Alkene derivatives intermolecular amination

Alkene hydroamination has been known for many years, but has been little used as a method in organic synthesis. Tobin Marks of Northwestern recently published a series of three papers that will make this transformation much mote readily accessible. In the first (J. Am. Chem. Soc. 125 12584,2003) he describes the use of a family of lanthanide-derived catalysts for intermolecular hydroamination of alkynes (to make imines, not illustrated) and alkenes. With aliphatic amines, the branched (Markownikov) product is observed, 1 — 2. With styrenes, the linear product is formed. When two alkenes are present, the reaction can proceed (3 —> 4) to form a ring, with impressive regioselectivity. 

The main steps in the currently accepted catalytic cycle of the Heck reaction are oxidative addition, carbopalla-dation (G=G insertion), and / -hydride elimination. It is well established that both, the insertion as well as the elimination step, are m-stereospecific. Only in some cases has formal /r/ / i--elimination been observed. For example, exposure of the l,3-dibromo-4-(dihydronaphthyloxy)benzene derivative 16 and an alkene 1-R to a palladium source in the presence of a base led to a sequential intra-intermolecular twofold Heck reaction furnishing the alkenylated tetracyclic products 17 in good to excellent yields (Scheme 9). " In the rate-determining step, the base removes a proton in an antiperiplanar orientation from the benzylic palladium intermediate. The best amine base was found to be l,4-diazabicyclo[2.2.2]octane, which apparently has an optimal shape for this proton abstraction. 

The [Ir(ppy)2bpy] complex photo-catalyses inter- and intramolecular C-H functionalisation reactions of tertiary amines under the visible light irradiation. Oxygen behaves as a chemical switch, triggering different reaction pathways and leading to different products from the same starting material. In anaerobic conditions, the intermolecular addition of iV,iV-dimethyl-anilines to electron-deficient alkenes yields y-amino nitriles. Aerobic conditions, on the other hand, favour a radical addition/ cyclisation reaction, leading to tetrahydroquinoline derivatives. The intramolecular version of the radical addition produces unexpectedly indole-3-carboxaldehyde derivatives. ... 

Intramolecular oxidative aminations of olefins have alsobeen studied, and many of these intramolecular processes were observed prior to the analogous intermolecular variants. The oxidative aminations of alkenes with arylamines and arylamine derivatives catalyzed by palladium complexes were shown by Hegedus to form indoles (Equation 16.120). These reactions were conducted with orf/io-allylaniline and ort/zo-allylaniline derivatives as substrate, Pd(NCMe)jCl2 as catalyst, and benzoquinone as oxidant. Intramolecular reactions of N-tosylated aliphatic amines were reported by Larock. ° For example, the tosylamide in Equation 16.121 imdergoes cyclization in high yield in the presence of dioxygen with Pd(OAc)j as catalyst in DMSO. A related reaction (Equation 16.122) was reported recently in toluene solvent with added pyridine. ... 

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