Development of C₂-Symmetric Chiral Spirocyclic Phase-Transfer Catalysts: Synthesis and Application to Asymmetric Alkylation of Glycinate Schiff Base

Abstract

A class of C 2 -symmetric chiral spirocyclic phasetransfer catalysts based on tetramethyl-1,1′-spirobiindane scaffold was synthesized from commercially available bisphenol A in 12 steps with 22−25% total yields, which features a more rigid and stable backbone and smaller dihedral angles and can be easily modified. These catalysts show high catalytic performance in the asymmetric alkylation of tert-butyl glycinate Schiff base at only 2 mol % catalyst loading, giving the target products with up to 92% yield and 98% ee.

Enantioselective β-Selective Addition of Isoxazolidin-5-ones to Allenoates Catalyzed by Quaternary Ammonium Salts

“…Relying on recent reports describing the straightforward synthesis of enantioenriched dialdehyde 5 starting from bisphenol C (4), 23 we were able to develop a procedure to access ammonium salts E as summarized in Scheme 2. 24 Very interestingly, during our initial studies to establish this route for catalysts E, we became aware of a very similar approach reported by the groups of Xu and Bai, 25 who utilized bisphenol A (lacking the two aromatic methyl groups) to access analogous catalyst systems. Remarkably, they showed that these catalysts can be very successfully used already for asymmetric -alkylations, thus demonstrating the potential of this new quaternary ammonium salt catalyst scaffold.…”

“…Analytical Details for Catalyst E1 24 Obtained by starting from (R)-7a (161 mg, 0.18 mmol) as an off-white solid; yield: 159 mg (80%); [] D 24 +96.5 (c 1.0, CHCl 3 ).…”

“…After completion (determined by TLC analysis), the crude product was concentrated under reduced pressure and purified by preparative TLC (silica gel, heptanes/Et 2 O 2:1) to obtain -addition products 12. 24 Obtained as a colorless oil, which solidified upon storage in a refrigerator when using 10 mol% of PPh 3 ; yield: 31.4 mg (84%, 0.084 mmol); R f (heptanes/Et 2 O 2:1) = 0.17.…”

Chiral Ammonium Salt Catalyzed Asymmetric Alkylation of Unactivated Amides

“…We next examined the catalytic activity of C 2 -symmetric chiral spirocyclic quaternary ammonium salts developed by our group recently. 16 To our delight, the catalyst 3b bearing two n-butyl groups attached to the N atom gave chiral product 4a with 56% yield and 23% ee (entry 8). Further screening of catalysts with different aryl groups as side chains showed no significant improvement of enantioselectivity (entries 9-14).…”

Dialkylamino and trialkylammonium groups in close proximity: intra- and intermolecular ways of formation, structural consequences, and properties. A case of metal-free directed ortho alkylation

“…On attempt to quaternise peri -di(pyrrolidino)naphthalene, methyl and ethyl transfer was observed in a practical manner, realised in this communication as a mild and metal-free directed ortho alkylation. The new data obtained expand the synthetic possibilities of compounds with two peri -nitrogen atoms and can be used in the future to create polyfunctional materials with close reaction centres including their chiral variants 19 and investigate nonclassical intramolecular hydrogen bonding with the participation of C–H bonds around the quaternised N atom. 20…”