Indolizidines, hydroamination

The scope of the lanthanide-mediated, intramolecular amination/cyclization reaction has been determined for the formation of substituted quinolizidines, indolizidines, and pyrrolizidines,1046 as well as tricyclic and tetracyclic aromatic nitrogen heterocycles.1047 The amide derivative OT ro-[ethylene-bis(indenyl)]ytterbium(m) bis(trimethyl-silyl)amide catalyzes the hydroamination of primary olefins in excellent yields.701 A facile intramolecular hydroamination process catalyzed by [(C5H4SiMe3)2Nd(/r-Me)]2 has also been reported. The lanthanide-catalyzed hydroamination enables a rapid access to 10,1 l-dihydro-5//-dibenzo[tf,rf]cyclohepten-5,10-imines (Scheme 283).1048... 

Hydroamination/bicyclization of aminodialkenes, aminodialkynes, and amino-alkenynes opens a straightforward route to pyrrolizidines and indolizidines in a tandem C-N and C-C bond forming process. An important prerequisite for the success of this reaction sequence is a sufficient lifetime of the rare-earth metal alkyl intermediate formed in the initial insertion process of the alkene/alkyne in the Ln-amide bond in order to permit the carbocyclization step (Scheme 9) [99,174],... 

Also the hydroamination/cyclization of chiral aminoallenes has been utilized in the synthesis of various alkaloid skeletons [120]. The pyrrolidine alkaloid ( + ) 197B (Scheme 11.25), as well as the indolizidine alkaloid (+) xenovenine (Scheme 11.26),... 

A versatile new approach that holds promise for the synthesis of a wide range of 5,8-disubstituted indolizidine alkaloids, although at present only as the racemates, has been reported by Shenvi and his team (Scheme 256). The process, which effectively results in a stereoselective hydroamination, entails hydroboration of dienyl amines 2032 in the presence of molecular iodine... 

Hydroamination has been found to be useful in racemic synthesis of various natural products. Helquist and coworkers recently synthesized ( ) momomorine I using Ag-catalyzed hydroamination/cyclization of amino-diyne as the key step. Monomorine I is an indolizidine alkaloid isolated from ant Monomorium pharaoins. Beller and coworkers found hydroamination useful in the synthesis of amphetamines. It is worth mentioning that amphetamine is a class of compounds having several biological activities such as a stimulant to the central nervous system, an antiinflammatory agent, and inhibitors of enzymes. ... 

Patil NT, Pahadi NK, Yamamoto Y. A new route for the synthesis of indolizidine (—)-209D excellent diastereoselectiv-ity in the intramolecular hydroamination of alkynes. Tetrahedron Lett. 2005 46(12) 2101-2103. 

Scheme 13 Synthesis of pyrrolizidines (n = 1) and indolizidines (n = 2) via hydroamination/ bicyclization [23, 139]...

More recently the catalyst scope was extended to organolithium species [24] however, the reaction is confined to activated (alkenyl)aminostilbenes and yields pyrrolizidine and indolizidine derivatives. A toluene-THF mixture was used as reaction medium and the presence of excess amount of lithium ferf-butyltritylamide was required to obtain the bicyclization product (16). In the presence of substoi-chiometric amounts of the lithium-amide, only the hydroamination product was observed. 

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