Computational Studies of Ion-Pair Separation of Benzylic Organolithium Compounds in THF: Importance of Explicit and Implicit Solvation

The Pd-catalyzed decarboxylative allylation of α-(diphenylmethylene)imino esters (1) or allyl diphenylglycinate imines (2) is an efficient method to construct new C(sp(3))-C(sp(3)) bonds. The detailed mechanism of this reaction was studied by theoretical calculations [ONIOM(B3LYP/LANL2DZ+p:PM6)] combined with experimental observations. The overall catalytic cycle was found to consist of three steps: oxidative addition, decarboxylation, and reductive allylation. The oxidative addition of 1 to [(dba)Pd(PPh(3))(2)] (dba = dibenzylideneacetone) produces an allylpalladium cation and a carboxylate anion with a low activation barrier of +9.1 kcal mol(-1). The following rate-determining decarboxylation proceeds via a solvent-exposed α-imino carboxylate anion rather than an O-ligated allylpalladium carboxylate with an activation barrier of +22.7 kcal mol(-1). The 2-azaallyl anion generated by this decarboxylation attacks the face of the allyl ligand opposite to the Pd center in an outer-sphere process to produce major product 3, with a lower activation barrier than that of the minor product 4. A positive linear Hammett correlation [ρ = 1.10 for the PPh(3) ligand] with the observed regioselectivity (3 versus 4) supports an outer-sphere pathway for the allylation step. When Pd combined with the bis(diphenylphosphino)butane (dppb) ligand is employed as a catalyst, the decarboxylation still proceeds via the free carboxylate anion without direct assistance of the cationic Pd center. Consistent with experimental observations, electron-withdrawing substituents on 2 were calculated to have lower activation barriers for decarboxylation and, thus, accelerate the overall reaction rates.

Section: Resultsmentioning

confidence: 99%

Mechanism of the Pd‐catalyzed Decarboxylative Allylation of α‐Imino Esters: Decarboxylation via Free Carboxylate Ion

Jiang

Yeagley

et al. 2012

“…[84][85][86][87][88][89] Moreover, considering the same symmetry number [90] (s = 2) for S2 (average C 2v ) and S3 (average C 2h ), and assuming the distortion modes and planarity to be similar for both porphyrin macrocycles, there is no obvious reason to expect any significant difference between the entropy energies of S2 and S3 (although the significant difference in their dipole moments may influence their entropy and/or enthalpy through solvation effects). [76,91] It is therefore reasonable to assume that, in our case, the variation in entropy for the interconversion of the S2 and S3 atropisomers must be at least negligible with respect to the highly enthalpic-dependent energy barriers to rotation. Thus, assuming DG°to be independent of the temperature (with DG°T = DH°ÀTDS°and DS°% 0) gives DG°% DH°, and the values of DG°of 115.2 and 116.9 kJ mol À1 for S2 and S3, respectively, at 355 K should be roughly the same as those at room temperature, which corresponds to a half-life in the range of months to a year at room temperature.…”

Section: Atropisomerisation Of S2 and S3mentioning

confidence: 99%

Tautomerism and Atropisomerism in Free‐Base (meso)‐Strapped Porphyrins: Static and Dynamic Aspects

