Process-Divergent Syntheses of 4- and 5-Sulfur-Functionalized 1,2,3-Triazoles via Copper-Catalyzed Azide-Alkyne Cycloadditions of 1-Phosphinyl-2-sulfanylethynes.

4-Sulfanyl-substituted 1,2,3-triazoles were provided regioselectively with good yields and broad scope via consecutive t -BuOK-promoted dephosphinylation of 1-phosphinyl-2-sulfanylethynes and copper-catalyzed azide-alkyne cycloadditions (CuAAC) with alkyl azides. Unsymmetrically substituted ditriazoles were successfully obtained using a tandem dephosphinylative CuAAC protocol with diazides. Direct CuAAC of the 1-phosphinyl-2-sulfanylethynes with azides afforded regioisomeric mixtures of 4-phosphinyl-5-sulfanyl- and 5-phosphinyl-4-sulfanyl-1,2,3-triazoles that were easily separable from one another. When the phosphinyl- and sulfanyl-substituted triazoles were treated with t -BuOK, the dephosphination proceeded smoothly, yielding the corresponding 5- and 4-sulfanyltriazoles, respectively. 5-(1-Aryl-1-hydroxymethyl)-4-sulfanyltriazoles were synthesized by stepwise treatment of 5-phosphinyl-4-sulfanyltriazole with MeMgBr and arylaldehydes. Additionally, Ph 2 P(O) and RS groups in the triazoles were easily converted to Ph 2 P and RSO 2 by PhSiH 3 -reduction and m -CPBA-oxidation, respectively. Following the dephosphinylative CuAAC of 1-phosphinyl-2-(4- t -butylphenylsulfanyl)ethyne with aryl azides and m -CPBA-oxidation, potent antagonists of pregnane X receptor LC-58 and LC-59 were successfully produced.