Stereoselective Synthesis of 4-Substituted 2,4-Dichloro-2-butenals by α- and γ-Regioselective Double Chlorination of Dienamine Catalysis

Abstract

The l-proline-catalyzed reaction of enolizable α,β-unsaturated aldehydes with N-chlorosuccinimide (NCS) gave the corresponding 4-substituted 2,4-dichloro-2-butenals with moderate yields and excellent diastereoselectivities (Z/E = >20/1) through consecutive double chlorination at the α- and γ-positions of the dienamine intermediate. The corresponding 2,4-dichloro-2-butenals contain a multireactive 1,3-dichloro allylic unit useful for the construction of Z-vinyl chlorides; the chloride on the allylic position was replaced with mild nucleophiles such as MeOH and EtOH via an SN2 substitution reaction, and its aldehyde moiety was used as a synthetic handle and transformed into an alcohol or a vinyl group. All products obtained after those synthetic manipulations maintained excellent diastereoselectivities (Z/E = >20/1).

Selective catalytic synthesis of new terpenic chlorides using NaDCC as an eco-friendly and highly stable FAC agent

“…Due to the high interest of vinyl chlorides in organic synthesis and biological activities, 19–21 the selective catalytic formation of vinylic chloride represents a good pathway for their direct one-step synthesis. The use of 2.5 eq.…”

“…of FeCl 2 , towards dichloride (u) as major product in good agreement with our previous study. 29 Due to the high interest of vinyl chlorides in organic synthesis and biological activities, [19][20][21] the selective catalytic Fig. 6 Reaction kinetics of the selective catalytic chlorination of carvone a using 0.5 and 2.5 eq.…”

“…[12][13][14][15][16] On the other hand, the vinylic chlorides are versatile chemicals that serve as valuable intermediates for the synthesis of natural product derivatives, vinyl polymers, adhesives, pharmaceuticals and agrochemical compounds. [17][18][19][20][21] The presence of vinylic chloride in a backbone structure enhances the reactivity of the adjacent carbon-carbon double bond, enabling diverse chemical modications such as oxidative or coupling reactions. 19,[22][23][24][25] Unlike their versatile importance in organic synthesis, few studies were devoted to vinylic halides preparation such as Barton synthesis from ketone-derived hydrazones, 26 from ketones via vinyl phosphate intermediates, 27 radical reaction of trichloromethylated substrates 18 or via stereospecic isomerization of allylic halides.…”

“…12–16 On the other hand, the vinylic chlorides are versatile chemicals that serve as valuable intermediates for the synthesis of natural product derivatives, vinyl polymers, adhesives, pharmaceuticals and agrochemical compounds. 17–21 The presence of vinylic chloride in a backbone structure enhances the reactivity of the adjacent carbon–carbon double bond, enabling diverse chemical modifications such as oxidative or coupling reactions. 19,22–25…”