A New Synthetic Approach to α-Chlorocinnamaldehydes

Abstract

A new simple and efficient transformation of aromatic aldehydes into a-chlorocinnamaldehydes is described. Catalytic olefination reaction of hydrazones of aromatic aldehydes with 2-trichloromethyl-1,3-dioxolane gives ethylene acetals of target alkenes in moderate to good yields. The reaction proceeds stereoselectively to form preferably Z-isomers.Olefination of carbonyl compounds, the R 1 R 2 C=O → R 1 R 2 C=CXY transformation, is one of the most successful synthetic routes to a variety of substituted alkenes. 1 In addition, many natural products possess various trisubstituted alkene moieties, and highly stereoselective construction of trisubstituted alkenes is one of the most challenging problems in synthetic organic chemistry. 2 Although many efficient and selective synthetic methods for the preparation of this important structural fragment have been devised for decades, there is still the need for a general and stereoselective method for an efficient synthesis of trisubstituted alkenes.Recently, we elaborated a novel approach to alkene synthesis, called catalytic olefination reaction (COR) of aldehydes and ketones. 3 It was found that N-unsubstituted hydrazones of carbonyl compounds could be smoothly converted to various substituted alkenes by treatment with polyhalogenoalkanes in the presence of catalytic amounts of CuCl. Based on COR we elaborated novel methods of synthesis of dichloroalkenes, dibromoalkenes, vinyl bromides, vinyl iodides, fluorine-containing alkenes, 1-chlorocinnamonitriles and 1-chlorocinnamates from aromatic and heteroaromatic carbonyl precursors. A possible mechanism of olefination was discussed and a catalytic cycle of COR was reported earlier. 4 This article is devoted to the synthesis of a-chlorocinnamaldehydes using catalytic olefination. a-Chlorocinnamaldehydes can be used as valuable building blocks for the synthesis of various heterocyclic systems. 5 Previously such compounds have been prepared using the Wittig approach, 6 HCl elimination from 2,3-dichloro-3-arylpropionaldehydes, 7 addition of 1-chloro-2,2-difluorovinyllithium to benzaldehyde, 8 chlorination of corresponding cinnamaldehydes 9 and thermal elimination of sulfinyl group from a-halo-a-sulfinylaldehydes. 10 We tried to use chloral as a polyhalogenated synthon in COR to prepare the corresponding a-chlorocinnamaldehydes. The hydrazone of 4-chlorobenzaldehyde was chosen as a model substrate. We have found that chloral could not be used as a reagent in COR because no formation of a-chlorocinnamaldehyde takes place. In the presence of chloral, the hydrazone is converted into corresponding sym-azine (according to GC/MS of reaction mixture). To modify the polyhalogenated synthon, we protected the chloral carbonyl group by transformation of chloral into 2-trichloromethyl-1,3-dioxolane. We started our investigation from optimization of reaction conditions because nature of solvent, base and amount of catalyst used in COR can influence the yield of product dramatically. Variation of bases (ammonia, ethylenediamine, triethylam...

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“…26, 27 Subsequent coupling of 14a with 4-hydroxyphenylboronic acid under Suzuki conditions proceeded smoothly to provide the desired product 12a in good yield (67%) (Scheme 2). …”

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