyl phenylhydrazones with phenylselenyl bromide furnished cyclic iminium salts, via attack of the imino nitrogen atom on the intermediate seleniranium ion. Hydride reduction of the iminium salts led to novel aminophenyl-substituted aza-D-homoestrones. The structures of the new products were determined by NMR (one- and two-dimensional) and MALDI-MS techniques, with C 70 fullerenes as matrix in the latter case.

Halogen Electrophile Induced Cyclization Route to IsoquinolineN-Oxides

Halogen Electrophile Induced Cyclization Route to Isoquinoline<i>N</i>-Oxides

Steroidal &amp;#948;-Alkenyl Oximes as Ambident Nucleophiles: Electrophile- Induced Formation of Oxazepane Derivatives in the Bis-Estrone Series

Electrophile-induced cyclization of steroidal δ-alkenyl oximes and oxime ethers and subsequent hydride reduction of the cyclic nitrones led to new halogenated or selenylated N-hydroxy- or N-benzyloxy-aza-D-homo-estrones. Starting from a 13β-D-secoestrone oxime or oxime ether, steroidal dimers were isolated in intermolecular 1,3-dipolar cycloaddition of the cyclic nitrone to the C=N double bond of the oxazepine intermediates.

Stereospecific aziridination of olefins via electrophile-induced cyclization of γ,δ-unsaturated imines and subsequent hydrolytic rearrangement

The olefinic bond of gamma,delta-unsaturated aldehydes underwent a net aziridination through electrophile-induced cyclization and subsequent rearrangement of the resulting cyclic iminium salts: this methodology allows the stereospecific introduction of aziridine moieties into cyclic systems.

A study of the oxepane synthesis by a 7-endo electrophile-induced cyclization reaction of alkenylsulfides. An approach towards the synthesis of septanosides

A procedure for the stereoselective synthesis of 2-deoxy-2-iodo-septanosides from pyranoses is reported. The procedure involves two reactions: Wittig-Horner olefination to give alkenyl sulfanyl derivatives, and electrophilic iodine-induced cyclization to give phenyl 2-deoxy- 2-iodo-1-thio-septanosides (20) or 2-deoxy-2-iodo-septanosides (26a,b), in this case by subsequent hydrolysis of a phenylsulfanyl group under the reaction conditions. The seven membered ring of septanosides was only formed in moderate to low yields, preferably through a 7-endo cyclization, when an isopropylidene group was present as protecting group. The use of benzyl groups as protecting moieties in the pyranose does not afford the septanoside ring. However, when the reactions conditions were forced using more basic media, the furanoside derivatives 3 were obtained.

Synthesis of chiral 1,5-disubstituted pyrrolidinones via electrophile-induced cyclization of 2-(3-butenyl)oxazolines derived from (1 R,2 S)- and (1 S,2 R)-norephedrine

Starting from (1 R,2 S)- and (1 S,2 R)-norephedrine, enantiomers of the corresponding 2-(3-butenyl)oxazolines were prepared in a two-step process. The cyclization of the intermediate alkenylamides with phenylselenyl bromide afforded cyclic imidates instead of the expected pyrrolidinones. The electrophile-induced cyclizations of 2-alkenyloxazolines with bromine or iodine produced diastereomeric mixtures of chiral 1,5-disubstituted pyrrolidinones. The ring closure of the all- cis (1 R,2 S,5 R)-diastereomer 7 with NaH resulted in the tetrahydropyrrolo[2,1- b]oxazol-5-one derivative 18, which was alternatively prepared by the cyclocondensation of (1 R,2 S)-norephedrine with levulinic acid.

Convenient Synthesis of Isoxazoles

A new route to substituted isoxazoles 3 involving an electrophile-induced cyclization of acetylenic O -methyl oximes 2 is reported. The reactions proceed with iodo-, bromo-, and seleno-electrophiles in good yields (55% to quant.) under mild conditions. A major advantage of the methodology is the availability of the starting materials 1 by Sonogashira coupling of readily available carboxylic acid chlorides with acetylenes.

