Mechanism and Origins of Z Selectivity of the Catalytic Hydroalkoxylation of Alkynes via Rhodium Vinylidene Complexes To Produce Enol Ethers

Abstract

We report the first theoretical study of transition-metal-catalyzed hydroalkoxylation of alkynes to produce enol ethers. The study utilizes density functional theory calculations (M06) to elucidate the mechanism and origins of Z selectivity of the anti-Markovnikov hydroalkoxylation of terminal alkynes with a Rh(I) 8-quinolinolato carbonyl chelate (1cat). The chosen system is, without any truncation, the realistic reaction of phenylacetylene and methanol with 1cat. Initiation of 1cat through phenylacetylene substitution for carbonyl generates the active catalyst, a Rh(I) η 2 -alkyne complex (3), which tautomerizes via an indirect 1,2hydrogen shift to the Rh(I) vinylidene complex 4. The oxygen nucleophile methanol attacks the electrophilic vinylidene C α , forming two stereoisomeric Rh(I) vinyl complexes (15 and 16), which ultimately lead to the (Z)-and (E)-enol ether products. These complexes undergo two ligand-mediated proton transfers to yield Rh(I) Fischer carbenes, which rearrange through a 1,2β-hydrogen shift to afford complexes with π-bound product enol ethers. Final substitution of phenylacetylene gives (Z)-and (E)-PhCHCHOMe and regenerates 3. The anti-Markovnikov regioselectivity stems from the Rh(I) vinylidene complex 4 with reversed C α and C β polarity. The stereoselectivity arises from the turnover-limiting transition states (TSs) for the Rh(I) carbene rearrangement: the Z-product-forming TS24 is sterically less congested and hence more stable than the E-product-forming TS25. The difference in energy (1.2 kcal/mol) between TS24 and TS25 gives a theoretical Z selectivity that agrees well with the experimental value. Calculations were also performed on the key TSs of reactions involving two other alkyne substrates, and the results corroborate the proposed mechanism. The findings taken together give an insight into the roles of the rhodium− quinolinolato chelate framework in directing phenylacetylene attack by trans effect, mediating hydrogen transfers through hydrogen bonding, and differentiating the energies of key TSs by steric repulsion.

A Triflamide‐Tethered N‐Heterocyclic Carbene–Rhodium(I) Catalyst for Hydroalkoxylation Reactions: Ligand‐Promoted Nucleophilic Activation of Alcohols

“…[2] However,addition reactions of weak nucleophiles such as water and alcohol remain achallenging task. [12] N-Heterocyclic carbene (NHC)-derived ligands are widely used in organometallic catalysis owing to their ability to form robust compounds with avariety of metal ions and for their relatively easy steric and electronic tunability. [4] Whereasmetal-catalyzed intramolecular hydroalkox-ylationsa re well reported, [5] intermolecular reactions between alcohols and alkynes are difficult [6] and often demandt he use of as trong base or harsh conditions.…”

“…[3] Enol ethers are important functionalities in organic synthesis and are used widely in cross-coupling,r ing-closing metathesis, and cycloaddition reactions and for the synthesis of pharmaceuticals. [12] N-Heterocyclic carbene (NHC)-derived ligands are widely used in organometallic catalysis owing to their ability to form robust compounds with avariety of metal ions and for their relatively easy steric and electronic tunability. [7] Kirchner reported the addition of allylic alcohols to phenylacetylene by using the [RuCl{tris(pyrazolyl)borate}(pyridine) 2 ]c atalyst.…”

“…[9] Kakiuchif irst reported the intermolecular anti-Markovnikov hydroalkoxylation of terminal acetylenes by using an 8-quinolinolato-ligated rhodium(I) dicarbonyl complex. [12] N-Heterocyclic carbene (NHC)-derived ligands are widely used in organometallic catalysis owing to their ability to form robust compounds with avariety of metal ions and for their relatively easy steric and electronic tunability. [11] Computational studies by Wang and co-workersr evealed that the 8-quinolinolato oxygen atom facilitated alcohold eprotonation to am ore potent On ucleophile, which readily added to the Rh-vinylidene followed by protont ransfers.…”

“…DFT calculations at the BPW91 level of theory were performed by using Gaussian09t or ationalize the probable mechanism depicted in Scheme 6. [12] Nevertheless, Rh-vinylidene intermediate B was computed to be endergonic by 8.1 kcal mol À1 .N ext, we optimized low-lyingi ntermediate C,f or which the methanolp roton migrates to the triflamide nitrogen atom (NÀH1 .06, O···H1 .73 ). Rearrangement of at erminal alkyne into av inylidene on am etal site has been studied extensively by computationala nd experimental techniques.…”

Intermolecular Hydroalkoxylation of Terminal Alkynes Catalyzed by a Dipyrrinato Rhodium(I) Complex with Unusual Selectivity

“…The observation that complex 2 only promotes the transformation of terminal alkynes suggests that complex 2 9 and supported by the computer simulation by Wang et al 19 Formation of such a complex involves migration of the terminal proton via a 1,2-β-hydride transfer before attack by the alcohol. The mechanism of the intermolecular hydroalkoxylation of terminal acetylenes using 2 would appear to be very different from the mechanism of intramolecular hydroalkoxylation of alkynes using the bpm-based complex 3 that we have intensively investigated in our laboratory.…”