Kinetic Resolution of Allyl Fluorides by Enantioselective Allylic Trifluoromethylation Based on Silicon‐Assisted CF Bond Cleavage

Abstract

Two birds, one stone! The first kinetic resolution of allyl fluorides was achieved by the development of an organocatalyzed enantioselective allylic trifluoromethylation. Two kinds of chiral fluorinated compounds, which incorporate C*F and C*CF3 units, respectively, can thus be accessed by a single transformation.

Enantioselective Trichloromethylation of MBH‐Fluorides with Chloroform Based on Silicon‐assisted C−F Activation and Carbanion Exchange Induced by a Ruppert–Prakash Reagent

“…Although there have been many reports on trichloromethylation reactions, enantioenriched trichloromethylated compounds attract less attention than others such as racemic compounds, and the method for direct enantioselective trichloromethylation is extremely rare . In recent years, we reported the enantioselective reactions of MBH‐acetates, carbonates, and fluorides with fluoromethylated nucleophiles under organocatalysis providing allylic monofluoro‐ and trifluoromethylated compounds in high yields with high enantioselectivities . During our research of the trifluoromethylation of MBH‐fluorides 1 with Me 3 SiCF 3 , we accidently noticed that allylic trichloromethylated compounds 2 were obtained predominantly instead of trifluoromethylated ones when the reaction was carried out in chloroform, HCCl 3 .…”

Solvent-controlled nucleophilic trifluoromethylthiolation of Morita–Baylis–Hillman carbonates: dual roles of DABCO in activating the Zard's trifluoromethylthiolation reagent and the MBH carbonates

“…The nucleophilic attack of H2O to ammonium salt intermediate C yields tert-butanol, N-octadecanol, carbon dioxide and regenerates DABCO for the catalytic cycle. Carbonate 5a is generated via the nucleophilic addition of N-octadecanol to ammonium salt intermediate C, but carbonate 6a can not be formed 10 because of the weak nucleophilicity of t-butoxyl anion.…”

“…[9] Moreover, Shibata has also reported a (DHQD)2PHAL-catalyzed kinetic resolution of allyl fluorides to synthesize chiral allyl fluorides and 45 trifluoromethylated compounds (Scheme 1). [10] To the best of our knowledge, only one case of forming the C(sp 3 )-SCF3 bond using Lewis bases catalyzed SN2'/SN2' substitution has been reported during the preparation of this manuscript. [11] With these precedents in mind and in 50 State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China.…”

“…In THF, 3a was formed exclusively (Table 1, entries 9-11). When the reaction was carried out in THF, lowering the temperature to 0 o C did not improve the yield of product 3a (Table 1, With the optimized reaction conditions in hand, we next investigated 10 the generality of this allylic trifluoromethylthiolation for synthesizing primary allylic SCF3 products ( Table 2). As for MBH carbonates 2b and 2c, the reaction afforded the desired products 3b and 3c with excellent yields and regioselectivities (Table 2, entries 1-2).…”

Asymmetrische Desymmetrisierung durch metallfreie C‐F‐Bindungsaktivierung: Synthese von 3,5‐Diaryl‐5‐fluormethyl‐oxazolidin‐2‐onen mit quartären Kohlenstoffzentren

“…Unseres Wissens sind bisher nur unsere eigenen beiden Berichte publiziert worden. [12] Obwohl eine enantioselektive C-F-Bindungsspaltung erreicht wurde,w aren bisher nur Allylfluoride,a lso Verbindungen mit aktivierten aliphatischen C sp3 -F-Bindungen, als Substrate einsetzbar.I nd ieser Arbeit berichten wir nun über die erfolgreiche asymmetrische Synthese von 3,5-Diaryl-5-fluormethyl-oxazolidin-2-onen 1 mit einem quartären Kohlenstoffzentrum mit hohen Enantioselektivitäten durch Spaltung von viel anspruchsvolleren, nichtaktivierten aliphatischen C sp3 -F-Bindungen (Schema 1). Die Anwendung chiraler,n ichtracemischer Ammoniumbifluoride als Katalysatoren und der Effekt ortho-substituierter Arylgruppen am prostereogenen Zentrum spielen eine Schlüsselrolle für den Erfolg dieser Reaktionen.…”