Mechanism Of Stereocontrol Research Articles

Stereoselective Catalysis Achieved through in Situ Desymmetrization of an Achiral Iron Catalyst Precursor.

Stereoselective catalysis is described that proceeds with catalyst control but without the need to synthesize preformed chiral catalysts or ligands. Iron-based catalysts were discovered to effect the stereoselective polymerization of lactides starting from a single achiral precursor and the proper choice of an achiral silanol additive. Spectroscopic analysis of the polymer revealed that the stereoselectivity originates from an enantiomorphic site rather than a chain end stereocontrol mechanism. Iron intermediates that are stereogenic at iron are proposed to form in situ as a result of desymmetrization that occurs from a change in the metal coordination number. The proposed mechanism is supported by a combination of spectroscopic measurements, model complexes, kinetic measurements, and DFT calculations.

Regio- and Diastereoselective and Enantiospecific Metal-Free C(sp(3) )-H Arylation: Facile Access to Optically Active 5-Aryl 2,5-Disubstituted Pyrrolidines.

Optically active 5-aryl 2,5-disubstituted pyrrolidines are the principal structural moiety of many bioactive compounds including natural products and catalysts for asymmetric synthesis. A highly regio- and diastereoselective and enantiospecific method for direct C-H arylation of aliphatic amine has been developed. Structurally diverse enantiopure arylated pyrrolidines were synthesized from commercially available starting materials, through a single-step three-component reaction under metal- and oxidant-free conditions. Furthermore, the complex analogous structure of CCK antagonist RP 66803 and angiotensin-converting enzyme inhibitors was easily constructed using the synthesized arylated pyrrolidine derivative. Detailed theoretical calculations (M06-2X/TZVPP/SMD//M06-2X/6-31+G(d,p) level) were also carried to investigate the mechanism and high level of stereocontrol involved in this direct sp(3) C-H arylation reaction. Preference for a given regio- and stereoselectivity in the arylated product can be explained through elucidation of the mechanism for dehydration, generating azomethine ylide, and for the final re-aromatization step. The calculated energies reveals that the re-aromatization step is essentially rate determining, accompanying an activation barrier of Δ(≠) G=25.6 kcal mol(-1) .

Stereoselectivity Switch between Zinc and Magnesium Initiators in the Polymerization of rac-Lactide: Different Coordination Chemistry, Different Stereocontrol Mechanisms

The preparation and characterization of several zinc and magnesium complexes bearing chiral aminophenolate ligands, [(S)- or (R)-L]ZnN(SiMe3)2 (1, 2), [(S)- or (R)-L]ZnOtBu (3, 4) and [(S)- or (R)-L]MgN(SiMe3)2 (5, 6) ((S)- or (R)-L = (S)- or (R)-2-{N-benzyl-N-[(1-nbutyl-2-pyrrolidinyl)methyl]}aminomethyl-4-methyl-6-tritylphenolate), have been reported. While the X-ray diffraction studies as well as the NMR spectroscopic data revealed that zinc and magnesium silylamido complexes possess similar structures both in the solid state and in solution, their catalytic performance toward rac-LA polymerization exhibited significant difference. The replacement of zinc center by magnesium realized an interesting stereoselectivity switch from isoselective (Pm = 0.80) to heteroselective (Pr = 0.81). The reactions of enantiopure zinc complexes 1 and 2 with (S)-methyl lactate or (R)-tert-butyl lactate resulted in the target lactate complexes 7–9 as a mixture of two diastereomers, but in different ratios. Two typical zin...

Terpenols as substituents for the diastereoselective formation of enantiomerically pure triple lithium-bridged helicate type-coordination compounds.

The terpenols l(-)-borneol, (1S2S3S5R)-3-pinanol, (-)-menthol, and (-)-myrtenol are easily available chiral alcohols for the preparation of enantiomerically pure catechol esters -H2. Those ligands are used for the hierarchical assembly of triple lithium-bridged dinuclear titanium(iv) triscatecholate helicates Li[Li3()6Ti2]. In solution, the dimeric species are in a solvent dependent equilibrium with the monomer Li2[()3Ti]. The equilibrium is studied by (1)H NMR. CD spectroscopy indicates that the configuration at the complex units of the enantiomerically pure dimeric α-chiral derivatives Li[Li3()6Ti2] is opposite to the configuration of the monomers Li2[()3Ti]. For the γ-chiral complex Li2[()3Ti] only a de of 25% is observed and in this case no interpretation of the mechanism of stereocontrol is possible.

