Aminocyclopropane amine

FACILE SYNTHESES OF AMINOCYCLOPROPANES N,N-DIBENZYL-iV-(2-ETHENYLCYCLOPROPYL)AMINE... 

Photochemical Fe(CO)5-induced rearrangement of silylated allyl amine 9 gave N-silylated enamine 1015, which on subsequent Cu-catalyzed cyclopropanation by methyl diazoacetate afforded cyclopropane derivative 11. The use of an optically active catalyst gave an asymmetric induction of 56% ee for the cis isomer and 20% ee for the trans isomer. Further acid-induced ring cleavage afforded the -formyl ester 12, whereas reduction and desilylation produced aminocyclopropane carboxylic acid 13 (equation 2). 

On the other hand, hydrozirconation-transmetalation to zinc, when carried out in THF, can be used to prepare allylic amines. When carried out in CH2CI2, however, a different reaction pathway is followed (Scheme 24). Even more, with a different order of introduction of the reagents, it is possible to obtain diastereoselectively homoaUyhc amines instead of the expected aminocyclopropanes. ... 

During the reaction of the doubly activated allyl halides with primary and secondary amines no 2-amino-substituted cyclopropane derivatives could be isolated, but instead ring-opened products are formed. Primary amines give rise to the formation of aldimines (332) while secondary amines afford formally substitution products (333) . The formation of these products can be explained by ring cleavage of non-isolable electrophilic 2-aminocyclopropanes (331) as outlined in equation 104. 

The isocyanates (9) were transformed into amino derivatives by standard reactions. Acid-sensitive aminocyclopropanes were obtained preferentially from benzyr ) -naphthyl or trifluorethyl-urethanes which were cleaved by hydrogen, EtSNa/DMF or alkaline hydrolysis. The hydrazinolysis of phthalimido compounds obtained from the urethane and phthalic anhydride also was useful Trimethylsilylethanol proved to be advantageous for the isocyanate-amine conversion the resulting urethanes gave amines upon addition of Bu4N p- 161 (e.g. synthesis of amine (21) from truns-crysanthemic acid via isocyanate (20) S equation 3). Contrarily to... 

An interesting, highly selective approach to both diastereomers of some aminocyclopropanes started with diesters of type 63 or 67. Saponification of 63 took place preferentially at the sterically less hindered trans- or exo-position (for references see Table 1). The free acid moiety in 64 could be transformed into an amino compound (66) via the carboxylic azide. Thereby, the ester carboxyl remained unaffected. On the other hand, the ester function of 64 could be converted into the amine (65) via the hydrazide without affecting the acid function (equation 10). Decarboxylation of 64 followed by ester amine... 

The Beckmann rearrangement also allowed the preparation of cyclopropyl-amines 183-189 yy accessible in 68-77 % yield from the reaction of the oxime (76) with tosyl chloride in dioxane or with trifluoroacetic anhydride in dimethoxy-ethane (equation 13). Bicyclic- and tricyclic aminocyclopropanes (79 and 81) could be obtained from ketones (78 and 80) and hydroxylaminic reagents (equations 14 and 15). Further examples are reported in Refs 188a-j. 

Dihydrochinolines 346 and 347 gave in most cases stereospecifically endo-cyano homoindoles (348) upon irradiation in ethanol (equation 85) ". 348 could be equilibrated to a 348/349 mixture upon irradiation in acetone, by heating or by treatment with BF3. An aminocyclopropane derivative was reported to be a side product of the photoaddition of amines to benzene ... 

Cis- and trons-aminals 385 and 230 which could easily be obtained from en-aminosulfonium salts (255) (Scheme 7) or chloroenamines (228) (see equation 54) were usedior the preparation of further sterically pure aminocyclopropanes (equations 93 and 94). 

J.K. Cha et al. developed a stereocontrolled synthesis of bicyclo[5.3.0]decan-3-ones from readily available acyclic substrates. Acyclic olefin-tethered amides were first subjected to the intramolecular Kulinkovich reaction to prepare bicyclic aminocyclopropanes. This was followed by a tandem ring-expansion-cyclization sequence triggered by aerobic oxidation. The reactive intermediates in this tandem process were aminium radicals (radical cations). The p-anisidine group was chosen to lower the amine oxidation potential. This substituent was crucial for the generation of the aminium radical (if Ar = phenyl, the ring aerobic oxidation is not feasible). 

Rearrangement of acyl azides into the corresponding isocyanates 3 is a stereospecific process which occurs with retention of configuration. This conversion usually takes place in refluxing benzene or toluene. The isocyanates thus obtained are subsequently converted into the corresponding amines by heating in dilute aqueous acid (e.g. hydrochloric or sulfuric acid). Acid-sensitive aminocyclopropanes can be obtained via their urethanes (e.g. 6), which may be selectively cleaved under neutral or basic conditions. ... 

The reaction of a simple primary amine, 1-aminocyclopropane, with aqueous lithium hypochlorite takes place readily at room temperature resulting in ring opening. Since the reaction competes with fragmentation to give ethene, the yield of 3-hydroxypropiononitrile, the ring-opened product, is modest (Table 15, entry 5). With 1-amino-1-methylcyclopropane, 4-hy-droxybutan-2-one is formed. 

Aminocyclopropane derivatives were similarly obtained from tertiary amines or nitriles. Whereas the reaction starting from amides requires the use of stoichiometric amount of titanium complexes, the reaction is catalytic with cyanoesters, giving l-azaspirocompounds. In all cases, the enantioselectivity remains too low to be synthetically useful, and efforts are thus needed to improve the enantioselectivity and/or to reduce the amount of catalyst. 

While intermolecular Kulinkovich-de Meijere reaction assembles cyclopropylamine, many have taken advantage of a pendent olefin at the substrates to synthesize bicycles. Cha converted olefinyl amide 51 to bicyclic amine 52 in excellent yields. Six and co-workers prepared eight bicyclic aminocyclopropanes including 54 (from substrate 53) with yields ranging from 26 to 87%. ... 

Interestingly, cyclopropanone hemiacetals provide a rapid way to prepare a-aminocyclopropane-carboxylic acids (ACCs) and phosphonic acids analogues (ACPs). Thus, asymmetric Strecker reaction of hemiacetal with an amine in acidic sodium cyanide selectively affords ci5 -a-aminocyclopropane-carbonitriles, precursors of ACC amino acid derivatives (eq 24). ... 

---