Synthesis of 3H-naphtho[2.1-b]pyran-2-carboxamides from cyclocoupling of b-naphthol, propargyl alcohols and isocyanide in the presence of Lewis acids Tauqir A. Nizami, Ruimao Hua * Department of Chemistry, Tsinghua University, Key Laboratory of Organic Optoelectronics & Molecular Engineering of Ministry of Education, Beijing, 100084, China article info Article history: Received 6 April 2018 Received in revised form 19 May 2018 Accepted 22 May 2018 Available online xxx Keywords: b-naphthol Propargyl alcohols Isocyanide Annulations naphtho[2.1-b]pyran abstract 3H-Naphtho[2.1-b]pyran-2-carboxamides (3H-Benzo[f]chromene-2-carboxamides) can be synthesized from a three-component cyclocoupling reaction of b-naphthol, propargyl alcohols and isocyanide in the presence of ZnI 2 and FeCl 3 under air atmosphere. The reaction is proposed to involve the formation of aryl-zinc (II) s-bond and its a-addition to isocyanide. © 2018 Elsevier Ltd. All rights reserved. 1. Introduction 2H-Chromene and 3H-naphtho[2.1-b]pyran are important O- heterocyclic motifs, which are well found in both natural products and synthesized molecules possessing interesting biological and physiological properties (Scheme 1 , I and II). 1 In addition, it has been well-known that amide moiety is the key component in some bio- molecules and drugs. 2 3H-Naphtho[2.1-b]pyran-2-carboxamides (Scheme 1 , III), incorporating above-mentioned O-heterocyclic motifs and a, b-unsaturated amide group, are expected to be an ideal and interesting scaffold for the future studies in developing bioac- tive molecules. On the other hand, propargyl alcohols have been well used as the versatile synthons in the syntheses of various O-heterocycles via their cyclocondensation, 3 3,3-diaryl-3H-naphtho[2,1-b]pyran, 4 3,3-dimethyl-3H-naphtho[2,1-b]pyran 5 could be prepared from a p-TsOH- or ReCl(CO) 5 -catalyzed cyclocondensation of 1,1-diaryl-2- propyn-1-ol or 2-methyl-3-butyn-2-ol with b-naphthol, respec- tively (Scheme 2a). As a continuation of our interest in synthesis of heterocyclic compounds from annulations protocols of alkyne 6 and propargyl compounds, 5,7 as well as Zn(II) salts have been well- applied as the versatile catalysts in the synthesis of heterocyclic compounds, 8 we therefore report here a three-component cyclo- coupling reaction of b-naphthol, propargyl alcohols and cyclohexyl isocyanide in the presence of ZnI 2 and FeCl 3 affording 3H-naphtho [2.1-b]pyran-2-carboxamides (Scheme 2b). 2. Results and discussion When a mixture of b-naphthol (1a), 2-methyl-4-phenyl-3- butyn-2-ol (2a, 1.3 equiv), cyclohexylisocyanide (3a, 2.0 equiv), ZnCl 2 (0.1 equiv) and K 3 PO 4 (1.0 equiv) in toluene was stirred at 80  C for 7 h under air, the cyclocoupling product of 3H-naphtho[2.1-b] pyran-2-carboxamide derivative (4aa) was obtained in 23% isolated yield (Table 1 , entry 1), the use of Cs 2 CO 3 or CsF, instead of K 3 PO 4 resulted in an increase of yields (Table 1 , entries 2e3). In the case of ZnI 2 and CsF used, 4aa could be obtained in 50% yield (Table 1 , entry 4). A combined use of ZnI 2 and FeCl 3 as the catalyst system, 4aa formed in 67e79% yields (Table 1 , entries 5e7). Under the similar reaction conditions as indicated entry 7, the yield of 4aa was greatly decreased with the decease of reaction temperature (60  C, 55%), and the yield could not be improved with a higher reaction tem- perature (100  C). As shown in entries 8e11, the solvent effect is * Corresponding author. E-mail address: ruimao@mail.tsinghua.edu.cn (R. Hua). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet https://doi.org/10.1016/j.tet.2018.05.060 0040-4020/© 2018 Elsevier Ltd. All rights reserved. Tetrahedron xxx (2018) 1e5 Please cite this article in press as: Nizami TA, Hua R, Synthesis of 3H-naphtho[2.1-b]pyran-2-carboxamides from cyclocoupling of b-naphthol, propargyl alcohols and isocyanide in the presence of Lewis acids, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.05.060