Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters

Leyah A. Schwartz; Michael Holmes; Gilmar A. Brito; Theo Goncalves; Jeffery Richardson; J. Craig Ruble; Kuo-Wei Huang; Michael J. Krische

doi:10.1021/jacs.8b11868

Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters

Leyah A. Schwartz, Michael Holmes, Gilmar A. Brito, Theo Goncalves, Jeffery Richardson, J. Craig Ruble, Kuo-Wei Huang, Michael J. Krische

Research output: Contribution to journal › Article › peer-review

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Abstract

Iridium complexes modified by the chiral phosphine ligand PhanePhos catalyze the 2-propanol-mediated reductive coupling of diverse 1,1-disubstituted allenes 1a-1u with fluoral hydrate 2a to form CF3-substituted secondary alcohols 3a-3u that incorporate acyclic quaternary carbon-containing stereodiads. By exploiting concentration-dependent stereoselectivity effects related to the interconversion of kinetic ( Z)- and thermodynamic ( E)-σ-allyliridium isomers, adducts 3a-3u are formed with complete levels of branched regioselectivity and high levels of anti-diastereo- and enantioselectivity. The utility of this method for construction of CF3-oxetanes and CF3-azetidines is illustrated by the formation of 4a and 6a, respectively. Studies of the reaction mechanism aimed at illuminating the singular effectiveness of PhanePhos as a supporting ligand in this and related transformations have led to the identification of a chromatographically stable cyclometalated iridium-( R)-PhanePhos complex, Ir-PP-I, that is catalytically competent for allene-fluoral reductive coupling and previously reported transfer hydrogenative C-C couplings of dienes or CF3-allenes with methanol. Deuterium labeling studies, reaction progress kinetic analysis (RPKA) and computational studies corroborate a catalytic mechanism involving rapid allene hydrometalation followed by turnover-limiting carbonyl addition. A computationally determined stereochemical model shows that the ortho-CH2 group of the cyclometalated iridium-PhanePhos complex plays a key role in directing diastereo- and enantioselectivity. The collective data provide key insights into the structural-interactional features of allyliridium complexes required to enforce nucleophilic character, which should inform the design of related cyclometalated catalysts for umpoled allylation.

Original language	English (US)
Pages (from-to)	2087-2096
Number of pages	10
Journal	Journal of the American Chemical Society
Volume	141
Issue number	5
DOIs	https://doi.org/10.1021/jacs.8b11868
State	Published - Jan 25 2019

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: The Robert A. Welch Foundation (F-0038), the NIH (RO1-GM069445, 1 S10 OD021508-01), and King Abdullah University of Science and Technology (KAUST) are acknowledged for partial support of this research. Eli Lilly and Company is acknowledged for LIFA postdoctoral fellowship funding (M.H.). Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) is acknowledged for postdoctoral fellowship support (G.B. 2017/00734-5). We thank Professor Donna G. Blackmond for assistance with RPKA. The service of Ibex, Shaheen 2 High Performance Computing Facilities was provided with financial support from KAUST.

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CCDC 1856475: Experimental Crystal Structure Determination : 3-(4-bromophenyl)-1,1,1-trifluoro-3-methylpent-4-en-2-yl 3,5-dinitrobenzoate
Schwartz, L. A. (Creator), Holmes, M. (Creator), Brito, G. A. (Creator), Goncalves, T. (Creator), Richardson, J. (Creator), Ruble, J. C. (Creator), Huang, K.-W. (Creator), Krische, M. J. (Creator), Schwartz, L. A. (Creator), Holmes, M. (Creator), Brito, G. A. (Creator), Richardson, J. (Creator), Ruble, J. C. (Creator) & Krische, M. J. (Creator), Cambridge Crystallographic Data Centre, Jan 30 2019
DOI: 10.5517/ccdc.csd.cc209t9g, http://hdl.handle.net/10754/664472
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Schwartz, L. A., Holmes, M., Brito, G. A., Goncalves, T., Richardson, J., Ruble, J. C., Huang, K.-W., & Krische, M. J. (2019). Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters. Journal of the American Chemical Society, 141(5), 2087-2096. https://doi.org/10.1021/jacs.8b11868

Schwartz, Leyah A. ; Holmes, Michael ; Brito, Gilmar A. et al. / Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters. In: Journal of the American Chemical Society. 2019 ; Vol. 141, No. 5. pp. 2087-2096.