Stereocontrol in dinuclear triple lithium-bridged titanium(IV) complexes: solving some stereochemical mysteries.

Compounds 1 a-f-H2 form "monomeric" triscatecholate titanium(IV) complexes [Ti(1 a-f)3](2-), which in the presence of Li cations are in equilibrium with the triple lithium-bridged "dimers" [Li3(Ti(1 a-f)3)2](-). The equilibrium strongly depends on the donor ability of the solvent. Usually, in solvents with high donor ability, the stereochemically labile monomer is preferred, whereas in nondonor solvents, the dimer is the major species. In the latter, the stereochemistry at the complex units is "locked". The configuration at the titanium(IV) triscatecholates is influenced by addition of chiral ammonium countercations. In this case, the induced stereochemical information at the monomer is transferred to the dimer. Alternatively, the configuration at the metal complexes can be controlled by enantiomerically pure ester side chains. Due to the different orientation of the ester groups in the monomer or dimer, opposite configurations of the triscatecholates were observed by circular dichroism (CD) spectroscopy for [Ti(1 c-e)3](2-) or [Li3(Ti(1 c-e)3)2](-). A surprising exception was found for the dimer [Li3(Ti(1 f)3)2](-). Herein, the dimer is the dominating species in weak donor (methanol), as well as strong donor (DMSO), solvents. This is due to the bulkiness of the ester substituent destabilizing the monomer. Due to the size of the substituent in [Li3(Ti(1 f)3)2](-) the esters have to adopt an unusual conformation in the dimer resulting in a stereocontrol of the small methyl group. Following this, opposite stereocontrol mechanisms were observed for the central metal-complex units of [Li3(Ti(1 c-e)3)2](-) or [Li3(Ti(1 f)3)2](-).

キラルリン酸触媒反応における反応制御·立体制御機構に関する理論的研究

The chiral BINOL-phosphoric acid is a well-designed asymmetric organocatalyst because it features the bifunctionality of the Brønsted acid (proton)/base (phosphoryl oxygen) and the conformational rigidity of the 3,3-substituents of the BINOL unit controlling the stereoselectivity through the hydrogen bonding network. Though the bifunctional activation has emerged as an important paradigm of chiral phosphoric acid catalyzed asymmetric reactions, it has remained elusive in most cases. Recently, we revealed the reaction mechanism as well as the stereocontrol mechanism by our computational two-step approach using (1) simplified chemical model and (2) realistic chemical model.

Ring-opening polymerization of ɛ-caprolactone and lactides promoted by salan- and salen-type yttrium amido complexes

The ring-opening polymerization (ROP) of cyclic esters such as ɛ-caprolactone (ɛ-CL), l- and rac-lactide, promoted by yttrium silylamido complexes bearing binaphthyl-bridged salen (1 and 2) and diamine bisphenolate salan ligands (3 and 4) is described.The yttrium silylamido complexes 1–4 are effective initiators for the ROP of ɛ-caprolactone, showing extremely high turnover frequencies (TOF up to 18000h−1) under mild reaction conditions. All complexes promote the ROP of rac-lactide in toluene solution at room temperature, providing atactic polymers with controlled molecular weights and relatively narrow polydispersities (Mw/Mn=1.73–1.99). Interestingly, in THF solution the same catalysts produce heterotactic polylactides with Pr between 0.58 and 0.91 via a chain-end stereocontrol mechanism. The salan complexes 3 and 4 are more active than the binaphthyl salen complexes 1 and 2, reasonably due to the presence of the more electron donating amino groups. On the other hand, the former resulted in a lower stereoselectivity than the latter. The rigidity of the “bridge” between the two nitrogen atoms seems to have a predominant role in governing the selectivity of the corresponding complexes, while the effect of the steric hindrance of the ortho substituents at the phenoxy rings appears less significant.

Stereospecific radical polymerization of optically active (S)-N-(2-hydroxy-1-phenylethyl) methacrylamide catalyzed by Lewis acids

The effects of Lewis acids, namely, rare earth metal trifluoromethanesulfonates, on the radical polymerization of (S)-N-(2-hydroxy-1-phenylethyl) methacrylamide were examined under various conditions. In the absence of Lewis acids, syndiotactic-rich polymers (r=84%) were obtained, whereas in the presence of a catalytic amount of Lewis acids, the polymerization proceeded in an isotactic-specific manner (m up to 64%). Polymerization solvents strongly influenced the effect of the Lewis acids. The polymerization in n-butyl alcohol showed the highest isotactic selectivity, whereas the polymerization in DMSO showed no isotacticity-enhancing effect. Further increases in the Lewis acid concentration and the polymerization temperature did not produce clear effects on the tacticity of the polymers. The interaction between the monomer and Lewis acids was investigated, and the plausible mechanism of stereocontrol in the radical polymerization of (S)-HPEMA was analyzed based on the Lewis acid-monomer interaction.

