Various Entries to Vinyl Chloride Derivatives and their Applications in Total Synthesis of Natural Products

Abstract

Our program of total synthesis of natural products stimulated our imagination and led us to design various methodologies to build the vinyl chloride function of our targets. The access to vinyl chlorides also offers an entry to the trisubstituted alkenes of pure configuration. Thanks to these methodologies we achieved the synthesis of complex structures such as (+)-oocydin A, a total synthesis that also led us to discover other useful new transformations.

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.…”

“…[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. 28 In contrast, the synthesis of allylic halides starting from allylic olens is widely reported.…”

“…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…”

“…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…”

Advancements in Enacyloxins Total Synthesis: Access to the Chlorinated Polyunsaturated Chain Peculiar to this Promising Family of Antibiotics

“…Kiyota et al utilized a similar hydroalumination-NCS trapping sequence to obtain a chlorinated fragment of enacyloxin, but further elaborations failed . Note that potassium ( Z )-2-chloroalk-1-enyl trifluoroborates cross-coupling gave access to chlorinated dienes of controlled configuration, as well as the Suzuki coupling of 1,1-dichloroalkenes we devised and used to achieve the total synthesis of oocydin A. − However, the elegant implementation of the Tsuji’s alkyne chloroallylation that Hoye et al used to close the oocydin A macrocycle let us glimpse interesting options to escape traditional HWE strategy. Giving Z -configured vinyl chlorides with high regio- and stereoselectivity, this chloroallylation method appeared particularly well suited, the introduced allyl providing a handy anchor point to elongate the polyenic chain.…”