Diastereoselective Trifluoromethylation of Chiral α,β‐Unsaturated N‐tert‐Butanesulfinyl Ketimines with Ruppert‐Prakash Reagent: Asymmetric Synthesis of α‐Tertiary Trifluoromethyl Allylic Amines

Abstract

The diastereoselective trifluoromethylation of chiral α,β‐unsaturated N‐tert‐butanesulfinyl ketimines with Ruppert‐Prakash reagent (TMSCF3) has been attained, which provided a convenient and straightforward method for the asymmetric synthesis of structurally diverse α‐tertiary trifluoromethyl allylic amines in high yields and with excellent diastereoselectivities (dr up to > 99:1). The stereochemical outcome of the present diastereoselective trifluoromethylation of the α,β‐unsaturated N‐tert‐butanesulfinyl ketimines suggested that a cyclic six‐membered transition state is involved in the reaction, which is remarkably different from that of the trifluoromethylation of N‐tert‐butanesulfinyl aldimines.

Copper (I)‐BOX Catalyzed Asymmetric 3‐Component Reaction for the Synthesis of Trifluoromethylated Propargylic Ethers and Anilines**

“…In particular, trifluoromethylated propargylic ethers and amines [4, 5] are valuable building blocks for synthetic and medicinal chemistry [6] . Reported catalytic enantioselective methods [7] for the synthesis of trifluoromethylated carbinols and anilines are based on (a) the addition of CF 3 ‐based nucleophiles to ynones, [7a, 8] (b) the addition of acetylides onto carbonyl compounds or imines, [9, 10] (c) the addition of carbon nucleophiles to trifluoromethylated alkynyl ketones or the reduction of the corresponding trifluoromethylated propargyl imines, [11, 12] or (d) the kinetic resolution of the propargyl alcohols (Scheme 1A) [6a] . Nevertheless, stoichiometric amounts of strong bases, lower or higher temperatures, expensive catalysts (Rh, Pd, among others), and/or additives are sometimes needed, leading to a narrow scope.…”

Electrochemically mediated fluoroalkylation/cyclization of unactivated alkenes: synthesis of polycyclic benzimidazoles containing a CF3 group

“…In this regard, the introduction of trifluoromethyl into drug candidates is a common research strategy in the field of pharmaceutical chemistry. Overall, the common reagents used to introduce trifluoromethyl are Ruppert's reagent, 2 Togni's reagent, 3 Langlois' reagent, 4 Umemoto's reagent, 5 and so on, the traditional process of which inevitably uses oxidizing or reducing reagents and generates waste that is harmful to the environment. 6 Therefore, the development of sustainable and efficient methods for the practical introduction of a CF 3 group into various molecular structures has received increasing attention.…”

Cu‐Catalyzed C(sp2−H)‐Trifluoromethylation of Aldehyde Hydrazones with Langlois Reagent

“…[8][9][10] Nucleophilic trifluoromethylation of chiral N-tertbutanesulfinylimines, which are activated to the nucleophilic additions by the adjacent sulfinyl moiety, using Ruppert-Prakash reagent gives the corresponding trifluoromethylated products with high diastereoselectivities and yields under mild conditions. [11][12][13][14][15] Catalytic enantioselective trifluoromethylation of the azomethine imines gives high yields of the corresponding α-trifluoromethylated amines. [16] We have recently developed the nucleophilic trifluoromethylation of N-(p-toluenesulfonyl)aldimines under nonacidic conditions, using Nheterocyclic carbene (NHC) catalysts.…”

“…Nucleophilic trifluoromethylation of N‐alkylimines using Ruppert‐Prakash reagent (CF 3 SiMe 3 ) under relatively strong acidic conditions gives the corresponding α‐trifluoromethylamines [8–10] . Nucleophilic trifluoromethylation of chiral N‐ tert ‐butanesulfinylimines, which are activated to the nucleophilic additions by the adjacent sulfinyl moiety, using Ruppert‐Prakash reagent gives the corresponding trifluoromethylated products with high diastereoselectivities and yields under mild conditions [11–15] . Catalytic enantioselective trifluoromethylation of the azomethine imines gives high yields of the corresponding α‐trifluoromethylated amines [16] .…”