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Review
. 2018 Jan 23;9(9):2398-2412.
doi: 10.1039/c7sc04679k. eCollection 2018 Mar 7.

Predictive and mechanistic multivariate linear regression models for reaction development

Celine B Santiago  1 , Jing-Yao Guo  1 , Matthew S Sigman  1
Affiliations
Review

Predictive and mechanistic multivariate linear regression models for reaction development

Celine B Santiago et al. Chem Sci. .

Abstract

Multivariate Linear Regression (MLR) models utilizing computationally-derived and empirically-derived physical organic molecular descriptors are described in this review. Several reports demonstrating the effectiveness of this methodological approach towards reaction optimization and mechanistic interrogation are discussed. A detailed protocol to access quantitative and predictive MLR models is provided as a guide for model development and parameter analysis.

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Figures

Fig. 1
Fig. 1. (A) Taft, (B) Charton, and (C) Sterimol steric parameters.
Fig. 2
Fig. 2. (A) Desymmetrization of bisphenol. (B) Charton–LFER model. (C) Sterimol–LFER model. (D) Nozaki–Hiyama–Kishi propargylation of acetophenone.
Fig. 3
Fig. 3. (A) Asymmetric addition of diethylzinc with benzaldehyde. (B) Charton-LFER model of mono- and di-N-substituted phosphoramide catalysts.
Fig. 4
Fig. 4. (A) Tolman cone angle. (B) Percent buried volume. (C) Nickel-catalysed Suzuki cross-coupling. (D) Rhodium-catalysed C–H activation.
Fig. 5
Fig. 5. (A) Hammett parameter. (B) Enantioselective alkene epoxidation reactions. (C) LFER model for epoxidation of 2,2-dimethylchromene 27. (D) LFER model for epoxidation of cis-β-methylstyrene 29.
Fig. 6
Fig. 6. (A) Sterimol MLR model for desymmetrization of bisphenol. (B) IR stretching frequency MLR model for desymmetrization of bisphenol.
Fig. 7
Fig. 7. (A) Correlation of benzoic acid pKa with benzoic acid group Löwdin partial charge QL(COOH). (B) Correlation of benzoic acid pKa with benzoic acid group natural population analysis (NPA) partial charge QN(COOH).
Fig. 8
Fig. 8. (A) Dehydrogenative Heck arylation of indoles with cis-alkenols. (B) Predictive model of enantioselectivity based on NBON,ox. (C) Predictive model represented in %ee.
Fig. 9
Fig. 9. (A) Ruthenium-catalysed olefin ethenolysis and ring opening metathesis polymerization (ROMP) of cis-cyclooctene. (B) Ethenolysis selectivity model of NMR principal component tensor σyy and percent buried volume %Vbur.
Fig. 10
Fig. 10. Predictive model for decomposition of pyridinium anolyte in relation to redox potential E1/2 and steric parameter Hst.
Fig. 11
Fig. 11. (A) Eπw and Dπw parameters. (B) Birman's kinetic resolution (C) palladium-catalysed 1,1-diarylation.
Fig. 12
Fig. 12. General scheme of model development.
Fig. 13
Fig. 13. Fluorination of allylic alcohols.
Fig. 14
Fig. 14. (A) Thiourea-catalysed asymmetric conjugate addition. (B) MLR model of enantioselectivity. (C) MLR model of diastereoselectivity. (D) Evaluation of optimal catalysts.
Fig. 15
Fig. 15. (A) Enantiodivergent fluorination of allylic alcohols. (B) Multivariate model of enantioselectivity. (C) Transition state analysis.
None
Celine B. Santiago
None
Jing-Yao Guo
None
Matthew S. Sigman
See this image and copyright information in PMC

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