Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
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Ag-Catalyzed Thiocyanofunctionalization of Terminal Alkynes To Access Alkynylthiocyanates and α‑Thiocyanoketones Jie Yang See and Yu Zhao* Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543
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ABSTRACT: Unprecedented one-pot thiocyanofunctionalizations of terminal alkynes to deliver alkynylthiocyanates and αthiocyanoketones using a silver-catalyzed procedure or under silver/gold relay catalysis is reported. These synthetically valuable organothiocyanates are accessed in high efficiency, and their derivatization into a variety of valuable sulfur-containing heterocycles and sulfides has also been demonstrated.
O
Scheme 1. Strategies for Thiocyanation Reactions
rganosulfur compounds are ubiquitous in our daily life; they are commonly present in the body as cysteine and methionine as well as in drugs such as penicillin, nelfinavir, and quatiapine.1 A vast amount of research has been devoted to the synthesis of new organosulfur compounds by C−S bond formation. Among various strategies, substitution of nucleophilic sulfides and metal-catalyzed C−S coupling are the more frequently utilized methods.2 However, most of these transformations involve the use of odorous and/or toxic reagents that are difficult to handle, thus leaving much room for improvement.3 Organothiocyanates are a valuable class of molecules and a versatile intermediate to various organosulfur compounds.4 They have been traditionally accessed from metal thiocyanate salts, which are an attractive choice of reagents due to their ease of handling and low toxicity.4b The scope of this synthetic strategy, however, remains limited. The preparation of valuable alkynylthiocyanates, for example, still requires the prefunctionalization of alkyne substrates such as iodonium triflates (Scheme 1a top).5 A great deal of progress have been made toward direct thiofunctionalization of alkynes.6 However, it was only in recent years that good progress has been made in the metal-catalyzed thiocyanation of readily available alkynes (Scheme 1a bottom).7 The introduction of new, efficient catalytic thiocyanate synthesis in producing synthetically flexible alkynylthiocyanates is still highly sought after. As an attractive, alternative approach, great advances have been made in the introduction of electrophilic thiocyanating reagents. N-Thiocyanosuccinimide (NTS), for example, has proven to be highly useful in C−S bond formation. Their utility, however, is mainly limited to thiocyanation of aromatic systems by electrophilic aromatic substitution or α-functionalization of carbonyl compounds.8 The development of metal-catalyzed © XXXX American Chemical Society
coupling using these easy-to-handle reagents will greatly expand their utility and open up new opportunities in organosulfur chemistry. Herein, we report unprecedented silver-catalyzed one-pot procedures for the thiocyanofunctionalizations of terminal alkynes to deliver alkynylthiocyanates as well as αthiocyanoketones. Not only are these compounds accessed in Received: October 4, 2018
A
DOI: 10.1021/acs.orglett.8b03162 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters high efficiency, they can also be derivatized to a range of sulfurcontaining heterocycles. The project was initiated by screening a variety of silver catalysts along with different thiocyanating reagents commonly used for alkyne functionalization. The thiocyanating reagents were modified with inspiration from commercially available halogenating reagents and from N-thiocyanosuccinimide, a reagent first synthesized by Still’s group.9 In the midst of our progress, Chen’s research group synthesized NTP and NTSc for use as a general-purpose thiocyanating reagent.10 The reaction of phenylacetylene with NTS was then screened with a variety of silver salts (Table 1). Silver salts were previously reported to be
Scheme 2. Substrate for Thiocyanation of Terminal Alkynes
Table 1. Optimization of Thiocyanation of Alkynea
entry
catalyst
SCN source
temp (°C)
yieldb (%)
1 2 3 4 5 6 7 8 9 10 11c
Ag2CO3 Ag2CO3 CuI Cu2O CuCl Ag2OAc AgI AgSO3CF3 Ag2O Ag2O Ag2O
NTS NTS NTS NTS NTS NTS NTS NTS NTS NTSc NTP
24 60 60 60 60 60 60 60 60 60 60
