Chiral phosphine-mediated intramolecular [3 + 2] annulation: enhanced enantioselectivity by achiral Brønsted acid

Abstract

Enantioselective intramolecular [3 + 2] annulation of chalcone–allenes catalyzed by amino acid-derived phosphines and achiral Brønsted acids has been developed.

Mechanism of Phosphine‐Catalyzed Allene Coupling Reactions: Advances in Theoretical Investigations

“…[23] As shown in Figure 3d, the multistep cyclization process starts from nucleophilic attack by 17 on the allenoate via transition state 19-ts,w hich has an energy barrier of 18.6 kcal mol À1 ,t o form the zwitterionic intermediate 20.W hen benzoica cid is used as ac o-catalyst, ah ydrogen-bonding complex 17' is formed through the hydrogen bond between the active catalyst 17 and benzoica cid. Recently,w ep erformed an investigation of the enantioselective intramolecular [3+ +2] annulation of chalcones 18 bearing an allene moiety.…”

“…[23] When ac hiral phosphine catalysti su sed, moderate to good enantioselective formation of the adduct has been observed experimentally. [23] When ac hiral phosphine catalysti su sed, moderate to good enantioselective formation of the adduct has been observed experimentally.…”

“…Recently,w ep erformed an investigation of the enantioselective intramolecular [3+ +2] annulation of chalcones 18 bearing an allene moiety. [23] As shown in Figure 3d, the multistep cyclization process starts from nucleophilic attack by 17 on the allenoate via transition state 19-ts,w hich has an energy barrier of 18.6 kcal mol À1 ,t o form the zwitterionic intermediate 20.W hen benzoica cid is used as ac o-catalyst, ah ydrogen-bonding complex 17' is formed through the hydrogen bond between the active catalyst 17 and benzoica cid. The nucleophilic addition of phosphine complex 22 takes place via transition state 19-ts' with a free energy barrier of only 15.3 kcal mol À1 ,w hich is 3.3 kcal mol À1 lower than that of the corresponding step without the benzoica cidc o-catalyst.…”

“…In another example, an intramolecular [3+ +2] annulation of 17,w hich contains both chalcone and allenoate moieties, could be catalyzed by phosphine catalysts. [23] When ac hiral phosphine catalysti su sed, moderate to good enantioselective formation of the adduct has been observed experimentally. When benzoica cid is used as an additive, the observed enantiomeric excess( ee)c an be enhanced to more than 99 %.…”

Enantioselective synthesis of mixed 3,3′-bisindoles via a phosphine-catalyzed umpolung γ-addition of 3′-indolyl-3-oxindoles to allenoates

“…We envisaged that the employment of prochiral pronucleophilic 3 0 -indolyl-3-oxindoles in a phosphine-mediated catalytic umpolung c-addition reaction may offer brand new synthetic perspectives -inversion of reactivities of substrates is especially noteworthy. The past decade has seen marvelous advancement of asymmetric phosphine catalysis [39][40][41][42][43][44][45], and in these endeavors, our group introduced a new family of amino acid-based bifunctional phosphines and applied them to a wide range of asymmetric transformations [46][47][48][49][50][51][52][53].…”