Hydroaminoalkylation of sterically hindered alkenes with N,N-dimethyl anilines using a scandium catalyst

Abstract

Atom-economical and regioselective C(sp3)–C(sp3) bond formation has been achieved by C(sp3)–H alkylation of N,N-dimethyl anilines with sterically demanding alkenes by scandium catalysis.

Scandium-Catalyzed para-Selective Alkylation of Aromatic Amines with Alkenes

“…However, substrate scope in this reaction was limited to the sterically bulky diarylamine because the electrophilic phosphonium cation used could be deactivated by the Lewis basic substrate, thus greatly restricting synthetic utility. In our previous study, we designed and synthesized scandium dialkyl complexes based on unsymmetric β-diketiminato ligands that were able to mediate regioselective hydroaminoalkylation of tertiary anilines with a variety of alkenes in combination with a borate compound . In contrast, when such a catalyst system was applied in the reactions of primary/secondary anilines with alkenes, it exclusively afforded para -selective C–H alkylation products in high yields with good functional group tolerance (Scheme c).…”

Titanium‐Catalyzed Intermolecular Hydroaminoalkylation of Alkenes with Tertiary Amines

“…[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.…”

“…Simplified catalytic cycle of the hydroaminoalkylation of alkenes with tertiary amines which includes a cationic metallaaziridine as the catalytically active species (M = Sc, n = 1 or M= Ti, n = 2). [7] Table 1: Scope of the titanium-catalyzed hydroaminoalkylation of various alkenes with N-methylpiperidine (1 a). [a] Entry Alkene Product Yield [%] [b] 1 99 2 31…”

“…However, alkene hydroaminoalkylation with tertiary amine substrates that do not contain an extra directing group could already be achieved in the presence of cationic scandium catalysts (Scheme 1 b). [7] Unfortunately, scandium must be regarded as a highly expensive metal [8] and the catalysts, which need to be synthesized by laborious processes, are only active at elevated temperatures of 70-120 8C. [7a,c,e] Based on our experiences in the development of titaniumcatalyzed hydroaminoalkylation reactions of alkenes, allenes, [9] and alkynes, [10] and the fact that non-toxic titanium is the second most abundant transition metal in the earths crust, [11] we recently started a project to identify an alternative, less expensive, titanium-based catalyst system for the intermolecular hydroaminoalkylation of alkenes with simple tertiary amines (Scheme 1 c).…”

Iridium‐Catalyzed C(sp3)−H Addition of Methyl Ethers across Intramolecular Carbon–Carbon Double Bonds Giving 2,3‐Dihydrobenzofurans

“…[5] However, activation of α-C (sp 3 )À H bonds of tertiary amines and ethers, in which no protic hydrogen on the heteroatoms is available, encounters general difficulties in promoting C(sp 3 )À H activation. Such difficulty has been overcome, at least in part, by using directing groups, [6] by scandium catalysts, [7] and by using photoredox catalysts [8] for the reactions of tertiary amines in C(sp 3 )À H addition reactions. However, utilization of ethers in such C (sp 3 )À H additions has been limited to unsaturated ethers capable of forming oxonium intermediates through a 1,5-H shift with Lewis acidic metal catalysts (Scheme 1-i) [9,10] along with Cu-and Co-mediated abstraction of a H radical from THF to form a 2tetrahydrofuranyl radical for addition to alkynes (Scheme 1-ii).…”