Stereoselective Syntheses of Highly Functionalized Imidazolidines and Oxazolidines via Ring-Opening Cyclization of Activated Aziridines and Epoxides with Amines and Aldehydes

Abstract

A mild one-pot stereospecific synthetic route to highly functionalized imidazolidines and oxazolidines via SN2-type ring-opening of the corresponding activated aziridines and epoxides with amines followed by p-toluenesulfonic acid (PTSA)-catalyzed intramolecular cyclization with aldehydes has been developed. The methodology tolerates a variety of functional groups and furnishes the desired products in high yields (up to 92%) with excellent stereoselectivities (de, ee > 99%). Interestingly, imidazolidines were formed as the cis-isomers, whereas oxazolidines were produced as trans-isomers exclusively.

2,5-Bis-(butylsulfanyl)-2,3-dihydro-4H-pyran-2-carbaldehyde in the synthesis of five-membered heterocycles

“…NMR 1 H (CDCl3): δ = 0.84 (t, 3H, J 7.2 Hz, CH3 (SBu)), 0.90 (t, 3H, J 7.3 Hz, CH3 (SBu)), 1.25-1.59 (m, 8H, SCH2CH2CH2 (2SBu)), 2.12-2.42 (m, 4H, CH2 at C-3' and C-4'), 2.50-2.60 (m, 4H, 2SCH2), 6.64 (s, 1H, H-4), 7.08 (s, 1H, =CH), 7.85 (s, H-2). NMR 13 (10), 168 (19), 152 (7), 127 (100), 123 (6), 99 (8), 85 (23), 83 (27), 57 (21), 43 (24)…”

“…It is known that fivemembered nitrogen-containing heterocycles such as oxazole, oxazoline and imidazolidine are important scaffolds for a wide range of naturally-occurring and synthetic bioactive compounds, pharmaceuticals, and additional functionally-important materials. [15][16][17][18][19][20]…”

p-Toluenesulfonic acid-promoted organic transformations for the generation of molecular complexity

“…Imidazolidine and oxazolidine skeletons are widely used as synthetic reagents and catalysts and are found in several natural products and bioactive compounds. 22 Prof. Ghorai 23 developed an effective and simple protocol for the synthesis of highly functional imidazolidines and oxazolidines using inexpensive and easily accessible starting materials (Scheme 14). In this approach, the activated aziridines and epoxides are opened regioselectively by a variety of amine nucleophiles, followed by one pot p -TSA-catalysed condensation with aldehydes producing the corresponding imidazolidines and oxazolidines.…”

Ring-Opening Cyclization (ROC) of Aziridines with Propargyl Alcohols: Synthesis of 3,4-Dihydro-2H-1,4-oxazines

“…For almost two decades, our group has been extensively involved in the synthesis of a wide array of N -heterocycles of contemporary biological and pharmacological interest via S N 2-type nucleophilic ring-opening of activated aziridines/azetidines followed by cyclization following either ROC or domino ring-opening cyclization (DROC) strategies . Recently, we have reported Zn­(OTf) 2 -catalyzed stereoselective synthesis of hexahydroimidazo­[1,2- a ]­quinolones via S N 2-type ring-opening hydroarylation–hydroamination cascade cyclization of activated aziridines with N -propargylanilines .…”