Divergent 2-Chloroquinazolin-4(3H)-one Rearrangement: Twisted-Cyclic Guanidine Formation or Ring-Fused N-Acylguanidines via a Domino Process |
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| Authors: | Gang Yan Bereket L. Zekarias Dr. Xiaoyu Li Victor A. Jaffett Ilia A. Guzei Prof. Dr. Jennifer E. Golden |
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| Affiliation: | 1. Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI, 53705 USA;2. Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI, 53706 USA;3. Molecular Structure Laboratory, Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI, 53706 USA |
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| Abstract: | A highly efficient 2-chloroquinazolin-4(3H)-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). |
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| Keywords: | domino guanidine quinazolinone rearrangement twisted guanidine |
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