Radical cyclization in heterocycle synthesis. 11.(1) A novel synthesis of alpha,beta-disubstituted gamma-lactones via sulfanyl radical addition-cyclization using hydroximates as a tether

A combination of sulfanyl radical addition-cyclization of dienes connected with hydroximates and subsequent conversion of the resulting cyclic hydroximate to the lactones provides a novel method for the construction of alpha,beta-disubstituted gamma-lactones. Upon treatment with thiophenol in the presence of AIBN, dienes connected with hydroximates smoothly underwent sulfanyl radical addition-cyclization to give cyclic cis- and trans-hydroximates. Hydrolysis of cyclic hydroximates gave the desired cis- and trans-lactones in high yield. This method was successfully applied to the practical synthesis of (+/-)-oxo-parabenzlactone.     

Radical cyclization in heterocycle synthesis. 12. Sulfanyl radical addition-addition-cyclization (SRAAC) of unbranched diynes and its application to the synthesis of A-ring fragment of 1alpha,25-dihydroxyvitamin D3

Sulfanyl radical addition-addition-cyclization (SRAAC) of unbranched diynes proceeded smoothly to give cyclized exo-olefins, while the sulfanyl radical addition-cyclization-addition (SRACA) of diynes having a quaternary carbon gave cyclized endo-olefins. This method was successfully applied to the synthesis of A-ring fragment of 1alpha,25-dihydroxyvitamin D3.     

Novel synthesis and functionalization of ortho-ortho disubstituted biphenyls and a highly condensed novel heterocycle using radical cyclization reaction

This paper describes a novel synthetic route for the preparation of ortho-ortho disubstituted biphenyls and compounds possessing highly condensed ring system represented by structures X and Y, respectively. Several approaches, such as intermolecular Grubb's olefin metathesis, Heck and, Suzuki reactions were incorporated to functionalize the core structures of X and Y making it suitable for the preparation of a library of compounds.     

Total synthesis of 10-norparvulenone and of O-methylasparvenone using a xanthate-mediated free radical addition-cyclization sequence

[reaction: see text] A short synthesis of (+/-)-10-norparvulenone and (+/-)-O-methylasparvenone was developed starting from commercially available m-methoxyphenol, hinging on a xanthate-mediated addition-cyclization sequence for the construction of the alpha-tetralone subunit.     

Intramolecular cyclization of phenol derivatives with CC double bond in a side chain

Intramolecular cyclization of phenol derivatives with CC double bond on a side chain was examined using copper and silver catalyst. For example, 2-allylphenol (1a) was converted to 2,3-dihydro-2-methylbenzofuran (2a) in 70% yield using Cu(OTf)₂ or in 90% yield using AgClO₄. This catalysis was applied to cyclization of 2-allylphenol derivatives, 2-(3-butenyl)phenol, benzoic acids with CC double bond, 2-allyl-N-tosylaniline, and 2-(3-butenyloxy)phenol. Furthermore, allyl phenyl ether was converted to 2a via Claisen rearrangement and cyclization.     

Diastereocontrol by a hydroxyl auxiliary in the synthesis of pyrrolidines via radical cyclization

[reaction: see text] Organoselenium precursors of 3-aza-5-hexenyl radicals carrying a 1-hydroxyalkyl group in the 2-position were prepared by addition of organometallic reagents to N-allyl-2-aziridinecarbonitrile, reduction of the resulting aziridine ketone, and regioselective benzeneselenol ring opening of the aziridine. Reductive radical cyclization was highly selective, affording the corresponding trans-2,4-disubstituted pyrrolidine (cis/trans ca. 1/10) as the major diastereomer. Recrystallization afforded material that was substantially more enriched in the trans isomer (cis/trans < 1/25).     

Radical cyclization of ynamides into six- or eight-membered rings. Application to the synthesis of a protoberberine analog

A straightforward formation of six- and eight-membered rings via the radical cyclization of specifically designed ynamides is reported. This strategy provides a protoberberine analog in only three steps by a radical cyclization cascade.     

A novel and efficient methodology for the C-C bond forming radical cyclization of hydrophobic substrates in water

[reaction: see text]. The combination of water-soluble radical initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane] (VA-061), water-soluble chain carrier 1-ethylpiperidine hypophosphite (EPHP), and surfactant cetyltrimethylammonium bromide (CTAB) was found to be the most suitable condition for effective radical cyclization in water for a variety of hydrophobic substrates.     

Synthesis,separation and N.M.R. spectra of three double bond isomers of leukotriene a methyl ester

The synthesis and h.p.l.c. separation of three double bond isomers of leukotriene A methyl ester is described, their stereochemistry being assigned by ¹H N.M.R.     

Formation of a Ti-C bond in reactions between the triphenylmethyl radical and titanium salts

Conclusions The feasibility of obtaining organometallic titanium compounds based on the recombination of the triphenylmethyl radical with Ti²⁺ and Ti³⁺ compounds was demonstrated.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2561–2563, November, 1976.     

