Optically active aziridines

This conversion has been used as a key step in the preparation of optically active aziridines from optically active 1,2-diols (prepared by 15-46). ° Even hydrogen can be the leaving group. Benzylic hydrogens have been replaced by N3 by treatment with HN3 in CHCI3 in the presence of DDQ (p. 1511). °°... 

Optically active aziridines have been prepared in high enantiomeric excess by the enzymatic resolution of meso diesters (94AG(E)599). For example, when the me o-bis(acetoxymethyl)aziridine (56) was subjected to enzymatic hydrolysis with lipase Amano P, the aziridine (57) was obtained in 98% ee (90TL6663). 

The required chiral sulfur ylide of type 59 is formed in a reaction with a diazo compound in the presence of an achiral metal catalyst. Subsequently, asymmetric reaction of the chiral ylide 59 with the C=N double bond of the imine proceeds diastereoselectively and enantioselectively, giving the optically active aziridine 57. The chiral sulfide catalyst released is then used for the next catalytic cycle. The cat-alytically active species in the asymmetric process is the sulfide, so this concept can also be regarded as an organocatalytic reaction. 

After transformation of the optically active aziridine 218 into the corresponding sulfide 219, oxidative chlorination and cyclization yields the /3-sultam 220 with the same configuration as the parent starting material (Scheme 74)... 

As an approach to the synthesis of piperidines with stereocontrol, multiple functionality, and flexibility, the authors employed a [3+3] cycloaddition reaction of a silylpropenyl acetate with aziridines in the presence of a palladium catalyst. The key intermediate is a palladium-trimethylenemethane (Pd-TMM) complex <03JOC4286>. Optically active aziridines gave enantiomerically pure piperidines. 

The efficient synthesis of optically active aziridines starting from optically active amines or amine derivatives, via the corresponding nitrenes or /V-acetoxy derivatives, has not as yet been realized. 

The optically active aziridine ( + )-20 was prepared from (—)-(Z)-cyclooclene, via the dihydro-triazole (+)-1981. Similarly, the optically active dihydrotriazole was obtained in low yield, from partially resolved, optically active 1,2-cyclononadiene109. These results are consistent with a concerted cycloaddition mechanism. 

The first group led by Hudlicky reported a synthesis of (-l-)-7-deoxypan-cratistatin (210) and (-l-)-pancratistatin (211) starting with a key intermediate, the optically active aziridine derivative 232 (derived from 3-bromo-15,2S-0-isopropylidenecyclohexa-3,5-diene) (155). A full paper regarding these efforts has been published (156) (Schemes 23 and 24). 

However, at this stage relatively little progress has been made in research on asymmetric catalytic carbene transfer to imines. In 1995, Jacobsen and Jorgensen reported independently that reaction of ethyl diazoacetate with selected imines can be catalyzed by copper salts [27,28]. In the former case [27], moderate levels of enantioselection were found to be imparted by bisoxazoline ligands associated with the copper catalyst (Scheme 11). The observation of racemic pyrrolidine byproducts in the reaction was taken to support a mechanism of catalysis involving initial formation of a copper-bound azomethine yhde intermediate (Scheme 12 ). Collapse of this intermediate to the optically active aziridine apparently competes with dissociation of the copper to a free azomethine ylide. The latter can react with fumarate formed by diazoester decomposition in a dipolar cycloaddition to afford racemic pyrrolidine. 

Chiral Aziridines.—The optically active aziridines [224 R = H, Me, Ph, 4-MeOC6H4, or 3,4-(MeO)2C6H3] were prepared by heating (223) with NaOEt. Each asymmetric carbon was of S configuration, and H n.m.r. spectra indicated that compounds (224) exist predominantly as the fra .s-conformers. 

By virtue of a deep understanding of his LnM3tris(BINOLate)3 complexes (Ln = rare-earth metal, M = alkali metal) based on evidence from X-ray analysis and other experiments, Shibasaki developed chiral heterobimetallic yttrium(in) lithium(i) tris(binaphtholate) complex 22, which can promote the catal) ic enantioselective aza-Michael reaction of metho g lamine to enones in excellent yields with up to 97% ee as a Lewis-acid-Lewis-acid cooperative catalyst (Scheme 2.17). Transformation of the 1,4-adducts 23 afforded the corresponding optically active aziridines 24 in high yields. 

Montanari and co-workers have prepared the first example of an optically active aziridine where the asymmetry is solely due to a tervalent, nonbridgehead nitrogen atom. Asymmetric chlorination of 2,2-diphenylaziridine with either (lR,2/ )-(—)-isobomyl hypochlorite or the (-f)-W-chloro-sulphoximine (651) gave reasonable yields of optically active 7V-chloro-2,2-diphenylaziridine. 

A 95% yield of tetramisole hydrochloride (59) is obtained by condensation of thiazolidin<2 one or -2-thione with 2-phenylaziridine in the presence of hydrogen chloride. Optically active aziridine yields optically active tetramisole. 

Furthermore, three achiral monothioimides (121) (Ar = Ph, 4-ClPh, and 4-MeOPh derivatives) crystallize in a chiral fashion and the soHd-state photolysis followed by acylation gives optically active aziridines (124), oxazoHdines (125), and P-lactams (126). 

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