Azidoformates, cycloadditions

The functionalized allene, DIMETHYL 2,3-PENTADIENEDIOATE, the first in the series, is an intriguing substrate for various addition and cycloaddition reactions. Finally, a new reagent, DI-ferf-BUTYL DICARBONATE, for he formation of A-f-BOC derivatives which eliminates the use o the hazardous fert-BUTYL AZIDOFORMATE (WARNING) is intrqduced. 

Analogously to ynamines and o, /3-acetylenic ketones, 4-aminobut-3-yn-2-ones react with 1,3-dipoles (68HCA443 73HCA2427 92KGS867). The reaction of 4-dimethylaminobut-3-yn-2-one with diphenylketene follows a route of [2-1-21-cycloaddition (30°C, THF, 1 h) to give 2-acetyl-3-dimethylamino-4,4-diphenyl-cyclobut-2-en-l-one (377) in 15% yield. With ethyl azidoformate (30°C, THF, 3 h), the tiiazole 378 is formed in 82% yield, whereas with phenyl isocyanate, the quinoline 379 is the product (by a [2- -4] scheme) in 70% yield (68HCA443). 

The reaction of ethyl azidoformate (93) with tetramethylallene yielded triazoline 94 and oxazoline 95 [88]. The triazoline 94 was formed by [3 + 2]-cycloaddition of azide 93 to the allene. The oxazoline 95 may result from [3 + 2]-cycloaddition of car-bethoxynitrene (96), which is formed from 93 by nitrogen evolution, to the allene or by the [2 +1] addition of the nitrene and subsequent rearrangement. 

The thione group of dithiazolethiones is a very reactive heterodipolarophile. In Scheme 18 are given cycloadditions with nitrile oxides <67BSF2239>, diphenylnitrilimine, and ethyl azidoformate <85JCS(P1)1205>. The primary adducts are spiro derivatives, but only compound (131), which is obtained from nitrile oxides is isolable at low temperature. All are decomposed to give respectively compounds (132)-(134) and occasionally nitriles and sulfur. Compound (134) reacts further with nitrilimine affording compound (135) which is also isolated. 

Gallagher and co-workers (11) reported the cycloadditions of electron-dehcient azides with the ketene-(5, 5)-acetals (46) (Scheme 9.11). Reaction of p-toluenesul-fonyl azide with 46 gave the unstable cycloadducts 47, which underwent rearrangement to afford compounds 48 in 24—89% yield. In the case of ethyl azidoformate. 

The stereoselective intermolecular cycloaddition of azides to chiral cyclopenta-none enamines was reported, but both product yields and enantiomeric excesses (ee) were low (24) (Scheme 9.24). Ethyl azidoformate (115) and A-mesyl azido-formamimidate (116) underwent 1,3-dipolar cycloaddition with the monosubsti-tuted chiral enamine 114 to give products 117 and 118 in low yields with ee of 24 and 18%, respectively. Intermolecular cycloaddition of the A-mesyl azidoforma-mhnidate 116 with the disubstituted C2-symmetric chiral enamine 119 proceeded with good diastereoselectivity to give compound 120 in 18% yield. On cleavage of the enamine unit, compound 120 afforded 118 with low ee. 

Aryl azide, acyl azide, sulfonyl azides, and azidoformate add to olefins by a 1,3-dipolar cycloaddition mechanism to yield triazoline. This addition also occurs with other unsaturated systems such as a,/S-unsaturated olefins, enam-ines, and cynamines [48]. 

The thione groups of dithiazolethiones are very reactive heterodipolarophiles. Several cycloadditions with nitrile oxides, diphenylnitrilimine, and ethyl azidoformate to give spiro derivatives have been reported <1996CHEC-II(4)517>. 

