Phenol-Containing Macrocyclic Diamides as New Catalysts in the Highly Regioselective Conversion of Epoxides to β-Hydroxy Thiocyanates

Abstract

The regioselective ring-opening reactions of some epoxides with ammonium thiocyanate in the presence of a series of new phenol-containing macrocyclic diamides and also dibenzo-18-crown-6-, 18-crown-6-, benzo-15-crown-5-, and pyridine-containing macrocyclic diamide have been studied. The epoxides were subject to cleavage by NH(4)SCN in the presence of these catalysts under mild reaction conditions in various aprotic solvents. In this study, reagents and conditions have been discovered with which the individual beta-hydroxy thiocyanates can be synthesized in high yield and with more than 90% regioselectivity. The results can be discussed in terms of a four-step mechanism: (1) formation of complex between catalyst and NH(4)SCN, (2) release of SCN(-) nucleophile from the complex, (3) reaction of the active nucleophile at the less sterically hindered site in the epoxide, and (4) regeneration of catalyst. The major advantages of this method are as follows: (1) high regioselectivity, (2) simple regeneration of catalyst, (3) its reuse through several cycles without a decrease in activity, and (4) ease of workup of the reaction.

Anticancer and Anti-inflammatory Sulfur-Containing Semisynthetic Derivatives of Sarcophine

“…13) The thiocyanohydrin intermediates of oxirane conversion with thiocyanate have been particularly difficult to isolate until recently where the regio and stereoselective synthesis and isolation of trans intermediate has been reported. [13][14][15][16] Additionally, a mixture of cis and trans thiocyanohydrin and 1,3-oxathiolan-2-imine intermediates was reported earlier from a steroid. 17) Compounds 3 and 4 represent the first regio and stereoselective synthesis and isolation of both intermedi-1120…”

“…13) Although the reaction mechanism was proposed in 1950's, the thiocyanohydrin intermediate was not isolated until recently. [13][14][15] Cyclic epoxides yield trans b-hydroxy thiocyanates under reasonably mild conditions and with proper catalyst. [14][15][16] These reactions are known to proceed with high regioselectivity, almost exclusively yielding anti-Markovnikov's products.…”

“…[13][14][15] Cyclic epoxides yield trans b-hydroxy thiocyanates under reasonably mild conditions and with proper catalyst. [14][15][16] These reactions are known to proceed with high regioselectivity, almost exclusively yielding anti-Markovnikov's products. [14][15][16] However in sarcophine, where the epoxide attached to a 14-membered macrocycle, sulfur attack was exclusively on the more substituted carbon as per Markovnikov's rule, suggesting a carbocation intermediate followed by a thermodynamically stable product.…”

“…[14][15][16] These reactions are known to proceed with high regioselectivity, almost exclusively yielding anti-Markovnikov's products. [14][15][16] However in sarcophine, where the epoxide attached to a 14-membered macrocycle, sulfur attack was exclusively on the more substituted carbon as per Markovnikov's rule, suggesting a carbocation intermediate followed by a thermodynamically stable product. The syn addition of the nucleophile resulted in the cis b-hydroxy thiocyanate 3.…”

Fast, Efficient and Regioselective Conversion of Epoxides to β-Hydroxy Thiocyanates with NH4SCN/Zeolite Molecular Sieve 4 Å under Solvent-Free Conditions

“…3 It is explained that the formation of thiiranes from the reaction of epoxides with thiocyanate ion has been occurred through the intermediacy of the corresponding β-hydroxy thiocyanates; however, this intermediate has not been isolated due to its rapid conversion to the corresponding thiirane. Literature review shows that hydroquinone, 4 HSCN, 5 DDQ, 6 Ti(O i Pr) 4 , 7 Ph 3 P(SCN) 2 , 8 TiCl 3 , 9 ZnCl 2 , 9 Pd(PPh 3 ) 4 , 10 TMSNCS/TBAF, 11 poly[N-(2-aminoethyl) acrylamido]trimethyl ammonium chloride (PTC), 12 GaCl3, 13 selectfluor, 14 metalloporphyrins, 15 dichloro(5,10,15,20-tetraphenylporphyrin) phosphorus (V) chloride [P(TPP)Cl 2 ]Cl, 16 tetraarylporphyrins, 17 PEG-SO3H, 18 thioxanthenone-fused azacrown ethers, 19 silica sulfuric acid, 20 Dowex-50X8, 21 2,6-bis[2-(o-aminophenoxy)methyl]-4-bromo-1-methoxybenzene (BABMB), 22 phenol-containing macrocyclic diamides, 23 2-phenyl-2-(2-pyridyl)imidazolidine (PPI), 24 B(HSO 4 ) 3 25 and Al(HSO 4 ) 3 /SiO 2 26 are the reagents which stabilize the produced β-hydroxy thiocyanate and therefore inhibit from the conversion to thiirane. In contrast to above mentioned protocols, it was also reported that conversion of epoxides to β-hydroxy thiocyanates can be achieved with high quantities of NH4SCN in the absence of any catalyst.…”