Premium
Divergent 2‐Chloroquinazolin‐4(3 H )‐one Rearrangement: Twisted‐Cyclic Guanidine Formation or Ring‐Fused N ‐Acylguanidines via a Domino Process
Author(s) -
Yan Gang,
Zekarias Bereket L.,
Li Xiaoyu,
Jaffett Victor A.,
Guzei Ilia A.,
Golden Jennifer E.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905219
Subject(s) - guanidine , amine gas treating , chemistry , ring (chemistry) , domino , intramolecular force , yield (engineering) , reagent , primary (astronomy) , diamine , cyclic amines , quinazolinone , combinatorial chemistry , stereochemistry , polymer chemistry , organic chemistry , materials science , metallurgy , catalysis , physics , astronomy
A highly efficient 2‐chloroquinazolin‐4(3 H )‐one rearrangement was developed that predictably generates either twisted‐cyclic or ring‐fused guanidines in a single operation, depending on the presence of a primary versus secondary amine in the accompanying diamine reagent. Exclusive formation of twisted‐cyclic guanidines results from pairing 2‐chloroquinazolinones with secondary diamines. Use of primary amine‐containing diamines permits a domino quinazolinone rearrangement/intramolecular cyclization, gated through ( E )‐twisted‐cyclic guanidines, to afford ring‐fused N ‐acylguanidines. This scalable, structurally tolerant transformation generated 55 guanidines and delivered twisted‐cyclic guanidines with robust plasma stability and an abbreviated total synthesis of an antitumor ring‐fused guanidine (4 steps, 55 % yield).