Pyrrolizidines, hydroamination bicyclization

As in the case of aminodialkenes (see above), hydroamination/bicyclizations of aminoalkenynes allow the regiospecific synthesis of pyrrolizidine skeletons (Eq. 4.87) [138, 303]. 

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],... 

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

Type 4 metallocene complexes catalyze the regioselective mtermolecular addition of primary amines to acetylenic, olefinic, and diene substrates at rates which are = 1/1000 those of the most rapid intramolecular analogues [165]. Variants such as the intramolecular hydroamination/cyclization of aminoallenes [166] and the intra- and intermolecular tandem C-N and C-C bond-forming processes of aminodialkenes, aminodialkynes, aminoallenynes, and aminoalkynes [167] were applied as new regio- and stereoselective approaches to naturally occurring alkaloids. For example, bicyclic pyrrolizidine intermediate E... 

Scheme 77). The product 239 was converted to (+)-pyrrolidine-197B 240. The tandem hydroamination/ cyclization of the allenylalkenylamine 241 occurred in the presence of the samarium catalyst 201 to give the bicyclic pyrrolizidine 242 in a high yield (Scheme 78). Hydrogenation of 242 led to (+)-xenovenine 243. 

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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