Aziridines allylic 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]. 

The (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

Because the aziridine part of such a molecule can be obtained easily from a double bond system, these reactions constitute a method for converting allyl alcohols into allyl amines via aziridination. 

Protected primary allylic amines 210 are obtained208 as mixtures of (E)- and (Z)-isomers by the combined action of an aldehyde RCHO (R = CgHn, Ph, 4-MeOCgH4, i-CNCgPLt, PhCH=CH etc.) and triphenylphosphine on the aziridine 207 by way of an equilibrium mixture of the betaines 208 and 209. 

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... 

Other types of allylic amination reactions include a variety of indirect approaches such as reduction of a,P-unsaturated imines and oximes, rearrangement of aziridines, and elimination of water from vicinal amino alcohols. However, these reactions will not be considered in this chapter [2]. 

Following the publication of our method, similar procedures were reported by two other groups. One involves the use of bromamine-T as a nitrogen source instead of CT for the aziridination of olefins [14] the other is the copper(I) triflate-catalyzed aziridination and allylic amination with CT trihydrate [7d] (Schemes 8 and 9). 

By a similar process, sodium telluride reacts with aziridine sulphonates 49 bearing a trityl or benzydryl group at the iV-atom affording the corresponding allylic amines 50 (Scheme 24).103... 

Primary allylic amines. Aziridines can be converted into allyl carbamates by reaction with ethyl chloroformate to form N-ethoxycarbonylaziridines followed by thermolysis in benzene at 200-250°, Rearrangement of trisubstituted ethoxycarbonylaziridines is regiospecific. 

The reaction of aryl azides with alkenes in the presence of aluminum trichloride gave different products depending on the structure and the geometry of the alkene, the reaction proceeds via the intermediacy of an aziridine 8 complexed with the Lewis acid. Thus aziridines 9 were cleanly obtained from cycloheptene and (Z)-cyclooctene, however, from cyclopentene and cyclohexene a mixture of allylic amines 10 and /5-chloro amines 11 was produced86- 87. The use of 4-chlorophenyl azide in the reaction with cyclohexene gave only a tar. 

The homologation of aziridines to give allylic amines is an attractive process to a very useful class of molecules. Thus, the reaction of N-protected aziridines with excess dimethylsulfonium methylide provides the homologated allylic amines in excellent yields (Scheme 50) <2005OL3295>. 

N-Allylation of aziridines is often complicated by side reactions. The classical solution to this problem, reductive amination, can also be problematic due to the increased strain energy of the aziridinium intermediate. A way to avoid this difficulty was developed by Yudin and co-workers <2005JA17516, 2004JA5086>. The results obtained showed that NH-aziridines such as 197 or 198 underwent a palladium-catalyzed allylic amination with various allyl acetates affording the desired allylated product 199 and 200 with high levels of regioselectivity and in high isolated yields (Scheme 54). 

Allyl amines 611 and pyrazoles 612 could be obtained by hydrazinolysis of 2-ketoaziridines 610 (Equation 127) <2006TL255>. A variety of aziridines, including N-unprotected, N-substituted, as well as bicyclic enamine and aminal types, were transformed into diversely substituted linear or cyclic products. The hydrazinolysis of homochiral aziridines proceeded without racemization and usually allylamines are obtained in greater yields than the pyrazoles in each case. Addition of hydrazines to /3-hydroxy acylsilanes 613 afforded 3-trimethylsilyl pyrazoles 614 (Equation 128) (TMS = trimethylsilyl group) <2000TL9791>. 

AUylic alcohols and amines. Isomerization of epoxides to allylic alcohols by Te-NaBH probably involves epitelluride intermediates. Formation of allylic amines from aziridines requires the presence of a sulfonyloxy group at the a-position. 

Intermolecular alkyl radical addition to imine derivatives proceeds in aqueous media when indium is used as an SET radical initiator. The one-pot reaction based on radical addition to glyoxylic hydrazone provides an a-amino acid (Scheme 8.94) [126]. A similar indium-mediated radical addition to an electron-deficient C-C bond gives the corresponding adduct. Chiral allylic amines are synthesized in high yields by treatment of 2-iodomethyl N-tosyl aziridines with indium in MeOH under reflux (Scheme 8.95) [127]. 

Of particular note, enantioselective intermolecular allylic amination is also pos sible using this protocol, and no competing aziridination is observed. Cyclic and linear alkenes were selectively aminated with high selectivities (27-31). 

Arylazides will decompose in the presence of [Co(TPP)] and unsaturated hydrocarbons to generate both aziridine and allylic amine product mixtures [88-90], Such a process is capable of oxidizing benzylic C-H bonds as well, though poor catalytic efficiency and problems with product over-oxidation limit the utility of these reactions [91, 92], Detailed kinetics analysis and Hammett studies have led Cenini and coworkers to propose a mechanism that does not involve a Co imido complex, as had been previously suggested. The observation of a Co(III) species by UV/vis spectroscopy strongly implicates a one-electron pathway for this particular amination method. 

Aziridine cleavage. Cob(I)alamin is prepared in situ by Zn reduction of hy-droxocob(III)alamin HCl in the presence of NH4CI. Fused mcso-aziridines are cleaved to chiral allylic amines. 

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