N,N-Diisopropyl-N-phosphonyl imines lead to efficient asymmetric synthesis of aziridine-2-carboxylic esters

Abstract

Highly diastereoselective asymmetric synthesis of chiral aziridine-2-carboxylic esters is reported for 20 examples with good yields (51–87%) and excellent diastereoselectivities (>99:1 dr for most cases). The modified N-phosphonyl imines are proven to be superior to previous imine auxiliaries for the aza Darzens reaction by using secondary isopropyl to replace primary benzyl group for N,N-diamino protection. In the meanwhile, a special operation by slowly adding the pre-cooled imine solution at −78 °C into the preformed β-bromo lithium enolate mixture at this temperature in the presence of 4 Å molecular sieves was found to be crucial in terms of yields and diastereoselectivity. The present method can provide an easy and general access to β-hydroxy α-amino acids and other important amino building blocks.

3-Arylaziridine-2-carboxylic Acid Derivatives and (3-Arylaziridin-2-yl)ketones: The Aziridination Approaches

“…There are chiral N-phosphinyl imines 2f1 , 2f2 [ 60 , 61 ] and chiral sulfimines 2f3 , 2f4 [ 62 , 63 , 64 ] presented ( Scheme 13 ). N-phosphinyl imines 2f1 have been successfully used in aza -Darzen reaction with enolates generated from esters 15b in ten examples of aziridines cis - 1a7 in 72–82% chemical yields and >80% de [ 60 ].…”

“…N-phosphinyl imines 2f1 have been successfully used in aza -Darzen reaction with enolates generated from esters 15b in ten examples of aziridines cis - 1a7 in 72–82% chemical yields and >80% de [ 60 ]. Better results have been achieved by imines 2f2 : 17 examples of aziridines cis - 1a7 with various 3–aryl substituents and four examples of different esters 1a7 (Ar = Ph) have been obtained in good chemical yields (51–87%) and >98% cis - selectivity [ 61 ]. Chiral tert -butanesulfinyl aldimines 2f3 , 2f4 and ketimines 2f5 were used in series of aziridines cis - 1a7 synthesis [ 62 ].…”

Recent Developments in Asymmetric Aziridination

“…[28] As shown in Scheme 16, their reaction with a pre-generated bbromo lithium enolate provided the corresponding chiral cis-aziridine-2-carboxylic esters in moderate to good yields (51-85%) and general high diastereoselectivities ranging from 92 to > 98% de. [28] As shown in Scheme 16, their reaction with a pre-generated bbromo lithium enolate provided the corresponding chiral cis-aziridine-2-carboxylic esters in moderate to good yields (51-85%) and general high diastereoselectivities ranging from 92 to > 98% de.…”

“…Later, Li et al. investigated other types of chiral imines as auxiliaries in aza‐Darzens reactions, such as N,N ‐diisopropyl‐ N ‐phosphonylimines 28. As shown in Scheme , their reaction with a pre‐generated β‐bromo lithium enolate provided the corresponding chiral cis‐ aziridine‐2‐carboxylic esters in moderate to good yields (51–85%) and general high diastereoselectivities ranging from 92 to >98% de .…”

One-Pot Synthesis of 3-Functionalized 4-Hydroxycoumarin under Catalyst-Free Conditions

“…The concept of group-assisted purification (GAP) techniques, which avoid traditional crystallization and chromatographic purification methods and reduce waste generation from silica and solvents, particularly toxic solvents, was first developed by Li’s group in the design of asymmetric synthesis of new imine reagents [ 21 , 22 ]. To date, GAP chemistry has been used in many asymmetric reactions [ 23 , 24 , 25 ] and MCRs [ 26 , 27 , 28 ]. As part of our current studies on the development of environmentally friendly routes to heterocyclic compounds [ 29 , 30 , 31 , 32 ], we now report an efficient and clean synthesis of 3-functionalized 4-hydroxycoumarin derivatives under catalyst-free conditions.…”