The fate of branched and linear isomers in the rhodium-catalyzed hydroformylation of 3,4,4-trimethylpent-1-ene

Abstract

In nonreversible hydroformylations, the computational evaluation of regio-and stereoselectivities from the relative energy barriers of the transition states (TS) for the alkyl-Rh intermediate formation step is possible, provided all low energy conformers are considered. In contrast, in reversible hydroformylations, also the subsequent reaction steps need to be taken into account to shed some light on mechanistic details. Thus, an extensive comparison of branched (B) and linear (L) reaction pathways for the Rh-catalyzed hydroformylation of 3,4,4-trimethylpent-1-ene (a bulky chiral substrate), going from a number of reactant complexes to products, has been carried out to rationalize the experimental result that pointed to reaction reversibility, although the value of the regioselectivity ratio (B:L = 15:85), based on alkyl-Rh TS free energies, computed under the hypothesis of nonreversibility, was in satisfactory agreement with the experimental one (5:95). A density functional theory approach at the B3P86/6-31G* level coupled to effective core potentials for Rh in the LanL2DZ valence basis set has been employed. By comparing the activation free energies involved in the various steps for the different reactant adducts, interestingly a similar behavior along all the linear pathways is found: the alkyl-Rh formation TS presents the highest barrier; thus, the reaction is nonreversible for all the linear isomers that invariably proceed to yield the linear aldehyde. Conversely, the behavior is quite different along the branched pathways. While some branched isomers eventually produce the corresponding aldehydes, two of the others follow distinct competing pathways, because b-hydride elimination occurs (a) to the terminal olefin-Rh complex (the starting material) that reacts again with the original regioselectivity, increasing the linear fraction, when the CO addition and insertion TS are higher than the alkyl-Rh TS and (b) to the internal olefin-Rh complex when the CO addition and insertion TS are higher than the relevant b-hydride elimination TS, but not than the alkyl-Rh TS. The solvent effect on the reversible profile, evaluated either in the supermolecule approach by adding a benzene molecule to the calculations or in the IEF-PCM framework (e = 2.247), does not bring about any substantial change in the profile, leaving unaltered the conclusions reached.

Dependence of the wittig reaction mechanism on the environment and on the substituents at the aldehyde group and at the phosphonium ylide

“…By examining stability and geometry, an impressive change upon substitution can be noticed in the PC 1 C 2 O dihedral angle for the reactant adduct with respect to the values taken in Ref. 33 (Tables 1 and 4).…”

“…The comparison with the results obtained for the real system 33, named “sys” in what follows, is performed in two stages. First of all, the effect of methyl groups instead of the phenyl rings at P and of the bulky chiral substituent (that is R 2 = SR replaced with CH 3 leading to acetaldehyde) at the aldehyde function has been modeled in both phases.…”

“…All calculations have been carried out with the Gaussian 03 system of programs 34 in the density functional theory (DFT) framework, employing a hybrid method, B3P86 35, 36, with the 6‐31G* basis set 37 (6d = Cartesian d functions). The B3P86 functionals performed very well in our previous studies on the Wittig reaction 33 and on regio‐ and diastereoselectivity of Rh‐catalyzed hydroformylations of several olefins 38–42. Thermal corrections for obtaining standard free energies for the various species at T = 298 K and 1 atm were calculated in the rigid rotator‐harmonic oscillator approximation 43: …”

“…Conversely, in our recent B3P86/6‐31G* investigation on the stepwise (i.e. via betaine) versus concerted mechanisms in the Wittig reaction of Ph 3 PCH 2 with a bulky chiral aldehyde, (2S,3R)‐2,4‐dimethyl‐3‐pyrrol‐1‐yl‐pentanal 33, hereafter R 2 is named SR for short, we got the impression that most of the effect was due to the steric hindrance and electronic properties of the substituents and to the environment. Therefore, we decided to study both mechanisms in the reactions with CH 3 CHO of Me 3 PCH 2 and Ph 3 PCH 2 in turn, in the gas phase and in THF solution (in the IEF‐PCM framework), employing the same computational level, to evaluate the reliability of simpler models.…”

Computational aspects of hydroformylation

“…114 The alkyl formation step is irreversible for all linear isomers that yield the linear aldehyde. Some branched Rh-alkyl isomers eventually afford the corresponding aldehydes as well, two others follow competing pathways due to the low relative barrier of b-hydride elimination.…”