No abstract

Palladium catalyzed cross-coupling reactions of (2E,4E)-5-bromo-2,4-pentadienal 1 with organozinc reagents gives an easy access to the corresponding (2E,4E)-2,4-dienals. The improved preparation of all trans 1 by isomerization of its (2E,4Z) isomer is reported.In the course of our studies about convergent synthesis of polyenic compounds, 1 we recently reported the preparation 2 of (2E,4E)-5-bromo-2,5-pentadienal 1. We 2 and others 3 have taken advantage of the carbonyl group's potential through Wittig, Grignard or oxidation reactions. In this paper, we report the use of 1 as a brominated vinylic entity in palladium catalyzed cross-coupling 4 without any protection of the aldehydic function 5 (Scheme 1). Their high efficiency in such processes, their easy access and low reactivity with aldehydes, 6 led us to select the mild organozinc reagents for this purpose. Scheme 1Aldehyde 1 was treated in standard conditions 7 with various organozinc species 2a-h, easily prepared in situ from corresponding bromomagnesium-(2a,c and f) or lithium-reagents (2b,d,e,g and h) and zinc bromide, in the presence of catalytic amounts of tetrakis(triphenylphoshine)palladium in THF. Results are reported in the table.In all cases, rapid reactions occurred (TLC analysis) at room temperature with alkyl, aryl, vinyl or alkynyl zinc reagents and corresponding (2E,4E) dienals 3a-h were isolated as single isomers. We never observed any addition of the organometallic species on the carbonyl group. Yields were generally good after flash chromatography purification.Dienals 2a-f were already described. 8,9 However, recent literature in this area shows that there is still a need for pratical synthetic methods. 1,8,9 Acetylenic aldehydes 3g and 3h are new. 10,11 They are potential precursors of 2,4,6-trienals by simple selective reduction of the triple bond. Moreover, the synthesis of alkyne 3h, bearing the labile trimethylsilyl group, 12 shows that functionalized dienic aldehydes are in the reach of this methodology.It is noteworthy that our strategy allows preparation of various (2E,4E) dienals in only one step from all trans aldehyde 1. Access to large amounts of this starting material remained a drawback to this method. Actually, its preparation by bromination of glutaconaldehyde potassium salt 4 (Scheme 2) afforded a mixture of 1 and its (2E,4Z) isomer 5 which were separated by flash chromatography or crystallization. 2 Therefore, a stereoselective route to all trans 1 as a single isomer constituted a synthetic challenge. Advantage has been taken of the two following points: i) each pure isomeric form 1 or 5 could be converted into the thermodynamic 50/50 mixture of isomers, by standing at room temperature in hydrated chloroform; ii) the (2E,4E) isomer 1 preferentially crystallizes in diethyl ether. 2 Scheme 2So, to the oily mixture of isomers 1 and 5 (ca. 70/30) dissolved in diethyl ether was added a catalytic amount of p-toluenesulfonic acid. Slow vacuum removing of the solvent at room temperature afforded a solid product. 200 MHz 1 H NMR...