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Synthesis of Chlorinated, Heteroatom‐Rich and Differently Fused Tricyclic β‐Lactams by Cu(I)‐Catalyzed Halogen Atom Transfer Radical Cyclization
Author(s) -
Dawra Nisha,
Ram Ram N.,
Thakur Sujeet K.
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202001195
Subject(s) - bicyclic molecule , chemistry , heteroatom , radical cyclization , tricyclic , intramolecular force , medicinal chemistry , catalysis , reactivity (psychology) , alkylation , halogen , ring (chemistry) , stereochemistry , organic chemistry , alternative medicine , pathology , medicine , alkyl
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‐3,4‐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.