Tetrahedron Letters xxx (2014) xxx–xxx Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet Digest Paper 1,3-Diyne chemistry: synthesis and derivations ⇑ ⇑ Wei Shi a, , Aiwen Lei b, a College of Science, Huazhong Agricultural University, Wuhan 430070, China b College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China article info abstract Article history: Conjugated diynes have attracted more and more attention not only for their unique rod like structures Received 4 January 2014 and wide existence in nature product, but also the abundant properties and derivations of them. Revised 22 February 2014 Although oxidative dimerization of alkynes or Cadiot–Chodkiewicz reactions were the main pathway Accepted 5 March 2014 and have achieved great success in the synthesis of diynes, oxidative cross coupling, FBW rearrangement Available online xxxx as well as diyne metathesis emerged rapidly recently. Moreover, diynes could be precursors of basic het- erocycles, which represented an emerging research area. This Letter will cover the recent progresses in Keyword: the synthesis and further derivations of diynes. Diyne chemistry Ó 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license Glaser–Eglinton–Hay coupling FBW rearrangement (http://creativecommons.org/licenses/by-nc-nd/3.0/). Cadiot–Chodkiewicz coupling Contents Introduction. ....................................................................................................... 00 Synthesis of diynes . .................................................................................... 00 Synthesis of symmetrical diynes . .......................................................................... 00 The oxidative Glaser–Eglinton–Hay coupling . ............................................................ 00 Modifications of Glaser–Eglinton–Hay coupling reactions . ............................................................ 00 Oxidative coupling from alkyne derivatives . ............................................................ 00 Reductive coupling to form symmetric diynes . ............................................................ 00 Synthesis of unsymmetric diynes. .......................................................................... 00 Cadiot–Chodkiewicz coupling and modifications . ............................................................ 00 Fritsch–Buttenberg–Wiechell (FBW) rearrangement. ............................................................ 00 Unsymmetric diynes directly from two different terminal alkynes . ......................................... 00 Other methods to unsymmetric diynes . ............................................................ 00 Heterocycles from diynes . .................................................................................... 00 Thiophenes and furans from diynes. .......................................................................... 00 Pyrroles from diynes . .......................................................................................... 00 Other heterocycles from diynes . .......................................................................... 00 Conclusion . ....................................................................................................... 00 References and notes. ........................................................................................ 00 Introduction have a detailed review on the theoretical studies on acetylenic scaffolds.1 Tykwinski et al. have prepared a series of 1,3-diynes 1,3-Diynes (referred to as diynes hereinafter) are a kind of con- and derivated polyynes (also known as carbyne) and characterized jugated diynes with unique structures (Scheme 1). They have a their structures using the methods including Raman, IR, XRD, etc.2 rod-like molecular shape with high rigidness. Chauvin and Lepetit In most cases, the four carbon atoms in diynes are arranged line- arly, although longer chains containing 8 or more linked sp hybrid- 3 ⇑ Tel./fax: +86 27 87284018 (W.S.); tel./fax: +86 27 68754672 (A.L.). ized carbon atoms may be slightly bent. The reported longest E-mail addresses: [email protected] (W. Shi), [email protected] carbyne is also shown in Scheme 1. (A. Lei). http://dx.doi.org/10.1016/j.tetlet.2014.03.022 0040-4039/Ó 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). Please cite this article in press as: Shi, W.; Lei, A. