Chiral Phosphoric Acid-Catalyzed Enantioselective and Diastereoselective Spiroketalizations

Abstract

Catalytic enantioselective and diastereoselective spiroketalizations with BINOL-derived chiral phosphoric acids are reported. The chiral catalyst can override the inherent preference for the formation of thermodynamic spiroketals, and highly selective formation of nonthermodynamic spiroketals could be achieved under the reaction conditions.

Asymmetric synthesis of optically active spiroacetals from alkynyl glycols catalyzed by gold complex/Brønsted acid binary system

“…11 More recently, Sarli groups also reported the synthesed of Spiro-N、O-ketals by the using chiral gold(I) complex. 12 Inspired by this finding and the previous work, 5,6 we proposed that the spiroacetals would accessed by cascade intramolecular hydroalkoxylation/ asymmetric At the outset of our study, we investigated a reaction of alkynyl glycols 1a in the presence of 5 mol% PPh 3 AuNTf and 15 mol% of chiral binol-derived phosphoric acid 4a in toluene at room temperature (Table 1, entry 1). To our delight, two different spiroacetal products 2a and 3a were afforded in a total yield of 78% and the ratio of 2:3 was 9:1.…”

Synthesis of 5,6- and 6,6-Spirocyclic Compounds

“…The dihydropyrans themselves are obtained via a variety of methods, the most recent of which include Suzuki-Miyaura strategies [72][73][74]. Other recent developments of Scheme 26 Spirocyclization of an endocyclic enol ether this method include the use of chiral phosphoric acids for the selective synthesis of mono-anomeric spiroacetals [75,76] and an intramolecular oxymercuration/reduction sequence [77,78].…”

“…Two studies using such catalysts for the stereoselective synthesis of spiroacetals have been reported. Nagorny et al [75] have used the chiral phosphoric acids (S)-TRIP 120 and its enantiomer to catalyze the asymmetric dehydrative spirocyclization of dihydropyrans 122 (Scheme 29). Treatment of the achiral substrates with (S)-TRIP afforded the doubly anomeric 6,6-and 6,7-spiroacetals 123 in excellent yield and selectivity.…”

“…Scheme 30 Use of (S)-and(R)-TRIP in the spirocyclization of chiral substrates [75] Using their imidophosphate dimer 121, unsubstituted dihydropyran and dihydrofuran alcohols 130 gave the corresponding spiroacetals 129 in good yield with excellent stereocontrol, favoring the contra-thermodynamic mono-anomeric spiroacetal (Scheme 32). The thermodynamic spiroacetal could also be obtained using ent-121 in comparable yield and enantioselectivity.…”

Einfach und dennoch herausfordernd: Neues zur asymmetrischen Synthese von Spiroketalen

“…Aromatische Spiroketale wurden mit diesem Konzept bisher nicht erhalten, doch dies sollte sehr wohl mçglich sein. [13] Die hier beschriebenen Arbeiten verdeutlichen, mit welchen Herausforderungen die Synthese von Spiroketalen in enantiomerenreiner Form verbunden ist. Die Gruppen von Ding und List bieten hierzu eindrucksvolle und elegante Lçsungsansätze aus dem Bereich der Metall-bzw.…”