Ethoxycarbonyl nitrene

Both compounds 190 and 193 are reduced to 9,10-diphenylanthracene (205) by zinc and acetic acid. However, more interest attaches to the formation of anthracenes from anthracen-9,10-imines in nonreducing conditions. The iV-ethoxycarbonyl derivative (192) decomposed at 215° in cyclohexane to 33% of 205, although curiously this product was not obtained if the solvent was previously degassed. Whether or not the reaction involves simple extrusion of ethoxycarbonyl nitrene could not be established, since the expected iV-cyclohexylurethane was not detected. The 9,10-epithioanthracene (194) loses sulfur thermally to give 205. ... 

The ring expansion of arenes by electron-deficient singlet nitrenes is by far the most versatile synthetic route to 1H -azepines. The first l//-azepines were prepared independently in 1963 by Hafner, and by Lwowski, and their coworkers. They found that ethoxycarbonyl-nitrene (Scheme 26, path a R=C02Et), generated by photolysis of ethyl azidoformate, adds to benzene to give initially the unstable azanorcaradiene (227), electrocyclic ring... 

It was formerly considered that nitrenes attack only the carbons atom of thiophene (84CHEC-(4)74i). Since 1984, several S,N-ylides formed by the attack of a nitrene on the ring sulfur atom of thiophene have been prepared (89AHC(45)l5l). Thus, ethoxycarbonyl nitrene with polyhalogenothiophenes forms the S,N-ylide (46) in 44% yield (84CC190). The X-ray crystal structure reveals that the sulfur in such ylides is pyramidal. 

In contrast to the above, the more reactive ethoxycarbonyl nitrene 4 is able to attack the carbonyl group of ketones forming three-membered rings such as compound 90 shown in Sch. 24. The ground state for this nitrene is the triplet state, meaning that the cycloaddition reaction occurs in at least two steps. Indeed is has been found that acetone can be attacked by the reactive intermediate 4 primarily at the carbonyl O-atom (see Sch. 24) the dipolar intermediate is able to add a second acetone molecule to yield the dioxazoline (compound 91) [21]. 

In contrast to that, benzoyl nitrene reacts with acetone yielding the five-membered ring even upon triplet sensitization by excitation of the carbonyl compound with light at wavelengths of >300 nm [20]. Thus, the reactivity of the aroyl nitrene seems to be principally different from that of the ethoxycarbonyl nitrene. 

Ethoxycarbonyl nitrene is able to add to compound 104a with a lower degree of stereoselectivity (d.e. 10%) compared with benzoylnitrene [22]. Nevertheless the addition of alkoxycarbonyl nitrene to unsaturated sugars such as compound 106 has been used in order to synthesize amino... 

In contrast with the metallated 7V-[(arylsulfonyl)oxy]carbamates, it has been known since 1965 that ethyl N-[(p-nitrobenzenesulfonyl)oxy]carbamate 6e is a precursor of nitrene, thus a-elimination of p-nitrobenzensulfonate ion (NsO-) from the anion of ethyl Af-[(p-nitrobenzenesulfonyl)oxy]carbamate 6e leads at room temperature to the formation of (ethoxycarbonyl)nitrene 18 [12a] (Scheme 7). 

Ethoxycarbonylamino acids.1 (Ethoxycarbonyl)nitrene (2), generated by thermolysis of N(ethoxycarbonyl)-N,0-bis(trimethylsilyl)hydroxylamine (l),2 reacts with ketene silyl acetals to form N-protected a-amino esters (3) in 25-70% yield. 

Suitable enamines can react with (ethoxycarbonyl)nitrene, generated from ethyl 7V-(4-nitrophenylsulphoxy)carbamate, giving relatively unstable aziridines103. Diaster-eoselective attack of this nitrene on the double bond of chiral enamine 98 and opening of the intermediate aziridine (197) afforded enantiomerically enriched 2-ethoxycarbony-laminocyclohexanone 198104,105 (equation 42). 

Ethoxycarbonyl nitrene is readily formed by thermolysis or photolysis of cthoxycarbonyl azide (ethyl azidoformate), as well as by the base-induced a-elimination of (4-nitrophenylsulfonyloxy)-carbamate9 13> 158> 159. 

Byproducts in the aziridination reaction with ethoxycarbonyl nitrene were the carbamates formed by insertion of singlet nitrene into the C — H bonds of an alkene (mainly allylic C — H bonds) and hydrocarbon solvent (mainly tertiary C —H bonds)12 14. The formation of carbamates in the photochemical aziridination of cyclohexene was reduced by working at a low concentration of cyclohexene in dichloromethane14. 

