Letter pubs.acs.org/OrgLett
Iron-Catalyzed Intermolecular Hydrothiolation of Internal Alkynes with Thiosalicylic Acids, and Sequential Intramolecular Cyclization Reaction Taro Sonehara, Shogo Murakami, Sae Yamazaki, and Motoi Kawatsura* Department of Chemistry, College of Humanities & Sciences, Nihon University, Sakurajosui, Setagaya-ku, Tokyo 156-8550, Japan S Supporting Information *
ABSTRACT: We demonstrate the iron-catalyzed intermolecular coupling of internal alkynes and thiosalicylic acid derivatives. The reaction was effectively catalyzed by the Fe(acac)2/1,10-phenanthroline catalyst in toluene/HFIP (hexafluoroisopropyl alcohol) as the reaction solvent and afforded several types of 1,3-oxathiine derivatives in moderate to high yields through the intermolecular hydrothiolation and sequential intramolecular cyclization.
T
reaction was realized using a palladium catalyst for the terminal alkynes.10 Based on this observation, to increase the yield of 3aa, we further investigated the Fe(acac)2/1,10-phen catalyzed reaction of 1a with 2a in other solvents, such as dioxane, methoxycyclopentane (CPME), iPrOH, or hexafluoroisopropyl alcohol (HFIP) (entries 8−11), and confirmed that, although the conversion of 1a was slow (80% conv), the reaction in HFIP gave the 1,3-oxathiine derivative 4aa in 69% NMR yield without 3aa (entry 11). Although the exact role of the HFIP is unclear, these results indicated that toluene is a suitable solvent for the Fe(acac)2/1,10-phen catalyzed intermolecular hydrothiolation of 1a with 2a, and the intramolecular cyclization of 3aa to 4aa occurred in the HFIP solvent. Based on this observation, we optimized the solvent for the selective formation of 4aa with a high yield and revealed that the reaction in the mixture of toluene and HFIP (1/1) afforded the intended products 4aa in 83% NMR yield as the sole product (entry 12). Furthermore, the highest yield (98% NMR yield, 90% isolated yield) was obtained when the reaction was performed in toluene/HFIP (3/2) (entry 13). With the optimal reaction conditions in hand, we examined the reactions of the trifluoromethyl group substituted internal alkynes 1b−z′′ with 2a, and the results are summarized in Table 2. The reaction of the phenyl and trifluoromethyl group substituted internal alkyne 1b with 2a gave the desired trifluoromethyl group possessing 1,3-oxathiine derivatives 4ba in 87% yield (Table 2, entry 1). The reactions of other alkynes, such as 1c and 1d, which possess alkyl substituents on the benzene ring, also afforded the intended products 4ca and 4da in 89% and 98% yields, respectively (entries 2 and 3). On the other hand, we confirmed that the reaction of the o-tolyl group substituted alkyne 1e resulted in a low yield (26%), and we observed the formation of hydrothiolated product 3ea in the 1 H NMR of crude materials (entry 4). The reactions of 1f−h,
he transition-metal catalyzed hydrofunctionalization of alkynes is one of the most versatile and atom economical reactions in the field of synthetic organic chemistry. The hydrothiolation of alkynes is also an important reaction because the reaction directly provides organosulfur compounds.1 Therefore, there are some reports about the metal-catalyzed or metal-free hydrothiolation of alkynes,2−4 but most of the reactions were accomplished for the terminal alkynes, and there are still limited examples of the reaction of internal alkynes.3 Additionally, iron is one of the most abundant and environmentally friendly metals on the earth, and iron was also employed as a catalyst for the various types of hydrofunctionalizations of alkynes.5 However, to the best of our knowledge, there is only one example of the iron-catalyzed intermolecular hydrothiolation of alkynes.3c On the other hand, we previously developed several types of iron-catalyzed reactions6 or metal-catalyzed transformations of the trifluoromethyl group possessing internal alkynes.7 Based on this background, we investigated the iron-catalyzed intermolecular hydrothiolation of the trifluoromethyl group possessing internal alkynes and revealed that the reaction with thiosalicylic acids provided the 1,3-oxathiine derivatives by the intermolecular hydrothiolation and sequential intramolecular cyclization. We first examined the reaction of the aryl and trifluoromethyl group substituted internal alkyne 1a8 with thiosalicylic acid (2a) in toluene at 120 °C and confirmed that no reactions occurred (Table 1, entry 1). To investigate this intended hydrothiolation reaction, we next examined the reactions in the presence of iron catalysts, such as FeCl3, FeCl2, Fe(acac)3, Fe(acac)2, Fe(OAc)2, or Fe(OTf)2, with 1,10-phen (1,10phenanthroline) as a ligand and revealed that some of the iron catalysts provided the hydrothiolated product 3aa9 (entries 2− 7). For example, we observed the high conversion of 1a (>98% conv) in the reaction using Fe(acac)2 and the formation of 3aa and 4aa10 in 72% and 9% NMR yields, respectively (entry 5). To the best of our knowledge, there is only one report about the synthesis of 1,3-oxathiine derivatives, such as 4aa, and the © XXXX American Chemical Society
Received: June 26, 2017
A
DOI: 10.1021/acs.orglett.7b01953 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Iron-Catalyzed Reaction of 1a with 2aa
Table 2. Iron-Catalyzed Reaction of Trifluoromethyl Group Substituted Internal Alkynes 1b−z with 2a in Toluene/ HFIPa
yieldb (%) entry
[Fe]
solvent
3aa
4aa
1 2 3 4 5 6 7 8 9 10 11 12 13 14d
− FeCl3 FeCl2 Fe(acac)3 Fe(acac)2 Fe(OAc)2 Fe(OTf)2 Fe(acac)2 Fe(acac)2 Fe(acac)2 Fe(acac)2 Fe(acac)2 Fe(acac)2 Fe(acac)2
toluene toluene toluene toluene toluene toluene toluene dioxane CPME i PrOH HFIP toluene/HFIP (1/1) toluene/HFIP (3/2) toluene/HFIP (3/2)
