Organolanthanide-Catalyzed Intra- and Intermolecular Tandem C−N and C−C Bond-Forming Processes of Aminodialkenes, Aminodialkynes, Aminoalkeneynes, and Aminoalkynes. New Regiospecific Approaches to Pyrrolizidine, Indolizidine, Pyrrole, and Pyrazine Skeletons

Abstract

This contribution describes catalytic tandem C−N and C−C bond-forming reactions involving the intramolecular hydroamination/bicyclization and intermolecular hydroamination/cyclization of olefins and alkynes using the organolanthanide complexes Cp‘ 2 LnCH(SiMe 3 ) 2 and Me 2 SiCp‘‘ 2 LnCH(SiMe 3 ) 2 (Cp‘ = η 5 -Me 5 C 5; Cp‘‘ = η 5 -Me 4 C 5; Ln = lanthanide) as precatalysts. In the case of the intramolecular processes, substrates of the structures RC⋮C(CH 2 ) a NH(CH 2 ) b C⋮CR, RC⋮C(CH 2 ) c NH(CH 2 ) d CH CH 2, and H 2 C CH−(CH 2 ) e NH(CH 2 ) f CH CH 2 are regiospecifically bicyclized to the corresponding pyrrolizidine and indolizidine skeletons, with turnover frequencies ranging from 2 to 777 h - 1 at 21 °C and isolated product yields ranging from 85 to 93%. In the case of e = 3 and f = 1 mediated by Cp‘ 2 Sm−, the kinetic rate law is zero-order in substrate concentration and first-order in lanthanide concentration. In the case of R = Ph, c = 3, and d = 1, the Cp‘ 2 Ln-catalyzed turnover frequencies fall precipitously with decreasing Ln +3 ionic radius. In the intermolecular processes, substrates of the type HC⋮CCH 2 NHR undergo regiospecific coupling and cyclization to the corresponding pyrroles with high turnover frequencies where R and N t (h - 1 ) are the following: CH 2 CHCH 2, 236 (60 °C); CH 3 CH 2 CH 2, 208 (60 °C); CH 2 CHCH 2 CH 2 CH 2, 58 (60 °C). In addition, hydroamination/cyclization processes after intermolecular insertion can be effected when R = CH 2 CHCH 2, to afford a 2,7-dimethyldipyrrolo[1,2- a:1‘,2‘- d ]pyrazine derivative via two successive intramolecular olefin insertion processes. The mechanism for such tandem C−N and C−C bond formations is postulated to involve turnover-limiting intra- or intermolecular alkene/alkyne insertion into the Ln−N functionality, followed by rapid intramolecular insertion of a pendant C C/C⋮C-containing functionality into the resulting Ln−C bond (prior to protonolysis). Such a scenario is consistent with well-documented, stepwise transformations in organo-f-element-catalyzed insertions of unsaturated carbon−carbon multiple bonds into metal−amide and metal−alkyl functionalities.