Synthesis of chiral (tetrazolyl)methyl-containing acrylates via silicon-induced organocatalytic kinetic resolution of Morita–Baylis–Hillman fluorides

Abstract

Reported herein is a new approach for the asymmetric installation of a (tetrazolyl)methyl group via Si/F activation using organocatalytic kinetic resolution of racemic MBH-fluorides.

Synthesis of fluoro-functionalized diaryl-λ3-iodonium salts and their cytotoxicity against human lymphoma U937 cells

“…Utilizing these reagents, we have successfully synthesized a wide variety of bioactive organofluorine compounds [ 24 – 30 ] including fluorinated thalidomide (antitumor) [ 24 ], fluorinated donepezil (cholinesterase inhibitor) [ 25 ], and fluorinated camptothecin (anticancer) [ 26 ]. During our research programs focused on the development of novel reagents for fluoro-functionalization [ 12 – 13 16 – 23 ], as well as the design and synthesis of biologically active fluorine-containing compounds [ 24 – 28 ], we noted that a series of fluoro-functionalization reagents could themselves be highly potential drug candidates. All of the reagents that we developed contain at least one fluorine atom in their structures, which may explain why they have potential biological activity [ 4 – 9 ].…”

Synthesis of Chiral gem-Difluoromethylene Compounds by Enantioselective Ethoxycarbonyldifluoromethylation of MBH Fluorides via Silicon-Assisted C–F Bond Activation

“…Our strategy of using MBH fluorides for enantioselective substitution reactions (and kinetic resolution) has quickly emerged as one of the most powerful tools for asymmetric allylic substitution reactions under organocatalysis, and several enantioselective reactions with or without kinetic resolution have been reported by us and others (Scheme ). , On the basis of this background work, we envisioned that enantioselective construction of the stereogenic “C-CF 2 -C*” unit could be achieved by a combination of MBH fluorides and suitably silylated “-CF 2 -C-” nucleophiles ( Si -CF 2 - C ) in the presence of cinchona alkaloids. Herein, we disclose the first enantioselective allylic substitution reaction of MBH fluorides with ethoxycarbonyl difluoromethyl trimethylsilane (Me 3 Si-CF 2 CO 2 Et) under cinchona alkaloid catalysis.…”

“…On the basis of our previous work, , we began by investigating the reaction of MBH fluoride 1a and Me 3 Si-CF 2 CO 2 Et using bis -cinchona alkaloid catalysts in dichloromethane (DCM) at −20 °C (Table ). In the catalyst screening, quinidine-based catalysts (DHQD) 2 PHAL, (DHQD) 2 PYR, and (DHQD) 2 AQN provided the desired ethoxycarbonyl difluoromethylene MBH product 2a with the ( S )-configuration in 69% yield (85% ee), 59% yield (81% ee), and 34% yield (60% ee), respectively (entries 1–3).…”

Cross‐ and Multi‐Coupling Reactions Using Monofluoroalkanes

“…Thus, the formed α,β‐unsaturated ester accepted the addition of the CF 3 anion in an enantioselective manner. A similar kinetic resolution was achieved by tetrazolylmethylation [54] and phosphonyldifluoromethylation [55] using the corresponding silane reagents.…”