Synthesis of functionalized CF3-containing heterocycles via [2,3]-sigmatropic rearrangement and sequential catalytic carbocyclization

Asymmetric Synthesis of Cyclic Fluorinated Amino Acids

“…Having in hands these aminodiene compounds, we focused our attention on the synthesis of the correspondingly substituted chiral tetrahydropyridines by a RCM protocol. Some previous works in the literature have already described RCM reactions with CF 3 ‐amines to obtain trifluoromethylated nitrogen heterocycles . Among the commercially available ruthenium‐based alkylidine Grubbs catalysts, we chose the air‐ and moisture‐stable Grubbs' second‐generation catalyst, which was widely used for the synthesis of sterically hindered poly‐substituted dienes, aminodienes, and large‐size rings.…”

Synthesis of Substituted α-Trifluoromethyl Piperidinic Derivatives

“…Thus, when imines 40 were treated with allylmagnesium bromide (THF, –78 °C) then allylated (NaH, allylbromide) dienes 42 were isolated in good yields and then involved in a ring-closing metathesis (RCM) using different catalysts such as G-I or the ruthenium catalyst J [39]. It is worth noting that the yields obtained with G-I are better than with catalyst J (Scheme 17) [40,41,42,43]. …”

“…Treatment of N , N -diallyl- N -methylamine by the diazo compound 44 in the presence of the copper catalyst [Cu(F 3 -acac) 2 ], produced ylide VIII which, after a [2,3]-sigmatropic rearrangement, led to the dienic derivatives 45 , precursor of the unsaturated piperidines 46 (Scheme 18) [43]. …”

“…Only the cycloadditions leading to the monocyclic piperidinic core will be reported thus, the [2 + 2]-cycloaddition of allenynes [46] and the Paulson-Khan reaction [38,43,47] will be excluded.…”

Access to Cyclic α‐CF3‐Substituted α‐Amino Acid Derivatives by Ring‐Closing Metathesis of Functionalized 1,7‐Enynes

“…We have previously described a convenient one‐step method for the synthesis of trifluoromethylated 1,7‐enynes that incorporates α‐aminocarboxylic and α‐aminophosphonic acids and utilizes a highly selective Cu II ‐catalyzed [2,3] sigmatropic rearrangement of the allyl group of an allylpropargyl‐containing nitrogen CF 3 ‐ylides14 [see Figure 1, Equation (1a)]. Herein, we disclose the synthesis of α‐CF 3 ‐α‐amino acid 1,7‐enynes with electron‐donating and electron‐withdrawing aryl, acyl, and aroyl groups on the triple bond and their RCEYM with commercially available Grubbs II and Hoveyda II catalysts to afford new fluorinated pipecolic acid derivatives that contain the synthetically useful 1,3‐diene moiety [see Figure 1, Equation (1b)].…”