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title = "Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters",

abstract = "Iridium complexes modified by the chiral phosphine ligand PhanePhos catalyze the 2-propanol-mediated reductive coupling of diverse 1,1-disubstituted allenes 1a-1u with fluoral hydrate 2a to form CF3-substituted secondary alcohols 3a-3u that incorporate acyclic quaternary carbon-containing stereodiads. By exploiting concentration-dependent stereoselectivity effects related to the interconversion of kinetic ( Z)- and thermodynamic ( E)-σ-allyliridium isomers, adducts 3a-3u are formed with complete levels of branched regioselectivity and high levels of anti-diastereo- and enantioselectivity. The utility of this method for construction of CF3-oxetanes and CF3-azetidines is illustrated by the formation of 4a and 6a, respectively. Studies of the reaction mechanism aimed at illuminating the singular effectiveness of PhanePhos as a supporting ligand in this and related transformations have led to the identification of a chromatographically stable cyclometalated iridium-( R)-PhanePhos complex, Ir-PP-I, that is catalytically competent for allene-fluoral reductive coupling and previously reported transfer hydrogenative C-C couplings of dienes or CF3-allenes with methanol. Deuterium labeling studies, reaction progress kinetic analysis (RPKA) and computational studies corroborate a catalytic mechanism involving rapid allene hydrometalation followed by turnover-limiting carbonyl addition. A computationally determined stereochemical model shows that the ortho-CH2 group of the cyclometalated iridium-PhanePhos complex plays a key role in directing diastereo- and enantioselectivity. The collective data provide key insights into the structural-interactional features of allyliridium complexes required to enforce nucleophilic character, which should inform the design of related cyclometalated catalysts for umpoled allylation.",

author = "Schwartz, {Leyah A.} and Michael Holmes and Brito, {Gilmar A.} and Theo Goncalves and Jeffery Richardson and Ruble, {J. Craig} and Kuo-Wei Huang and Krische, {Michael J.}",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: The Robert A. Welch Foundation (F-0038), the NIH (RO1-GM069445, 1 S10 OD021508-01), and King Abdullah University of Science and Technology (KAUST) are acknowledged for partial support of this research. Eli Lilly and Company is acknowledged for LIFA postdoctoral fellowship funding (M.H.). Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo (FAPESP) is acknowledged for postdoctoral fellowship support (G.B. 2017/00734-5). We thank Professor Donna G. Blackmond for assistance with RPKA. The service of Ibex, Shaheen 2 High Performance Computing Facilities was provided with financial support from KAUST.",

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Schwartz, LA, Holmes, M, Brito, GA, Goncalves, T, Richardson, J, Ruble, JC, Huang, K-W & Krische, MJ 2019, 'Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters', Journal of the American Chemical Society, vol. 141, no. 5, pp. 2087-2096. https://doi.org/10.1021/jacs.8b11868

Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters. / Schwartz, Leyah A.; Holmes, Michael; Brito, Gilmar A. et al.
In: Journal of the American Chemical Society, Vol. 141, No. 5, 25.01.2019, p. 2087-2096.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters

AU - Schwartz, Leyah A.

AU - Holmes, Michael

AU - Brito, Gilmar A.

AU - Goncalves, Theo

AU - Richardson, Jeffery

AU - Ruble, J. Craig

AU - Huang, Kuo-Wei

AU - Krische, Michael J.

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: The Robert A. Welch Foundation (F-0038), the NIH (RO1-GM069445, 1 S10 OD021508-01), and King Abdullah University of Science and Technology (KAUST) are acknowledged for partial support of this research. Eli Lilly and Company is acknowledged for LIFA postdoctoral fellowship funding (M.H.). Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) is acknowledged for postdoctoral fellowship support (G.B. 2017/00734-5). We thank Professor Donna G. Blackmond for assistance with RPKA. The service of Ibex, Shaheen 2 High Performance Computing Facilities was provided with financial support from KAUST.

