Mild, Rhodium-Catalyzed Intramolecular Hydroamination of Unactivated Terminal and Internal Alkenes with Primary and Secondary Amines

Abstract

The hydroamination of olefins 1 is one of the simplest and most atom-economical methods to prepare alkylamines, and much effort has now been spent to develop catalysts for this process. Some of most reactive catalysts contain lanthanides 2 and group IV transition metals. 3 However, the high sensitivity of these catalysts toward air and moisture and their low tolerance of polar functional groups have limited their use and motivated efforts to develop late-metal hydroamination catalysts. Although several catalysts based on late metals have been published for additions of amines to vinylarenes [4][5][6] and for the addition of amides and sulfonamides to alkenes, allenes, and dienes, 7 few catalysts for additions of amines to alkenes, arguably the most important donors and acceptors, have been reported.The existing late-metal catalyst for the intramolecular additions of amines to olefins 8 is generated from [PtCl 2 (H 2 CdCH 2 )] 2 and PPh 3 . This system operates at 120 °C, catalyzes only reactions of secondary amines, not primary amines, and catalyzes additions to only terminal olefins, not internal olefins. 9 Moreover, this catalyst requires substituents that bias the substrate toward cyclization. Alterative palladium catalysts for additions of amides and carbamates at lower temperature have been reported, 10 but these N−H bond donors require installation and removal of the activating group in most synthetic sequences and do not provide products that would result from addition of a secondary amine. Thus, a catalyst that tolerates polar functional groups and that induces additions of both primary and secondary amines without activating groups to both terminal and internal alkenes is needed.We report the identification of such a system. We report a rhodium catalyst for the hydroamination of terminal and internal alkenes with primary and secondary amines, with or without substituents that favor cyclization to form five-or six-membered ring products. In addition to spanning a broader scope of amine and alkene than other late metal catalysts, this system operates in the presence of functional groups, including esters and free hydroxyl groups, which do not tolerate early metal and lanthanide catalysts. These results demonstrate that complexes of group 9 metals, which are classic catalysts for alkene hydrogenation and hydrosilylation, can also be made useful for alkene hydroamination. Stimulated by our previous studies on rhodium-catalyzed additions of amines to vinylarenes, 5,6 we investigated combinations of rhodium precursors and dative ligands as catalysts for cyclization of the N-methyl aminopentene in eq 1. Experiments to develop conditions for the cyclization of aminoalkene 1 are summarized in Table 1. These reactions were conducted at 70 °C over 7 h, unless otherwise stated.Reaction of aminoalkene 1 in the presence of 2.5 mol % [Rh-(COD) 2 ]BF 4 and 2.5 mol % DPEphos, which catalyzed the anti-Markovnikov hydroamination of vinylarenes,6 formed none of the cyclized pyrrolidine product. The major product of this ...

Rhodium Phosphine−π-Arene Intermediates in the Hydroamination of Alkenes

“…A second set of experiments were run in the presence of 10 mol % added COD, which is present in the catalyst precursor and was present in our preparative reactions of secondary aminoalkenes initiated with isolated acetonitrile complex 2 27. The added COD appeared to stabilize the catalyst, but to retard the cyclization.…”

Intramolecular Hydroamination of Unbiased and Functionalized Primary Aminoalkenes Catalyzed by a Rhodium Aminophosphine Complex

“…Although data with this original catalyst35 and that with catalysts based on copper,34 rhodium,37 and iridium40,46 reported since this time demonstrated that primary aminoalkenes can undergo cyclization, reactions of such such amines catalyzed by these systems have significant limitations. First, the cyclization of primary aminoalkenes catalyzed by late-metal systems has been limited to cases that are biased toward cyclization by a Thorpe-Ingold effect; second, these reactions were limited to aminoalkenes containing terminal olefins; third, these reactions required high temperatures (>100 °C); and fourth, reactions of primary aminolkenes containing a second functional group have not been reported with any catalyst.…”

Synthesis of Saturated Heterocycles via Metal-Catalyzed Alkene Hydroamination or Hydroalkoxylation Reactions

“…Since then, ligated rhodium complexes have been developed as catalysts for the intramolecular hydroamination of unactivated aminoalkenes containing a basic amine functionality [40]. In particular, rhodium complexes have been the first class of catalysts to demonstrate reactivity with substrates that contain a primary amine donor [41], and also tolerate a wide range of polar functionality. The most effective catalysts to date are monocationic at the rhodium center and are proposed to react via the nucleophilic addition pathway (Scheme 3).…”

“…Hartwig and Liu subsequently reported a rhodium catalyst bearing the Davephos ligand that exhibits excellent activity for hydroamination of unactivated alkenes containing both primary and secondary amines (Scheme 24) [41]. Substituted aminoalkenes containing a wide range of functionality, such as aryl nitriles, esters, and alcohols (53, Ar ¼ 4-ClC 6 H 4 , 4-CNC 6 H 4 , 4-CO 2 MeC 6 H 4 ), were cyclized at relatively mild temperatures to form pyrrolidines and piperidines selectively.…”