Chiral aziridines synthesis

McCoull, W., Davis, F. A. Recent synthetic applications of chiral aziridines. Synthesis 2000,1347-1365. 

Table 1.16 Chiral tert-butylsulfinylimines in asymmetric aziridine synthesis.

Saito has recently reported high yields and enantioselectivities in aziridine synthesis through reactions between aryl- or vinyl-substituted N-sulfonyl imines and aryl bromides in the presence of base and mediated by a chiral sulfide 122 (Scheme 1.41) [66]. Aryl substituents with electron-withdrawing and -donating groups gave modest transxis selectivities (around 3 1) with high enantioselectiv-... 

In addition, these authors have developed the synthesis of chiral aziridine... 

At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

Oxidative amination of carbamates, sulfamates, and sulfonamides has broad utility for the preparation of value-added heterocyclic structures. Both dimeric rhodium complexes and ruthenium porphyrins are effective catalysts for saturated C-H bond functionalization, affording products in high yields and with excellent chemo-, regio-, and diastereocontrol. Initial efforts to develop these methods into practical asymmetric processes give promise that such achievements will someday be realized. Alkene aziridina-tion using sulfamates and sulfonamides has witnessed dramatic improvement with the advent of protocols that obviate use of capricious iminoiodinanes. Complexes of rhodium, ruthenium, and copper all enjoy application in this context and will continue to evolve as both achiral and chiral catalysts for aziridine synthesis. The invention of new methods for the selective and efficient intermolecular amination of saturated C-H bonds still stands, however, as one of the great challenges. 

For reviews about the asymmetric synthesis of chiral aziridines, see (a)... 

Kawahata and Goodman utilized a chiral aziridine 166 as a simple precursor for the synthesis of / -aminoacids <1999TL2271>. The chiral aziridine is prepared in five steps from the corresponding allylic alcohol via a Sharpless asymmetric epoxidation. A one-electron reduction of aziridine 166 with SmG provided the ring-opened aziridine. Protection of the resulting amine as the BOC-derivative provided a 1.6 1 mixture of the BOC-amino ester diaster-eomers 167a and 167b in 66% yield (Equation 50). 

An asymmetric aziridine synthesis was reported through an aza-Darzens reaction of T-diphenylphosphinylimines with a chiral a-bromo enolate of 582 (R = GOGH2Br) <2006T3694>. Asymmetric /7-halomethoxylation catalyzed by silver(l) <2006TA210>, yy -dihydroxylation <2000TA1027>, and epoxidation with different oxidants <2004T6657> of unsaturated sultams 582 (R = GOGR =GR R ) were performed. 

As part of an ongoing research program directed toward the use of chiral aziridines in asymmetric synthesis [36], Andersson, Tanner and co-workers have recently reported the detailed results of their own findings in the field of catalytic asymmetric dialkylzinc alkylation of imines [37dj. Tanner et al. had previously communicated their success in the catalytic asymmetric addition of organolith-ium reagents to imines with C2-symmetric bis(aziridines) [37a, 37b]. This was followed by a preliminary report on the use of aziridino alcohols as well as simple aziridines for the addition of diethylzinc to M-diphenylphosphinoylimines [37c]. The most recent report is an extension of this study, and includes the detailed preparation of the ligands [37d]. 

The addition of aldehydes to carbenoids derived from the Cu-catalyzed decomposition of ArCHNj to form stilbene epoxides is subject to asymmetric induction by 1,3-oxathiane 47 prepared from 10-mercaptoisobomeol and acetaldehyde. The attack of sulfonium ylides derived from 48 on aldehydes also affords epoxides of high optical purity. The same principle underlies a synthesis of chiral aziridines. ... 

Chiral aziridine-2-carboxylates. The generation of enolates and their subsequent cyclization occur when P-benzyloxyamino carbonyl compounds are treated with TiCl -EtjN. Since the chiral substrates are readily available, this reaction realizes a valuable synthesis of chiral aziridines. 

Chiral aziridines have become available starting from oxirane 34 with inversion at the chiral center, as illustrated with the synthesis of 147." As described below, these aziridines can be elaborated with preservation of stereochemistry to afford a wide variety of derivatives. 

D. Tanner, Stereocontrolled synthesis via chiral aziridines. Pure Appl. Chem., 65 (1993) 1319-1328. 

D. Tanner, Chiral aziridines. Their synthesis and use in stereoselective transformations, Angew. Chem., Int. Ed. Engl, 33 (1994) 599-619. 

The synthesis of various proline derivatives has received attention this year. A route to proline itself from pyrrolidine in 45% overall yield has been reported, which appears to be an improvement on previous multistage methods.A one-pot synthesis of racemic 4-hydroxyproline in 30—40% yield from glyoxal and oxaloacetic acid has been developed, and a total synthesis of all four dias-tereoisomers of 3-hydroxy-5-methylproline has been achieved. An asymmetric synthesis of prolines is by addition of malonate carbanions to chiral aziridines derived from amino-acids. ... 

At the same time, Antilla et al. developed a vaulted biphenanthrol (VAPOL)-based magnesium phosphate 20b mediated asymmetric aza-Darzens reaction for the synthesis of chiral aziridine derivatives. The catalyst was prepared in an identical procedure to the previously described process with VAPOL-derived phosphate and magnesium fert-butoxide, and applied in the enantioselective aza-Darzens reaction of N-benzoyl imines 23 and ot-chloro-1,3-diketone 24. The process formed a series of substituted aziridines 25 bearing various substituents at the aromatic ring, with good... 

---