Mechanistic insight into the ruthenium-catalysed anti-Markovnikov hydration of alkynes using a self-assembled complex: a crucial role for ligand-assisted proton shuttle processes

Abstract

A combined computational and experimental study is presented that investigates the mechanism of the anti-Markovnikov hydration of phenylacetylene by [Ru(η(5)-C5H5)(6-DPPAP)(3-DPICon)](+) (where 6-DPPAP = 6-(diphenylphosphino)-N-pivaloyl-2-aminopyridine) and 3-DPICon = 3-diphenylphosphinoisoquinolone). The proposed mechanism, modelled using density functional calculations, involves an initial alkyne-vinylidene tautomerism, which occurs via a ligand-assisted proton shuttle (LAPS) mechanism. Intramolecular ligand assistance from the 6-DPPAP and 3-DPICon ligands, particularly the basic nitrogen of 6-DPPAP, is also involved in subsequent stages of the mechanism and three LAPS processes in total are observed. The self-assembled ligand backbone helps to create a water-binding pocket close to the metal centre, which facilitates nucleophilic attack of water at the vinylidene α-carbon and mediates protonation and deprotonation of subsequent acyl and vinyl intermediates. Experimental evidence is also presented for a novel non-productive catalyst deactivation pathway, which appears to arise from an initial lactam-lactim tautomerism of the 3-DPICon ligand followed by coupling with a vinylidene.

Phosphoramidate-Assisted Alkyne Activation: Probing the Mechanism of Proton Shuttling in a N,O-Chelated Cp*Ir(III) Complex

“…21 In a system where the proton shuttling site is nitrogen-based, during the second LAPS transition state, the hydrogen atom sits roughly equidistant between nitrogen and the -carbon (N-H: 1.34 Å vs. C-H: 1.39 Å). 20 A number of isomers for vinylidene 4 were located. TS3a4a leads directly to 4a, which displays  1 -N coordination.…”

Five‐Membered Ruthenacycles: Ligand‐Assisted Alkyne Insertion into 1,3‐N,S‐Chelated Ruthenium Borate Species

“…[30,31] In this regard, Rh and Ru metals are found to be active catalysts for the addition of No rSnucleophiles to terminal alkynes yieldingC ÀNo rC ÀSb onds, mostly through anti-Markovnikov addition. [14,30,32] Hence, the formation of 4-5 or 6-7 might be assumed to have occurred through initial activation of the alkyne followedb yt he proton transfer from alkynet ot he basic N,S-benzothiazolyl group and as ubsequent intramolecular anti-Markovnikova ddition of No rSof the benzo-thiazolyl moiety to the alkyne. The reactions might proceed through the ligand-assisted proton shuttle( LAPS) mechanism in which the nucleophilic sites, No rS, of the benzothiazolyl moiety in 2a' would act as the internal base for proton shuttling thereby assisting both in the CÀHb ond activation as well as in the formation steps.…”

“…[12] Very recently,M aseras et al established that ruthenium complexes [Ru(X)H(CO)(PiPr 3 ) 2 ]( X= kO 2 ÀOC(O)Me or Cl) can be utilized for the activationo fa lkyne CÀHb ond through proton shuttle followed by ac oncerted metalation-deprotonation (CMD). [13] The activation of terminal alkynes by ruthenium and iridium complexes has also been established throughl igandassisted protons huttle (LAPS) mechanism; [10c, [13][14][15] the LAPS mechanism for some alkyne-vinylidene tautomerizations has been proposed in Scheme 1. [10c] Although av ariety of transition metal boron complexes are knowni nt he literature, [16][17][18] their chemistryw ith small organic molecules has not been explored so far.…”

In Water Markovnikov Hydration and One‐Pot Reductive Hydroamination of Terminal Alkynes under Ruthenium Nanoparticle Catalysis

“…On the other hand, the anti‐Markovnikov water addition is a prerogative of Ru based catalysts such as [CpRu(PR 3 ) 2 ]X supported by phosphine ligands as dppe, PMe 3 , PMePh 2 , PMe 2 Ph and dppb , . Other Ru based catalysts work properly, giving the aldehyde product when applied to terminal alkynes , . Different metal triflates have also been employed as catalysts, and even metal‐free conditions based on strong protic acids have been described , .…”