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

Abstract

The 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-3,4dihydropyrimidine-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 Nallyl 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.[a] Dr. N. DawraMehr Chand Mahajan DAV College for Women Sector 36-A, Chandigarh,

Radical Cyclization-Initiated Difunctionalization Reactions of Alkenes and Alkynes

“…A Cu-catalyzed radical reaction of allyl bicyclic β -lactam for the synthesis of tricyclic β -lactams has been reported by Dawra and coworkers in 2020. The reaction of allyl bicyclic β -lactam 125 under the catalysis of CuCl/PMDETA in DCE at room temperature gave products 126 or 127 in good to excellent yields ( Scheme 31 ) [ 57 ]. Between two alkenyl groups ( S -allyl and N -allyl) the competitive experiments revealed that the ATRC is more favorable to the S -allyl group than the N -allyl group.…”