Coupled Organolanthanide-Catalyzed C−N/C−C Bond Formation Processes. Efficient Regiospecific Assembly of Pyrrolizidine and Indolizidine Skeletons in a Single Catalytic Reaction

Organolanthanide-Catalyzed Intramolecular Hydroamination/Cyclization of Aminoalkynes

“…In the presence of the paramagnetic Nd 3+ (4 f 3 ) and Sm 3+ (4 f 5 ) catalysts, only paramagnetically broadened amine product and substrate 1 H NMR resonances are detected during catalytic turnover at room temperature. This behavior is analogous to that observed during aminoolefin hydroamination/cyclization and can be associated with rapid intramolecular exchange of bound amine and amide groups as well as intermolecular exchange of bound and free amine (substrate and product) groups involving complexes of the type Cp‘ 2 LnNHR(NH 2 R) x . 7c,d …”

“…In regard to turnover frequency, the present cyclizations are ∼10−100× more rapid than the corresponding aminoolefin transformations for the same catalyst, temperature, and reaction conditions 7d. Indeed, N t for process 9 → 10 considerably exceeds the rate that can be accurately measured at room temperature.…”

“…The goal of this investigation was to examine the scope, stereoselectivity, lanthanide ion sensitivity, ancillary ligand sensitivity, kinetics, and mechanism of the organolanthanide-catalyzed intramolecular hydroamination/cyclization of aminoalkynes. This study represents an extension of, and comparison to, our previous investigation of the catalytic hydroamination/cyclization of unprotected aminoolefins. 7c-g In the ensuing discussion, we focus on reaction scope, alkyne substituent effects on the reaction, metal ion size and ancillary ligand effects on the reaction, and kinetics and the rate law.…”

“…As in the case of organolanthanide-catalyzed hydroamination/cyclization of aminoolefins, 7c-g the reaction of Cp‘ 2 NdCH(SiMe 3 ) 2 , Cp‘ 2 SmCH(SiMe 3 ) 2 , and Me 2 SiCp‘‘ 2 SmCH(SiMe 3 ) 2 with aminoalkynes effects distinctive color changes associated with catalytic initiation and termination. Thus, the original green and orange solutions of the Nd and Sm hydrocarbyl precatalysts, respectively, in C 6 D 6 or C 7 D 8 instantaneously turn to the characteristic blue and yellow colors of the corresponding amine−amide complexes 7c,d in conjunction with the initiation of catalytic turnover.…”

“…Alkyne insertion into Ln−N bonds (step 1) is estimated to be ∼35 kcal/mol more exothermic than for olefins, − while amine protonolysis of the resulting Ln−C bond (step 2) is estimated to be ∼10−20 kcal/mol less exothermic (approximately thermoneutral). If the insertion of alkyne functionalities into Ln−N bonds were indeed efficient and analogous to those transformations established for aminoolefins, 7c-g, such aminoalkyne-based catalytic processes would offer a route to a diverse variety of heterocycles and natural product skeletons (e.g., indolizidines, quinolizidines) as well as a complement to recently reported organo group 4-centered stoichiometric 4a,d,e and catalytic 4 alkyne hydroamination processes which proceed via an entirely different (noninsertive) mechanistic pathway 4f 2 Simplified Catalytic Cycle for the Hydroamination/Cyclization of Aminoalkynes …”