Transition-metal-catalyzed hydroaminoalkylations of alkenes have made great progress over the last decade and are heading to become a viable alternative to the industrial synthesis of amines through hydroformylation of alkenes and subsequent reductive amination. In the past, one major obstacle of this progress has been an inability to apply these reactions to the most important amines, methylamine and dimethylamine. Herein, we report the first successful use of dimethylamine in catalytic hydroaminoalkylations of alkenes with good yields. We also report applicability for a variety of alkenes to show the tolerance of the reaction towards different functional groups. Additionally, we present a catalytic dihydroaminoalkylation reaction using dimethylamine, which has never been reported before.

The scientific interest in catalytic hydroaminoalkylation reactions of alkenes has vastly increased over the past decade, but these reactions have struggled to become a viable option for general laboratory or industrial use because of reaction times of several days. The titanium‐based catalytic system introduced in this work not only reduces the reaction time by several orders of magnitude, into the range of minutes, but the catalyst is also demonstrated to be easily available from common starting materials, at a cost of approximately 1 € per millimole of catalyst. We were also able to formally perform C−H activation of methylamine and achieve coupling to a broad variety of alkenes, through silyl protection of the amine and simple deprotection by water.

The first cationic titanium catalyst system for the intermolecular hydroaminoalkylation of alkenes with various tertiary alkylamines is presented. Corresponding reactions which involve the addition of the a-CÀH bond of a tertiary amine across the CÀC double bond of an alkene take place at temperatures close to room temperature with excellent regioselectivity to deliver the branched products exclusively. Interestingly, for selected amines, a-C À H bond activation occurs not only at N-methyl but also at N-methylene groups.Tertiary amines are important structural motifs in natural products (e.g. alkaloids) and are indispensable for the development of agrochemicals or pharmaceuticals. [1] For example, more than 15 % of the 200 top selling small molecule drugs in 2018 contain a tertiary amine moiety. [1b] An attractive synthetic approach for the synthesis of various amines that has raised a lot of attention in recent years is the hydroaminoalkylation of alkenes which allows the 100 % atom economic addition of the a-C À H bond of simple amines across the C À C double bond of alkenes (Scheme 1). [2] Corresponding addition reactions can be achieved with late transition metal catalysts, [3] following a photo-catalytic approach, [4] or most efficiently with early transition metal catalysts. [5][6][7] In the latter case, neutral group 4 [5] and 5 [6] metal catalysts have extensively been used for a plethora of successful hydroaminoalkylation reactions of alkenes with primary or secondary amines (Scheme 1 a) but unfortunately, tertiary amines do not react successfully with alkenes in the presence of these catalysts. This lack of reactivity must be regarded as a severe restriction to the use of hydroaminoalkylation reactions, because it prohibits the use of simple tertiary amines as starting materials for the synthesis of more sophisticated tertiary amine products. Although a few late transition metal-catalyzed hydroaminoalkylation reactions with tertiary amines have been reported, [3,4] in these cases, the amine must contain an additional metal-binding directing

The first examples of early-transition-metal-catalyzed hydroaminoalkylation reactions of allenes are reported. Initial studies performed with secondary aminoallenes led to the identification of a suitable titanium catalyst and revealed that under the reaction conditions, the initially formed hydroaminoalkylation products undergo an unexpected titanium-catalyzed rearrangement to form the thermodynamically more stable allylamines. The assumption that this rearrangement involves a reactive allylic cation intermediate provides a simple explanation of the fact that no successful early-transition-metal-catalyzed hydroaminoalkylations of allenes have previously been reported. As a result of the generation of the corresponding cation, the titanium-catalyzed intermolecular hydroaminoalkylation of propa-1,2-diene unexpectedly gives an aminocyclopentane product formed by incorporation of two equivalents of propa-1,2-diene.

The synthesis of three new sterically crowded titanium complexes which all possess an identical formamidinato ligand, two dimethylamido ligands and in addition, a 2‐aminopyridinato ligand that contains either an N‐methyl, an N‐phenyl, or an N‐cyclohexyl substituent is presented. All new complexes are easily accessible from a common titanium mono(formamidinate) precursor and correspondingly N‐substituted 2‐aminopyridines. Furthermore, the new complexes are used as catalysts for selected hydroamination and hydroaminoalkylation reactions and finally, the catalytic performance of the new catalysts is compared with the performance of the titanium mono(formamidinate) precursor.