JACS: sukbok Chang group realizes stereoselective haloamidation of alkynes catalyzed by IR (III)

As an effective method to directly construct C-N bond, transition metal mediated amino transfer reaction has attracted extensive attention of researchers The key to the success of this method is the ingenious combination of electrophilic metal carbenes and nucleophiles Although C-H amination and aziridination have been widely studied, there are only a few reports related to alkynes Recently, sukbok Chang Group took NaX (x = CL / BR) as halide source, and realized the stereoselective scheme 1C of alkynes catalyzed by IR (III) with ligand participation Relevant articles were published on J am Chem SOC (DOI: 10.1021 / JACS 8b08134) (source: J am Chem SOC.) the author envisions using the ligand participation strategy to make the ligand of the catalyst coordinate with the metal center through [3 + 2] cycloaddition (scheme 1b) If a stable metal ring can be formed in this process, the rearrangement of the secondary Curtius will be inhibited, and finally vinyl lactam compounds will be formed In order to verify the strategy of ligand participation, 8-hydroxyquinoline was used as model κ 2-N, o-chelate, and IR complex I (scheme 2) was simply prepared In the presence of nabarf 4, iridium complex I reacts with alkynodioxazolone 1 to obtain vinyl lactam IR species II in good yield The above results clearly show that the 8-hydroxyquinoline ligands in I also participate in the reaction during the insertion of alkynes into the assumed IR imide intermediate III by [3 + 2] cycloaddition (source: J am Chem SOC.) later, the authors expect to apply the ligand participation strategy to the development of catalytic reactions It is speculated that two monodentate ligands (x) will replace κ 2-N in the IR center, and O-bidentate ligands will form a key IR intermediate containing κ 1-x and κ 2-N, and X ligands, which can complete the catalytic cycle through appropriate protonation The mechanism of haloamidation (CL or BR) was designed The substrate 1 of alkynodioxazolone will coordinate with the IR center of species IV to obtain the addition product V; then V will undergo oxidative coupling to produce acyl carbene VI and release CO2 at the same time Then the imides were transferred to alkynes to obtain the metal ring intermediate VIII In the final stage, the obtained VIII will be protonated to form the target product 2, and the catalytic active substance IV will be regenerated at the same time (source: J am Chem SOC.) based on the above considerations, the author used Cp * IR system to explore the ligand involved in the chloroacylation reaction It is gratifying to note that in the presence of AcOH, ethynodioxazolone 1 can be treated with [Cp * IRCL 2] 2 to form vinyl lactam product 2 of Z-type single stereoisomer Then, the author used NaCl as chlorine source to further screen the reaction conditions (Table 1) In the cosolvent system CH2Cl2 / cf3ch2oh (2:1), 1 reacts with 1.25 mol% of [Cp * ircl2] 2 at 40 ℃, and the product 2 with excellent z-selectivity can be obtained in quantitative yield (source: J am Chem SOC.) then, the author investigated the universality of IR (III) catalyzed chloroamidation using different substrates (Table 2) γ - (aryl) alkynyl dioxazolone with various substituents on phenyl can be cyclized smoothly, and the product 2 - 6 has excellent Z - selectivity The substituent of phenyl with benzofuran or benzothiophene can also be compatible (7,8) It should be noted that even if the substrate contains conjugated diacetyl, the insertion of nitrogen guest only occurs at the γ - position (9) At the junction of oxazolidone and alkynyl group, alkyl substitution has a certain effect on the reaction efficiency (10,11) The isoindoline derivatives 12 - 14 can be obtained under the standard conditions by using phenyl, cyclohexenyl and cyclopropyl substituted o-acetylene dioxazones However, the presence of large steric tert butyl leads to a decrease in the cyclization efficiency (15) For more complex molecules, the reaction can also proceed smoothly (16) The enantiomeric substrates 17 and 19 are cyclized in a stereoscopic manner to form products 18 and 20, respectively (source: J am Chem SOC.) since iridium carbene can be efficiently transferred to a variety of C-H bonds, the chemical selectivity of the reaction between alkynyl and C (SP 3) - H bonds was investigated The results show that in the presence of γ - aliphatic or benzyl C-H bond, γ - alkyne insertion is specific, substrates 21 and 23 form chloroamidation products 22 and 24, respectively, without the production of γ - lactam products 22 'and 24' Finally, NaBr was used instead of NaCl to successfully extend the reaction to bromidation In the presence of NaBr / 15-crown-5 and nabarf 4, dioxazolone 25 was successfully cyclized and the corresponding bromoalkenyl lactam 26 was quantitatively formed, and then the product 27 (EQ 1) was rapidly desbrominated The substrate 28 derived from benzoic acid formed z-bromovinyl isoindolinone 29 (EQ 2) in high yield (source: J am Chem SOC.) conclusion: sukbok Chang research group first developed the insertion method of IR (III) catalytic imide into alkyne by using the strategy of ligand participation Based on the [3 + 2] cycloaddition reaction of Cp * IR (III) (κ 2 - N, O - chelate) with alkynodioxazolone, the author used [Cp * ircl2] 2 as the pre catalyst, NaX salt (x = CL or BR) as the halide source, and established the method of catalytic halide amination, and synthesized Z - (halovinyl) lactam derivatives with high efficiency and high stereoselectivity.