Catalytic enantioselective aza-Reformatsky reaction with seven-membered cyclic imines dibenzo[b,f][1,4]oxazepines

Abstract

A catalytic enantioselective aza-Reformatsky reaction with cyclic dibenzo[b,f][1,4]oxazepines and ethyl iodoacetate is reported.

Enantioselective addition of Et2Zn to seven‐membered cyclic imines catalyzed by a (R)-VAPOL-Zn(II) complex

“…When (R)-VANOL (L8) was used as a ligand (entry 8), 3a was afforded in 40% yield, but almost as a racemic mixture. Subsequently, we decided to test different chiral aminoalcohols, such as quinine (L9) or diaryl prolinol ligands (L10-L13) used successfully in enantioselective zinc mediated reactions, 13,20 but the enantioselectivities observed were very low. Only Trost ligand 21 L14 (entry 14) gave some asymmetric induction (20% ee).…”

Recent developments in the asymmetric Reformatsky-type reaction

“…In 2017, a related chiral ligand 69 employed at only 10–20 mol % of catalyst loading was reported by the same authors to be capable of catalyzing in combination with ZnMe 2 in ethyl acetate as solvent at 0 °C the enantioselective aza-Reformatsky reaction of seven-membered cyclic imines, such as dibenzo[ b , f ][1,4]oxazepines (X = O) and dibenzo[ b , f ][1,4]thiazepine (X = S) 70a–p [ 50 ]. As shown in Scheme 27 , the reaction of these electrophiles with ethyl iodoacetate ( 47 ) led to the corresponding chiral β-amino esters 71a–p with both high yields (77–99%) and enantioselectivities (79–94% ee).…”

“… Aza-Reformatsky reaction of dibenzo[ b,f ][1,4]oxazepines and dibenzo[ b,f ][1,4]thiazepine with ethyl iodoacetate in the presence of a chiral diarylprolinol ligand [ 50 ]. …”

Catalytic Asymmetric Reactions Involving the Seven‐Membered Cyclic Imine Moieties Present in Dibenzo[b,f][1,4]oxazepines

“…Despite the great potential of catalytic asymmetric aza‐Reformatsky reactions in organic synthesis, they are scarcely mentioned in the literature . Very recently Pedro and Vila described catalytic enantioselective aza‐Reformatsky reactions with dibenzo[ b , f ][1,4]oxazepines as electrophiles. In that report, the authors described the use of a readily available diarylprolinol as a chiral ligand, ZnMe 2 as a zinc source and ethyl iodoacetate as nucleophile in the presence of air, leading to the synthesis of chiral ethyl 2‐(10,11‐dihydrodibenzo[ b , f ][1,4]oxazepin‐11‐yl)acetate derivatives with excellent yields (up to 98 %) and high enantioselectivities (up to 94 % ee ; Scheme ).…”