The asymmetric synthesis of aziridines

An improved procedure for the preparation of chiral nonracemic N-tosyl-2-alkylaziridines and N,2-dialkylaziridines on multigram-scale

“…General procedure for the synthesis of aziridines 4a-g Et 3 N (1.5 mmol) was added over a cooled (0ºC) solution of the starting N-alkyl β-amino alcohol 1a-d (1.0 mmol), TsCl (1.2 mmol) and DMAP (5mg) in dry CH 2 Cl 2 (100 mL). The mixture was allowed to reach r.t. and stirred at this temperature for 24h., after which a saturated NH 4 Cl solution (50 mL) was added. The mixture was extracted with CH 2 Cl 2 (3 x 30 mL) and the organic fractions were collected, dried over Na 2 SO 4 , filtered and the solvent removed in vacuo affording the wanted aziridines 4a-g after flash column chromatography purification (hexanes/AcOEt 8:2).…”

“…3 For these reasons, many methods have been developed for the asymmetric synthesis of such important chiral intermediates, most of them focused on transformation of substrates from the chiral pool, like α-amino acids or derivatives. 4 Very recently we have reported a very efficient stereoselective ring-opening reaction of aziridines with chiral enolates under double stereodifferentiation conditions, which allowed us to obtain α-methyl-γ-amino amide derivatives in a highly stereoselective way (scheme 1). 5 During our studies, we found that the presence of an electron withdrawing group such as a para-toluenesulfonyl group at the aziridine nitrogen atom which stabilizes the developing negative charge during the reaction was crucial for the ring-opening reaction to occur.…”

Synthesis of N–H vinylaziridines: a comparative study

“…9 Existing enantioselective synthetic routes to aziridines include asymmetric aziridination of alkenes and ringclosure of vicinal hydroxy azides or amino alcohols. 1,10 In an ongoing project, efficient syntheses of both vicinal amino alcohols and N-H vinylaziridines are of great importance, and ring-closure of amino alcohols became the most straightforward route to aziridines. There are several procedures for ring-closure of β-amino alcohols to Nsubstituted aziridines, and the plethora of methods encouraged us to perform a comparative study to find out which is the most effective in the formation of N-H vinylaziridines.…”

“…We chose amino alcohol 1 as model substrate, and the desired transformation to aziridine 2 is shown in Scheme 1. The transformation can be conducted in three general ways: 1) direct ring-closure of amino alcohol 1 to yield aziridine 2 is the most effective strategy, but suffers from the low reactivity of 1; 10 2) Activation of the hydroxy group of 1 into a better leaving group, which should facilitate ringclosure; 3) protection of the amino moiety of 1 should also increase the reactivity towards ring-closure, although a deprotection step is needed to yield 2. The two latter methods need high-yielding reaction steps to compete with the direct ring-closure, as several steps are needed to achieve the desired transformation.…”

Stereodivergent Synthesis of Chiral 2-Alkenylaziridines: Palladium(0)-Catalyzed 2,3-cis-Selective Aziridination and Base-Mediated 2,3-trans-Selective Aziridination

“…[2][3][4][5][6][7][8] Particularly, aziridines bearing an alkenyl [9][10][11][12][13][14] or ethynyl group [15][16][17][18] on one of the aziridine-ring carbon atoms have proven to be extremely useful intermediates for asymmetric preparation of such compounds as alkaloids, 9,10) b-lactams, [11][12][13] vinylglycines, 14) amino allenes, 15,16) amino alcohols, 17,18) and (E)-alkene dipeptide isosteres. [19][20][21][22] Although some stereoselective syntheses of enantiomerically pure 2-alkenylaziridines have been reported, most of the reported methods consist of two processes, formation of the aziridine ring and construction of the olefinic moiety, via several steps.…”