Synthesis of Heterocyclic and Carbocyclic Fluoro-olefins by Ring-Closing Metathesis

Abstract

[reaction: see text] Ring-closing metathesis (RCM) of vinyl fluoride-containing dienes in the presence of ruthenium alkylidene carbene complex 11 proceeded efficiently to give six- and seven-membered cyclic vinyl fluorides. The RCM reaction was used to prepare amine- and sulfamide-linked cyclo-olefins, as well as carbocyclic systems, from a simple commercial fluoro-olefin.

A Ring‐Closing Metathesis Pathway to Fluorovinyl‐Containing Nitrogen Heterocyles

“…In fact, during the course of our work RCM of vinyl fluorides and trifluoromethylated olefins, [19] the Weinreb group published the first successful examples of vinyl chloride metathesis [20] and soon thereafter, the Brown group reported the first examples of vinyl fluoride ring-closing metathesis. [21] More recently, the Haufe group published examples of fluoroacrylate ringclosing metathesis. [22] These examples once more emphasize the versatility of the RCM technique, giving facile access to potentially useful cyclic vinyl fluoride-containing heterocycles.…”

“…The first vinyl fluoride-containing metathesis precursor 22 was obtained by standard protection of 2-amino-4-pentenoic acid (6, allylglycine) as the corresponding Boc-protected methyl ester (21), followed by alkylation with 1-chloro-2-fluoro-2-propene using NaH in DMF in 79 % overall yield (Scheme 4). Other specifically functionalized metathesis precursors were also synthesized ( Table 2).…”

Synthetic Methods for Fluorinated Olefins

“…[77] RCM reactions of the sulfonamide-tethered substrates 60 were catalyzed by the second-generation Grubbs catalyst to give the seven-membered products 61 containing (E)-fluoro-olefin moieties in excellent yields. As shown in Scheme 47, Haufe and co-workers found that the α-fluoroacrylamide 62 functions efficiently as a substrate for RCM.…”

An Improved Ring‐Closing Metathesis Approach to Fluorinated and Trifluoromethylated Nitrogen Heterocycles

“…[4] In developing such general methods, one strategy is application of proven ring-closure methodology to appropriate fluorine-containing precursor molecules. This is exemplified by work of the Brown group who successfully applied ring-closing metathesis (RCM) on vinyl fluoride-containing substrates to prepare fluorinated analogues of seven-membered heterocyclic HIV protease inhibitors, [5] and related work from the Haufe group. [6] At the same time, we were developing a similar RCM approach to prepare small libraries of fluorinated [7] and trifluoromethylated [8] nitrogen heterocycles, including the development of a route to a new trifluoromethyl-containing allylating reagent.…”