Opposing Auxiliary Conformations Produce the Same Torquoselectivity in an Oxazolidinone-Directed Nazarov Cyclization

Most applications of chiral oxazolidinone auxiliaries in asymmetric synthesis operate through a common set of stereocontrol principles. That is, the oxazolidinone is made to adopt a specific, coplanar conformation with respect to the prochiral substrate, and reaction occurs preferentially at whichever stereoheterotopic face is not blocked by the substituents on the oxazolidinone. In contrast to these principles, we report here the discovery of an alternative mechanism of oxazolidinone-based stereocontrol that does not require coplanarity and is driven instead by allylic strain. This pathway has been uncovered through computational studies of an asymmetric Nazarov cyclization. Chiral oxazolidinone auxiliaries provide essentially complete control over the torquoselectivity of ring closure and the regioselectivity of subsequent deprotonation. Density functional theory calculations (M06-2X//B3LYP) reveal that in the transition state of 4π electrocyclic ring closure, the oxazolidinone ring and the cyclizing pentadienyl cation are distorted from coplanarity in a manner that gives two transition state conformations of similar energy. These two conformers are distinguished by a 180° flip in the auxiliary orientation such that in one conformer the oxazolidinone carbonyl is oriented toward the OH of the pentadienyl cation (syn-conformer) and in the other it is oriented away from this OH (anti-conformer). Surprisingly, both conformations induce the same sense of torquoselectivity, with a 3-5 kcal/mol preference for the C5-β epimer of the ring-closed cation. In both conformations, the conrotatory mode that leads to the C5-α epimer is disfavored due to higher levels of allylic strain between the oxazolidinone substituent and adjacent groups on the pentadienyl cation (R(4) and OH). The excellent torquoselectivities obtained in the oxazolidinone-directed Nazarov cyclization suggest that the allylic strain-driven stereoinduction pathway represents a viable alternative mechanism of stereocontrol for reactions of sterically congested substrates that lie outside of the traditional coplanar (N-acyloxazolidinone) paradigm.

Rare-Earth Half-Sandwich Dialkyl and Homoleptic Trialkyl Complexes for Rapid and Stereoselective Polymerization of a Conjugated Polar Olefin

Under ambient conditions, discrete half-sandwich rare-earth (RE) dialkyls, [η5-(1,3-(SiMe3)2C9H5)]]RE(CH2SiMe3)2(THF) (RE = Sc, Y, Dy, Lu), catalyze rapid and stereoselective coordination polymerization of β-methyl-α-methylene-γ-butyrolactone (βMMBL), a conjugated polar olefin and a member of the naturally occurring or biomass-derived methylene butyrolactone family. Within the present RE series, the complex of the largest ion (Dy3+) exhibits the highest activity, achieving a high turnover frequency of 390 min–1, and also produces the highly isotactic polymer PβMMBL (mm = 91.0%). This stereoregular polymer is thermally robust, with a high glass-transition temperature of 280 °C, and is resistant to all common organic solvents. Other half-sandwich RE catalysts of the series are also highly active and produce polymers with a similarly high isotacticity. Intriguingly, even simple homoleptic hydrocarbyl RE complexes, RE(CH2SiMe3)3(THF)2 (RE = Sc, Y, Dy, Lu), also afford highly isotactic polymer PβMMBL, despite their much lower polymerization activity, except for the Lu complex, which maintains its high activity for both types of complexes. Computational studies of both half-sandwich and simple hydrocarbyl yttrium complexes have revealed a stereocontrol mechanism that well explains the observed high stereoselectivity of βMMBL polymerization by both types of catalysts. Specifically, the experimental stereoselectivity can be well rationalized with a monometallic propagation mechanism through predominantly chain-end stereocontrol in the coordination–addition polymerization. In this mechanism, formation of an isotactic polymer chiefly originates from interactions between the methyl groups on the chiral β-C atom of the five-membered ring of both the coordinated monomer and the last inserted βMMBL unit of the chain, and the auxiliary ligand on the metal makes a negligible contribution to the stereocontrol of the polymerization.

