Examination of the Role of Taft-Type Steric Parameters in Asymmetric Catalysis

Sigman, Matthew S.; Miller, Jeremie J.

doi:10.1021/jo901698t

Cited by 90 publications

(54 citation statements)

References 83 publications

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“…2 as a change in the mechanism of asymmetric induction, either by global conformational shift of the ligand/catalyst structure or congestion of the catalyst active site, leading to reaction at a different coordination site 65 . However, we also considered that this observed break in linearity was potentially due to an imperfect application of the Charton parameters.…”

Section: Limitations Of Charton Parametersmentioning

confidence: 99%

Multidimensional steric parameters in the analysis of asymmetric catalytic reactions

2012

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Although asymmetric catalysis is universally dependent on spatial interactions to impart specific chirality on a given substrate, examination of steric effects in these catalytic systems remains empirical. Previous efforts by our group and others have seen correlation between steric parameters developed by Charton and simple substituents in both substrate and ligand; however, more complex substituents were not found to be correlative. Here, we review and compare the steric parameters common in quantitative structure activity relationships (QSAR), a common method for pharmaceutical function optimization, and how they might be applied in asymmetric catalysis, as the two fields are undeniably similar. We re-evaluate steric/enantioselection relationships, which we previously analysed with Charton steric parameters, using the more sophisticated Sterimol parameters developed by Verloop and co-workers in a QSAR context. Use of these Sterimol parameters led to strong correlations in numerous processes where Charton parameters had previously failed. Sterimol parameterization also allows for greater mechanistic insight into the key elements of asymmetric induction within these systems.

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Section: Limitations Of Charton Parametersmentioning

confidence: 99%

Multidimensional steric parameters in the analysis of asymmetric catalytic reactions

2012

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“…For the Tsuji-Trost reaction, steric influences on the activation barrier have been modeled using explicit probes. 17 More recently, Sigman and co-workers 41 demonstrated that selectivities in the Tsuji-Trost reaction can be reproduced using a linear correlation with Charton steric parameters. 42 We therefore attempted a correlation between the Charton value of the 2-substituents and the logarithm of the observed regioselectivity, as shown in Table 3.…”

Section: Resultsmentioning

confidence: 99%

Breaking conjugation: unusual regioselectivity with 2-substituted allylic substrates in the Tsuji–Trost reaction

et al. 2014

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η3-Allyl palladium complexes are key intermediates in Tsuji-Trost allylic substitution reactions. It is well known that (η3-1-aryl-3-alkyl substituted allyl)Pd intermediates result in nucleophilic attack at the alkyl substituted terminus. In contrast, the chemistry of (η3-1,2,3-trisubstituted allyl)Pd intermediates is relatively unexplored. Herein we probe the regioselectivity with 1,2,3-trisubstituted allylic substrates in Tsuji-Trost allylic substitution reactions. DFT investigation of cationic (η3-1-Ph-2-B(pin)-3-alkyl-allyl)Pd(PPh3)2 intermediates predict that nucleophilic attack should occur preferentially on anti-allyls rather than the syn-isomers to generate benzylic substitution products under Curtin-Hammett conditions. Experimentally, systematic studies with 1,2,3-trisubstituted allylic substrates revealed that a Linear Free Energy Relationship (LFER) is observed when Charton steric parameters of the C-2 substituents are plotted against the log of the ratio of regioisomers. Bulkier C-2 substituents in 1,2,3-trisubstituted η3-allyl palladium intermediates provide stronger preference for nucleophilic attack at anti-oriented benzylic termini. Additionally, the geometry of 1,4-elimination products supports the presence of anti-allyl palladium intermediates.

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“…6 In contrast to the extensive application of QSAR methods to probe biological problems, these methods have only recently been applied to problems in chemical reactivity and selectivity, primarily in relation to catalytic systems. 7 An area of catalysis for which QSAR methods exhibit high potential for applicability is Phase Transfer Catalysis (PTC).…”

Section: Introductionmentioning

confidence: 99%

A Systematic Investigation of Quaternary Ammonium Ions as Asymmetric Phase-Transfer Catalysts. Application of Quantitative Structure Activity/Selectivity Relationships

2011

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While the synthetic utility of asymmetric phase transfer catalysis continues to expand, the number of proven catalyst types and design criteria remains limited. At the origin of this scarcity is a lack in understanding of how catalyst structural features affect the rate and enantioselectivity of phase transfer catalyzed reactions. Described in this paper is the development of quantitative structure-activity relationships (QSAR) and -selectivity relationships (QSSR) for the alkylation of a protected glycine imine with libraries of quaternary ammonium ion catalysts. Catalyst descriptors including ammonium ion accessibility, interfacial adsorption affinity, and partition coefficient were found to correlate meaningfully with catalyst activity. The physical nature of the descriptors was rationalized through differing contributions of the interfacial and extraction mechanisms to the reaction under study. The variation in the observed enantioselectivity was rationalized employing a comparative molecular field analysis (CoMFA) using both the steric and electrostatic fields of the catalysts. A qualitative analysis of the developed model reveals preferred regions for catalyst binding to afford both configurations of the alkylated product.

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Examination of the Role of Taft-Type Steric Parameters in Asymmetric Catalysis

Cited by 90 publications

References 83 publications

Multidimensional steric parameters in the analysis of asymmetric catalytic reactions

Multidimensional steric parameters in the analysis of asymmetric catalytic reactions

Breaking conjugation: unusual regioselectivity with 2-substituted allylic substrates in the Tsuji–Trost reaction

A Systematic Investigation of Quaternary Ammonium Ions as Asymmetric Phase-Transfer Catalysts. Application of Quantitative Structure Activity/Selectivity Relationships

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