1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Organic & Supramolecular Chemistry Metal- and Solvent-Free Phosphine Mediated Synthesis of Multisubstituted Furans via Intramolecular Annulation of 1, 4-Enediones Venkatachalam Rajeshkumar,* Chinnaraj Neelamegam, Lisa John, and Sambandam Anandan [a] This paper describes the synthesis of multisubstituted furans through tricyclohexylphophine mediated intramolecular annu- lation of 1, 4-enediones under solvent-free greener reaction conditions. The reaction proceeds via nucleophilic attack of P (Cy) 3 on the β-carbon of 1, 4-enediones to form oxaphosphe- tanes with new C–O bond formation which further eliminates O =P(Cy) 3 to afford furans. The present methodology is compatible with a wide range of substrates and enabled the synthesis of a broad range of biologically significant furan derivatives in good to excellent yields (55–93%). Introduction Furans are one of the most significant five-membered hetero- cyclic motifs and widely occurring in many of the natural products and pharmaceuticals. [1] Furan containing compounds display diverse biological properties such as anticancer, anti- bacterial, antimicrobial, antibiotic, and antihypertensive (Fig- ure 1). [1,2] On the other hand, furans show potential applications in material sciences such as dye-sensitized solar cell and polymer materials. [3] In addition, furans are versatile building blocks for the construction of many of the significant drugs [4] and polyaromatic hydrocarbons [5] by Diels-Alder reaction with different dienophiles. Traditionally, furans were synthesized from 1, 4-diketones by Paal-Knorr [6] method under acidic conditions and by Feist- Benary synthesis [7] through the reaction of α-halogen ketones and 1, 3-dicarbonyl compounds. However, these reactions are carried out under harsh reaction conditions and limited substrate tolerance due to acidic reaction conditions. Recent literature has displayed the synthesis of multi-substituted furans by Co-catalyzed radical cyclization of alkynes with α- diazocarbonyls. [8] In this context, Glorius’s research group reported the synthesis of arylated furans by Rh-catalyzed arylation and cycloisomerization of cyclopropenes. [9] On the other hand, Clark’s group has demonstrated the phosphine- mediated synthesis of 2-acyl furans from ynenones under the oxygen atmosphere. [10] Literature reveals that furans can be obtained from 1,4-enediones by reduction with HCOOH and Pd/C followed by cyclization under acidic medium. [11] Although several methods have been developed for the synthesis of multisubsituted furans, there is still strong demand and continuous research focusing on the development of greener approaches under transition metal- and solvent-free reaction conditions. [12] From this point of view, the development of solvent-free and an efficient straightforward synthetic route from simple and inexpensive reagents is highly desirable. Here, we report the phosphine mediated synthesis of highly substituted furans from 1, 4-enediones under solvent-free environmental friendly reaction conditions (Scheme 1). Results and Discussion We initiated our optimization studies to examine the nature of the present protocol for the synthesis of furan by using simple 1, 4-enedione (1a) as the model substrate and the results are summarized in Table 1. Initially, we treated the substrate 1a with triphenylphosphine (PPh 3 ) in 1, 2-dichlorobenzene as a [a] Dr. V. Rajeshkumar, C. Neelamegam, L. John, Prof. S. Anandan Department of Chemistry, National Institute of Technology Tiruchirappalli, Tamil Nadu-620015, India E-mail: vrajesh@nitt.edu orgrajeshkumar@gmail.com Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201802728 Figure 1. Structures of selected furan-based natural products and pharma- ceuticals. Full Papers DOI: 10.1002/slct.201802728 11606 ChemistrySelect 2018, 3,11606–11609 © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim