Scalable Synthesis of N-Acylaziridines from N-Tosylaziridines

Abstract

N-Acylaziridines are important starting materials for the synthesis of chiral amine derivatives. The traditional methods for producing these activated aziridines have significant drawbacks. The gram scale synthesis of N-acylaziridines by deprotection of N-tosylaziridines and reprotection with N-hydroxysuccinimide derivatives is described. Mono- and disubstituted aziridines perform well, with complete retention of stereochemical purity. The consistently moderate yields are linked to the N-tosylaziridine deprotection step, while acylation with N-hydroxysuccinimide derivatives is highly efficient.

Chemoenzymatic Total Synthesis of ent-Oxycodone: Second-, Third-, and Fourth-Generation Strategies

“…The coupling of 2-bromoisovanillin (10) (to become the A-ring) and cis-dihydrodiol (20) (to become the C-ring) could be performed using the Mitsunobu reaction. cis-Dihydrodiol (20) is produced from phenethyl acetate (35) by enzymatic dihydroxylation, as previously reported. 21 The first Henry reaction would allow the introduction of nitrogen functionality, whereas the second would produce the B-ring with two stereocenters at C-14 and C-9 (Scheme 3).…”

Ammonium Salt‐Catalyzed Ring‐Opening of Aryl‐Aziridines with β‐Keto Esters

“…Unfortunately, during these optimization attempts we observed a very strong influence of the starting material quality on the stereoselectivity of the reaction. First, the aziridine 4 has to be rather clean and especially even very minor quantities of iodine residues originating from the synthesis route lead to a significant decrease of the e.r . In addition, the used β‐keto ester 1 has to be “perfectly clean” as well, as we observed that batches of 1a that contained very small quantities of unidentified impurities (less than 1 % by 1 H NMR) resulted in reduced enantioselectivities down to e.r .…”

Palladium(II)‐Catalyzed C3‐Selective Friedel–Crafts Reaction of Indoles with Aziridines

“…We initially turned our attention to the ring‐opening reaction of 2‐aryl‐ N ‐tosylaziridines, which are readily available from the aziridination of styrene derivatives, with N ‐methylindole. First, we tested a range of Lewis acid catalysts in this reaction and Cu(OTf) 2 (Table , entry 1) and Sc(OTf) 3 (Table , entry 2) both provided the desired product ( 3 ) in good‐to‐moderate yields, but both reactions were accompanied by an inseparable impurity.…”

“…al. : 1‐tosyl‐2‐phenyl aziridine ( 1 a ), 2‐( p ‐tolyl)‐1‐tosylaziridine ( 1 b ), 2‐(4‐bromophenyl)‐1‐tosylaziridine ( 1 c ), 2‐(2‐chlorophenyl)‐1‐tosylaziridine ( 1 d ), 2‐(4‐iodophenyl)‐1‐tosylaziridine ( 1 e ), 2‐(naphthalen‐2‐yl)‐1‐tosylaziridine ( 1 f ), and 1‐tosyl‐2‐methyl‐2‐phenylaziridine ( 4 ) …”