Aziridines stereoselective ring opening

One of the key steps in the synthesis of actinomycin D (241 Scheme 3.88) and its serine analogue involved the regio- and stereoselective ring-opening of aziridine 238 with the acid 239 [138, 139]. This transformation took place in methylene... 

The preparation of the required t/ireo-3-methylcysteine component in this synthesis, used the stereoselective ring opening of aziridinesJ62-63 It was shown to be possible to maintain stereospecificity of the reaction using the aziridine ring as an intermediate. 

The photoreactions of pyridinium salts in water give 6-azabicyclo[3.1.0]hex-3-en-2-ols or the corresponding ethers, which can undergo regio- and stereoselective ring-openings of the aziridine by attack of nncleophiles under acidic conditions. These products are useful starting materials for synthesis. " ... 

Cycloadditions. Direct cycloaddition of Me3SiCHN2 to Ai-sulfonylimines afford aziridines with high cij-selectivity. Due to stereoselective ring opening and replacement of the silyl group by a carbon chain offered by the products, synthetic potentials are indicated. 

Fnrther treatment of a-amino homoallylic alcohol 185 with triflic anhydride formed the intermediate aziridine 187 that undergoes regio and stereoselective ring opening to yield the a-hydroxy homoallylic amines 189 (Scheme 25.28). ° These protocols are immensely useful owing to the versatility in obtaining complimentary homoallylic alcohols and amines. 

Substituted 2-haloaziridines are also known to undergo a number of reactions without ring opening. For example, displacement of chlorine in (264) with various nucleophilic reagents has been found to occur with overall inversion of stereochemistry about the aziridine ring (65JA4538). The displacements followed first order kinetics and faster rates were noted for (264 R = Me) than for (264 R = H). The observed inversion was ascribed to either ion pairing and/or stereoselectivity. 

Ring-opening of aziridine-2-carboxylates with alcohols has been reported to give (3-alkoxy-a-amino esters [16, 102]. Treatment of as-aziridine 127 (Scheme 3.45) with alcohol in the presence of a catalytic amount of boron trifluoride etherate afforded P-alkoxy-ot-amino esters 128 in 57-100% yields [16,102a], The reaction is both regio- and stereoselective, affording 128 as the only product. 

With Sulfur Nucleophiles N-Carboxy-protected aziridine-2-carboxylates react with thiols to give P-mercapto-ot-amino acid derivatives. The reaction is usually catalyzed by BF3 and the yields range from fair to excellent [15, 16, 108-111]. With N-unprotected 3-substituted aziridine-2-carboxylates, the ring-opening with thiols usually takes place with anti stereoselectivity, especially in the case of the C-3 aliphatic substituted substrates. In cases in which C-3 is aromatic, however, the stereoselectivity has been found to be a function of the substitution pattern on the aromatic ring 3-p-methoxy ph eri yl-su bs li In led aziridines 143a (Scheme 3.51) and... 

Recently, Lee and co-workers reported an efficient method for the preparation of enantiomerically pure oxazolidin-2-ones from aziridine-2-carboxylates 186 (Scheme 3.68) [128]. This one-pot aziridine ring-opening and subsequent intramolecular cyclization process was highly regio- and stereoselective, affording 187 in high yield. 

Certain reagents promote ring opening and subsequent cyclization to give other heterocycles. For example, di-tert-butyl dicarbonate induces the stereoselective ring transformation of N-alkyl aziridines 159 into oxazolidin-2-ones 160 <96TET2097>. 

Transition state energies have been determined by computation (PM3 and AMI) for the reaction of norbomadiene 74a (X=CH2) and 7-isopropylidenenorbomadiene 74b (X is C=CMe2) with the 1,3 dipoles 23 formed from ring-opening of the A -phenyl and A -benzyl derivatives of aziridine 22 (see, Table 1). These data demonstrate the preference for formation of exo,exo-isomers 75 with norbomadiene in the A -benzyl series, however the energy difference between the transition states for the A -phenyl series is much closer and accords with the drop in stereoselectivity. Introduction of the isopropylidene substituent into the 7-position of the dipolarophile favours formation of the bent-frame isomers 76, especially in the A -phenyl series. These predictions accord well with the stereoselectivities observed experimentally. 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

Using the lithium enolate of a-bromopropionate, trans and cis /V-(p-toluenesul-finyl)-2-methyl-2-carbomethoxy aziridines 191 were prepared from (S)-47.101-103 The -isomers predominate. Regio- and stereoselective aziridine ring-opening leads to efficient asymmetric syntheses of (-)-a-methylphenylalanine (192),102 (+)-a-methyl-p-phenylserine (193),102 (+)-2-methyl-3-phenylpropanoic acid (194a),103 and (-)-2-methyl-3-aminopentanoic acid (194b).103... 

With trifluoromethyl-substituted azomethine ylides, generated in situ by the ring opening of CAV-2-bcnzoyl-l -methyl-3-(trifluoromcthyl)aziridine (2)124 or by protonation of trifluoro-methylated thioamidinium salts, 25 1,3-dipolar cycloadditions with both electron-deficient and electron-rich alkenes can be achieved rcgiosclcctively. However, stereoselectivity depends on both the ylide configuration and electronic interactions. 

Azomethine ylides 221 of the ester-stabilized type can be generated by ring opening of the corresponding ring-fused aziridines and can cycloadd to 2-aryl-1-azirines in a stereoselective manner to give 222 (86JCS(P1)1119). 

Diels-Alder reactions of enantiomerically enriched 2H-azirine 3-phosphon-ates (281), a new class of chiral iminodienophiles, and dienes stereoselectively furnish optically pure, bicyclic aziridine adducts (282). Hydrogenation of (282) results in a ring opening that affords the first examples of optically pure quaternary piperidine phosphonates. Two step synthesis of an enantiomeric pure cyclic phosphite (283) and its application as a chiral phosphorus nucleophile in the asymmetric Michael addition to nitroalkenes (284) provides an efficient... 

---