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.03.022 2 W. Shi, A. Lei / Tetrahedron Letters xxx (2014) xxx–xxx R R' 1,3-diyne 1,4-diphenylbuta-1,3-diyne calculated structure of the diphenyl diyne t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu Longest carbyne containing 44 sp hybridized carbons t-Bu t-Bu Scheme 1. Rigid structure of 1,3-diyne. Because of the rigid structure, diynes are easy to stack in crystal Synthesis of symmetrical diynes cells and form a needle-like crystalline solid. This instinct charac- terization means diynes could be easily recrystallized and purified Symmetric diynes could be generated simply from the oxidative from other byproducts. More importantly, diynes are thermally coupling of the corresponding terminal alkynes (or their deriva- and moisture stable. Although highly unsaturated, the conjugation tions such as alkynyl metallic reagents or 1-halo-alkynes), as of the carbon atoms provided extra stability. According to the shown in Scheme 2. Theoretically, pathways directly from alkynes authors’ experience, pure diynes could be prepared and stored un- are more easy-handling with better atom efficiency than other der normal conditions, and remain the same for years. This advan- methods, and hence much more widely used. In most cases, copper tage has made the diynes as one of the most easily handled organic was employed either as a catalyst or additive. Since Glaser had re- architectures. ported the earliest example, and followed modifications made by On the other side, the highly unsaturated carbon chains could Eglinton and Hay, this copper mediated oxidative coupling of ter- also exhibit fascinating reaction properties under special condi- minal alkynes is generally called Glaser–Eglinton–Hay coupling. tions. It is known that 1,3-diynes could undergo polymerization Besides this name reaction, other methods have offered an alterna- upon the irradiation of UV light. This reaction could lead to the tive possible synthetic route by replacing the alkynes with deriva- cross-linking between different carbon chains and has been widely tions of alkynes, and have shown certain advantages in some cases. used in material field.4 Moreover, diynes could be attacked by nucleophiles such as The oxidative Glaser–Eglinton–Hay coupling amines, alcohols, and sulfides. For example, diynes could react Symmetrical diynes are the earliest diynes prepared in labora- with water, primary amines, hydroxylamines, or hydrogen sulfide tories. The first report was published in 1869 by Carl Glaser.10 In to form 5-membered heterocycles like furans,5 pyrazoles,6 pyr- this Letter, phenylacetylene reacted with cuprous chloride to form roles,5b,7 isoxazoles,8 and thiophenes.5a,9 Diynes could be also a phenylacetylide, and this yellow insoluble solid could dimerize to oxidized to form complex structures, which were used as the form the 1,4-diphenylbuta-1,3-diyne in the presence of oxygen precursor of some organic dyes like indigo.10 smoothly (Scheme 3). The unusual structure, relative stability, and abundant potential Glaser coupling of terminal alkynes could achieve the diynes reactivity have together made the diynes as important building with moderate yields. This could be partially due to the instability blocks in organic synthesis and material science. More and more of the copper acetylide, the intermediate of the process. On the reports have emerged to discuss the synthesis and application of other hand, for those aromatic ethynyl compounds, good yields diynes recently. There have also been a few reviews on the nature were observed, while for a broader scope of aliphatic alkynes, the of occurrence of diynes, synthesis of acetylenic scaffolds, and reac- Glaser coupling failed to give satisfactory results. tivity of alkynes. However, few reviews concerning the synthetic The modification of Glaser coupling was then carried out. Addi- pathways as well as the applications of this magic structure were tives such as ammonium salts were introduced and in some cases published. As a witness of the rapid development of diyne chemis- improved the efficiency.11 In 1956, Eglinton and Galbraith found try in the recent decades, this review would summarize the syn- that stoichiometric or excess Cu(OAc)2 in methanolic pyridine thetic pathways of diynes, as well as their further derivations. could accelerate the dimerization of alkynes.12 Later, Hay had found that pyridine served also as ligand in this process. Using this 13 Synthesis of diynes method, Hay prepared the polymer containing the diyne group (Scheme 4). Diynes could be divided into two kinds: symmetrical or unsym- In 1962, Hay had found that some amines could be a better li- 14 metrical, according to the substituent groups linked to both sides gand for this process. TMEDA (N,N,N0,N0-tetramethylethylenedi- of the buta-1,3-diyne structure. While earlier reports focused on amine) was proved to be suitable in the dimerization of terminal the