Hydride-Promoted Ring Expansion of 2-Azaspiropyrrolinium Salts: An Approach Towards the Synthesis of (-)-Nitramine

An enantioselective approach toward the synthesis of the spiroalkaloid (-)-nitramine was achieved by electrophile-induced cyclization of a suitably substituted and protected chiral α-allylcy-clohexanecarboxaldimine. Its hydride-promoted ring expansion after spirocyclization gave rise to the competitive formation of isomeric spiropyrrolidines and a spiropiperidine, the latter being further transformed into (-)-nitramine.

Electrophilic Selenocyclization in 2‐ene‐1,5‐Diol Systems: Unexpected Oxetane vs. Tetrahydrofuran Formation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Electrophilic selenocyclization in 2-ene-1,5-diol systems: unexpected oxetane vs. tetrahydrofuran formation

Electrophile-induced cyclization of ( E)- and ( Z)-2-ene-1,5-diols to tetrahydrofurans and oxetanes is described. Significant differences between the present report and previous work have been noted. A tentative model is proposed.

Stereoselective Synthesis of Homochiral Substituted Tetrahydrothiophenes by Electrophile‐Promoted Thioetherification.

AbstractFor Abstract see ChemInform Abstract in Full Text.

ALKATRIENYL SULFOXIDES AND SULFONES. PART III.1 5-METH YL-3-(METHYLSULFON YL)HEXA-1,3,4-TRIENE - SYNTHESIS AND ELECTROPHILE-INDUCED CYCLIZATION REACTIONS

Article ALKATRIENYL SULFOXIDES AND SULFONES. PART III.1 5-METH YL-3-(METHYLSULFON YL)HEXA-1,3,4-TRIENE - SYNTHESIS AND ELECTROPHILE-INDUCED CYCLIZATION REACTIONS was published on December 1, 2003 in the journal Heterocyclic Communications (volume 9, issue 6).

Stereoselective Synthesis of Homochiral Substituted Tetrahydrothiophenes by Electrophile-Promoted Thioetherification

In this paper we study the electrophile-promoted cyclization of 2-sulfanyl-4-penten-1-ol and 1-sulfanyl-4-penten-2-ol derivatives as a way of preparing cyclic sulfides. The reaction is completely chemoselective and always proceeds by activation of the sulfur centre. The reaction of 2-sulfanyl-4-penten-1-ol derivatives proceeds by a 5-endo mode. Unsaturated thiol 6 undergoes iodine-promoted cyclothioetherification to give the tetrahydrothiophene 9 in moderate yields and with excellent regio- and stereoselectivity. However, when the reaction starts from the benzyl sulfide 7, a diastereomeric mixture of 9 and 10 is obtained in good yields. Selenium-promoted cyclization of unsaturated thioacetate 5 provides the selenyltetrahydrothiophene 12 or the sulfanyl acetate 13, depending on the selenium reagent used. On the other hand, electrophile-induced cyclization of 1-sulfanyl-4-penten-2-ol derivatives 23−25 depends on the electrophile used. Iodothioetherification of benzyl sulfide 25 followed by oxidation affords unsaturated sulfone 26 as a result of 6-endo-cyclization, dehydroiodination and oxidation. In contrast, selenothiocyclization of 24 with PhSeX results in the formation of the 5-exo tetrahydrothiophenes 29/30 and/or 31/32. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Bifunctionalized Allenes. Part V. 3-Sulfinyl-2,5-dihydro-1,2l5-oxaphosphol-2-ones and 3-Phosphoryl-1,2l4-oxathiol- 2(5H)-ones from 1-Sulfinyl-substituted Phosphorylated Allenes

3-Sulfinyl-2,5-dihydro-1,2λ 5 -oxaphosphol-2-ones (3) and 3-phosphoryl-1,2λ 4 -oxathiol-2(5H)-ones (4) were synthesized in good yields via electrophile-induced cyclization reactions of 1-sulfinyl-substituted phosphorylated allenes (1) and (2). Bromination of dimethyl 1-sulfinyl-1,2-alkadiene-1-phosphonates (1) led to formation of 4-bromo-3-sulfinyl-2,5-dihydro-1,2λ 5 -oxaphosphol-2-ones (3), while the reaction with methyl 1-diphenylphosphoryl-1,2-alkadiene-1-sulfinates (2) afforded 4-bromo-3-diphenylphosphoryl-1,2λ 4 -oxathiol-2(5H)-ones (4).