Novel Synthesis of 4-Fluoropyridines Based on 2-Fluoroallylic Alcohols by Succeeding Ireland-Claisen and Aza-Cope Rearrangements as Key Steps

Wittmann, Ulrich; Tranel, Frank; Fröhlich, Roland; Haufe, Günter

doi:10.1055/s-2006-942411

Cited by 4 publications

(1 citation statement)

References 3 publications

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“…Modified conditions of the original Kazmaier variation of the Ireland-Claisen rearrangement enabled the synthesis of a variety of Nprotected 4-fluoro-2-aminoalk-4-enecarboxylic acids, which were transformed to the target free aminoacids by Ndeprotection of the TFA-protected products with ammonia in methanol (Scheme 55). [99] When optically active fluorinated allylic alcohols were used, complete chirality transfer was detected in the products. [100] Furthermore, we performed the first synthesis of fluorinated primary allylic amines using an Overman rearrangement based on secondary 2-fluoroallylic alcohols.…”

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

Selective Synthesis of Monofluorinated Compounds Applying Amine/HF Reagents

Haufe

2023

The Chemical Record

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For nucleophilic monofluorination, amine/HF reagents such as Et3N⋅3HF, Pyr⋅9HF (Olah's reagent) and similar combinations belong to the most frequently used fluoride sources, whereupon the selectivity of these reagents can be very different depending of its acidity, the nucleophilicity of the fluoride equivalent, and the structure of the particular substrate. These reagents can be used safely in ordinary chemistry laboratories for nucleophilic substitution reactions by fluoride at sp3‐hybridized carbon centers. For ring opening reactions of epoxides, the regio‐ and stereoselectivity is very much depending of the nature of the epoxide and the acidity of the HF reagent favoring either SN1 or SN2 type reactions. Similarly, the outcome of halofluorination and similar reactions with sulfur or seleno electrophiles can be controlled by the particular combination of the electrophile and the fluoride source. Examples for the application of these reaction types for the synthesis of fluorine‐containing analogues of natural products or biologically relevant compounds are in the focus of this personal account.

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Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

Selective Synthesis of Monofluorinated Compounds Applying Amine/HF Reagents

Haufe

2023

The Chemical Record

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Stereoselective Synthesis of Mono-fluoroalkenes

Hara

2012

Topics in Current Chemistry

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Synthesis of α-(Pentafluorosulfanyl)- and α-(Trifluoromethyl)-Substituted Carboxylic Acid Derivatives by Ireland–Claisen Rearrangement

et al. 2017

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Earlier studies have shown that [3,3]-sigmatropic rearrangements of allyl esters are useful for the construction of fluorine-containing carboxylic acid derivatives. This paper describes the synthesis of 3-aryl-pent-4-enoic acid derivatives bearing either a pentafluorosulfanyl (SF) or a trifluoromethyl (CF) substituent in the 2-position by treatment of corresponding SF- or CF-acetates of p-substituted cinnamyl alcohols with triethylamine followed by trimethylsilyl triflate (TMSOTf). This Ireland-Claisen rearrangement delivered approximate 1:1 mixtures of syn/anti diastereoisomers due to tiny differences (<0.5 kcal/mol) both in the energy of (Z)/(E)-isomeric ester enolates and in the alternative Zimmerman-Traxler transition states of model compounds as shown by DFT calculations. Acidic reaction conditions have to be avoided since addition of the reagents in opposite sequence (first TMSOTf then EtN) led to oligomerization of the cinnamyl SF- and CF-acetates. Treatment of the corresponding regioisomeric 1-phenyl-prop-2-en-1-yl acetates under the latter conditions resulted in [1,3]-sigmatropic rearrangement and subsequent oligomerization of the intermediately formed cinnamyl esters. When EtN was added first followed by TMSOTf, no further reaction of the formed ester was detected.

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Novel Synthesis of 4-Fluoropyridines Based on 2-Fluoroallylic Alcohols by Succeeding Ireland-Claisen and Aza-Cope Rearrangements as Key Steps

Cited by 4 publications

References 3 publications

Selective Synthesis of Monofluorinated Compounds Applying Amine/HF Reagents

Selective Synthesis of Monofluorinated Compounds Applying Amine/HF Reagents

Stereoselective Synthesis of Mono-fluoroalkenes

Synthesis of α-(Pentafluorosulfanyl)- and α-(Trifluoromethyl)-Substituted Carboxylic Acid Derivatives by Ireland–Claisen Rearrangement

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