(±)-tert-Butylphenylphosphinothioic acid was resolved into (R
p)-(+) tert-butylphenylphosphinothioic acids 129 according to a standard procedure. The (±)- and (R
p)-phosphinothioic acids were converted into (±)- and (R
p)-tert-butylphenylthionophosphinochloridates 139 respectively by treatment with either thionyl chloride or oxalyl chloride in dichloromethane, with enantiomeric purity for the (R
p)-product being in excess of 98%. Treatment of the chloridates with sodiated aryloxide or thio-aryloxide in DMF provided via a nucleophilic substitution reaction which proceeded with clean inversion to give O-phenyl (±)-tert-butylphenylthionophosphinate (±)-137, O-phenyl (R
p)-tert-butylphenylthionophosphinate (R
p)-137, S-phenyl (±)-tert-butylphenylthionophosphinate (±)-145, S-phenyl (R
p)-tert-butyl-phenylthionophosphinate (R
p)-145, O-1-naphthyl (±)-tert-butylphenylthionophosphinate (±)-142, O-1-naphthyl (R
p)-tert-butylphenylthionophosphinate (R
p)-142, O-2-naphthyl (±)-tert-butylphenylthionophosphinate (±)-143, O-2-naphthyl (R
p)-tert-butylphenylthionophosphinate (R
p)-143, O-(2-bromo-3-pyridyl) (±)-tert-butylphenylthionophosphinate (±)-141, O-(2-bromo-3-pyridyl) (R
p)-tert-butylphenylthionophosphinate (R
p)-141, S-2-bromophenyl (±)tert- butylphenylthionophosphinate (±)-146, and S-2-bromophenyl (R
p)-tert-butyl-phenylthionophosphinate (R
p)-146 in high yields. Similarly, each of pyrrole, indole and imidazole were deprotonated with sodium hydride and treated with each of (±)- and (R
p)-(±)-thionophosphinochloridate to give N-pyrrolyl (±)-tert-butylphenylthionophosphinoamidate (±)-153, (R
p)-tert-butylphenylthionophosphinoamidate (R
p)-153, N-indolyl (±)-tert-butylphenylthionophosphinoamidate (±)-154, N-indolyl (R
p)-tert- butylphenylthionophosphinoamidate (R
p)-154, and N-imidazolyl (±)-tert-butylphenylthionophosphinoamidate (±)-155, also in high yields. That inversion occurs in these reactions was confirmed by X-ray crystallographic determinations on compounds (R
p)-142 and (R
p)-145.
The foregoing compounds were treated either with tert-butyllithium n-butyllithium in THF at -78 °C followed by warming to induce rearrangement of the intermediate metallated compound. In this way, O-phenyl (±)-tert-butylphenylthionophosphinate was converted into (±)-tert-butyl(2-hydroxyphenyl)phenylphosphine sulfide (±)-164 (17%), O-phenyl (R
p)-tert-butylphenylthionophosphinate into (R
p)-tert-butyl(2-hydroxyphenyl)phenylphosphine sulfide (R
p)-164 (17%), O-(2-bromo-3-pyridyl) (±)-tert-butylphenylthionophosphinate into (±)-tert-butyl(6-hydroxypyrid-2-yl)phenylphosphine sulfide (±)-165 (76%), O-(2-bromo-3-pyridyl) (R
p)-tert-butylphenylthionophosphinate into (R
p)-tert-butyl(6-hydroxypyrid-2-yl)phenylphosphine sulfide (R
p)-165 (71%), N-pyrrolyl (±)-tert- butylphenylthionophosphinoamidate into (±)-tert-butylphenyl(pyrrol-2-yl) phosphine sulfide (±)169 (78%), N-pyrrolyl (R
p)-tert- butylphenylthionophinoamidate into (R
p)-tert-butylphenyl(pyrrol-2-yl)phosphine sulfide (R
p)-169, N-indolyl (±)-tert-butyl- phenylthionophosphinoamidate into (±)-tert-butylphenyl(indol-2-yl)phosphine sulfide (±)-170 (90%), and N-indolyl (R
p)-tert-butylphenylthionophosphinoamidate into (R
p)-tert-butylphenyl(indol-2-yl)phosphine sulfide (R
p)-170 (99%). For the optically active compounds, stereoselectivity was complete in all cases; as established by X-ray crystallographic determinations on compounds 169, the rearrangements proceed with retention.
(±)- and (R
p)-tert-butylphenylthionophosphinochloridates were reduced by lithium naphthalenide in THF to give (±)-tert-butylphenylphosphine sulfide (±)-131 (76%) and (R
p)-tert-butylphenylphosphine sulfide (R
p)-131 (62%) whose NMR spectra indicated the small mount of the P(III) tautomer also present. When the reaction mixtures from the foregoing were each treated with methyl iodide, (±)- and (R
p)-tert-butylmethylphenylphosphine sulfide 159 were obtained in good yields. Treatment of each of the chloridates with aqueous ammonia in DMF gave (±)- and (R
p)-tert-butylphenylthionophosphinoamidate 148 in high yields.
Attempts to activate the hydroxyl group in phosphinothioic acid to nucleophilic dispacement by conversion into tosylate, mesylate or triflate were not successful.
Post a Comment