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N2 - Iridium complexes modified by the chiral phosphine ligand PhanePhos catalyze the 2-propanol-mediated reductive coupling of diverse 1,1-disubstituted allenes 1a-1u with fluoral hydrate 2a to form CF3-substituted secondary alcohols 3a-3u that incorporate acyclic quaternary carbon-containing stereodiads. By exploiting concentration-dependent stereoselectivity effects related to the interconversion of kinetic ( Z)- and thermodynamic ( E)-σ-allyliridium isomers, adducts 3a-3u are formed with complete levels of branched regioselectivity and high levels of anti-diastereo- and enantioselectivity. The utility of this method for construction of CF3-oxetanes and CF3-azetidines is illustrated by the formation of 4a and 6a, respectively. Studies of the reaction mechanism aimed at illuminating the singular effectiveness of PhanePhos as a supporting ligand in this and related transformations have led to the identification of a chromatographically stable cyclometalated iridium-( R)-PhanePhos complex, Ir-PP-I, that is catalytically competent for allene-fluoral reductive coupling and previously reported transfer hydrogenative C-C couplings of dienes or CF3-allenes with methanol. Deuterium labeling studies, reaction progress kinetic analysis (RPKA) and computational studies corroborate a catalytic mechanism involving rapid allene hydrometalation followed by turnover-limiting carbonyl addition. A computationally determined stereochemical model shows that the ortho-CH2 group of the cyclometalated iridium-PhanePhos complex plays a key role in directing diastereo- and enantioselectivity. The collective data provide key insights into the structural-interactional features of allyliridium complexes required to enforce nucleophilic character, which should inform the design of related cyclometalated catalysts for umpoled allylation.

AB - Iridium complexes modified by the chiral phosphine ligand PhanePhos catalyze the 2-propanol-mediated reductive coupling of diverse 1,1-disubstituted allenes 1a-1u with fluoral hydrate 2a to form CF3-substituted secondary alcohols 3a-3u that incorporate acyclic quaternary carbon-containing stereodiads. By exploiting concentration-dependent stereoselectivity effects related to the interconversion of kinetic ( Z)- and thermodynamic ( E)-σ-allyliridium isomers, adducts 3a-3u are formed with complete levels of branched regioselectivity and high levels of anti-diastereo- and enantioselectivity. The utility of this method for construction of CF3-oxetanes and CF3-azetidines is illustrated by the formation of 4a and 6a, respectively. Studies of the reaction mechanism aimed at illuminating the singular effectiveness of PhanePhos as a supporting ligand in this and related transformations have led to the identification of a chromatographically stable cyclometalated iridium-( R)-PhanePhos complex, Ir-PP-I, that is catalytically competent for allene-fluoral reductive coupling and previously reported transfer hydrogenative C-C couplings of dienes or CF3-allenes with methanol. Deuterium labeling studies, reaction progress kinetic analysis (RPKA) and computational studies corroborate a catalytic mechanism involving rapid allene hydrometalation followed by turnover-limiting carbonyl addition. A computationally determined stereochemical model shows that the ortho-CH2 group of the cyclometalated iridium-PhanePhos complex plays a key role in directing diastereo- and enantioselectivity. The collective data provide key insights into the structural-interactional features of allyliridium complexes required to enforce nucleophilic character, which should inform the design of related cyclometalated catalysts for umpoled allylation.

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Schwartz LA, Holmes M, Brito GA, Goncalves T, Richardson J, Ruble JC et al. Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters. Journal of the American Chemical Society. 2019 Jan 25;141(5):2087-2096. doi: 10.1021/jacs.8b11868

Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters

Abstract

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Datasets

CCDC 1856475: Experimental Crystal Structure Determination : 3-(4-bromophenyl)-1,1,1-trifluoro-3-methylpent-4-en-2-yl 3,5-dinitrobenzoate

Cite this