Diazo cyclic

XXIII xxin, 1st 1936 3458-3554 Two Cyclic Nitrogens. Stem nuclei Piperazine, 4. Diazo-... 

Diazotization of aminoazoles with free cyclic NH groups can give diazo anhydrides which show many of the normal reactions of diazoniums (67AHC(8U). In the pyrazole series these diazo anhydrides are particularly stable. 

The first /3 -lactam was produced by addition of a ketene to an imine and there are now many examples of this type of approach. The ketenes are most frequently generated in situ from acid chlorides by dehydrohalogenation, but have also been produced from diazo ketones, by heating of alkoxyacetylenes and in the case of certain cyanoketenes by thermolysis of the cyclic precursors (162) and (163). 

In the discussion on the structure of the aliphatic diazo compounds, the question of the existence of isomeric diazo compounds with three-membered rings was never considered. It wms therefore a surprise when the cyclic diazo compounds, i.e. the diazirines, became known their preparation wms published independently by Paulsen and by Schmitz and Ohme. ... 

The cyclic diazo compounds (diazirines 65) are very unreactive compounds. Specially noticeable is the absence of the reactivity toward electrophilic reagents which is characteristic of the linear isomers. Acids or aldehydes which react smoothly with the aliphatic diazo compounds are without action on the cyclic diazo compounds. Iodine does not attack the cyclic diazo compounds. 

The proof of the three-membered structure of the diazirines concludes the discussion on the three-membered ring structure of the aliphatic diazo compounds. The knowm linear aliphatic diazo compounds and the newly prepared cyclic diazo compounds (diazirines) are two independent classes of compounds completely different in their physical and chemical properties. An interconversion of the linear and cyclic diazo compounds has not so far been possible. 

With cyclic a-diazo ketones, e.g. a-diazo cyclohexanone 9, the rearrangement results in a ring contraction by one carbon " ... 

Ring contraction of cyclic diazo ketones (Wolff)... 

The rhodium-mediated reaction of 69 with 2,3-dihydrofuran (a formal dipolar cycloaddition of a cyclic diazo dicarbonyl compound with a vinyl ether) yields 70. Corrqiound 70 can be transformed in a number of steps to 71 a,b <96TL2391>. 

These reactions involve addition of the diazo ester to an adduct of the carbonyl compound and the Lewis acid. Elimination of nitrogen then triggers migration. Triethyloxonium tetrafluoroborate also effects ring expansion of cyclic ketones by ethyl diazoacetate.83... 

B. Ring expansion of cyclic ketones using diazo compounds... 

While screening for p-lactam antibiotics stable to p-lactamases, a strain of Streptomyces lactamdurans was found to contain several such agents which have a 6-a-methoxy group whose electronic and steric properties protect the antibiotic from enzymatic attack. Cephamycin C (29a), one of these substances, is not of commercial value, but side chain exchange has led to much more potent materials. Of the various ways of effecting this transformation, one of the more direct is to react cephamycin C with nitrous acid so that the aliphatic diazo product (29b) decomposes by secondary amide participation giving cyclic iminoether 30. The imino ether moiety solvolyzes more readily than the p-lactam to produce 7-aminocephamycinic... 

Photolysis of the first known cyclic a-diazo-p-oxophosphine oxide 49 is unsuccessful with regard to phosphene formation. There is no evidence for a P/C-phenyl shift, which should lead to 51, nor for a P/C-alkyl shift, which would afford 52 via ring contraction, since none of the expected phosphinic esters could be isolated in methanolM). 

The known examples of carbenoid insertion into an S—H bond have been supplemented by the Rh2(OAc)4-catalyzed synthesis of a-phenylthioketones from a-diazoketones and thiophenol 327). By this method, a number of primary and secondary acyclic a-diazoketones, ethyl diazoacetate and cyclic diazoketones such as 2-diazocyclopentanone, 2-diazo-6-methylcyclohexanone and 2-diazocyclohepta-none were converted at room temperature in good to high yield. 

