Azirines, reaction with hydrogen

Catalyt c hydrogenation (palladium or Raney nickel catalyst) surprisingly results in reduction of the carbon-nitrogen single bond rather than the double bond.4,12,40 The imines, or possibly enamines, are usually not isolated and their existence has only been inferred in most instances. Harvey and Ratts have shown that this reaction with azirine (165) does not proceed first to the aziridine which is then reduced to 166, since aziridine (167) is inert to hydrogen and palladium on carbon.40... 

The reaction of 2//-azirines (e.g.. 1) with hydrogen fluoride in pyridine [pyridinium poly(hy-drogen fluoride). Olah s reagent] gives /f,/f-difluoro amines (e.g., 7) or a-fluoro ketones (e.g., 5) (Table 10). In some cases, pyrazines (e.g.. 9) are the main reaction products (Table IQj 31-35 2//-Azirines arc more reactive than aziridines towards pyridinium poly(hydrogcn... 

Possible pathways to the pyridopyridazinones are shown in Scheme 3. One route (path a) involves initial 1,3-dipolar cycloaddition of the JV-imine with the cyclopropenone and subsequent opening of the cyclopropanone ring with transfer of the amino hydrogen to afford 41. An alternate route (path b) is very similar to that proposed for the reaction with 2//-azirines (Section IV,A,6). 

The use of potassium <-butoxide as the base directly produced a low yield of 1-azirine contaminated with propiophenone. However, Nair has reported that azirine (37) can be prepared from hydrazone (34) in 63% yield by using the dimethylsulfinyl carbanion as the base. Even if the a-hydrogen is tertiary, this does not always ensure success of the reaction. Treatment of 38 with sodium isopropoxide... 

The photochemical cycloaddition of azirine 35 with cyclopentanone has been found to depend on the experimental conditions. When 35 is irradiated and cyclopentanone is slowly added, the expected s/ /ro-S-oxazoline 53 is the main productHowever, when the cyclopentanone is irradiated first and the irradiation is continued in the presence of azirine 35, the sole product is 3-oxazoline 54. Under the latter conditions, cyclopentanone reacts first by a Norrish type I cleavage and hydrogen transfer to yield 4-pentenal. This aldehyde reacts faster with the nitrile ylide than does the cyclic ketone still present, so that only 54 is formed. Norcamphor and camphor also react with azirine 35 under photolytic conditions via the Norrish type I reaction route to give 3-oxazolines 55 and 56. 

When both a-positions of the oxime possess active hydrogen, the regiochemistry of the Hoch-Campbell reaction prefers the side with more available hydrogens— indicating the process is kinetically controlled. In case of oxime 36, azirine 37 was not formed. Instead, azirine 38 was obtained exclusively. Addition of the third equivalent of the Grignard reagent delivered aziridine 39 as a mixture of two diastereomers. 

There have been a number of reports where alicyclic-bridged precursors underwent an IAAC reaction. Thus, the dioxolane (203b), formed from triflate (203a), cyclized in situ to a tricyclic triazoline (Scheme 63).113 Treatment of this triazoline with sodium ethoxide converted it to a diazopyrrolidine in 86% yield, which underwent smooth catalytic hydrogenation in 89% yield. The (Z)-azidoalkene (204), bridged by a (3-lactam, cyclized at 20 °C to triazoline (205).114 The triazoline (205) extruded nitrogen at 80 C providing a tricyclic aziridine. The ( )-isomer of (204) did not cyclize to a triazoline but instead produced an azirine, presumably via a nitrene intermediate. 

Apparently, this method is affected by the type of hydrogen that is available on the a-carbon. As Sato and previous workers discovered, this reaction proceeds well if the a-hydrogen is tertiary. Thus, spiro-1-azirine (33) is prepared in 80% yield when 32 is treated with sodium isopropoxide. 

The reaction of 34, which contains a secondary hydrogen alpha to the hydrazone, with sodium isopropoxide gave a mixture of alkoxy-aziridines (35 and 36). On heating, 35 and 36 partially eliminated isopropanol to give the 1-azirine (37). 

One of the best known reactions of 1-azirines is the acid/catalyzed hydrolysis to aminoketones. Since the Neber reaction also accomplishes this same synthetic end, this reaction may appear to have little practical value. This is not the situation because with the Neber reaction there is no control over the aminoketone that will be obtained from a given ketone. For example, when oxime (127) derived from benzyl methyl ketone (126) is subjected to the Neber reaction aminoketone 128 is obtained.59 The amino function is substituted for the most acidic a-hydrogen. The isomeric aminoketone (132) that could not be prepared by the Neber reaction can be formed by the hydrolysis of 1-azirine (131). The synthesis of this 1-azirine has been accomplished from allyl benzene (129) through vinyl azide (130) using iodine azide.22... 

The reaction of azirines with Grignard reagents is an anomalous reaction of imines. Normally an a-hydrogen is abstracted to give the enamine anion which is unreactive toward further attack of the Grignard reagent.64 The enamine derived from a 1-azirine is a 2-azirine (146) it is an unknown and probably unstable compound (Section I,A). 

The reaction of 2//-azirines with pyridinium poly(hydrogen fluoride) can be carried out in benzene, tetrahydrofuran, or without solvent, under mild conditions and short reaction times. 

Difluoro Amines and a-Fluoro Ketones by the Reaction of 2//-Azirines with Pyridinium Poly(hydrogen fluoride) General Procedure ... 

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