Cocatalyst effect in propylene polymerization reactions with post-metallocene catalysts

Effect of cocatalysts on the performance of three post-metallocene catalysts based on complexes I–III in Scheme 1 is studied by comparing their activity in the presence of two cocatalysts, MAO and a combination of AlEt2Cl and MgBu2, in propylene polymerization reactions. The second cocatalyst produces significantly more active catalysts. Analysis of GPC, DSC and 13C NMR data for the polymers suggests that the activity increase is caused by the formation of new types of active centers. Some of the new centers are isospecific and operate according to the enantiomorphic stereocontrol mechanism.

Mechanism of Isotactic Styrene Polymerization with a C6F5-Substituted Bis(phenoxyimine) Titanium System

We report a combined, experimental and theoretical, study of styrene polymerization to clarify the regio- and stereocontrol mechanism operating with a C6F5-substituted bis(phenoxyimine) titanium dichloride complex. Styrene homopolymerization, styrene–propene and styrene–ethene–propene copolymerizations have been carried out to this aim. A combination of 13C NMR analysis of the chain-end groups and of the microstructure of the homopolymers and copolymers reveals that styrene polymerization is highly regioselective and occurs prevalently through 2,1-monomer insertion. DFT calculations evidenced that steric interaction between the growing chain and the monomer in the transition state insertion stage is at the origin of this selectivity. The formation of isotactic polystyrene with a chain-end like microstructure is rationalized on the base of a mechanism similar to that proposed for the syndiospecific propene polymerization catalyzed by bis(phenoxyimine) titanium dichloride complexes. Finally, a general stereocontrol mechanism operative in olefin polymerization with this class of complexes is proposed.

Stereoselectivity in Metallocene-Catalyzed Coordination Polymerization of Renewable Methylene Butyrolactones: From Stereo-random to Stereo-perfect Polymers

Coordination polymerization of renewable α-methylene-γ-(methyl)butyrolactones by chiral C(2)-symmetric zirconocene catalysts produces stereo-random, highly stereo-regular, or perfectly stereo-regular polymers, depending on the monomer and catalyst structures. Computational studies yield a fundamental understanding of the stereocontrol mechanism governing these new polymerization reactions mediated by chiral metallocenium catalysts.

Polymerization of olefins catalyzed by a dichloride complex of titanium with a dioxolane dicarbonate ligand: The promoting effect of LiCl and MgCl2

The polymerizations of propylene and ethylene with two postmetallocene catalysts [(4R,5R)-2,2-dimethyl-α,α,α′,α′-tetra(perfluorophenyl)-1,3-dioxolane-4,5-dimethanol]TiCl2 · MgCl2 and [(4R,5R)-2,2-dimethyl-α,α,α′,α′-tetra-(perfluorophenyl-1,3-dioxolane-4,5-dimethanol]TiCl2· (LiCl)2 are studied. The first catalyst shows higher activity in both reactions and forms a lower molecular mass PP. This PP is characterized by a wide molecular-mass distribution that can be described by a set of five or six Flory components with different average molecular masses. Along with heterogeneity with respect to kinetic parameters, there is heterogeneity with respect to stereospecificity. Some of the sites form a high-molecular-mass highly isotactic polymer whose melting point is ≥150°C, whereas other sites produce syndiotactic and atactic PPs. For the most isospecific sites, a stereocontrol mechanism similar to the mechanism typical for metallocene catalysts with C1-symmetry is advanced. The catalysts under study are composed of the [(4R,5R)-2,2-dimethyl-α,α,α′,α′-tetra(perfluorophenyl)-1,3-dioxolane-4,5-dimethanol]TiCl2 complex supported on LiCl and MgCl2, respectively.

DFT Investigation of the Tacticity Control during Styrene Polymerization Catalyzed by Single-Component Allyl ansa-Lanthanidocenes {(C5H4CMe2(9-C13H8)}Ln(C3H5)

Theoretical methods (DFT) were used to investigate the syndiospecificity of the styrene polymerization catalyzed by single-site, single-component allyl ansa-lanthanidocenes {(C5H4CMe2(9-C13H8)}Ln(C3H5). Two limiting chain-end stereocontrol mechanisms were studied, namely, frontside “migratory” insertion through a site epimerization and site stereoconfiguration independent backside insertion on a “stationary” polymer chain. Four consecutive insertions of styrene were computed to reveal that (i) backside insertions are more favorable than, or at least as favorable as, frontside insertions, and (ii) the formation of a syndiotactic polymer is controlled by the thermodynamics. Moreover, the odd (first and third) insertions are of 2,1-down-si-type and are kinetically favored over the 2,1-up-re-ones. This control is the conjunction of two effects: minimization of styrene−styrene and styrene(phenyl ring)−fluorenyl repulsions and (iii) the steric hindrance of the polymer chain induces for the fourth insertion an e...

