Atom‐Economic Catalytic Direct Substitution of N,O‐Acetals with Simple Ketones

Abstract

A general and powerful catalytic protocol for the direct amidoalkylation of simple enolizable ketones is described, with use of the Lewis superacid Sn(NTf2)4 as a catalyst under thermal conditions. A complete and rational study directed towards the development of efficient conditions for the coupling of a wide range of reaction partner combinations, including the most recalcitrant ones, is presented. The synthetic potential of the reaction is demonstrated through the use of a large set of both carbonyl and N,O‐acetalic substrates, providing the corresponding amidoalkylated ketones in 49–99 % yield, by using very low catalyst loadings (≤ 1 mol‐%).

Catalytic Asymmetric Additions of Enol Silanes to In Situ Generated Cyclic, AliphaticN‐Acyliminium Ions

“…[7][8][9][10] The concepts of asymmetric anion-binding catalysis and of asymmetric counteranion directed catalysis (ACDC) appear to be particularly promising in controlling Nacyliminium ion reactivity, and chiral thiourea derivatives and BINOL-derived phosphoric acids have indeed been used in this context. [11-16, 23, 24] However, despite the versatility of cyclic, aliphatic N-(exo-acyl)iminium ions, [25][26][27][28][29][30][31] controlling their reactivity via enantiopure counteranion remained elusive. Previous approaches invariably required in situ generated chiral nucleophiles, significantly limiting their scope.…”

Katalytische asymmetrische Additionen von Enolsilanen an in situ erzeugte zyklische, aliphatischeN‐Acyliminiumionen

“…[7][8][9][10] Die Konzepte der asymmetrischen Anionenbindungskatalyse und der asymmetrischen gegenanionvermittelten Katalyse (ACDC) scheinen besonders vielversprechend zu sein, um die Reaktivität von N-Acyliminiumionen zu kontrollieren, und tatsächlich wurden chirale Thioharnstoffderivate und von BINOL abgeleitete Phosphorsäuren in diesem Zusammenhang einge-setzt. [11-16, 23, 24] Trotz der Vielseitigkeit der zyklischen, aliphatischen N-(exo-Acyl)iminiumionen, [25][26][27][28][29][30][31] blieb die Kontrolle ihrer Reaktivität über ein enantiomerenreines Gegenanion unerreicht. Bisherige Ansätze erforderten stets in situ erzeugte chirale Nukleophile, was ihre Anwendungsmöglichkeiten erheblich einschränkte.…”

Enamine-mediated Mannich reaction of cyclicN,O-acetals and amido acetals: the multigram synthesis of pyrrolidine alkaloid precursors

“…The selected examples include the Lewis acidic polyoxotungstate catalysed reaction of N-Boc protected 2-hydroxypyrrolidine with silyl enol ethers reported by Thorimbert and coworkers. 6 A series of papers [7][8][9][10][11][12] by Dalla and coworkers describe the synthesis of 2-(acylmethylene)pyrrolidines utilizing enantiopure N,O-acetals derived 13 from various hydroxy acids, succinic anhydride and pyroglutamic acid. Lewis and Brønsted superacids Sn(NTf 2 ) 4 [7][8][9] and HNTf 2 10,11 were employed as catalysts, as well as triisopropylsilyl trifluoromethanesulfonate.…”