JACS: IR catalyzed intermolecular branched selective allylic C-H amidation of nonactivated terminal olefins

Since there are nitrogen-containing functional groups in bioactive molecules, the reaction of constructing C-N bond is widely used in the field of pharmaceutical chemistry At present, allyl C-H amination is realized by C-H insertion of metal carbene or nucleophilic amination of allyl metal species produced by C-H activation Despite the above progress, it is still challenging to control the chemical and regional selectivity in intermolecular C-H amination For example, the reaction of terminal alkenes with metal carbene species has poor chemical selectivity, mainly resulting in aziridine rather than C-H amination products (scheme 1a (I)) Later, white and Liu team realized the linear amination between olefins and amines (scheme 1a (II)) under the catalysis of PD (II) On this basis, in recent years, researchers have developed a variety of methods to synthesize linear allylamine On the other hand, the branch chain selective allylic C-H amination of terminal alkenes is usually realized by intramolecular way Recently, the team of Professor Tomislav rovis of Columbia University reported that IR (III) catalyzes the intermolecular branched chain selective allyl C-H amidation of non activated terminal olefins Relevant research results were published in J am Chem SOC (DOI: 10.1021 / JACS 9b00237) (source: J am Chem SOC.) recently, Blakey research group reported the intermolecular allylic C-H amidation of β - substituted styrene, and its reaction with allylic benzene showed unique linear selectivity (angelw Chem Int ed 2017, 56, 13666) In contrast, the author found that under the catalysis of [Cp * RhCl 2] 2, the allyl C-H amidation of terminal olefin 1a and methyldioxazolone 2A mainly resulted in branched chain amidation product 3A (Table 1, entry 1) It is believed that this is due to the formation and insertion of nitrogen oxides at electron rich sites Then through the screening of catalysts, additives and bases, the author found that the amidation product 3A was obtained by the reaction of 1a and 2A in DCE at 35 ℃ with [Cp * ircl2] 2 as catalyst, agntf 2 as additive and LiOAc as base, and the regioselectivity was excellent (source: J am Chem SOC.) after obtaining the best conditions, the author investigated the application range of different end olefins (scheme 2) The reaction is resistant to a variety of functional groups (such as a variety of functional groups containing oxygen, nitrogen or aromatics, as well as bromine, cyano, carboxylic acid, etc.), and the corresponding amidation product 3B - 3M can be obtained successfully, with good yield and regional selectivity In addition, the reaction activity of the substrate with high allylic heteroatom was decreased At high temperature, the product 3N and 3O could only be obtained in medium yield In addition, allylcyclohexane 3P with steric hindrance can also tolerate the reaction very well The allylic aromatics with electron rich and electron poor substituents were also investigated The regioselectivity of the product 3Q - 3S decreased from > 20:1 to 2.6:1 after the p-methoxy substituent was changed to trifluoromethyl substituent (source: J am Chem SOC.) next, the author discussed the universality of dioxazolone (scheme 3) The primary, secondary and tertiary alkyl groups of oxazolidone were all tolerable, and the reaction activity was not significantly reduced (4B - 4F) In addition, the electron donor and electron acceptor substituted phenyldioxazolone also had good tolerance (4G - 4J) Alkenyl substituted oxazolidone can also be obtained in a medium yield of 4K (source: J am Chem SOC.) finally, based on the mechanism experiment, the author speculates that the reaction undergoes the following catalytic cycle process (scheme 5) The active catalyst may be Cp * IR (III) (I) with unsaturated cation monoacetyl coordination, which is produced by [Cp * IRCL 2] 2, agntf 2 and LiOAc Alkenes are coordinated and irreversibly metallized to form allyl IR (III) species (III) Through N-O bond cleavage and CO 2 release, IR (III) forms a key allyl IR nitrogen guest species (IV) Then, IV was transferred and inserted, protonated and demetallized to produce amide products, and then to generate active catalyst (source: J am Chem SOC.) Summary: the author developed IR (III) - catalyzed branched chain selective allyl C-H amidation The insertion of inner IR - carbene after allyl C-H activation is the key to branch chain selectivity This study opens up a new way for the functionalization of terminal olefins.