Stereocontrol during the radical polymerization of methyl methacrylates with combined Lewis acids: Aluminium trichloride (AlCl3) and iron dichloride tetrahydrate

The radical polymerization of methyl methacrylate (MMA) was carried out in the presence of combined Lewis acids of the AlCl3-FeCl2 system. Compared with the polymerization produced in the presence of single Lewis acids, AlCl3 or FeCl2, the MMA polymerization in the presence of AlCl3-FeCl2 composite in CHCl3 or 1-butanol produced a polymer with a higher isotacticity and in toluene produced a polymer with a much higher isotacticity (mm = 50%). The molecular weight and polydispersity of PMMA in the presence of Lewis acids were similar with those in the absence of Lewis acids, although Lewis acids decelerate the polymerization of MMA. The effects of the Lewis acids were greater in a solvent with a lower polarity. A possible stereocontrol mechanism of the polymerization was proposed. The Lewis acid composite of AlCl3-FeCl2 readily formed a complex with growing species. These complexes possessed apparent bulkiness that changes the direction of monomer addition to the growing radical center.

Mechanism of Stereocontrol in Methyl Methacrylate Polymerization Promoted byC1-Symmetric Metallocenes

The mechanism of stereoselectivity in methyl methacrylate (MMA) monometallic polymerization promoted by the C1-symmetric ansa-Me2C(Cp)(Ind)Zr-based zirconocene, presenting two diastereotopic coordination sites, was investigated within density functional theory. At variance from the case of propene polymerization, our results suggest that MMA addition is stereoselective when the growing chain is in the more hindered as well as in the more open diastereotopic coordination site. In both cases the same enantioface of the enolate bond of the ester enolate growing chain is selected, although selectivity is higher when the growing chain is in the more hindered diastereotopic coordination site. Further, there is no substantial energy difference between these two situations, which indicates that the moderate isotacticity of the produced PMMA is consistent with an almost regular chain-migratory mechanism. The different stereoselectivity of the two diastereotopic sites is due to different steric interaction between ...

Stereocontrol mechanism in CO/p-methylstyrene copolymerisation catalysed by aryl-α-diimine Pd(ii) complexes

Structural analysis of the first steps of isotactic CO/p-methylstyrene copolymerisation, catalysed by aryl-alpha-diimine Pd(II) complexes, highlights the influence of steric effects on the stereoselectivity of olefin insertion.

Stereospecificity in Metallocene Catalyzed Acrylate Polymerizations: The Chiral Orientation of the Growing Chain Selects Its Own Chain End Enantioface

The mechanism of stereocontrol in the site-controlled stereospecific polymerization of methyl methacrylate (MMA) with C2- and CS-symmetric zirconocenes is investigated with a DFT based approach. Our model explains the experimentally observed isospecificity in MMA polymerization with the C2-symmetric rac-C2H4(Ind)2Zr-based system as well as the experimentally observed syndiospecificity in MMA polymerization with the CS-symmetric Me2C(Cp)(Flu)Zr-based system. In both cases, the chiral metallocene induces a chiral orientation of the ester enolate growing chain. In turn, the chirally oriented growing chain selects its own enantioface. Comparison with the mechanism of stereocontrol operative in the case of propene polymerization by the same zirconocenes is performed to stress similarities and differences. Although analogies are expected, surprising differences also exist. The most peculiar is that the in the case of 1-olefins, the enantioselective event is selection between the enantiofaces of the prochiral monomer. Instead, in the case of acrylates, the enantioselective event is selection between the enantiofaces of the prochiral growing chain.

Polymerizations of vinyl-cyclohexane in the presence of C2, C2 v, and Cs zirconocene-based catalysts

Polymerizations of vinyl-cyclohexane (VCH) in the presence of catalytic systems based on zirconocenes belonging to C 2, C 2 v or C s symmetry group were performed. All polymers were analyzed by 13C NMR spectroscopy and show isotactic microstructure. A steric control mechanism, involving a like 1,3-asymmetric induction of the chiral carbon of the last inserted unit on the chirality of the incoming monomer coordination, is proposed. This would be the only stereocontrol mechanism in the presence of a C 2 v -symmetry catalyst, and it would enforce or overcome site control in case of active species with C 2 and C s -symmetry, respectively.