Note pubs.acs.org/joc
Cite This: J. Org. Chem. 2017, 82, 11829-11835
Rhodium(III)-Catalyzed C−H Alkynylation of Ferrocenes with Hypervalent Iodine Reagents Shao-Bo Wang,‡ Qing Gu,† and Shu-Li You*,†,‡ †
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 LinglingLu, Shanghai 200032, China ‡ School of Physical Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China S Supporting Information *
ABSTRACT: Rapid access to mono- or dialkynylation of ferrocene with ethynylbenziodoxolones as the alkynylation reagents was achieved via rhodium-catalyzed direct C−H bond functionalization at room temperature. Mono- and dialkynylation were easily modulated by varying the sterical volume of the directing group, such as pyridine and isoquinoline, and amount of hypervalent iodine reagents. A wide range of ferrocene-based alkynylation products could be obtained in up to 94% yield, and a gram-scale reaction also proceeded smoothly with high efficiency.
A
H bond functionalization is highly desirable. To our knowledge, the recent development of direct C−H functionalization of ferrocenes12 mainly focused on alkylation,13 alkenylation,13b,14 arylation,15 and others.16 Herein, we report rhodium-catalyzed C−H bond mono/dialkynylation of ferrocene derivatives with EBXs. We initially chose 2-ferrocenylpyridine (1a) and TIPS-EBX (2a) as the model substrates to optimize the reaction conditions. As shown in Table 1, in the presence of 2.5 mol % of [RhCp*Cl2]2 and 0.1 equiv of Zn(OTf)2 as the activator for both catalyst and EBX reagents,3f,7a the reaction of 1a (0.1 mmol) with 2a (1.1 equiv) in DCE at room temperature afforded the monoalkynyl product (3aa) and dialkynyl product (4aa) in 21 and 20% yield, respectively (Table 1, entry 1). When the reaction was performed with 0.2 equiv of Zn(OTf)2 at 40 or 60 °C, there was no positive influence on the yield of 3aa; however, the yield of 4aa was slightly improved (Table 1, entries 2 and 3). After screening the solvents at room temperature, MeOH was found to be the best choice to give 4aa in 40% yield with only 9% yield of 3aa (Table 1, entries 4− 7). When the amount of 2a was increased to 2.3 equiv, the yield of 4aa was further improved to 64% with 5% yield of 3aa (Table 1, entry 8). To our delight, by switching the additive Zn(OTf)2 (0.2 equiv) to AgSbF6 (0.2 equiv), the yield of 4aa was increased to 86% probably because AgSbF6 was a more efficient and irreversible chloride absorption reagent (Table 1, entry 9).3f,7a When the reaction was performed in 0.2 mmol scale, the yield of 4aa was further improved to 92% (Table 1, entry 10). Thus, the optimal reaction conditions were obtained
lkynes are extensively used building blocks in synthetic chemistry and materials science.1 It is therefore particularly attractive for chemists to develop efficient approaches to install an alkynyl functional group at the specific position of molecules. For this goal to be achieved, both nucleophilic and electrophilic alkynylation reagents have been developed.1d Compared to the well-explored nucleophilic alkynylation reactions, recently, electrophilic alkynylation reactions have attracted the interest of synthetic chemists. Of particular note, significant progress has been made by employing transitionmetal-catalyzed C−H bond direct functionalization.2 Ethynylbenziodoxolone (EBX),3 readily synthesized on a large scale, is an air-stable, versatile, and powerful alkynylation reagent. Pioneering studies on alkynylation of electron-rich aromatic substrates such as indole, pyrrole, furan, thiophene, and aniline derivatives with EBXs were achieved by Waser and co-workers using either Au or Pd catalysts.3f,4 Recently, cobalt(III)catalyzed C−H alkynylation of indoles was accomplished by Shi and co-workers.5 Notably, more elegant examples on orthoC−H alkynylation of electron-poor arenes by using a transition metal catalyst based on a directing-group strategy were reported independently by Loh,6 Li,7 Glorius,8 and other groups.9 Ferrocenyl alkynes and their derivatives have been intensively studied in the area of advanced materials and functional molecules because of their unique electronic and structural properties.10 To date, the introduction of an alkynyl group on the ferrocene backbone was mainly achieved by employing a Pd-catalyzed cross-coupling reaction of ferrocenyl halides with terminal alkynes, such as the Sonogashira coupling reaction, and the addition of ferrocenyl lithium to arylsulfonylacetylenes.11 However, for those methods, prefunctionalization of ferrocenes and multistep synthesis are generally required. Therefore, the direct alkynylation of ferrocene by means of C− © 2017 American Chemical Society
Special Issue: Hypervalent Iodine Reagents Received: April 4, 2017 Published: May 3, 2017 11829
DOI: 10.1021/acs.joc.7b00775 J. Org. Chem. 2017, 82, 11829−11835
Note
The Journal of Organic Chemistry Table 1. Optimization of Reaction Conditionsa
entry
temp. (°C)
2a (× equiv)
solvent (0.1 M)
additive (× equiv)
3aa (%)b
4aa (%)b
1 2 3 4 5 6 7 8 9d 10e
rt 40 60 rt rt rt rt rt rt rt
1.1 1.1 1.1 1.1 1.1 1.1 1.1 2.3 2.3 2.3
DCE DCE DCE dioxane THF MeOH HFIP MeOH MeOH MeOH
Zn(OTf)2 (0.1) Zn(OTf)2 (0.2) Zn(OTf)2 (0.2) Zn(OTf)2 (0.2) Zn(OTf)2 (0.2) Zn(OTf)2 (0.2) Zn(OTf)2 (0.2) Zn(OTf)2 (0.2) AgSbF6 (0.2) AgSbF6 (0.2)
21 17 17 12 17 9 21 5
