Letter pubs.acs.org/OrgLett
Synthesis of Quinoline Derivatives via Cu-Catalyzed Cascade Annulation of Heterocumulenes, Alkynes, and Diaryliodonium Salts Yue Chi,†,§ Haihan Yan,†,§ Wen-Xiong Zhang,*,†,‡ and Zhenfeng Xi† †
Beijing National Laboratory for Molecular Sciences, and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China ‡ State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China S Supporting Information *
ABSTRACT: CuOTf-catalyzed substituent-controlled cascade [2 + 2 + 2] and [4 + 2] annulation reactions among heterocumulenes, alkynes, and diaryliodonium salts were achieved. Various quinoline derivatives could be obtained in good yields with excellent selectivity. This methodology provided a novel pathway to activate heterocumulenes via a unique highly reactive cationic intermediate. The reaction process was well elucidated by density functional theory calculations.
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carbodiimide.6 Very recently, we reported a Cu-catalyzed reaction between carbodiimides and diaryliodonium salts to synthesize 2-aminopyrimidines.7 Herein, we report a CuOTfcatalyzed three-component [2 + 2 + 2] annulation reaction of carbodiimides, internal alkynes, and diaryliodonium salts8 to construct efficiently iminoquinolines (Scheme 1c). In this process, the activation strategy of carbodiimides by diaryliodonium salts plays a vital role. Interestingly, such strategy can be applied in [2 + 2 + 2] or [4 + 2] annulation reaction of isothiocynates, alkynes, and diaryliodonium salts to synthesize various quinolines or thiacyclic compounds. This present method provides a regioselective, convenient, and direct way via use of simple and commercial available reagents to construct quinoline derivatives, which are widely used as drug molecules and fluorescence materials (Figure 1).9,10 Diphenyliodonium salts (X = PF6−, Cl−, or OTf−) 1, N,N′diisopropylcarbodiimide (iPrNCNiPr, DIC) 2a, and diphenylacetylene 3a were chosen as a model reaction. As a control experiment, no product could be obtained without
ransition-metal-catalyzed cascade annulation of alkynes is an interesting and attractive subject in the construction of important cyclic compounds.1 Carbodiimides (RNCNR) have ranked as one of the most important classes of nitrogen sources to construct N-containing compounds in synthetic organic chemistry.2 However, cascade annulation between alkynes and carbodiimides is still limited.3−5 Hou and other groups developed the intermolecular catalytic addition of terminal alkynes to carbodiimides yielding amidines, in which there was no annulation cyclic compound (Scheme 1a).4 Although the intramolecular annulation between carbodiimides and internal alkynes, e.g., Pauson−Khand-type reactions, has been reported (Scheme 1b),5 this methodology could not be applied in an intermolecular manner. Thus, a new strategy to effect the intermolecular annulation between carbodiimides and alkynes is required. We are interested in the reactivity of Scheme 1. Reactions between Carbodiimides and Alkynes
Figure 1. Representative examples of quinoline derivatives. Received: April 5, 2017 Published: May 8, 2017 © 2017 American Chemical Society
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DOI: 10.1021/acs.orglett.7b01025 Org. Lett. 2017, 19, 2694−2697
Letter
Organic Letters catalyst (Table 1, entry 1). When this reaction was carried out in DCE at 120 °C with Cu(OTf)2 as the catalyst (Table 1,
Scheme 2. Synthesis of Quinoline Derivatives 4a−m
Table 1. Optimization of Reaction Conditions
entry
solvent
X−
catalyst
temp (°C)
yielda (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15c
DCE DCE C6H6 toluene THF DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE
PF6− PF6− PF6− PF6− PF6− Cl− OTf− PF6− PF6− PF6− PF6− PF6− PF6− PF6− PF6−
none Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 Cu(OTf)2 CuSO4 Cu(OAc)2 CuCl2 CuCl Cul CuOTf•1/2 C6H6 CuOTf·1/2 C6H6 CuOTf·1/2 C6H6
120 120 120 120 120 120 120 120 120 120 120 120 120 60 120
0 73 (66b)
