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Review
. 2017 Mar 19;22(3):483.
doi: 10.3390/molecules22030483.

Synthesis of Substituted α-Trifluoromethyl Piperidinic Derivatives

Sarah Rioton  1 , Domingo Gomez Pardo  2 , Janine Cossy  3
Affiliations
Review

Synthesis of Substituted α-Trifluoromethyl Piperidinic Derivatives

Sarah Rioton et al. Molecules. .

Abstract

A comprehensive survey of pathways leading to the generation of α-trifluoromethyl monocyclic piperidinic derivatives is provided (65 references). These compounds have been synthesized either from 6-membered rings e.g., pipecolic acid or lactam derivatives by introduction a trifluoromethyl group, from pyridine or pyridinone derivatives by reduction, and from 5-membered rings e.g., prolinol derivatives by ring expansion, from linear amines by cyclization or from dienes/dienophiles by [4 + 2]-cycloaddition.

Keywords: cyclization; cycloaddition; fluorine; nitrogen heterocycles; piperidine; ring expansion; trifluoromethyl group.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Precursors of α-trifluoromethyl piperidinic derivatives.
Scheme 2
Scheme 2
Synthesis of 2-trifluoromethyl piperidine from pipecolic acid.
Scheme 3
Scheme 3
Hydrogenation of α-trifluoromethylpyridine.
Scheme 4
Scheme 4
Hydrogenation of trifluoromethylpyridinones.
Scheme 5
Scheme 5
Synthesis of α-trifluoromethylpiperidines from δ-lactams.
Scheme 6
Scheme 6
Synthesis of α-trifluoromethylpiperidine from δ-lactam via enamine.
Scheme 7
Scheme 7
Synthesis of α-trifluoromethylpiperidine from δ-lactam via imine.
Scheme 8
Scheme 8
Synthesis of α-trifluoromethylpiperidine from an imine by reduction.
Scheme 9
Scheme 9
Synthesis of 2-(trifluoromethyl)-2-ethylphosphonate piperidine from imine.
Scheme 10
Scheme 10
Synthesis of α-trifluoromethylpiperidines by Ugi-type reactions.
Scheme 11
Scheme 11
Synthesis of α-trifluoromethylpiperidines by Friedel-Craft reactions with pyrroles.
Scheme 12
Scheme 12
Synthesis of α-trifluoromethylpiperidines by a Friedel-Craft reaction with indoles.
Scheme 13
Scheme 13
Synthesis of α,α-disubstituted piperidines.
Scheme 14
Scheme 14
Synthesis of C3-substituted α-trifluoromethylpiperidines from l-proline.
Figure 1
Figure 1
Catalysts for olefin metathesis.
Scheme 15
Scheme 15
Synthesis of α-trifluoromethylpiperidine from trifluoromethylhemiacetal.
Scheme 16
Scheme 16
Synthesis of α-trifluoromethylpiperidines from trifluoromethylimines.
Scheme 17
Scheme 17
Synthesis of α,α-disubstituted unsaturated piperidines from trifluoromethylimines.
Scheme 18
Scheme 18
Synthesis of α,α-disubstituted piperidines from trifluorodiazo derivatives.
Scheme 19
Scheme 19
Synthesis of α-trifluoromethylpiperidines using a ROM/RCM sequence.
Scheme 20
Scheme 20
Synthesis of α-trifluoromethylpiperidines by a RCM to enynes.
Scheme 20
Scheme 20
Synthesis of α-trifluoromethylpiperidines by a RCM to enynes.
Scheme 21
Scheme 21
Synthesis of piperidinones by an aza Diels-Alder reaction.
Scheme 22
Scheme 22
Aza Diels-Alder reaction with 1-azadienes.
Scheme 23
Scheme 23
Synthesis of α-trifluoromethylpiperidine by aza-Michael addition.
Scheme 24
Scheme 24
Synthesis of chiral α-trifluoromethylpiperidines.
Scheme 25
Scheme 25
Synthesis of α-trifluoromethylpipecolic acid derivatives.
Scheme 26
Scheme 26
Synthesis of α-trifluoromethylpiperidines by electrophilic-induced cyclization.
Scheme 27
Scheme 27
Synthesis of α-trifluoromethylpiperidines by an intramolecular Mannich reaction.
Scheme 28
Scheme 28
Synthesis of an α-trifluoromethylpiperidine by a silyl-aza-Prins reaction.
Scheme 29
Scheme 29
Synthesis of a trifluoromethyllactam from a ketoester.
Scheme 30
Scheme 30
Synthesis of a trifluoromethyllactam from a trifluoromethylhemiacetal.
Scheme 31
Scheme 31
Synthesis of an α-trifluoromethylpiperidine by lactamization.
Scheme 32
Scheme 32
Synthesis of unsaturated lactams from carboxylic trifluoromethyl ketones.
Scheme 33
Scheme 33
Synthesis of highly substituted α-trifluoromethylpiperidines.
Scheme 34
Scheme 34
Synthesis of α-trifluoromethylpiperidines from trifluoromethylaziridines.
Scheme 35
Scheme 35
Synthesis of α-trifluoromethylpiperidino-epoxides.
See this image and copyright information in PMC

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