Cyclopropylamines rearrangement

Rearrangements Emmons found the reagent suitable for Beckmann rearrangements giving water soluble amides. Thus methyl cyclopropyl ketoxime in the medium of 1, 2-dimethoyethane was treated under reflux with stirring with trifluoroacetic anhydride in 1 hr. and refluxed for 1 hr. more. The cyclopropylamine was obtained. 

Bicyclic lactams 22 with an incorporated cyclopropylamine unit were formed in the three-componenl reaction of pentacarbonyl(dimethylaminocarbene)chromium(0) (21) with di-phenylacetylene and imines. The products, of course, are not formed by way of a cyclo-propanation step of the carbene unit, but rather by way of an intermediately formed coordinated enamino ketone which is trapped in situ by the imine. Instead of the expected [2-1-2] or [4-1-2] cycloadducts, bicyclic lactams are produced through a multistep rearrangement process. 

The high efficiency and stereospecificity of the Curtius rearrangement allows unlimited access to a large variety of cyclopropylamines, both racemic and optically active. Typical examples are given in Tables 2 and 3. 

The synthesis of cyclopropylamines is also conveniently realized through the Hofmann rearrangement of carboxylic amides. Hofmann degradation of cyclopropanecarboxamide gives access to the parent cyclopropylamine (17) in an excellent yield of 82%. ... 

Cyclopropylamine (17) is also prepared in 85% yield by Beckmann rearrangement of the ben-zenesulfonate of l-(cyelopropyl)ethanone oxime (23) followed by alkaline hydrolysis of the resulting amides with potassium hydroxide in water. Cyclopropylmethylamine (24) is isolated as a byproduct in 11% yield. 

Cyclopropanaminyl radicals have been far less studied. When generated by hydrogen abstraction from cyclopropylamines, they rearrange too rapidly for observation by EPR spectro-... 

Upon flash vacuum pyrolysis or under silver nitrate catalysis, a variety of 2-ethenyl-sub-stituted cyclopropylamines 146 cleanly undergo a vinylcyclopropane to cyclopentene rearrangement [129] and afford high yields (up to 95%) of 4-aminocyclopent-l-enes 147, some of which have unprecedented substitution patterns (Scheme 11.37) [130],... 

Dimethyl(succinimido)sulfonium fluorosulfate 2, easily prepared from /V-chlorosuccinimide (1), dimethyl sulfide, and methyl fluorosulfate, reacted with 1-dialkylaminocycloalkenes 3 to give fair yields of (2-dialkylaminocycloalk-l-enyl)dimethylsulfonium fluorosulfates 4 or their thermally rearranged allylic isomers 5.22 23 At elevated temperatures 4 or 5, respectively, reacted with nucleophiles Nu to give c -bicyclo[n.l.O]alkanes 8 or 9 via (Z,Z)-2-aminoallyl cation 6 or trans-bicyclo[n.l. 0]alkanes 12 via ( , Z)-2-aminoallyl cation 10, in fair to excellent yield.23 " 42 Normally, ra-annulated cyclopropylamines 8, resulting from kinetically preferred attack of... 

Another system, which has attracted much interest, is that of the cyclopropyl-methyl cation, for similar reasons to the 2-norbomyl systems namely, the great ease of solvolysis of cyclopropyhnethyl substrates accompanied by formation of rearrangement products. Of particular interest is that regardless of the method of generation of the cationic species the ratio of products is always very similar. Both hydrolysis of cyclopropylmethyl chloride under conditions favoring 1 substitution and diazotization of cyclopropylamine produce cyclobutanol and but-3-en-l-ol as well as cyclopropyhnethanol in approximately 47%, 5%, and 48% yields respectively. Moreover, diazotization of cyclobutylamine also produces the same three alcohols in the same ratios (Scheme 2.38). 

Fig. 4.19 Although a nitrogen radical cation can be detected by rearrangements of cyclopropylamine probes in reactions with horseradish peroxidase (HRP), similar re-...

An efficient and highly stereoselective fluorinative aza-semipinacol rearrangement, in the presence of enantiopure phosphate anion derived from the acids (260), has been described. Under optimised conditions, cyclopropylamines (258) were transformed into p-fluoro cyclobutylimines (259) in good yields and high levels of diastereo- and enantiocontrol (Scheme 69). ... 

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