Gould and coworkers have extensively studied the biosyntheses of the kinamycins, and this work was recently reviewed [5a]. Feeding studies established that the carbo-cyclic skeletons of the kinamycins are constructed from 10 equivalents of 5-acetyl coenzyme A, and the pathway shown in Scheme 3.4 was proposed. The pathway begins with formation of the natural product dehydrorabelomycin (29). A novel ring contraction then occurs to form the cyclopentadienone 30. Feeding studies with /V-15-ammonium sulfate established that the diazo functional group is then installed... 

Mejla-Oneto and Padwa have explored intramolecular [3+2] cycloaddition reactions of push-pull dipoles across heteroaromatic jr-systems induced by microwave irradiation [465]. The push-pull dipoles were generated from the rhodium(II)-cata-lyzed reaction of a diazo imide precursor containing a tethered heteroaromatic ring. In the example shown in Scheme 6.276, microwave heating of a solution of the diazo imide precursor in dry benzene in the presence of a catalytic amount of rhodium I) pivalate and 4 A molecular sieves for 2 h at 70 °C produced a transient cyclic carbonyl ylide dipole, which spontaneously underwent cydoaddition across the tethered benzofuran Jt-system to form a pentacyclic structure related to alkaloids of the vindoline type. 

The photolysis of cyclic diazo ketones in hydroxylic solvents leads to ring contracted carboxylic acid derivatives via this ketocarbene -> ketene rearrangement. Examples of such reactions are given in (2.24)239) and (2.25) 240). In this last example a photoequilibrium between the diazo ketone and its valence isomer, a diazirine, has been observed, both products then eliminating nitrogen to afford the cyclobutane carboxylic acid. 

Cyclic 2-diazo-1,3-diketones have also been utilized to react with diketene to afford the corresponding methylfurans in moderate yields <00JCS(P1)2121>. 

It was demonstrated (83) that the reaction of dinitrostyrenes (28) with aryl diazo compounds RR CN2 afford nitronates (24 g) in good yields. These products contain the nitro group at the C-4 atom in the trans position with respect to the substituent at C-5 (if R =H). Since the reaction mechanism remains unknown, the direct formation of cyclic nitronates (24 g) from pyrazolines A without the intermediate formation of cyclopropanes also cannot be ruled out. 

To select between these two alternative structures it was necessary to synthesize a labeled analog. Three hydrogen atoms of the methyl moiety of the ester group were substituted for deuterium. One of the principal pathways of fragmentation of [M N2]+ ions involves the loss of CH3 radical. Since all R substitutes in diazo ketones 4-1 were also methyls it was important to detect what group exactly is eliminated from the [M N2]+ ion. The spectrum of deuterated sample has confirmed that the methyl radical of the ester moiety leaves the parent ion. As a result the cyclic structure 4-2 was selected as the most probable. The ketene structure 4-3 is hardly able to trigger this process, while for heterocyclic ion 4-2 it is highly favorable (Scheme 5.22). 

FORMATION AND PHOTOCHEMICAL WOLFF REARRANGEMENT OF CYCLIC a-DIAZO KETONES D-NORANDROST-5-EN-3 -0L-16-CARB0XYLIC ACIDS, 52, 53 FORMIC ACID, AZIDO—, tert-BUTYL ESTER, 50, 9 Formylation, with acetic formic anhydride, 50, 2 p-FORMYLBENZENESULFONAMIDE, ... 

Diazirines are the cyclic isomers of the alphatic diazo compounds. Both the diaziridines and the diazirines are starting materials for the synthesis of alkyl hydrazines. 3,3-Pentamethyl-enediaziridine can be hydrolyzed quantitatively to hydrazine. Methylamine may be substituted for ammonia in the procedure resulting in l-methyl-3,3-pentamethylenediaziridine (m.p. 35-36°, yield 62% of theoretical) and then methyl hydrazine. Use of ethylenediamine leads to ethylene bis-hydrazine via a bifunctional diaziridine (m.p. 143-144°, yield 48% of theoretical). Ammonia can also be replaced by w-propylamine or cydo-hexylamine cyclohexanone by acetone. 

Insertion of the carbenes, via a low-lying singlet state close to the ground-state triplet, generated by photolysis of the diazo compounds (128), into the CO bond of cyclic ether solvents (THF, THP, dioxane) gave rise to polyether-bridged azulenes such as (129). ... 

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