Ring allyl amines

The reaction of the vinylcyclopropanedicarboxylate 301 with amines affords an allylic amine via the 7r-allylpalladium complex 302[50]. Similarly, three-membered ring A -tosyl-2-(l,3-butadienyl)aziridine (303) and the four-mem-bered ring azetidine 304 can be rearranged to the five- and six-membered ring unsaturated cyclic amines[183]. 

The first of the nudeophilic ring-opening reactions of vinylaziridines discussed in this section is diborane reduction, developed by Laurent and coworkers in 1976 (Scheme 2.24). Treatment of N-unsubstituted vinylaziridines 89 with B2H6 gives allyl amines 92 by SN2 reduction via cyclic intermediates 90 [40]. In contrast, treatment with 9-BBN gives 2-(hydroxyethyl)aziridines 93 after oxidative workup (Scheme 2.25) [41]. 

Electron transfer to vinylaziridines results in ring-opening reactions, yielding allyl amines. Treatment of 268 with SmI2/DMEA (N,N-dimethylethanolamine) provided allyl amine 269 as a 2 1 mixture of olefmic isomers in 88% yield (Scheme 2.66) [97]. 

The unsaturated oximes 224 (see Table 21) were readily prepared by AT-alkyl-ation of allyl amines with a-bromoketones or O-silyl-a-bromoaldoximes. Heating the oximes 224 in toluene under an argon atm at 110 -180 °C smoothly led to isoxazolidines 225 in good yields with cis ring junction stereochemistry. Even when three stereocenters were generated, as in 225 g-1, a single stereoisomer... 

Heterocycles can be employed as precursors for the synthesis of pyrazoles. Pyrazoles can be synthesized by three-membered ring substrates. For example, allyl amines 12 and pyrazoles 13 could be obtained by hydrazinolysis of 2-ketoaziridines 11 <06TL255>. Regioselective ring opening of 3-aryl-2-benzoyl-l,l-cyclopropanedicarbonitriles 14 with hydrazine provided a new process for the synthesis of 5-aryl-3-phenylpyrazoles 15 <06JHC495>. 

Selenium diimides react with unsaturated organic compounds. (tBuN)2Se is an in situ reagent for allylic amination of olefins and acetylenes. Improved procedures for the diamination of 1,3-dienes have been developed using (RN)2Se (R = /wu-toluenesulfonyl, ort/zo-nitrobenzenesulfonyl).156 The reaction of A iV -dialkyl selenium diimides with fe(amino)stannylenes produces four-membered SnNSeN ring systems.157... 

Scheme 9.42 (Sj-Nicotine via allylic amination in combination with ring-closing metathesis.

Gamez-Montaho et al. described an Ugi variation where the carboxylic acid was replaced with an amide [68]. The amide oxygen is nucleophilic enough to effect ring closure to oxazole intermediates 44, which then undergo aza-Diels-Alder reaction with the double bond of the allylic amine component to form oxa-bridged heterocycles 45, which can either be isolated as a separate class of compounds or converted to pyrrolopyridines 46 by treatment with TEA (Scheme 8). 

The combination of allylic amination, ring-closing metathesis, and a free radical cyclization provides a convenient approach to the dihydrobenzo[b]indoline skeleton, as illustrated in Scheme 10.10. The rhodium-catalyzed aUylic amination of 43 with the lithium anion of 2-iodo-(N-4-methoxybenzenesulfonyl)arrihne furnished the corresponding N-(arylsulfonyl)aniline 44. The diene 44 was then subjected to ring-closing metathesis and subsequently treated with tris(trimethylsilyl)silane and triethylborane to afford the dihydrobenzojhjindole derivative 46a in 85% yield [14, 43]. 

The domino sequence leading to the conversion of 30 to 31 was performed without isolation of the intermediates. The sequence is thought to proceed as shown in Scheme 7.6. Treatment of 30 with benzaldehyde with azeotropic removal of water led to the protection of the amine as the benzaldehyde imine 33, which was directly mesylated to give 34. The solution of 34 was treated with allylamine (4 equiv.) and autoclaved at 112°C for 15 h to provide 31 in 80% yield after acidic hydrolysis. It is assumed that the benzaldehyde imine of 33 is exchanged with allyl amine to form the aminomesylate 35, which undergoes fast ring closure to the aziridine 36. Then allylamine adds to the... 

Additionally, 1,2-dihydroxyethylene dipeptide analogues without the C-terminal carboxylic acid have been used to obtain aspartyl proteases inhibitors.[641 These efforts include stereoselective alkylation of imines, one-pot reductive amination of epoxy ketones, ring opening of epoxides with sodium azide, diastereoselective dihydroxylation of allylic amines, and enzymatic resolution and stereocontrolled intramolecular amidation. 

Dihydropyrroles have recently become readily available by ring-closing metathesis. For this purpose, N-acylated or N-sulfonylated bis(allyl)amines are treated with catalytic amounts of a ruthenium carbene complex, whereupon cyclization to the dihydropyrrole occurs (Entries 6 and 7, Table 15.3 [30,31]). Catalysis by carbene complexes is most efficient in aprotic, non-nucleophilic solvents, and can also be conducted on hydrophobic supports such as cross-linked polystyrene. Free amines or other soft nucleophiles might, however, compete with the alkene for electrophilic attack by the catalyst, and should therefore be avoided. 

Despite the similarity between compound 1 and (-)-swainsonine, a different retrosynthetic strategy was devised for the synthesis of (-)-swainsonine (Scheme 3).19 The ring rearrangement yielded the hydropyrrolidine 5, which was prepared from the precursor 6. The enantiometrically pure oxazolidine derivative 7 was a suitable chiral starting material, as it was efficiently synthesised from the diol 8. As with the synthesis of 1, a palladium (0) catalysed allylic amination was carried out in the presence of ligand L (Scheme 2)14 to give 7 with an ee of 97%, which was increased to >99% on recrystallisation with dichloromethane/hexane. 

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). 

The product of the allylic amination process is set up for a ring-closing-ring-opening metathesis process, and subsequent elaboration to alkaloid derivatives. 

A fourth type of product, a carbamate RNHCOOR , can be obtained from primary or secondary amines, if these are treated with CO, O2, and an alcohol R OH in the presence of a catalyst. " Primary amines react with dimethyl carbonate in supercritical CO2 (see p. 414) to give a carbamate. " Carbamates can also be obtained from nitroso compounds, by treatment with CO, R OH, Pd(OAc)2, and Cu(OAc)2, " and from nitro compounds. " When allylic amines (R2C=CHRCHRNR 2) are treated with CO and a palladium-phosphine catalyst, the CO inserts to produce the p,y-unsa-turated amides (R2C=CHRCHRCONR 2) in good yields. " Ring-expanded lactams are obtained from cyclic amines via a similar reaction (see also, 16-22). Silyloxy carbamates (RNHC02SiR 3) can be prepared by the reaction of a primary amine with carbon dioxide and triethylamine, followed by reaction with triisopropylsilyl triflate and tetrabutylammonium fluoride. ... 

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