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

Abstract

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, Ph2P(O) and RS groups in the triazoles were easily converted to Ph2P and RSO2 by PhSiH3-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.

Nickel-Catalyzed Site-Selective C3–H Functionalization of Quinolines with Electrophilic Reagents at Room Temperature

“…The versatility of this method was further verified by the formation of C–C bonds with cyclohexenone, diethyl 2-ethylidenemalonate, 4-fluorobenzoyl chloride, diphenylcarbamic chloride, and stearic anhydride as electrophiles. In addition, considering the wide applications of arylphosphorus compounds, we also tried and realized the construction of the C–P bond by the cross-coupling reaction between quinoline and diphenylphosphinyl chloride. The above cross-coupling reactions proceeded smoothly to produce 12k–12p in 47% to 85% isolated yields (Scheme ).…”

Sulfur‐Containing 1,2,3‐Triazoles: Synthesis and Properties

“…Synthesis and transformations of sulfur-and phosphoruscontaining 1,2,3-triazoles. [131] successive reaction with MeMgBr and aldehydes, 4-sulfanyl-5- and 157). [131] It was worth mentioning that 1-phosphinyl-2sulfanylethynes 144 were efficient substances to synthesize sulfur-and phosphorus-containing 1,2,3-triazoles, which proceeded a lot of transformations to produce functionalized sulfur-containing 1,2,3-triazoles.…”

“…[131] successive reaction with MeMgBr and aldehydes, 4-sulfanyl-5- and 157). [131] It was worth mentioning that 1-phosphinyl-2sulfanylethynes 144 were efficient substances to synthesize sulfur-and phosphorus-containing 1,2,3-triazoles, which proceeded a lot of transformations to produce functionalized sulfur-containing 1,2,3-triazoles. Besides, 144 was also applied in production of functionalized 4-sulfanyl-1,2,3-triazoles.…”

“…We developed a thermal [3+2] cycloaddition between azide 155 and 1‐phosphinyl‐2‐sulfonylethyne 154 which was generated from 1‐phosphinyl‐2‐sulfanyl ethyne 144 a by oxidation. Treatment of 144 a with m ‐CPBA gave 154 , which proceeded the thermal [3+2] cycloaddition with 155 without purification to afford a mixture of 5‐phosphinyl‐4‐sulfonyl and 4‐phosphinyl‐5‐sulfonyltriazoles ( 156 and 157 ) [131] . It was worth mentioning that 1‐phosphinyl‐2‐sulfanylethynes 144 were efficient substances to synthesize sulfur‐ and phosphorus‐containing 1,2,3‐triazoles, which proceeded a lot of transformations to produce functionalized sulfur‐containing 1,2,3‐triazoles.…”

Synthesis of Alkynyl Sulfides: Alkynyl Trifluoromethyl Sulfides and Thiocyanates

“…Besides these above methods, an alternative approach to synthesize 1‐phosphinyl‐2‐sulfanyl ethynes from disulfides, Zn and 1‐bromo‐2‐diphenylphosphinyl ethyne was also developed in very recently [49] . Compared to the Cu‐catalyzed cross‐coupling, [38] this alternative approach proceeded smoothly without any additives.…”