Selective CF Bond Activation: Substitution of Unactivated Alkyl Fluorides using YbI₃

Abstract

Eine harte Nuss: Aliphatische Kohlenstoff‐Fluor‐Einfachbindungen sind vergleichsweise stark und nicht leicht zu spalten. Ein neues Verfahren nutzt YbI3, um C‐F‐ in C‐I‐Bindungen umzuwandeln. Diese Umwandlung verläuft unter milden Bedingungen und ist außergewöhnlich selektiv für Alkylfluoride, auch in Gegenwart verschiedener funktioneller Gruppen.

Catalytic Enantioselective and Diastereoselective Allylic Alkylation with Fluoroenolates: Efficient Access to C3‐Fluorinated and All‐Carbon Quaternary Oxindoles

“…[22] In this context, progress with aliphatic substrates has been largely limited by the chemical inertness and stability of the C sp 3 ÀFb ond. Intriguing reports on fluoride/ halide exchange [23] and aliphatic CÀFbond cleavage followed by carbon-heteroatom [24] or carbon-carbon coupling [25] have emerged in the last few years.S elective transformations that proceed under mild conditions and in the presence of other functional groups,however, are rare and particularly difficult. We have identified au nique defluorination pathway that provides new possibilities for selective CÀCb ond formation.…”

“…Theuse of expensive and moisturesensitive bases such as BSA in asymmetric allylic alkylations is common and we were delighted to find that the introduction of triethylamine furnished av enue for improving the diastereoselectivity in combination with economic and operational advantages.O ptimization of the temperature finally led to the production of 3da in excellent yield and ee,a nd more than 19:1 d.r. at À30 8 8C( entries [21][22][23]. It is noteworthy that this method is equally successful with fluorooxindoles that carry removable protecting groups at the lactam nitrogen atom, such as benzyl, para-methoxyphenyl (PMP), and para-benzyloxyphenyl moieties (see below).…”

Chemodivergent Csp 3 ─F bond functionalization and cross-electrophile alkyl-alkyl coupling with alkyl fluorides

“…Because the cleavage of the C─F bond is highly endothermic, the relatively low BDE of a typical C─C bond (85 kcal/mol) does not provide the necessary thermodynamic driving force to achieve C─F functionalization under mild conditions. Reports on proelectrophilic C─F bond activation with ytterbium, silicon, and lanthanide Lewis acids ( 4 , 5 , 12 , 14 , 18 , 21 , 22 , 30 ) and C─F bond cleavage observed in our laboratory during the synthesis and derivatization of fluorinated oxindoles, nitriles, nitromethyl ketones, as well as alkyl, benzyl and aryl fluorides ( 19 , 39 – 42 ) encouraged us to investigate whether broadly applicable, chemodivergent C─F bond cleavage using alkyl fluorides either as proelectrophiles or as pronucleophiles is possible when coupled with the generation of a stable inorganic fluoride salt. Following our previous work with fluorinated oxindoles and through serendipitous screening of reaction conditions, we found that the fluorooxindole 1 undergoes reductive defluorination in the presence of trimethylsilyl iodide (TMSI).…”

“…Substantial progress has been made with aryl fluorides, while aliphatic substrates continue to be very challenging. Csp 3 ─F bond functionalization has been achieved, for example, with reactive Lewis acids or via hydrogen bond assistance, and used for carbon-heteroatom bond formation ( 12 – 14 ), carbon-carbon coupling ( 15 – 20 ), and halide exchange ( 21 – 23 ). With the exception of allylic, propargylic, and benzylic fluorides ( 24 – 30 ), low functional group compatibility, limited synthetic utility and competing rearrangement, elimination, or other side reactions, particularly when harsh reaction conditions need to be applied, have remained persistent problems despite some recently reported remarkable advances ( 31 – 37 ).…”

Katalytische enantioselektive und diastereoselektive allylische Alkylierung mit Fluorenolaten: Synthese von C3‐fluorierten und quartären Oxindolen

“…Die stetig zunehmende Verfügbarkeit von fluorierten Verbindungen hat neuerliches Interesse an Strategien fürdie Aktivierung von C-F-Bindungen geweckt. [22] Allerdings blieben große Fortschritte mit aliphatischen Substraten wegen der chemischen Inertheit und Stabilitätd er C sp 3 -F-Bindung aus.S ehr interessante Berichte über Fluor-Halogen-Austausch [23] und aliphatische C-F-Bindungsspaltung mit nachfolgender Kohlenstoff-Heteroatom- [24] oder Kohlenstoff-Kohlenstoff-Bindungsbildung [25] sind in den letzten Jahren erschienen. Selektive Tr ansformationen, die unter milden Bedingungen und in Anwesenheit von anderen funktionellen Gruppen erfolgen, sind jedoch selten und besonders schwierig.W ir haben einen einzigartigen Defluorierungsweg identifiziert, der neue Mçglichkeiten fürd ie selektive C-C-Bindungsbildung bietet.…”