Studies toward the synthesis of alpha-fluorinated phosphonates via tin-mediated cleavage of alpha-fluoro-alpha-(pyrimidin-2-ylsulfonyl)alkylphosphonates. Intramolecular cyclization of the alpha-phosphonyl radicals.
Treatment of the alpha carbanions generated from several alpha-(pyrimidin-2-ylsulfonyl)alkylphosphonates with Selectfluor gave high yields of the alpha-fluoro-alpha-(pyrimidin-2-ylsulfonyl)alkylphoshonates, which were desulfonylated [Bu(3)SnH/2,2'-azobisisobutyronitrile (AIBN)/benzene or toluene/Delta] to give alpha-fluoroalkylphosphonates. "Catalytic" tin hydride, generated from tributyltin chloride and excess polymethylhydrosiloxane in the presence of potassium fluoride, also effected removal of the pi-deficient alpha-(pyrimidin-2-ylsulfonyl) group from the phosphonate esters. Substitution of Bu(3)SnD for Bu(3)SnH gave access to alpha-deuterium-labeled phosphonates. Prolonged treatment of alpha-(pyridin-2-ylsulfonyl)alkylphosphonate with excess Bu(3)SnH/AIBN or catalytic tin hydride also effected desulfonylation but in moderate yields. This represents a mild new methodology for removal of the synthetically useful pi-deficient heterocyclic sulfone moiety and an alternative route for the preparation of alpha-fluorinated phosphonates. Desulfonylation is suggested to proceed via attack of tin radical at an oxygen (or sulfur) atom of the sulfonyl group to give a stabilized alpha-phosphonyl radical intermediate. The latter was found to undergo 5-exo-trig ring closure to give the corresponding 2-methylcyclopentylphosphonates. Treatment of diethyl 1-bromohex-6-enylphosphonate with Bu(3)SnH/AIBN produced an analogous mixture of ring-closure products. Treatment of [(2-bromo-5- methoxyphenyl)(fluoro)(pyrimidin-2-ylsulfonyl)]methylphosphonate with Bu(3)SnH resulted in an intramolecular radical [1,5]-ipso substitution reaction and migration of the pyrimidinyl ring to give fluoro[5-methoxy-2-(pyrimidin-2-yl)phenyl]methylphosphonate.
Wnuk
Stanislaw F
SF
Department of Chemistry, Florida International University, Miami, Florida 33199, USA. wnuk@fiu.edu
Bergolla
Luis A
LA
Garcia
Pedro I
PI
D000473:Alkanes / Q000737:chemistry; D000478:Alkylation; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D004952:Esters / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis; D011743:Pyrimidines / Q000138:chemical synthesis; D013237:Stereoisomerism; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry; D014001:Tin / Q000737:chemistry*
D000473:Alkanes; D004952:Esters; D006845:Hydrocarbons, Fluorinated; D063065:Organophosphonates; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D014001:Tin