Starting from 2-(2-(2-aminophenylthio)-l//-pyrrol-l-yl)acetic acid 60, available through two synthetic steps from o-aminothiophenol, 9//-pyrrolo[2,l -b 1,3,6]bcnzothiadiazocine-10(l l//)-one 61 was obtained in 54% yield (Scheme 11, Section 14.08.5.4 <1995JHC683>). Azidoformate 51 derived from chiral enol ether, when irradiated, gives 3,6-dioxazocan-2-one derivative 52 by a highly diastereoselective intramolecular cycloaddition (Scheme 9, Section 14.08.5.3 <1999EJO2709>). 

Cycloaddition of phenyl azide (106, R = Ph) with methylenecyclopropanes (105) followed by photolysis of the primary products (107) yielded spiro compounds (108), in which the aziridine ring could easily be cleaved by acids leading to 109 and (equation 22). Alternatively, compound 108 (R = COOMe) was formed directly upon irradiation of methyl azidoformate (106) in the presence of excess 105 ... 

The 1,3,4-oxadiazole system is formed on cycloaddition of carbo-alkoxy nitrenes to nitriles. The photolysis of ethyl azidoformate in acetonitrile yielded 2-ethoxy-5-methyl-l,3,4-oxadiazole (210) (yields 52-60%) With benzonitriles yields were much lower . 

Reaction with ethoxyacetyiene. The cycloaddition of ethyl azidoformate with ethoxyacetylene (room temperature, 35 days) is nonregiospecific and leads to the formation of about equal amounts of l-carboethoxy-5-ethoxy-l,2,3-triazole (1) and l-carboethoxy-4-ethoxy-l,2,3-triazole (2). In addition, a trace of the N-2 triazole (3)... 

Note, however, that the reaction of methyl azidoformate with the strained olefin norbornene (11 proceeds by a 1,3-cycloaddition to give the unstable triuzoline adduct (2), which decomposes in refluxing toluene to give the aziridine (3,40%) theimide (4, S3%),gndjtyn-2>norbomene-7-methylcurbamBte (5). ... 

Cycloaddition Cyanogen azide. Ethyl azidoformate. Tetracyanoethylene (cyclobutane formation). Trimethylsilyl azide. 

The thermal or photolytic decomposition of carbonyl azides in the presence of dipole acceptors such as acetylenes provides a valuable method for the construction of oxazoles. Thus the reaction of ethyl azidoformate with either diphenyl- or diethylacetylene produces mainly the 2-ethoxy-oxazole (77 ).166 166 The reaction involves the 1,3-dipolar cycloaddition of carbethoxy nitrene (76b) to the alkyne to give the oxazole (77). On the... 

Thermolysis of ethyl azidoformate, however, produces ethoxycarbonylnitrene, which by a [2+1] cycloaddition reacts with alkenes to form aziridines. The mechanism is thus influenced by the azide substituent Rh... 

It has subsequently been shown <86TL1105> that (146) and (147) are unique only in regard to their stability and not with respect to attack of nitrene at the sulfur atom. In a reinvestigation of the reaction of ethyl azidoformate with several thiophenes it has been shown that S,N-ylides are indeed formed as transient products in every case these could be trapped by cycloaddition with acenaphthylene (see Section 2.10.3.3) leading to fluoranthene derivatives. 

In what the authors suggest might be the first example of a [1 + 3]dipolar cycloaddition, mesoionic-4>thiazolones (130) give imidazolinones (132) upon reaction with ethyl azidoformate, in a multistep process which may proceed via the strained bicycle (131). A similar loss of sulphur occurred during an attempted synthesis of the thienodiazepinone (133), the isolated product being the pyrrolo[l,2-a]imidaz-2(3//)-one derivative (134)/ ... 

Some intramolecular cycloaddition reactions of alkyl azidoformates are particularly successful and have useful applications in synthesis. An example is a route to derivatives of (-)-bestatin, an aminopeptidase inhibitor, in which the key steps are the formation of the bicyclic aziridine 25 followed by ring opening (Scheme 6.13). ... 

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