Synthesis of polycyclic guanidines by cyclocondensation reactions of N-amidinyliminium ions.
A new method for the synthesis of polycyclic guanidines is described. The N-amidinyliminium ion generated from alpha-(phenylthio)amidine precursor 16 by reaction with Cu(OTf)(2) undergoes cyclocondensation with 1,3-dienes, styrenes, and beta-dicarbonyl compounds to give 1-iminohexahydropyrrolo[1,2-c]pyrimidines having side chains at C3 and C7. In all cases, major products have a cis relationship of the C7 side chain and angular C4a hydrogen, whereas C3 side chains are incorporated with lower stereoselectivity (dr = 2--5:1) in cyclocondensations with dienes and styrenes to give stereoisomer 39 as the major product. In contrast to most cycloadditions of alkenes with N-acyliminium ions, cyclocondensations of alkenes with N-amidinyliminium ions proceed by a stepwise pathway. Cyclocondensation of the cognate ureido aminal 31 with styrene provides the rare 2-imino-5,6-dihydro-4H-1,3-oxazine derivative 32, rather than a pyrimidine as the major product. The high stereoselectivity observed in condensations of 16 with benzyl acetoacetate to afford Biginelli adduct 29 supports the intermediacy of N-amidinyliminium ions in related tethered Biginelli condensations of guanidines reported earlier from our laboratories.
Overman
L E
LE
Department of Chemistry, 516 Rowland Hall, University of California, Irvine, California 92697-2025, USA. leoverma@uci.edu
Wolfe
J P
JP
D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry; D003300:Copper; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000578:Amidines; D006146:Guanidines; D007097:Imines; D007202:Indicators and Reagents; D011083:Polycyclic Compounds; D003300:Copper