Aziridine ring oxazolidines

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. 

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

The same group prepared N-(/S-D-glucopyranosyl)oxazolidine-2,4-diones [146] and N-(/l-D-glucopyranosyl)imidazolidine-2,4-diones [147] by desulfurization-condensation of glucosyl isothiocyanate with a-hydroxyacids and J -substituted a-aminoacids, respectively, in the presence of silver triflu-oroacetate and triethylamine. 4-Glucosyl-l,2,4-oxadiazolidine-5-thiones were also prepared by reaction of protected glucosyl isothiocyanates with an ox-aziridine ring [148]. 

Incorporation of carbon dioxide into the aziridine ring gives oxazolidin-2-ones (4.35) [83, 155-174]. 

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>. 

C, and then three molecular equivalents of acetyl chloride and triethy-lamine were added. Three types of acetylated materials, 11, 12, and 13, were isolated accompanied by a small amount of thioketone 7 and thioamide 9 (Scheme 8 and Table 6). All of the acetylated materials showed optical activity. For the reaction of 6a, 84% ee of 2-(acetylthio)aziridine 11a, 50% ee of 4-(acetyl-thio)oxazoline 12a, and 20% ee of 4-(acetylthio)oxazolidin-2-one 13a were obtained in 39,10, and 16% yields, respectively. In the reaction of 6b,c, the corresponding optically active materials 11-13 were obtained as shown in Table 9. The formation of oxazoline 12 involves the rearrangement ofAT-acyl aziridines, which occurs by intramolecular attack of the carbonyl oxygen at the ring carbon to cause rupture of the system. 

Azomethine ylides can be generated from oxazolidines in the liquid phase by thermolysis and in the gas phase by FVP (90TL6017 92T8947). Depending on the other substituents and the FVP conditions, from 2-isopropyloxazolidines (41) either aziridines or enamines, or a mixture of them, are obtained by ring closure or hydrogen shift of the azomethine ylide. 

Aliphatic aldehydes and ketones react with aziridines to form relatively stable half aminals, eg, aziridine reacts with formaldehyde to form Ai-hydroxymethylaziridine [20276-43-1]. Half aminals can be converted to full aminals by reaction with a further secondary amine, isomerized to oxazolidines by the action of heat or used in a Mannich reaction for the ring aminomethylation of phenols, although this reaction gives only moderate yields (218-227). 

Arylcyclopropanes and their heterocyclic analogues are liable to electron transfer induced fragmentation of a carbon-carbon bond that in some cases leads to synthetically useful products. Thus, 1,2-diarylcyclopropanes [240-243] as well as 2,3-diaryloxirans [244-246] and -aziridines (in the last case, also 2-monophenyl derivatives) [247,248] are cleaved upon photoinduced electron transfer sensitization. The final result, after back electron transfer, is trans-cis isomerization of the ring. In the presence of a suitable trap, however, a cycloaddition reaction takes place, involving either the radical cation or the ylide. Thus, dioxoles, ozonides or azodioxoles, respectively, are formed in the presence of oxygen and oxazolidines have been obtained from cyclopropanes in the presence of nitrogen oxide (Sch. 23). 

Dipolar cycloaddition methodology has also been utilized in a one-pot three-component system to generate oxazolidines 292 <2005T6088>. Reactions between sulfonyl azides and vinyl ethers, for example 289, generated aziridine intermediates 290, which then reacted via ring-opened zwitterionic intermediate 291 with aldehydes to generate the oxazolidines in good yields (Scheme 82). 

Amino alcohols. By decomposition of allylic azidoformates to produce bicyclic oxazolidinone substrates for ring opening reactions, a stereoselective entry into jyn-1,2-amino alcohols is delineated. Thus, after treatment of the aziridines with organocopper species, trani-4,5-disubstituted oxazolidin-2-ones (14 examples, 55-91%) are obtained. 

The reaction with azomethine ylides is an important dass of [3+2]pyrrolidine derivatives of > (Figure 2.60). Immonium salts, aziridines, oxazolidines or silylated ammonium compounds are sources of the yUde structure. The sequence is often carried out according to Prato in a first step an amino acid (like N-methylglycine) is reacted with an aldehyde or ketone. Subsequent reaction with C > then gives the desired pyrrolidine derivative. A multitude of these is accessible by choosing suitable functionalization of the nitrogen atom or the two carbon atoms in the ring (e.g., by choice of a functionalized aldehyde). 

Preparation by Ring-contraction. The photofragmentation of oxazolidines, e.g. (262 R = H or Ph, = aryl), provides a new route to aziridines. The reaction proceeds via the elimination of an aldehyde. 

In 2007, Frauenrath and Flock described the double bond isomerisation of 5-methyl-4//-l,3-dioxin performed upon catalysis with [Nil2(i ,i )-Me-DU-PHOS], which afforded the corresponding chiral dioxins in excellent enantioselectivities of up to 95% ee, along with good yields (Scheme 10.18). These products were further aziridinated and then ring-opened to lead to chiral 4-methyl-l,3-oxazolidine-4-carbaldehydes with 73% de. 

Ghorai et al. reported on regioselective ring opening of monosubstituted A -tosyl aziridines 230 with different aliphatic and aromatic carbonyl compounds, followed by alkylative cyclization with C—N bond formation to give 1,3-oxazolidines 232 with high yields, excellent cis selectivity, and good enantiomeric excess.The oxazolidines can be easily converted into nonracemic amino alcohol 233 by mild acidic treatment (Scheme 40.49). 

According to the proposed mechanism, Lewis acid coordinated reactive aziridine undergoes an Sat2 type nucleophilic ring opening with the carbonyl compounds followed by the C—N bond cyclization to produce the oxazolidine 232 (Scheme 40.50.). 

---