Asymmetric Diels−Alder Reactions Catalyzed by a Triflic Acid Activated Chiral Oxazaborolidine

Abstract

This paper reports a new method for the generation of chiral Lewis superacids by protonation of a non-Lewis acidic oxazaborolidine (1) with triflic acid. The resulting cationic species (3) are powerful and highly enantioselective catalysts for the Diels-Alder reaction of various 1,3-dienes with alpha,beta-enals. An optimization study (see Table 1) led to the selection of reaction conditions and catalysts (6A and 6B) which are very effective. The reactions are simple to conduct, reproducible, and economical, since only ca. 6 mol % of catalyst is required. In addition, the chiral catalyst precursor is readily recovered for reuse (>95% efficiency) and is commercially available. The broad scope of the process is documented by the 14 examples listed in Table 2. The absolute stereochemical course of the Diels-Alder reactions catalyzed by 6A and 6B was successfully predicted on the basis of the mechanistic principles which have recently been formulated for this type of catalytic enantioselective reaction involving re-face attack by the diene on complex 7. The mode of generation of Lewis superacids 6A and 6B allows an approximate comparison (or scale) connecting the catalytic power Lewis and protic acids.

Enantioselektive Katalyse mit kationischen Oxazaborolidinen

“…In der Folge wurden dann protische Säuren zur Aktivierung von 1 getestet, und die besten Ergebnisse wurden mit Trifluormethansulfonsäure (TfOH) erzielt. [6] Die 1 H-NMR-Analyse einer äquimolaren Mischung von 1 (R = Me) und TfOH in CDCl 3 bei À80 8C zeigte das Vorliegen zweier protonierter Spezies, 5 und 6, in einem Verhältnis 1.5:1 bei einer Konzentration von 0.05 m (Schema 3). Mit Methansulfonsäure und schwächeren Säuren blieb die Protonierung von 1 (R = Me) unvollständig.…”

“…In Versuchen zur Optimierung der Ausbeute und Enantioselektivität dieser Reaktion, bei denen neben anderen Reaktionsparametern der Substituent am Bor variiert wurde (Tabelle 1), ergab ein o-Tolyl-Substituent am Bor die besten Ergebnisse. [6] Der CAryl-Substituent 3,5-Dimethylphenyl (m-Xylyl oder Mexyl) lieferte geringfügig bessere Ergebnisse als Phenyl, vermutlich wegen seiner höheren Basizität in seiner Funktion als be-nachbarte p-reiche aromatische Gruppe. [1,5,7] Angesichts des bevorzugten Vorübergangszustands 8 (Abbildung 1), den wir ähnlich in früheren Arbeiten schon beschrieben hatten, [1,7] entsprach die hoch enantioselektive Bildung des Addukts 7 aus Cyclopentadien und 2-Methylacrolein der Erwartung.…”

Bicyclo[2.2.2]octanes: Close structural mimics of the nuclear receptor-binding motif of steroid receptor coactivators

“…28,29 The structure of a minor isomer was tentatively assigned as regioisomer 10c, based on steric energy calculations (MacroModel), which predicted it to be the third most stable isomer (The steric energy values for the three isomers are given in brackets). Further synthesis was done on the major, desired isomer, 10a.…”

“…26 Because of secondary orbital overlap, Diels-Alder reactions, when run under conditions of kinetic control, particularly with Lewis acid catalysis, favor products with endo stereochemistry. 27,28 In the reaction of diene 8 with methacrolein 9, three distinct aldehyde peaks were observed between 9.25 and 9.65 ppm, indicating that three isomeric products were formed (Scheme 3). We expected that the 5-alkyl substituent on the 1,3-cyclohexadiene would control facial selectivity, directing dienophile approach from the less hindered side to give the desired stereoisomer, the one having the new dimethylene bridge anti to the C-5 group.…”

Towards the total synthesis of (-)-phorbol for novel anti-cancer studies

“…The method reported by Corey et al 76 for the preparation of the CBS-oxazaborolidine catalyst involved the reaction of amino alcohol 2.18 with boroxine 2.19 using a Soxhlett extractor. In our hands this method failed to afford the desired product, rather a polymeric mixture was observed.…”