Asymmetric Synthesis of N‐Fused 1,3‐Oxazolidines via Pd‐Catalyzed Decarboxylative (3+2) Cycloaddition

Abstract

Efficient synthesis of optically active Nfused 1,3-oxazolidines containing quaternary and tertiary stereocenters was achieved via Pd-catalyzed asymmetric (3 + 2) cycloadditions of sulfamatederived cyclic imines and vinylethylene carbonates. Using a chiral phosphoramidite ligand, the cycloadditions proceeded effectively providing sulfamidate-fused 1,3-oxazolidines in high yields (up to 96%) with stereoselectivities (up to 25:1 dr; > 99% ee). Additionally, the scale-up reaction and further transformations of the product were also achieved demonstrating the synthetic utility toward the construction of useful heterocycles such as chiral oxazoline bearing a quaternary stereocenter.Scheme 2. Gram-scale synthesis of sulfamidate-fused 1,3-oxazolidine 3 a and its further applications.

Synthesis of 2-Oxazolines from Ring Opening Isomerization of 3-Amido-2-Phenyl Azetidines

“…The results (Table 1) showed that the isomerization of 3a did not occur at reflux in 1,2dichloroethane ( The isomerization of amide 3a was examined in different conditions (Scheme 3, Table 1). The results (Table 1) showed that the isomerization of 3a did not occur at reflux in 1,2dichloroethane ( [6][7][8][9][10][11][12][13][14][15][16]. In search for a better additive, we explored Brønsted acids such as HClO4, CF3SO3H, CH3COOH and CF3COOH (TFA).…”

“…They are also widely applied as synthetic intermediates, protecting, activating and directing groups in organic synthesis. In addition, the optically active 2-oxazolines are valuable chiral building blocks and famous ligands for asymmetric catalysis [ 7 , 8 , 9 , 10 , 11 ]. There are numerous methods that have been developed for the preparation of 2-oxazolines [ 12 , 13 , 14 , 15 ].…”

Advances in Palladium‐Catalyzed Decarboxylative Cycloadditions of Cyclic Carbonates, Carbamates and Lactones

“…The regioselectivity significantly depended on the ligand. Employing chiral phosphoramidite L3 as ligand, regiospecific [3+2] cycloadducts 1,3‐oxazolidines 15 were obtained in high yields (up to 96 %) and stereoselectivities (up to 25 : 1 dr, >99 % ee ) (eq 1) [12a] . Whereas using chiral phosphine ( S )‐SegPhos as ligand, the seven‐membered 1,3‐oxazepines 16 were mainly obtained in good yields (up to 89 %) and enantioselectivities (up to 80 % ee ) via a [5+2] cycloaddition reaction (eq 2) [12b] .…”

Recent Advances in the Construction of Quaternary Stereocenters via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

“…In 2018, the Kim group described a highly enantio-and diastereoselective [3+2] cycloaddition reaction of vinylethylene carbonates (VECs) and sulfamate-derived cyclic imines (Scheme 16). 50 Two chiral centers were established via Pd-catalyzed DAAA employing CpPd(allyl) and a chiral phosphoramidite ligand L7. The desired sulfamidate-fused 1,3-oxazolidines were obtained in up to 96% yield and excellent diastereoselectivities (up to 25:1 dr) and enantioselectivities (up to 99% ee).…”