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

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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'2LnCH(SiMe3)2 and Me2SiCp''2LnCH(SiMe3)2 (Cp' = η5-Me5C5; Cp'' = η5-Me4C5; Ln = lanthanide) as precatalysts. In the case of the intramolecular processes, substrates of the structures RC⋮C(CH2)aNH(CH2)bC⋮CR, RC⋮C(CH2)cNH(CH2)dCHCH2, and H2CCH−(CH2)eNH(CH2)fCHCH2 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'2Sm−, 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'2Ln-catalyzed turnover frequencies fall precipitously with decreasing Ln+3 ionic radius. In the intermolecular processes, substrates of the type HC⋮CCH2NHR undergo regiospecific coupling and cyclization to the corresponding pyrroles with high turnover frequencies where R and Nt (h-1) are the following: CH2CHCH2, 236 (60 °C); CH3CH2CH2, 208 (60 °C); CH2CHCH2CH2CH2, 58 (60 °C). In addition, hydroamination/cyclization processes after intermolecular insertion can be effected when R = CH2CHCH2, 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 CC/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.

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