428867-11-2Relevant academic research and scientific papers
Studies toward the synthesis of α-fluorinated phosphonates via tin-mediated cleavage of α-fluoro-α-(pyrimidin-2-ylsulfonyl) alkylphosphonates. Intramolecular cyclization of the α-phosphonyl radicals
Wnuk, Stanislaw F.,Bergolla, Luis A.,Garcia Jr., Pedro I.
, p. 3065 - 3071 (2007/10/03)
Treatment of the α carbanions generated from several α-(pyrimidin-2-ylsulfonyl)alkylphosphonates with Selectfluor gave high yields of the α-fluoro-α-(pyrimidin-2-ylsulfonyl)alkylphoshonates, which were desulfonylated [Bu3SnH/2,2'-azobisisobutyronitrile (AIBN)/benzene or toluene/Δ to give α-fluoroalkylphosphonates. "Catalytic" tin hydride, generated from tributyltin chloride and excess polymethylhydrosiloxane in the presence of potassium fluoride, also effected removal of the π-deficient α-(pyrimidin-2-ylsulfonyl) group from the phosphonate esters. Substitution of Bu3SnD for Bu3SnH gave access to α-deuterium-labeled phosphonates. Prolonged treatment of α-(pyridin-2-ylsulfonyl)alkylphosphonate with excess Bu3SnH/AIBN or catalytic tin hydride also effected desulfonylation but in moderate yields. This represents a mild new methodology for removal of the synthetically useful π-deficient heterocyclic sulfone moiety and an alternative route for the preparation of α-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 α-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 Bu3SnH/AIBN produced an analogous mixture of ring-closure products. Treatment of [(2-bromo-5-methoxyphenyl)(fluoro)(pyrimidin-2-ylsulfonyl)]methylphosphonate with Bu3SnH 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)phenyllmethylphosphonate.
