Stereoselective One‐Pot Sequential Dehydrochlorination/trans‐Hydrofluorination Reaction of β‐Chloro‐α,β‐unsaturated Aldehydes or Ketones: Facile Access to (Z)‐β‐Fluoro‐β‐arylenals/β‐Fluoro‐β‐arylenones

Abstract

Them onofluoroalkenes ubstructure shows ah igh potentiala saf luorinated synthon in organic synthesis. However, control of the Z/E stereoselectivity of multi-substituted monofluoroalkenep roducts in one-pot reactions still remains ac hallenge. An unprecedented one-pot approach for the highly regio-ands tereoselective preparation of functionalized (Z)-b-monofluoro tri-substituted alkenes from readily available b-chloro-a,b-unsaturated aldehydes or ketones has been explored. Mechanistic studies demonstrated that the reactioni si nitiated by dehy-drochlorination of the substrates to give alkynyl aldehydes/ketones,f ollowed by their trans-hydrofluorination. It is worth mentioning that af luorinating reagent with suitable basicity andn ucleophilicity plays ak ey role in promoting the formationo f( Z)-bfluoro-b-aryl tri-substituted monofluoroalkenes.

Synthesis of β-Fluoro-α,β-Unsaturated Amides from the Fragmentation of Morpholine 3,3,3-Trifluoropropanamide by Grignard Reagents

“…The characteristic J HF(trans) is 34.2 Hz, and all characterization data for (Z)-14 matched the reported values. 14 These data suggest that the transformation of the morpholine amide to a ketone occurs with inversion of the stereochemistry of the fluoroalkene. These results broaden the potential utility of reagent 1 in the stereoselective synthesis of fluoroalkenes and are currently under investigation.…”

“…The ketone (14) was isolated exclusively as the (Z)fluoroalkene; TMEDA improved the selectivity and yields. The characteristic J HF(trans) is 34.2 Hz, and all characterization data for (Z)-14 matched the reported values.…”

“…Currently, there are general methods to synthesize α-fluoro-α,β-unsaturated carbonyl compounds, , such as the Julia olefination, the Peterson olefination, the Horner–Wadsworth–Emmons reaction, and a Reformatsky addition/elimination process . Unfortunately, fewer methods exist for the preparation of β-fluoro-α,β-unsaturated carbonyl compounds, and most are limited by low yields and poor stereoselectivities. − Notable recent exceptions are the hydrofluorination of alkynes using gold catalysts that provide access to ( Z )-β-fluoro-α,β-unsaturated carbonyl compounds and the chromium-mediated reductive coupling of CBrF 2 -containing compounds with aldehydes to give ( E )-β-fluoro-α,β-unsaturated amides (Scheme ). The two shortcomings of the latter transformation are the stoichiometric amounts of chromium and the need of CBrF 2 -containing compounds, which are difficult to access.…”

One-Pot Synthesis of (Z)-β-Halovinyl Ketones via the Cascade of Sonogashira Coupling and Hydrohalogenation

“…The methods to form β-halovinyl ketones from ynones generally involve regioselective hydrohalogenation of electron-deficient carbon-carbon triple bond. In these cases, a variety of halogen sources have been employed, including HCl, SnCl 4 , AlBr 3 , TMSCl, and LiBr (Scheme 1A) (Kundu and Chaudhuri, 1991;Shchukin and Vasilyev, 2008;Yang et al, 2011;Semenova et al, 2013;Yan et al, 2015;Zeng et al, 2017;Zhang et al, 2017). However, those methods suffer from relatively low stereoselectivity, which limits their synthetic applications.…”

Synthesis of Polysubstituted 2H‐Pyran‐2‐ones or Phenols via One‐Pot Reaction of (E)‐β‐Chlorovinyl Ketones and Electron‐Withdrawing Group Substituted Acetates or β‐Diketones

“…The nucleophilic mode of β ‐chlorovinyl ketones has been investigated in the aldol reaction,[13b] halogenation,[13c] and sulfenylation,[13d] whereas the exploration of electrophilic mode was limited in using ketimine ester,[13e] methyl cyanoacetate,[13f] and imino ester as nucleophiles,[13g] which led to the formation of 3‐methylenepyrrolidines (Scheme a), 6‐cyano‐2 H ‐pyran‐2‐ones (Scheme b), and 2‐imino‐pyranones (Scheme c), respectively. To further scrutinize the electrophilic character of β ‐chlorovinyl ketones, inspired by our previous report on an in situ generated electrophilic allenone intermediate from β ‐chlorovinyl ketone for furan synthesis, we envisioned that base‐promoted tandem reaction of β ‐chlorovinyl ketone with active methylene compounds. Herein, we report that the diverse electrophilic pathways of ( E )‐ β ‐chlorovinyl ketones could be achieved by using various electron‐withdrawing group substituted acetates and β ‐diketones as nucelophilic species.…”