Abstract
Herein, we report an efficient method for the synthesis of (Z)-β-halovinyl ketones through a one-pot Sonogashira coupling and hydrohalogenation reaction promoted by palladium-copper catalyst and Brønsted acid. The ynone intermediates are generated in situ from readily available acid chlorides and terminal alkynes at room temperature, which are directly converted to (Z)-β-halovinyl ketones by treating with triflic acid. This method avoids the use of an external halogen source and features broad substrate scope, high yield, and good to excellent stereoselectivity.
Highlights
The palladium and copper-catalyzed cross-coupling reaction of terminal alkynes with aryl or vinyl halides, known as Sonogashira reaction, has emerged as a powerful method for the synthesis of substituted alkynes in recent decades (Sonogashira et al, 1975; Sonogashira, 2002)
We commenced our study with the synthesis of β-chlorovinyl ketone 3a through a cross-coupling reaction of phenylacetylene 1 with benzoyl chloride 2 under the catalysis of PdCl2(PPh3)3 and CuI followed by Brønsted acid treatment (Table 1)
After systematic optimization of the reaction conditions, we found that the best reaction conditions: 1.0 equivalent of phenylacetylene reacts with 1.3 equivalent of benzoyl chloride in the presence of 2 mol% of PdCl2(PPh3)2, 4 mol% of CuI, and 1.2 equivalent of triethylamine in 1,2-dichloroethane (0.4 M) at room temperature for 10 min, treat the reaction mixture with 1.5 equivalent of triflic acid for 4 h at room temperature. The stereoselectivity for this transformation is up to 91/9 (Z/E) and (Z)-β-chlorovinyl ketone 3a was obtained in 87% yield (Table 1, entry 14)
Summary
The palladium and copper-catalyzed cross-coupling reaction of terminal alkynes with aryl or vinyl halides, known as Sonogashira reaction, has emerged as a powerful method for the synthesis of substituted alkynes in recent decades (Sonogashira et al, 1975; Sonogashira, 2002). One of the common ways to prepare the precursor ynones is the Sonogashira cross-coupling reaction as mentioned above (Kokubo et al, 1996; Hua et al, 2005; Kashiwabara et al, 2005, 2008; Iwai et al, 2009, 2012; Kashiwabara and Tanaka, 2011) This hydrohalogenation strategy for β-halovinyl ketone synthesis requires a multi-step synthetic procedure (Scheme 1A). This method shows good stereoselectivity, high yield, and broad substrate scope
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