Mechanistic Studies of Ruthenium-Catalyzed Anti-Markovnikov Hydroamination of Vinylarenes:  Intermediates and Evidence for Catalysis through π-Arene Complexes

Abstract

Studies are described that reveal the steps of the anti-Markovnikov hydroamination of vinylarenes with alkylamines catalyzed by Ru(COD)(2-methylallyl)2, bis(diphenylphosphino)pentane, and TfOH. Treatment of the catalyst components with an excess of styrene under the catalytic reaction conditions afforded a new ruthenium eta6-styrene complex with an ancillary tridentate PCP ligand. This ruthenium complex was active as catalyst for the hydroamination of styrene with morpholine to give the anti-Markovnikov adduct as a single regioisomer in high yield. Studies of the reactivity of the eta6-styrene complex revealed two reactions that comprise a catalytic cycle for anti-Markovnikov hydroamination: nucleophilic addition of morpholine to the ruthenium eta6-styrene complex to afford a ruthenium eta6-(2-aminoethyl)benzene complex and arene exchange of the ruthenium eta6-(2-aminoethyl)benzene complex with styrene to regenerate the ruthenium eta6-styrene complex. The addition of morpholine and the exchange of arene occurred with comparable rates. These results strongly suggest that the ruthenium-catalyzed anti-Markovnikov addition of alkylamines to vinylarenes occurs by a new reaction mechanism for hydroamination involving nucleophilic attack on the eta6-vinylarene complex and exchange of the aminoalkylarene complex product with free vinylarene. This mechanism is a rare example of catalytic chemistry through pi-arene complexes. These mechanistic data were used to select derivatives of the DPPP ligand that improve the rates of the catalytic process.

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…Mechanistic investigations have shown that in this case, the nucleophilic attack of the formally anionic ligand is the turnover-limiting step [95,115,132], and indeed, many η 3 -allyl/benzyl complexes have been identified when monitoring such reactions [94,115,132]. Both the reaction rate and the site of nucleophilic attack can be attenuated with judicious ligand selection [56,105,132]. For example, chelating diphosphines with large bite angles are known to destabilize the η 3 -allyl complexes and render them more susceptible to nucleophilic attack, thereby resulting in enhanced reactivity [132].…”

“…With styrene derivatives, the Markovnikov product is commonly obtained, as rationalized by the proposed mechanism. However, reliable methods for obtaining the anti-Markovnikov product have been developed using Ru-catalyzed hydroamination of vinyl arenes, in which η 6 -arene complexes are key catalytic intermediates (Scheme 15.17) [105,133]. This species promotes a nucleophilic attack at the β-carbon atom and catalytic turnover is achieved to realize selective anti-Markovnikov hydroamination with select amine nucleophiles [133].…”

About the Inhibition of Grignard Reagent Formation by p‐Dinitrobenzene: Comparing the Mechanism of Grignard Reagent Formation and the SRN1 Mechanism

“…[113] In contrast, aryl halides substituted by alkoxy groups (well known to decrease the electron affinity of these substrates) have repeatedly been reported as providing good yields of Grignard reagents. [114,115] Note, however, that the preparation of nitroaromatic Grignard reagents is feasible by halogen-magnesium exchange. [116] Our first entry into the field of comparing the S RN 1 and Grignard reagent formation mechanisms was motivated by observations of metal-vapour-synthesised magnesium reacting with alkyl halides.…”

Titanium‐Catalyzed Intermolecular Hydroamination of Vinylarenes

“…[8,9] Significant research activity has focused on the use of late-transition-metal complexes for intermolecular hydroamination reactions of olefins, featuring iridium, [10][11][12] rhodium, [13][14][15][16][17][18] nickel, [19,20] palladium, [21][22][23][24] platinum, [25,26] and ruthenium. [27,28] The high cost of these complexes, their stabilizing ligands, or the additives constitute a limitation of these protocols. Recently, we reported a Group 4 metal catalyzed [29] intermolecular [30] hydroamination of norbornene.…”