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Synthesis of alpha,beta-Unsaturated N-Sulfonyl Imides through Zinc-Catalyzed Intermolecular Oxidation of N-Sulfonyl Ynamides Fei Pan, Chao Shu, Yi-Fan Ping, Yi-Fei Pan, Peng-Peng Ruan, Qian-Ran Fei, and Long-Wu Ye J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01608 • Publication Date (Web): 30 Sep 2015 Downloaded from http://pubs.acs.org on October 1, 2015
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The Journal of Organic Chemistry
Synthesis of α,β-Unsaturated N-Sulfonyl Imides through Zinc-Catalyzed Intermolecular Oxidation of N-Sulfonyl Ynamides Fei Pan,† Chao Shu,† Yi-Fan Ping,† Yi-Fei Pan,† Peng-Peng Ruan,† Qian-Ran Fei,† and Long-Wu Ye*,†,‡ †
State Key Laboratory of Physical Chemistry of Solid Surfaces & The Key Laboratory for Chemical
Biology of Fujian Province, Department of Chemistry, Xiamen University, Xiamen 361005, P. R. China ‡
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences Shanghai 200032, P. R. China
[email protected] RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the journal that you are submitting your paper to)
R3 R1
R2 N PG
Zn(OTf)2 (10 mol %) N-oxide (2.0 equiv) dry PhCl, 80 oC, 1 h
O
R3
R1
N R2 PG 15 examples 58-84% yield
oxidative non-noble metal catalysis
wide substrate scope
valuable products
readily available starting materials
mild reaction conditions
simple procedure
ABSTRACT: A novel zinc-catalyzed intermolecular oxidation of N-sulfonyl ynamides has been developed. A variety of functionalized α,β-unsaturated N-sulfonyl imides are readily accessed by
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utilizing this approach, thus providing a viable alternative to synthetically useful α,β-unsaturated imides. Importantly, the reaction is proposed to proceed by a vinyligous E2-type elimination pathway, but not metal carbene pathway.
Introduction α,β-Unsaturated amides represent an important type of organic compounds because of their frequent occurrence in many bioactive natural products as well as pharmaceuticals.1 In addition, they can also serve as valuable building blocks used in a wide range of organic reactions2 and in the synthesis of polymeric materials.3 However, compared to the synthesis of α,β-unsaturated esters and amides, access to α,β-unsaturated N-sulfonyl imides remains scarce.4 Therefore, the development of novel and general methods for their efficient and practical synthesis of is highly desirable. In recent years, particular attention has been paid to the gold-catalyzed intermolecular alkyne oxidation by N-oxides.5-6 This approach has enabled an easy access to α,β-unsaturated carbonyl compounds using readily available and safer alkynes to replace hazardous α–diazo ketones as precursors in the realm of carbene chemistry.7 For example, Zhang and co-workers reported a gold-catalyzed intermolecular alkyne oxidation, involving a gold carbene as the most likely intermediate, for the highly regioselective synthesis of -unsaturated carbonyls, (Scheme 1a).8 Simultaneouly, Davies and coworkers also described a general route for the synthesis of -unsaturated imides by a gold-catalyzed intermolecular oxidation of ynamides, where a 1,2-C-H insertion into the gold carbenoid intermediate was proposed (Scheme 1b).9 In our recent study on the ynamide chemistry,10-11 we developed the first non-noble metal-catalyzed alkyne oxidation, leading to the highly site-selective synthesis of versatile isoquinolones and β-carbolines.11a With this in mind, we envisioned that the synthesis of unsaturated imides might be achieved by a non-noble metal-catalyzed ynamide oxidation (Scheme 1c).12 In this context, we wish to report a zinc-catalyzed intermolecular oxidation of N-sulfonyl ynamides providing ready access to various -unsaturated N-sulfonyl imides in moderate to good yields.
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The Journal of Organic Chemistry
Importantly, mechanistic studies reveal that the reaction is proposed to occur by a vinyligous E2-type elimination pathway, which is substantially different from the related gold-catalyzed alkyne oxidation. Scheme 1. Synthesis of α,β-Unsaturated Imides by Intermolecular Oxidation of Ynamides a) Zhang et al. (ref. 8) R1
R4
[Au]
R2
R3
N-oxide
O R1
R4 R3
b) Davies et al. (ref. 9) PG N R1
R4 R3
O
R2
[Au]
O PG
N-oxide
[Au] plausible intermidiate
R2 R3
N R1
c) Present Work PG N R1
R4 R3
Zn(OTf)2
O PG
N-oxide
N R1
R2 R3
Results and Discussion At the outset, N-sulfonyl ynamide 1a was chosen as the model substrate and some of the results are outlined in Table 1. To our delight, the initial catalyst investigation showed that most Lewis acid catalysts displayed good reactivity to furnish the desired α,β-unsaturated N-sulfonyl imide 2a (Table 1, entries 1-6), and Zn(OTf)2 was found to be the best one (Table 1, entry 6). These results suggest that the metal carbene pathway is less likely in such an oxidative catalysis. Notably, proton acids such as MsOH and HOTf were not effective in promoting this reaction (Table 1, entries 7-8).13 A subsequent N-oxide screening revealed that 8-ethylquinoline N-oxide 3a gave the best result, and E:Z selectivity slightly varied with different N-oxides (Table 1, entry 9-13). In addition, it was found that the screening of the amount of the N-oxide (Table 1, entries 14-15) and other solvents such as DCE and toluene (Table 1, entries 16-17) could not further improve the reaction. Table 1. Optimization of Reaction Conditionsa
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entry
catalyst
oxidant (3/4)
E/Zb
yield (%)c
1
In(OTf)3
3a (R = Et)
2.5/1
72
2
Sm(OTf)3
3a (R = Et)
2.5/1
64
3
Sc(OTf)3
3a (R = Et)
2.3/1
66
4
Y(OTf)3
3a (R = Et)
2.5/1
62
5
Yb(OTf)3
3a (R = Et)
2.1/1
69
6
Zn(OTf)2
3a (R = Et)
2.6/1
80
7
MsOH
3a (R = Et)
-