The addition of ethoxycarbonyl nitrene, generated by photolysis of ethoxycarbonyl azide or by a-elimination of 4-methylphenylsulfonyl carbamate, to conjugated dienes gave aziridines by 1,2-addition and dihydrooxazoles by rearrangement of the aziridines, generally with low overall yield18. 

The reaction of ethoxycarbonyl nitrene, generated by decomposition of the azide or by the a-elimination method, with enamines gave mixtures of aminimides and a-amino ketone derivatives30.. V-Methoxycarbonyl. A -cyano and N-sulfonyl azides reacted with 1,2-31 and 1,4-dihy-dropyridines32 to afford directly the corresponding aziridines 9 and 10. The configuration of the aziridine 10, relative to the R substituent, was not determined. 

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. 

Of particular mechanistic interest is the photochemistry of ethyl azidoformate which does not normally undergo the Curtius rearrangement (the migratory aptitude of the . oxy group is low), and where the nitrene can be efficiently trap. d, e.g. by acetylenes and nitriles . Lwowski was able to establish the spin state of carbethoxynitrene (ethoxycarbonyl nitrene ) by an elegant method adapted from the work of Skcll on carbenes " - It is based on the assumption, fully justified by the results, that a singlet species deficient in two electrons will add stereospecifically to a double bond. A triplet reactant can accept only one electron at a time and will close the bond with the second electron only after one of the spins has... 

Ethoxycarbonyl nitrene has been termed until recently carbethoxynitrene. We are retaining the older nomenclature in this article, to conform with the extensive work of Lwowski. 

Some 5-membered heteroaromatics react with ethoxycarbonyl-nitrene to form derivatJves of iV-ethoxycarbonylpyrroIes . For example, 2,5-dimethylthiophene gave, in 18% yield, 2,5-dimethyl-iV-ethoxycarbonylpyrrole. This is most easily explained by postulating a 1,4-bridged intermediate ... 

TL5025> with (ethoxycarbonyl)nitrene have been reported. An attempt at asymmetric azi-ridination using a chiral A-nosylcarbamate was reported, but a low yield and low stereoinduction were observed <92T7979>. The a-elimination approach to (ethoxycarbonyl)nitrene is a generally milder and more efficient route to, /V-(ethoxycarbonyl)aziridines than the use of ethyl azidoformate. 

A cyclopropane containing a C-N bond was also obtained when a mixture of ethyl azidoformate and 1-ethoxy-1-trimethylsiloxycyclopropane in acetonitrile was photolyzed at room temperature. The product, l-ethoxy-2-(ethoxycarbonylamino)-l-trimethylsiloxycyclopropane(19), formally resulted from a substitution reaction, but the product is in fact generated by insertion of (ethoxycarbonyl)nitrene into a cyelopropyl C-H bond, keeping the cyclopropane ring intact.Interestingly, if the reactants are dissolved in dimethylformamide or dimethyl sulfoxide and are heated instead, quite different reactions take place. 

The l,6,6a-l -trithiapentalene system (178) reacts with ethoxycarbonyl-nitrene to give, after ring expansion, the little-known 1,3,2-dithiazine derivative (181) (Scheme 20) <83CJCli6i>. The mechanism is believed to proceed by attack of the nitrene at the nucleophilic S position to give intermediate (179) which then is subject to insertion of the nitrogen into the S,—Sea bond. The final product is obtained after cleavage of the Se—Sea bond in (180). 

Ethoxycarbonyl-nitren (I) reagiert durch Insertion in die N — H-Bindung von Carbonsaure-ethylester-imi-den zu Carbonsaure-(ethoxycarbonyl-hydrazonid)-ethylestern (bis 38%)118 ... 

V-ethoxycarbonyl nitrene to an intermediate azepine (33a) (itself formed by nitrene addition to 1.4-di-f-butyl-benzene) gives a 1,2-adduct (34a) which is in equilibrium with the Cope rearrangement product (34b) at 130C. The adducts (34) rearrange under the reaction conditions to give the 1,4-adducts (35a) and (35b). 43... 

Considerable synthetic use has been made of ethyl azidoformate. Typical reactions of this are the additions to double bonds as a path to aziridines. Thus addition of ethoxycarbonyl nitrene to l-ethoxy-2-methyl-l-trimethylsilyloxypropene affords the aziridine 612 that can be ring opened to yield (75%) the diester 613. Addition of the same nitrene to siloxydienes has also been reported One of the common reactions of ethoxycarbonyl nitrene is addition to arenes as a route to azepines. An example of this process is seen in the synthesis of the hexafluoroazepine 614 by addition of the nitrene to... 

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