A C₂‐Chiral Bis(amidinium) Catalyst for a Diels−Alder Reaction Constituting the Key Step of the Quinkert−Dane Estrone Synthesis

Abstract

A novel C 2 -chiral bis(amidinium) salt 12 has been synthesised from 5-(tert-butyl)isophthalic acid. The hydrogenbond-mediated association of dienophiles 3a and 3b with the chiral host molecule 12 accelerates the Diels−Alder reactions with diene 2 by more than three orders of magnitude. In addition, enantioselective formation of the desired adducts is (ϩ)-Estrone 1 and related 19-nor steroids form a prominent group of targets for organic synthesis.[1] Up to now, a considerable number of useful synthetic strategies have been proposed. Dane's early suggestion to assemble the steroidal skeleton in a DielsϪAlder reaction of diene 2 and the unsaturated diketone 3a as dienophile is certainly among them.[2] Upon closer examination, however, the reaction of 2 and 3a turned out to produce mainly the wrong adduct, rac-4a, accompanied by small amounts of the useful intermediate rac-5a (Scheme 1). [3] As in other cases of DielsϪAlder reactions, the ratio of constitutional isomers in the cycloaddition of diene 2 and dienophiles of type 3 is sensitive to the presence of Lewis acids. Thus, it has been shown by Quinkert and co-workers

Modulation der Acidität – hoch acide Brønsted‐Säuren in der asymmetrischen Katalyse

“…Als Katalysator fungierte hier ein chirales Amidiniumsalz, das die gewünschten Produkte in guten Selektivitäten lieferte. [16] Eine effizientere Methode wurde wenig später von Yamamoto und Nakashima am Beispiel einer Reaktion von Ethylvinylketon mit verschiedensten Dienen beschrieben. [6] [17] Der hohe sterische Anspruch der 3,3'-Arylreste schützt vermutlich den Katalysator ent-16 b vor einer ähnlichen Nebenreaktion.…”

Copper(II)- and Palladium(II)-Catalyzed Enantioselective Claisen Rearrangement of Allyloxy- and Propargyloxy-Indoles to Quaternary Oxindoles and Spirocyclic Lactones

“…Bisamidinium catalyst C1 21 gave complete conversion and 16% enantiomeric excess while 80% conversion and racemic product were observed with sulfonamide C2 . Urea C3 also gave 80% conversion, with 6% enantiomeric excess.…”

Modulating the Acidity: Highly Acidic Brønsted Acids in Asymmetric Catalysis

“…The first example of a Brønsted acid catalyzed enantioselective Diels-Alder reaction employing unsaturated diketones as the dienophiles and chiral amidinium ions catalysts was described by Göbel and co-workers, and products were obtained with good selectivity. [16] A more effective protocol was later established by Yamamoto and co-workers, who investigated the reaction of ethyl vinyl ketone with various dienes. [6] The first attempts were conducted with catalytic amounts of the well-known, BPA ent-15 a.…”