Nucleophilic Fluoromethylation of Aldehydes with Fluorobis(phenylsulfonyl)methane: The Importance of Strong Li–O Coordination and Fluorine Substitution for CC Bond Formation

Abstract

The tighter, the better! Fluorobis(phenylsulfonyl)methane reacts readily with aldehydes to give addition products in excellent yields (see scheme; LiHMDS=lithium hexamethyldisilazide), which is in sharp contrast to previous findings. Both strong Li–O coordination at low temperature and fluorine substitution play important roles in successful CC bond formation.

The unique fluorine effects in organic reactions: recent facts and insights into fluoroalkylations

“…An example is the nucleophilic addition reaction between (PhSO 2 ) 2 CHF and an aldehyde reported by us (Scheme 11). 34 This reaction was previously considered to be unattainable because of the steric hindrance of the (PhSO 2 ) 2 CF group. We accomplished the reaction by using lithium hexamethyldisilazide (LiHMDS) as the base to promote the formation of the alcoholate.…”

“…Taking together, the Li-O interaction and the fluorine substitution simultaneously promote this aldehyde addition reaction. 34 2.10 Asymmetric Mannich-type reaction of a-CF 3 amide through bidentate coordination: stabilization effect of CF 3 vs. b-fluoride elimination…”

Reagenzien für die selektive Fluormethylierung: Herausforderungen der Organofluorchemie

“…. Darüber hinaus wurden die Zugabe von 23 zu Carbonylverbindungen, α,β‐ungesättigten Carbonylverbindungen und zu funktionalisierten Alkinen sowie die enantioselektive Synthese von tertiären Allylfluoriden durch eine Iridium‐katalysierte Allylfluormethylierung mit 23 von Hu, Vesely und Hartwig beschrieben . Von der reduktiven Spaltung der Sulfonylsubstituenten zu den entsprechenden Fluormethylderivaten, wie bei den anderen zuvor besprochenen Beispielen, wurde allerdings nichts berichtet.…”

The Nucleophilicity of Persistent α‐Monofluoromethide Anions

“…Similarly, the urea‐catalyzed reactions between α‐fluoro‐α‐nitro(benzenesulfonyl)methane and chalcones are also more rapid than those of nitro(benzenesulfonyl)methane ,. Furthermore, despite that the nucleophilic addition of (PhSO 2 ) 2 CFLi to benzaldehyde leads to the corresponding alcohol in high yield, no adduct was obtained in the reaction with (PhSO 2 ) 2 CHLi or (PhSO 2 ) 2 CClLi under similar reaction conditions . Although these observations provide valuable information on overall fluorine effects in nucleophilic fluoroalkylations, they may not reflect the nucleophilic reactivities of the fluorocarbanions, an intrinsic kinetic property by definition .…”