Highly Enantioselective Hetero‐Diels–Alder Reaction of 1,3‐Bis(silyloxy)‐1,3‐dienes with Aldehydes Catalyzed by Chiral Disulfonimide

Abstract

Originating from observation by Danishefsky et al. that hetero-Diels-Alder (HDA) reactions of 1-methoxy-3-(trimethylsilyloxy)butadiene (Danishefskys diene) with aldehydes are accelerated by Lewis acids [Eq. (1); TMS = trimethylsilyl], [1] asymmetric variants became extensively studied and utilized in the synthesis of enantioenriched six-membered oxygen-containing heterocycles.[2] Indeed, several efficient metal-based chiral Lewis acids have been developed for this reaction.[3] Recently, Rawal and co-workers introduced a metal-free, hydrogen-bonding catalyst for asymmetric HDA reactions of 1-dimethylamino-3-tert-butyldimethylsilyloxy-1,3-butadiene (Rawals diene) with aldehydes [Eq. (1), TBS = tert-butyldimethylsilyl].[4] Despite all this progress however, the present catalytic systems for asymmetric HDA reactions are largely limited to the originally introduced dienes, and substituted and functionalized dienes have proven to be highly challenging substrates.[3c,e,g, 5] As a consequence, only few catalytic asymmetric syntheses of 2,6-disubstituted dihydropyrones have been reported and the catalytic enantioselective synthesis of 2,5,6-trisubstituted dihydropyrones is entirely unknown. [6,7] Herein, we report a highly enantioselective HDA reaction of aldehydes with substituted 1,3-bis(silyloxy)-1,3-dienes catalyzed by a novel, highly fluorinated, chiral disulfonimide [Eq. (2)].Recently our group has introduced chiral disulfonimides (DSI) as effective catalysts of asymmetric Mukaiyama and vinylogous Mukaiyama aldol reactions with aldehydes. [8,9] We hypothesized that such a catalyst could also promote the mechanistically related HDA reactions of 1,3-bis(silyloxy)-1,3-dienes, which surprisingly have previously been utilized only in non-asymmetric catalysis. [10][11][12] Our interest in this particular transformation was further stimulated by speculating that the lack of established catalytic asymmetric HDA reactions might stem from a competing silylium-catalyzed background reaction.[13] We had previously shown that disulfonimide-based catalysis offers an efficient solution to this problem in Mukaiyama aldolizations.To explore the principal utility of our DSI catalysts in HDA reactions, we initially studied our previously used chiral disulfonimide catalyst 1 in the reaction of 2-naphthaldehyde with the commercially available diene 3. These experiments showed that the product 4 could indeed be obtained in the presence of 5 mol % of catalyst 1 at À78 8C in Et 2 O in good yield and reasonable enantioselectivity (Table 1, entry 1). We reasoned that improving the steric and electronic properties of the catalyst by incorporating large perfluorinated substitu- e.r.

Chiral 1,1′‐Binaphthyl‐2,2′‐Disulfonic Acid (BINSA) and Its Derivatives for Asymmetric Catalysis

“…Moreover, by taking advantage of a Mukaiyama aldol reaction mechanism, List and co-workers developed a highly efficient catalytic enantioselective hetero Diels-Alder reaction (Scheme 26). [28] As well as Danishefskys diene, the reactions of the challenging 1,3-bisA C H T U N G T R E N N U N G (silyloxy)-1,3-dienes with Scheme 23. Catalytic enantioselective Mukaiyama aldol reaction with the use of (R)-24 a.…”

Asymmetrische Gegenanionen‐vermittelte Katalyse: Konzept, Definition und Anwendungen

“…[72] Diese ersten Befunde lassen darauf schließen, dass unser neuartiger Organo-Lewis-Säure-Aktivierungsmodus verhältnismäßig allgemein sein und gegebenenfalls auf verschiedene andere, über silylierte Nucleophile verlaufende Prozesse anwendbar sein kçnnte. Beispielsweise konnte unter Verwendung des Dienophils 97 und Katalysators 84 b das Diels-Alder-Produkt 98 in ausgezeichneter Ausbeute und Enantioselektivität erhalten werden.…”

“…Beispielsweise konnte unter Verwendung des Dienophils 97 und Katalysators 84 b das Diels-Alder-Produkt 98 in ausgezeichneter Ausbeute und Enantioselektivität erhalten werden. [72] Diese ersten Befunde lassen darauf schließen, dass unser neuartiger Organo-Lewis-Säure-Aktivierungsmodus verhältnismäßig allgemein sein und gegebenenfalls auf verschiedene andere, über silylierte Nucleophile verlaufende Prozesse anwendbar sein kçnnte.…”

“…Vinyloge und bisvinyloge, Gegenanionen-vermittelte Mukaiyama-Aldolreaktionen und Hetero-Diels-Alder-Reaktion; TFA = Trifluoressigsäure. [71,72] Asymmetrische Katalyse…”

Asymmetric Counteranion‐Directed Catalytic Hosomi–Sakurai Reaction

“…[15] Strong encouragement for this concept came from our previous success in catalyzing related Si-transfer processes with chiral disulfonimides. [11][12][13] We started our investigations by testing the methallylation of benzaldehyde (2 a) with methallyltrimethylsilane (3 a) using disulfonimide catalyst 1 b (Scheme 1), which had proven to be the best catalyst in our studies on the Mukaiyama aldol reaction. [11,12] Utilizing catalyst 1 b we obtained the methallylation product 4 a with an encouraging enantiomeric ratio (e.r.)…”