Communication pubs.acs.org/Organometallics
Calcium-Catalyzed Bis-hydrothiolation of Unactivated Alkynes Providing Dithioacetals Martin Hut’ka, Tetsu Tsubogo, and Shu̅ Kobayashi* Department of Chemistry, School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan S Supporting Information *
ABSTRACT: Bis-hydrothiolation of alkynes providing anti-Markovnikov dithioacetals is reported. Lewis-acidic Ca(OSO2C4F9)2 (Ca(ONf)2) was synthesized for the first time and was shown to be an excellent catalyst for the transformation. The reaction is highly selective and has a wide substrate scope. It was revealed that vinyl sulfides were intermediates for this transformation and that Ca(ONf)2 efficiently catalyzed the unprecedented reactions of unactivated vinyl sulfides with thiols to afford the dithioacetals in good to high yields.
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radius. In spite of these interesting properties, the use of Ca in organic synthesis has been limited.12 While additions of amines, phosphines, and alcohols to alkynes catalyzed by calcium complexes have been reported,13−16 Ca amides or basic Ca complexes have been used for these reactions, in which Ca complexes work as strong bases to deprotonate hydrogens of the substrates, and successful examples have been mostly limited to intramolecular additions. To our knowledge, there is no example of addition of thiols (RSH) to alkynes catalyzed by calcium catalysts. We started investigating the reaction of phenylacetylene (1a) with benzylthiol (2a). When the reaction was conducted in the presence of 10 mol % of Ca(N(SiMe3)2)217 at 60 °C in THF, anti-Markovnikov vinyl sulfide 4a was obtained in 70% yield with an E/Z mixture (E/Z = 10/90) (Table 1, entry 1). We then examined Lewis-acidic Ca complexes. Recently, it has been reported that some Lewis-acidic Ca complexes such as Ca(OTf)2, Ca(NTf2)2, and Ca(NTf2)2/Bu4NPF6 have interesting catalytic activities in several reactions.18−20 We tested Ca(OTf)2 and Ca(NTf2)2 under identical reaction conditions and found that 4a was obtained in good yields as an E/Z mixture (entries 2 and 3). We then focused on a more Lewisacidic Ca complex, calcium nonafluorobutanesulfonate (Ca(OSO2C4F9)2 = Ca(ONf)2).21 Ca(ONf)2 could be prepared from CaCO3 and C4F9SO3H (Scheme 2).22 It was found that in the presence of Ca(ONf)2 the reaction of 1a with 2a proceeded smoothly to afford 4a and β-dithioacetal 7a in 45% and 43% yields, respectively (entry 4). When the reaction was conducted at 100 °C in 1,4-dioxane, 7a was obtained in 84% yield with a small amount of 4a (entry 5). The reaction also proceeded smoothly in 1,2-diethoxyethane (DEE) (entry 6). Relatively longer reaction time led us to consider the use of a microwave apparatus to accelerate the reaction. Under modified
ydrothiolation of an alkyne provides Markovnikov adduct 3 and/or anti-Markovnikov adduct 4 (Scheme 1).1−5 In
Scheme 1. Hydrothiolations of Terminal Alkynes
general, 3 is formed by Brønsted acid- or transition metalcatalyzed reactions, while 4 is produced by radical-mediated, Brønsted base-catalyzed, or transition metal-catalyzed reactions. For the formation of 4, while an E/Z mixture is obtained by radical-mediated reactions, Brønsted base-catalyzed reactions give 4Z and transition metal-catalyzed reactions afford 4E or 4Z selectively. In most cases, the addition stops at the stage of vinyl sulfides (the first addition); however, the successive second addition occurs in some cases. While Markovnikov adduct 3 gives α-dithioacetal (5) and vicinal dithioether (6), antiMarkovnikov adduct 4 provides 6 and another dithioacetal, βdithioacetal (7). Dithioacetals are useful and versatile compounds6−9 and are generally synthesized from carbonyl compounds.10 Compared with this standard method, direct bishydrothiolation of alkynes represents a more atom-economical route to dithioacetals. However, this route has not been well explored; in particular, the route to 7 is very limited.11 In this paper, we describe a highly selective and efficient route from 1 to 7 using a novel, very Lewis-acidic calcium catalyst. Calcium is abundant, less toxic, and inexpensive, so the use of Ca in place of rare elements is desirable. Chemically, Ca has lower electron negativity, its stable oxidation state is 2, and there are various coordination sites because of its large ionic © XXXX American Chemical Society
Special Issue: Catalytic and Organometallic Chemistry of EarthAbundant Metals Received: April 27, 2014
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dx.doi.org/10.1021/om500442u | Organometallics XXXX, XXX, XXX−XXX
Organometallics
Communication
Table 1. Optimization of the Reaction Conditions
entry
catalyst
1 2 3 4 5
Ca(N(SiMe3)2)2 Ca(OTf)2 Ca(NTf2)2 Ca(ONf)2 Ca(ONf)2
6 7b 8b,c
Ca(ONf)2 Ca(ONf)2 Ca(ONf)2
conditions THF, 24 h, 60 °C THF, 24 h, 60 °C THF, 24 h, 60 °C THF, 24 h 60 °C dioxane,a 24 h, 100 °C DEE, 24 h, 100 °C DEE, 6 h, 100 °C DEE, 4 h, 100 °C
Table 3. Bis-hydrothiolation of Alkynes with Dithiols
4a (%)
4a (E/ Z)
70 75 55 45