Urbani

Torres

2014

We report herein some outstanding examples of atropisomerism and tautomerism in five (meso-)strapped porphyrins. Porphyrins S0-S4 have been synthesised, characterised and studied in detail by spectroscopic and spectrometric techniques, and their isomeric purity verified by HPLC analysis. In particular, they exhibit perfectly well-defined NMR spectra that display distinct patterns depending on their average symmetry at room temperature: C2v , D2d , C2h , C2v , and D2h for S0-S4, respectively. NH tautomerism was evidenced by variable-low-temperature (1) H NMR experiments in [D2 ]dichloromethane performed on S0 (Δ${G{{{\ne}\hfill \atop {\rm 298K}\hfill}}}$=48±1 kJ mol(-1) ) and S1 (Δ${G{{{\ne}\hfill \atop {\rm 298K}\hfill}}}$=55±3 kJ mol(-1) ), which has led to an understanding of the average spectra observed for the five porphyrins at room temperature. On the other hand, S2 and S3 are stable atropisomers at room temperature, easily separated and characterised, as a result of restricted rotation of their strapped bridges due to their high rotational barrier energies. Upon heating to 82 °C, they slowly equilibrate to a thermodynamic ratio of 64:36 in favour of the more stable S2 isomer. This atropisomerisation process was evidenced by (1) H NMR spectroscopy and monitored by HPLC, from which high rotational energy barriers of 115.2 (Δ${G{{{\ne}\hfill \atop {\rm S2}\rightarrow {\rm S3}\hfill}}}$) and 116.9 kJ mol(-1) (Δ${G{{{\ne}\hfill \atop {\rm S2}\rightarrow {\rm S3}\hfill}}}$) were deduced.

“…It thus seems likely that solvent electrostriction plays a significant role in the kinetics and thermodynamics of many ionogenic reactions, including the enantiomerization of stabilized organolithium compounds in ethereal solvents 1f. 11, 28…”

Section: Methodsmentioning

confidence: 99%

Incremental Solvation Precedes Ion‐Pair Separation in Enantiomerization of a Cyano‐Stabilized Grignard Reagent

Gao

Carlier

2011

Self Cite

[a] Dedicated to Professor K. Barry Sharpless on the occasion of his 70th birthday Configurationally stable enantioenriched organolithium compounds are important in asymmetric synthesis.[1] Studies of the enantiomerization pathways of these compounds are useful for improving the stereochemical outcome of these reactions, and provide insight into the structure and dynamics of these compounds.[1a, f, 2] The composition of the organic fragment, [1a, f, 2a, d] the presence of additives, [2d, 3] and the identity of the solvent [2d, 4] are all known to affect configurational stability. In contrast, few such studies have been reported for enantioenriched organomagnesium compounds, perhaps reflecting the relative paucity of these reagents.[5] Herein we report Eyring analyses and reaction order studies of the racemization of enantioenriched Grignard reagent 2 in ethereal solvents. Enantiomerization rates increase in the order Et 2 O < 2-methylTHF < THF. A highly negative activation entropy for enantiomerization ((À49 AE 4) eu) is seen under conditions where reaction is zero-order in [Et 2 O] and first-order in [Mg]. These results are consistent with an ion-pair separation enantiomerization mechanism wherein association of solvent precedes rupture of the Mg À C bond. To our knowledge this is the first experimental determination of the timing of incremental solvation and ion-pair separation for a Group I or II organometallic reagent.We previously reported [5h] that enantioenriched cyano-stabilized Grignard reagent 2 could be prepared by Mg/Br exchange [6] of enantiopure a-bromonitrile (S)-1 with iPrMgCl (Scheme 1). The overall transformation of (S)-1 to [D 1 ]-3 was shown to favor retention, and measurements of the e.r. of [D 1 ]-3 with increasing delay time t demonstrated that 2 possessed a racemization half life (t 1/2 A C H T U N G T R E N N U N G (rac)) of 11.4 h in Et 2 O at 173 K. The extrapolated e.r. at t = 0 for 2 from these experiments was 91:9, suggesting that Mg/Br exchange was not perfectly retentive.To explore the role of solvent in the enantiomerization process, we reinvestigated this reaction in Et 2 O, 2-methyltetrahydrofuran (2-MeTHF), and THF, at several temperatures. A key feature of our reinvestigation was the use of a precooled CH 3 OD quench in place of room-temperature D 2 O.[7] Delay times t varied from 60 to 3600 s and > 95 % recovery of [D 1 ]-3 (> 98 % deuterium incorporation) was obtained after workup even at the shortest time points (60 s) at 175 K. First-order rate constants for enantiomerization of 2 (k enant ) derive from slopes (À2k enant ) of the plots of ln-versus delay time t (Figure 1).[8]