Aziridines carbamate derivatives

The triazoles (45) and (46) are converted smoothly to aziridines (47) using a mercury light source <89HCA882>. Allied to this research is the observation that the triazoles (48) and (49) rearrange under acid catalysis to yield the carbamate derivative (50) via cationic intermediates <90C342>. 

Salt 12 (20 mol%) was able to promote the aziridination of aliphatic and aromatic a,p-unsaturated ketones, using tosylated carbamate derivatives and Na COj as base at room temperature, yielding the corresponding aziridines in high yields, diastereo- and enantioselectivities [10]. The reaction seems to be tolerant towards steric and electronic demands on the starting olefin systems. These reaction conditions were also applied to cyclohexenone and p-methyl cyclohexenone, leading to the corresponding aziridine with 98% and 73% ee, respectively. 

More recent developments in the field of the Pirkle-type CSPs are the mixed r-donor/ r-acceptor phases such as the Whelk-Of and the Whelk-02 phases.The Whelk-Of is useful for the separation of underiva-tized enantiomers from a number of families, including amides, epoxides, esters, ureas, carbamates, ethers, aziridines, phosphonates, aldehydes, ketones, carboxylic acids, alcohols and non-steroidal anti-inflammatory drugs.It has been used for the separation of warfarin, aryl-amides,aryl-epoxides and aryl-sulphoxides. The phase has broader applicability than the original Pirkle phases. The broad versatility observed on this phase compares with the polysaccharide-derived CSPs... 

One transformation that is closely related to the synthesis of carbamate esters from alcohols, amines and C02, is the formation of cyclic urethanes, such as oxazolidin-2-ones, by reaction of C02 with 1,2-amino alcohols or their formally dehydrated derivatives, aziridines. 

Some interesting intramolecular variants have been reported. For example, homoallylic alcohols (e.g. 139) can be treated with sulfamoyl chloride to form the corresponding sulfamates (140), which then engage in a direct intramolecular copper-catalyzed aziridination mediated by iodosylbenzene <02OL2481>. A carbamate tether is also effective in delivering the nitrene center to the olefin, as is the case with the cyclohexenyl derivative 142, which spontaneously cyclizes in the presence of iodosylbenzene <02OL2137>. The acetoxy-aminoquinazolinone 144 is converted to the lactone 145 via intramolecular aziridination upon treatment with lead tetraacetate and hexamethyldisilazane (HMDS) <02TL2083>. 

The reaction proceeds with total regio- and diastereoselectivity, as shown by H-NMR spectroscopy. /J-Iodo isocyanates are generally unstable, their purification is difficult and it is convenient to convert them into more stable derivatives. /Hodo carbamates were readily and stereose-lectively prepared by warming the isocyanate with an appropriate alcohol and successive thermal nucleophilic displacement yielding 2-oxazolidinones, e.g., 19 - 20 (see Table 3). Furthermore, when trans-iodo isocyanates were treated with an alcohol in basic medium, the carbamates form first and were immediately converted into the corresponding aziridines, e.g, 19 -> 21. 

Ethoxycarbonylamino)cyclohcxanoncs were obtained in low yield by hydrolysis of the aziridines formed by the addition of ethoxycarbonyl nitrene, generated in situ from 4-nitro-phenylsulfonyl carbamates, to enamines prepared from substituted cyclohexanones61,62. By the same method, optically active 2-(ethoxycarbonylamino)cyclohexanone 3 was prepared in low yield from the enamine 1 derived from an optically active 2-substituted pyrrolidine63. 

Minakata and coworkers also reported the asymmetric aziridination reactions of electron-deficient olefins using cinchona-based PTCs 33-37 and N-chloro-N-sodio carbamate as an oxidant [32]. Moderate values of the ee were obtained. Comparative experiments revealed that the electron-deficient olefin bearing both the dimethylpyr-azole and the di-isopropylpyrazole groups turned out to be a better Michael acceptor than that bearing the oxazolidinone substituent. The modification of the R-substit-uent of the cinchona-derived anthracenylmethylated ammonium salts 35-37 did not have any effect on the enantioselectivity (Scheme 5.26). 

A synthesis of 3 starting from a conformationally flexible D-mannitol A-Boc bis-aziridine derivative 81 has been reported (Scheme 14). The cyclic carbamate-protected pyrrolidine 82 was obtained from 81 via the regioselective bis-aziridine ring opening with Li2NiBr4, followed by Ag+-promoted intramolecular substitution of the bromide by the N -Boc group in 75% overall yield. Nitrous acid deamination of 82 with isoamyl nitrite led, in 50% yield, to a 1 1 mixture of cyclic carbamate protected pyrrolidines 84 and 85 via the intermediate... 

Aliphatic and aromatic amines are also widely available from nature or industry. However, studies on their chemical transformation through transition metal-catalysed carbon-nitrogen bond cleavage are relatively scarce. Recently, several nickel-catalysed transformation of amine derivatives including aryl or benzylammonium salts, N-atyl amides and carbamates, as well as JV-sulfonyl aziridines were reported. 

Making use of the stereochemically matched combination of a chiral auxiliary and a chiral ammonium catalyst, Minakata and coworkers succeeded in developing a highly diastereoselective aziridination of electron-deficient alkenes with iV-carbamate chloramine salts [60]. For example, in the presence of a cinchonidine-derived ammonium salt as an organocatalyst, the reaction of the enone that has L-mentho-pyrazole moiety as an auxiliary with iV-Boc chloramine salt gave diastereochemicaUy pure aziridine in 77% yield (Scheme 2.39). 

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