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

Abstract

The synthesis of highly functionalized fluorinated piperidines is described. The key step in this synthesis is a ring‐closing metathesis reaction involving fluoride‐substituted olefins, which leads to the corresponding cyclic vinyl fluorides. Several sequences to arrive at differently substituted piperidines have been evaluated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Nitrogen-Containing Organofluorine Compounds through Metathesis Reactions

“…Similar results were obtained by Rutjes et al (Le. 59 -> 60), but the synthesis of a five-membered trifluoromethylated lactam was unsuccessful (39)(40) Figure 11. Synthesis of fluorinated lactams.…”

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

“…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. [9] Inspired by these successful approaches, we aimed to extend this methodology to a complementary pathway, which is retrosynthetically outlined in Scheme 1.…”

Preparation of Sugar β‐Amino Acid Derivatives with Cyclic Structures by Ring‐Closing Metathesis

“…[2a,4] Because of the growing interest in fluorinated organic compounds due to their specific biological interest, [5] monofluorinated cyclic α-amino esters have been prepared by using the same strategy starting from N-2-fluoroprop-2-enyl substrates. [6] We have also explored the formation of various cyclic derivatives from α-amino esters containing α-CF 3 and phosphonate analogs. [7] Other types of non-natural cyclic 1-amino-1-carboxylic acid derivatives of different sizes were also prepared from substrates with two geminal olefinic branches grafted at the α-carbon atom of the final product.…”