Carbamate //- aziridin

The procedure reported here, which is that of Hassner and Heathcock, is more convenient than the Wenker synthesis of aziridines and appears to be more general. It represents a simple route from olefins to aziridines (via j8-iodo carbamates). Aziridines are also useful as intermediates in the synthesis of amino alcohols and heterocyclic systems. ... 

The most salient commonality among the 210 carcinogens that are positive in Salmonella is the electrophilicity that is intrinsic to the molecule or introduced by enzymatic modification. The former can be thought of as ultimate mutagens and include known or presumable alkylating and acylating agents diazo compounds, nitrosamides, nitrosoureas, dimethylcarbamyl chloride, diaryl alkynyl carbamates, aziridines, oxiranes, thiirane,... 

P-chlorocarbamates which can be converted to aziridines and alkyloxazoUdones (93,115). A/-Chloro-A/-sodiourethane reacts with organoboranes forming A/-alkylcarbamates (114), and with olefins, catalyzed by Os, forming vicinal hydroxy carbamates (116). 

Either the iodo carbamate (96) or the iodo amine salt (94) from above can be converted to the aziridine by refluxing about 2.5 g of the respective product in 100 ml of ethanol which contains 10 ml of water and 10 g of potassium hydroxide for ca. 2 hr. The aziridine is then isolated by pouring the basic reaction mixture into 250 ml water and extracting with 200 ml ether. The ether extract is washed several times with water and dried (MgS04). Evaporation of the ether on a steam bath yields 2j5,3j5-iminocholestane (95, 25-95 %) as a clear oil which solidifies on standing mp 103-105°. This aziridine is not easily crystallized. 

K2CO3, MeOH, 67% yield. These conditions were used to cleave a methyl carbamate from an aziridine. ... 

Very reactive nitrogen mustards and aziridine-containing molecules are usually too toxic for general therapeutic use, but find use in neoplastic disease. Benzodepa (182) is such an agent. Treatment of ethyl carbamate with phosphorous pentachloride leads to cyanate 180 which readily adds benzyl alcohol to produce carbamate 181. Displacement of the active... 

Allylic carbamates have also been cyclized to carbamate-linked fused-ring aziridines. The cyclization of homoallylic carbamates to the corresponding aziridines has not been successful until a recent report <06CC4501>. The reaction of homoallylic carbamate 63 with a rhodium catalyst and iodosobenzene provides moderate yields of the fused-ring aziridine 64. The major byproduct of this reaction is the C-H insertion product 65. The relative amounts of the aziridine to the C-H insertion product could be modulated by the choice of rhodium catalyst. The use of Rh2(OAc)4 provides a 68 14 ratio of aziridine C-H insertion product, while Rh2(oct)4 provides a slightly better 71 6 ratio. 

Nakagawa devised a concise synthetic route to physostigimine (169) where the key step involves the alkylative cyclization of 1,3-dimethylindole (167) with (Z)-aziridine catalyzed by Sc(OTf)3 and TMSC1 to give 168, which, in turn, can be converted into 169 . A similar asymmetric approach to this natural product was also developed by these authors via treatment of tryptophan carbamates with the Corey-Kim reagent so as to induce intramolecular cyclization to the pyrrolo-indole skeleton . 

Bromoethylamine (11.133, R = Br, Fig. 11.18) is a potent nephrotoxin used to create an experimental model of nephropathy. Its mechanism of toxicity is postulated to involve perturbation of mitochondrial function, and its metabolism was investigated in a search for toxic metabolites. In rat plasma, 2-bromoethylamine was converted to aziridine (11.134), formed by intramolecular nucleophilic substitution and bromide elimination [155], Another major metabolite was oxazolidin-2-one (11.136). This peculiar metabolite resulted from the reaction of 2-bromoethylamine with endogenous carbonate to form carbamic acid 11.135, followed by cyclization-elimination to oxazoli-din-2-one. In aqueous media containing excess carbonate, the formation of... 

In rats administered 2-bromoethylamine, urinary aziridine accounted for 15-45% of the dose. The carbamate 11.135 was not detected in urine, whereas oxazolidin-2-one and a tertiary metabolite, 5-hydroxy oxazolidin-2-one, accounted for 0 - 20% and 2 - 12% of the dose, respectively [156], The innocuity of oxazolidin-2-one led to the suggestion that either aziridine or 2-bromoethylamine itself is responsible for mitochondrial toxicity. These studies show that the nephrotoxic 2-haloethylamines undergo two competitive cyclizations with halide elimination, one probably a reaction of toxification, the other clearly a reaction of detoxification. 

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... 

The reaction of azetidines with dinitrogen pentoxide is found to reflect the reduced ring strain in this system compared to aziridines.Accordingly, while the carbamate and V-alkyl... 

Intramolecular rhodium-catalyzed carbamate C-H insertion has broad utility for substrates fashioned from most 1° and 3° alcohols. As is typically observed, 3° and benzylic C-H bonds are favored over other C-H centers for amination of this type. Stereospecific oxidation of optically pure 3° units greatly facilitates the preparation of enantiomeric tetrasubstituted carbinolamines, and should find future applications in synthesis vide infra). Importantly, use of PhI(OAc)2 as a terminal oxidant for this process has enabled reactions with a class of starting materials (that is, 1° carbamates) for which iminoiodi-nane synthesis has not proven possible. Thus, by obviating the need for such reagents, substrate scope for this process and related aziridination reactions is significantly expanded vide infra). Looking forward, the versatility of this method for C-N bond formation will be advanced further with the advent of chiral catalysts for diastero- and enantio-controlled C-H insertion. In addition, new catalysts may increase the range of 2° alkanol-based carbamates that perform as viable substrates for this process. 

Oxidative amination of carbamates, sulfamates, and sulfonamides has broad utility for the preparation of value-added heterocyclic structures. Both dimeric rhodium complexes and ruthenium porphyrins are effective catalysts for saturated C-H bond functionalization, affording products in high yields and with excellent chemo-, regio-, and diastereocontrol. Initial efforts to develop these methods into practical asymmetric processes give promise that such achievements will someday be realized. Alkene aziridina-tion using sulfamates and sulfonamides has witnessed dramatic improvement with the advent of protocols that obviate use of capricious iminoiodinanes. Complexes of rhodium, ruthenium, and copper all enjoy application in this context and will continue to evolve as both achiral and chiral catalysts for aziridine synthesis. The invention of new methods for the selective and efficient intermolecular amination of saturated C-H bonds still stands, however, as one of the great challenges. 

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