Radical deoxygenation of alcohols and intermolecular carbon-carbon bond formation with surfactant-type radical chain carriers in water

An efficient and mild method is developed for radical deoxygenation of alcohols and formation of carbon-carbon bonds in water without adding additives such as surfactants. The reaction was applied to synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides that are potent anti-HIV agents. The reaction afforded environmentally benign reaction conditions.     

Effective synthesis of diiodinated picene and dibenzo[a,h]anthracene by AuCl-catalyzed double cyclization

6,13-Diiododibenzo[a,h]anthracene and 5,8-diiodopicene were synthesized by AuCl-catalyzed double cyclization. The highly selective reaction yielded a new class of peri-halogenated fused aromatics.     

A facile tandem radical cyclization route to propellanes and its application to a total synthesis of modhephene

A facile and versatile tandem radical cyclization route to propellanes from dieneyne compounds was developed and was applied to the total synthesis of modhephene.     

Carbon-carbon bond formation by ‘double activation’. The synthesis of piperolide and fadyenolide intermediates.

Buenolide anions do not react with orthoesters and butenolides do not react with carbocations derived from acetals and orthoesters. However double activation of the butenolide (as the carbanion) and the alkoxyalkanes (as the stabilised carbocations) leads to high yield carbon-carbon bond formation of some generality.     

Free radical reactions for heterocycle synthesis. Part 7: 2-Bromobenzoic acids as building blocks in the construction of spirobenzolactones and spirobenzolactams

A straightforward 2-step parallel synthesis for structurally diversified spiro compounds is developed. 2-Bromobenzoic acids are used as common building blocks to couple with a series of conjugated enoles or enamines. Sequential intramolecular free radical Michael additions lead to formation of spirobenzolactones, spirobenzolactams, spirobenzolactone-lactams, spiorbenzolactone-thiolactones, spiordilactones, and bridged-spirolactones.     

Intramolecular cyclization of ruthenium vinylidene complexes with a tethering vinyl group: facile cleavage and reconstruction of the C-C double bond

Protonation of ruthenium acetylide complexes [M]-*C*CCPh2CH2CH=CH2 (2a, [M] = (eta5-C5H5)(P(OPh)3)(PPh3)Ru; 2a', [M] = (eta5-C5H5)(dppp)Ru; *C = 13C-labeled carbon atom) with HBF4 in ether produces [[M]=*C=CHCH2CPh2*CH=CH2][BF4] (4, 4') exclusively via a metathesis process of the terminal vinyl group with the *C=*C of the resulting vinylidene group. For 4 in methanol, bond reconstruction of the two labeled *C atoms readily takes place via a retro-metathesis process followed by a cyclization of the resulting vinylidene ligand giving the cyclic carbene complex 5, which is fully characterized by single-crystal X-ray diffraction analysis. The protonation of 2a in MeOH is followed by a cyclization, also giving 5. Deuterium-labeling study indicates that the C-C bond formation of this cyclization proceeds simultaneously with the formation of 4 consistent with facile cleavage and reconstruction of C=C bonds. For comparison, complex 4 in alcohol yields, besides 5, the corresponding alkoxycyclohexene 6. Formation of 6 from 4 also involves a skeletal rearrangement with reconstruction of the C=C bond. Interestingly, [[Ru']=*C=C(Me)CH2CPh2*CH=CH2][BF4] (8') originally from a complex with two connected labeled carbon atoms also undergoes reestablishment of the *C=*C bond yielding the cyclic allenyl complex 9'. 13C-labeling studies clearly reveal the reestablishment of two C=C double bonds in the transformation of both 4 to 5 and 8' to 9'. The proposed mechanism implicates a cyclobutylidene intermediate formed either via a regiospecific [2+2] cycloaddition of two double bonds in the ruthenium vinylidene 4 or via a cyclization of 4 giving a nonclassical ion intermediate followed by a 1,2-alkyl shift.     

Formal radical cyclization onto benzene rings: a general method and its use in the synthesis of ent-nocardione A

An indirect method is described for effecting radical cyclization onto a benzene ring. Cross-conjugated dienones 6, which are readily prepared from phenols, undergo radical cyclization (6 --> 7 --> 8), and the products (8) are easily aromatized. The method has been applied to the synthesis of ent-nocardione A (21).     

Tandem radical cyclization-based strategy for the synthesis of oxa- and aza-cages: a case of fragmentation versus cyclization

A new strategy for the synthesis of oxa- and aza-cage compounds based on tandem radical cyclizations is described. The iodides 1 lead to oxa-cages 3 after two tandem radical cyclizations. The ester 10aa on reaction with n-Bu₃SnH and AIBN gives rise to the oxa-cage 12aa after two tandem 5-exo-trig cyclizations. On the other hand, reaction of the ketones 17aa and 21 under similar conditions furnished the oxa-cages 20aa and 23, respectively, via a double 5-exo-trig tandem radical cyclization followed by fragmentation.