Epoxide aminolysis

Zaborenko N, Bedore MW, Jamison TF et al (2011) Kinetic and scale-up investigations of epoxide aminolysis in microreactors at high temperatures and pressures. Org Process Res Dev 15 131-139... 

Ring expansions of suitable /3-lactams can also be achieved on treatment with base rearrangement of the Af-substituted azetidin-2-ones (133) occurs in the presence of LDA to give (134) (72JA9261). Aminolysis of the /3-lactam epoxide (135) and the aldehyde (137) affords (136) and (138) respectively (81JHC1239). 

Ring-opening with heteroatomic nucleophiles is certainly among the most thoroughly studied behavior of epoxides, and this reaction continues to be a versatile workhorse of synthetic utility. This is exemplified in the recent literature by the examples of the p-cyclodextrin-catalyzed aminolysis of simple epoxides by aniline derivatives (i.e., 53 - 54) <00SL339> and the synthesis of oxa-azacrown ethers through the treatment of Ws-epoxides 55 with diamines 56. Yields in the latter synthesis are sensitive to the size of the macrocycle and substitution on the bis-epoxide <00TL1019>. 

Catalysis of the aminolysis of epoxides by lanthanide triflates (ytterbium, neodymium and gadolinium trifluoromethanesulphonate) has been reported (e.g. equation 26)68. 

Scheme 13. Enzyme-catalyzed aminolysis and azidolysis of epoxides...

Bartoni, G. Bosco, M. Carlone, A. Locatelli, M. Massaccesi, M. Melehiorre, P., Sambri, L. (2004) Asymmetric aminolysis of aromatic epoxides A facile catalytic enantioselective synthesis of a z-P-amino aleohols Org. Lett., 6 2173-2176. 

Mai, E. Schneider, C. (2007) Scandium-bipyridine-catalyzed enantioselective aminolysis of meso-epoxides., Chem. Eur. J., 13 2729-2741. 

Keywords epoxide, ammonium acetate, aminolysis, microwave irradiation, [1-amino alcohol... 

Keywords epoxide, primary amine, montmorillonite K-10, aminolysis, micro-wave irradiation, /t-amino alcohol... 

One example of neighboring-group participation without the formation of cationic intermediates is the aminolysis of 2-bromoethanols (last example, Scheme4.49). In this instance epoxide formation and opening must be faster or as fast as direct bimolecular substitution of bromide by the amine otherwise no rearranged product would be observed. 

Aminolysis of dissymmetric epoxides by BSMA has been shown to regio- and stereospecifically yield the corresponding iV-bis(trimethylsilyl)methyl (3-aminoalco-hols.224 Double addition has not been observed in these transformations. 

The efficiency of this method was demonstrated in a total synthesis of the antibiotic (-r)-tetrahy-drocerulenin 28 (Scheme 8) and (-h)-cerulenin [11]. Irradiation of complex 22 in the presence of the chiral iV-vinyl-oxazolidinone 24, which is easily prepared from the amino carbene complex 23 [12], leads to the cyclobutanone 25 with high diastereoselectivity. Regioselective Baeyer-Villiger oxidation followed by base-induced elimination of the chiral carbamate yields the butenolide 26 in high enantiomeric purity. This is finally converted, using Nozoe s protocol [13], to the target molecule 28 by diastereo-selective epoxidation (- 27) and subsequent aminolysis. 

In SP preparation of oxazolidinones, the carbamate SP hnker 1.47 attached to a hydroxymethyl SP resin (105) was alkylated with a tosyl-epoxide and cyclized/cleaved at the end of the synthesis by aminolysis of the epoxide with spontaneous cyclization of the amino-alcohol to release the pure oxazohdinone into solution. 

The same differential behavior can be observed with amine nucleophiles. For example, calcium triflate promotes the aminolysis of propene oxide 84 with benzylamine to give 1-(A -benzyl)amino-2-propanol 85, the result of attack at the less substituted site <03T2435>, and which is also seen in the solventless reaction of epoxides with heterocyclic amines under the catalysis of ytterbium(III) triflate <03SC2989>. Conversely, zinc chloride directs the attack of aniline on styrene oxide 34 at the more substituted carbon center <03TL6026>. A ruthenium catalyst in the presence of tin chloride also results in an SNl-type substitution behavior with aniline derivatives (e.g., 88), but further provides for subsequent cyclization of the intermediate amino alcohol, thus representing an interesting synthesis of 2-substituted indoles (e.g., 89) <03TL2975>. 

Overman and Flippin utilized diethylaluminum amides for facile aminolysis of epoxides [71], The procedure involved treating a primary or secondary amine in CH2CI2 with EtsAl (1 equiv.) at room temperature for 30 min, then reaction with epoxide (1 equiv.) overnight. Hydrolysis of the resulting amino aluminate eventually afforded the /8-amino alcohol product in good yield. Aminolysis of cyclopentene oxide with diethylaluminum anilide is shown in Sch. 43 as a typical example. 

The methanolysis, azidolysis, and aminolysis of epoxy benzyl ethers and epoxy alcohols have been reported <93JOCl22l>. All the epoxides studied showed a tendency toward C-3 selectivity when a Lewis-acidic metal cation (Li+, Mg2+, or Zn2+) was added to the reaction mixture, suggesting that the nucleophilic attack in these instances is chelation-controlled (Equation (11), and see Table 2). 

A mild and efficient method for the aminolysis of oxiranes in aprotic solvents using metal ion salts of Li+, Na+, Mg2+, Ca2+, and Zn2+ as Lewis acid has been reported <90TL4661). The reaction rates depend, in addition to the nature of the amine and epoxide, also on the type of the metal ion of the catalyst salt. The stereoselectivity observed in these reactions is complete inversion of configuration. Epoxy carboxylic acids are cleanly ring-opened by primary amines at C-2 to provide a-amino-/ -hydroxy acids <92TL2497>. 

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