Halogen Atom Transfer Radical Cyclization Research Articles

Synthesis of Chlorinated, Heteroatom‐Rich and Differently Fused Tricyclic β‐Lactams by Cu(I)‐Catalyzed Halogen Atom Transfer Radical Cyclization

AbstractThe application of Cu (I)‐catalyzed halogen atom transfer radical cyclization (ATRC) for the synthesis of two different series of chlorinated, heteroatom rich and differently fused tricyclic β‐lactams has been demonstrated. N‐substituted‐3,4‐dihydropyrimidine‐2(1H)‐thiones synthesized by Biginelli reaction were used as starting materials for this synthetic pathway which upon S‐allylation/alkylation furnished 2‐allylthio/alkylthio‐1,4‐dihydropyrimidines (cyclic imines). Staudinger reaction of these cyclic imines with dichloroketene was employed to obtain the bicyclic dichloro‐S‐allyl/N‐allyl‐β‐lactams, which upon subsequent Cu(I)‐catalyzed ATRC produced two different series of tricyclic β‐lactams. The difference in the relative behavior of N‐allyl bicyclic dichloro‐β‐lactams and S‐allyl bicyclic dichloro‐β‐lactams towards ATRC was also introspected in terms of their relative rates of cyclization, the amount of catalyst loading needed and the stabilities of tricyclic‐β‐lactams obtained after cyclization. To study the relative reactivity of N‐allyl group and S‐allyl group towards ATRC, the bicyclic dichloro‐β‐lactams having both S‐allyl and N‐allyl groups were synthesized. The intramolecular competitive experiments revealed the high reactivity of S‐allyl group towards ATRC than the N‐allyl group.

Synthesis and molecular crystal of 3-Chloro-2-(1-chloro-1-methyl-ethyl)-2,3-dihydro-1H-naphtho[2,1-b]oxepin-4-one

CuCl/TMEDA-promoted halogen atom transfer radical cyclization (HATRC) of dichloroacetic acid 1-(3-methyl-but-2-enyl)-naphthalen-2-yl ester in refluxing DCE gave chlorine containing 7-member lactone 3-Chloro-2-(1-chloro-1-methyl-ethyl)-2,3-dihydro-1H-naphtho[2,1-b]oxepin-4-one via 7-exo trig radical cyclization reaction. The structure of the Lactone was confirmed by X-ray diffraction data.

An efficient method for the synthesis of some chlorinated and heteroatom rich triazole-linked β-lactam glycoconjugates

The synthetic utility of chlorinated bicyclic C-fused tetrahydrofuro[3,2-c] azetidin-2-ones synthesized in our laboratory by Cu(I)-catalyzed halogen atom transfer radical cyclization (ATRC) has been illustrated through the synthesis of some novel β-lactam glycoconjugates. The chlorine atom of the chloromethyl side chain of the bicyclic C-fused tetrahydrofuro[3,2-c] azetidin-2-ones was subjected to nucleophilic substitution with azide group followed by Cu(I)-catalyzed azide-alkyne click reaction (CuAAC) with propargyl glycosides to generate the desirous β-lactam glycoconjugates. A sequential optimization of the reaction procedure for CuAAC was carried out to obtain an efficient catalyst system to achieve β-lactam glycoconjugates in good yields. The β-lactam glycoconjugates are the compounds of interesting architecture and structurally suitable for bioactivity evaluation. Therefore, these β-lactam glycoconjugates were screened for in vitro antibacterial activity. Additionally, a representative β-lactam glycoconjugate was also tested for biocompatibility and cytotoxic activity against L929 cancer cell lines.

ChemInform Abstract: An Unusual Decarboxylative Benzannulation and Biaryl Formation During Copper(I)‐Promoted Halogen Atom Transfer Radical Cyclization of 2‐Allylaryl Trichloroacetates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of 2,4-disubstituted 3-chlorofurans and the effect of the chlorine substituent in furan Diels–Alder reactions

2,4-Disubstituted 3-chlorofurans were synthesized in 42–69% overall yields by CuCl/bpy-catalyzed halogen atom transfer radical cyclization of 1-substituted 2,2,2-trichloroethyl allyl ethers to 2-substituted 3,3-dichloro-4-(1-chloroalkyl)tetrahydrofurans followed by base promoted dehydrochlorination. Diels–Alder reactions of 4-substituted 2-(2-furyl)-, 2-styryl-, and 2-crotyl-3-chlorofurans with dimethyl acetylenedicarboxylate occurred exclusively on the chlorofurano diene moieties and not on the non-chlorinated furano diene or the chlorinated exocyclic diene alternatives, demonstrating the predominance of the halogen effect in the furan Diels–Alder reaction.

An unusual decarboxylative benzannulation and biaryl formation during copper(I)-promoted halogen atom transfer radical cyclization of 2-allylaryl trichloroacetates

CuCl/bpy-promoted halogen atom transfer radical cyclization of 2-allylaryl trichloroacetates in refluxing benzene gave benzannulated chloroarenes and benzannulated symmetrical biaryls along with reductive dehalogenation products. The unusual decarboxylative benzannulation and biaryl formation might be explained by a further intramolecular radical addition on the benzene ring of the eight-membered lactone intermediate, initially formed through 8- endo- trig halogen atom transfer radical cyclization, followed by decarboxylation, radical dimerization and dehydrochlorination reactions.

Synthesis of Highly Functionalized Spiro‐Indoles by a Halogen Atom Transfer Radical Cyclization.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access the actual ChemInform Abstract, please click on HTML or PDF.

Synthesis of highly functionalised spiro-indoles by a halogen atom transfer radical cyclization

The halogen atom transfer radical cyclization (HATRC) has been evaluated on N-(indolylmethyl)trichloroacetamides under Cu(I)Cl catalysis using nitrogen containing ligands. The ring closure leads to the formation of 3,3-spiro-3H-indoles in moderate to good yields by a 5-exo-mechanism. Derivatives with an N-electron withdrawing substituent also lead to a 5-exo-trig and not to a 6-endo-trig cyclization.

Intramolecular Diels−Alder Cycloaddition ofN-Allyl-N-(2-furylmethyl)amides − First Step of a New Route Towards the Synthesis of a Densely Functionalized Pyrrolizidine Ring

The intramolecular Diels−Alder reaction of N-allyl-N-(2-furylmethyl)amides to exo-N-acyl-3-aza-10-oxatricyclo[5.2.1.01,5]dec-8-enes is described. The cycloaddition is controlled not only by the size of the amide appendage, but also by electronegativity of the amide. An example of a new approach towards the synthesis of a highly functionalized pyrrolizidine ring, which links this Diels−Alder cycloaddition to an halogen atom transfer radical cyclization, is reported.

ChemInform Abstract: Halogen Atom Transfer Radical Cyclization of N‐Allyl‐N‐benzyl‐2,2‐dihaloamides to 2‐Pyrrolidinones, Promoted by Fe0—FeCl3 or CuCl—TMEDA.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Halogen atom transfer radical cyclization of N-allyl-N-benzyl-2,2-dihaloamides to 2-pyrrolidinones, promoted by Fe0-FeCl3 or CuCl-TMEDA

Abstract The halogen atom transfer radical cyclization of a N-allyl-N-benzyl-2,2-dihaloamides to 2-pyrrolidinones has been carried out in high yields under mild conditions, in a reaction promoted by CuCl-TMEDA or Fe0-FeCl3 in acetonitrile or N,N-dimethylformamide, respectively.