Design and Synthesis of Modular Oxazoline Ligands for the Enantioselective Chromium-Catalyzed Addition of Allyl Bromide to Ketones

Miller, Jeremie J.; Sigman, Matthew S.

doi:10.1021/ja068915m

Cited by 121 publications

(61 citation statements)

References 11 publications

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“…Preparation of Prolinethioamide 3 [10] To a stirred solution of N-Boc-l-proline (1.25 g, 5.81 mmol) in CH 2 Cl 2 , Et 3 N (1.2 mL, 8.71 mmol) was slowly added at 0 8C. After the solution had been stirred for 10 min, isobutyl chloroformate (875 mL, 6.67 mmol) was added dropwise to the reaction mixture at 0 8C.…”

Section: Methodsmentioning

confidence: 99%

A Novel Proline‐Valinol Thioamide Small Organic Molecule for a Highly Enantioselective Direct Aldol Reaction

Wang¹,

Chen²,

Liu³

et al. 2009

Adv Synth Catal

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A new prolinethioamide compound 4, prepared from readily available natural amino acid lproline and amino alcohol l-valinol, has been found to be an active catalyst for the direct aldol reaction of various aldehydes with acetone, cyclohexanone or cyclopentanone at 0 8C. Using only 2 mol% loading of this organocatalyst, the reaction could give high enantioselectivity with up to 96% enantiomeric excess for the reaction of 2-nitrobenzaldehyde with acetone. And as for the cyclohexanone, the excellent diastereoselectivity (anti/syn: 99/1) and enantioselectivity (99% ee) could be achieved when reacted with 3-nitrobenzaldehyde in water in the presence of this thioamide 4. This structurally simple catalyst is a highly efficient prolinethioamide derivative, and the terminal hydroxy group in this catalyst is a primary alcohol which is different from the previously reported prerequisite secondary or tertiary alcohol of pro-A C H T U N G T R E N N U N G linamides. Our results suggest a new strategy in the design of diversiform organic catalysts for direct asymmetric aldol reactions and related transformations.

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Section: Methodsmentioning

confidence: 99%

A Novel Proline‐Valinol Thioamide Small Organic Molecule for a Highly Enantioselective Direct Aldol Reaction

Wang¹,

Chen²,

Liu³

et al. 2009

Adv Synth Catal

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“…7 present a maximum which is nearest the modified Charton values for ligand 1d. The model correctly predicts the catalyst which we had previously optimized and published for the allylation of a variety of aromatic ketones including acetophenone (21). Again, this ligand was not utilized in the analysis.…”

Section: Resultsmentioning

confidence: 91%

“…We had hoped that the resulting LFERs would be a useful tool in optimizing ligands as well as de novo catalyst design. However, at the conclusion of these studies, we were puzzled at the observed breaks in the linear correlations mitigating the ability to predict the outcome of entirely new catalyst structures by extrapolation (20,21). Herein, we report a more sophisticated approach to the problem in which a library of catalysts is used to generate a three-dimensional relationship of free energy to substituent size leading to successful predictions of catalyst performance.…”

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confidence: 99%

Predicting and optimizing asymmetric catalyst performance using the principles of experimental design and steric parameters

Harper

Sigman

2011

Proc. Natl. Acad. Sci. U.S.A.

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Using a modular amino acid based chiral ligand motif, a library of ligands was synthesized systematically varying the substituents at two positions. The effects of these changes on ligand structure were probed in the enantioselective allylation of benzaldehyde, acetophenone, and methylethyl ketone under Nozaki-HiyamaKishi conditions. The resulting three-dimensional datasets allowed for the construction of mathematical surface models which describe the interplay of substituent effects on enantioselectivity for a given reaction. The surface models were both extrapolated and manipulated to predict the enantioselective outcomes of several previously untested ligands. Analyses were also used to predict optimal ligand structure of a minimal dataset. Within the dataset, a linear free energy relationship was also discovered and a direct comparison of both the linear prediction as well as the threedimensional prediction illustrates the potential predictive power of using a three-dimensional model approach to asymmetric catalyst development.A centerpiece of modern organic chemistry is the development of new catalytic enantioselective methods to obtain valuable enantiomerically enriched synthetic building blocks (1, 2). Asymmetric catalysis, in practice, initiates from the discovery of a new catalytic reaction or identification of a reaction of interest. Subsequently, a number of chiral ligand classes are experimentally explored in hope of finding a "lead" which generates a promising enantiomeric ratio (er). Further optimization of the reaction conditions and ligand structure can ultimately yield a mature catalytic asymmetric method. This process is highly empirical and the results can be unsatisfactory for a given reaction. The empiricism inherent in reaction development has been addressed by computational chemistry via stereocartography and various other methods (3-10). Even with the impressive impact computational chemistry has had on the field, the small energy differences in the diastereomeric transition states (∼2-3 kcal∕mol or 8.2-12.3 kJ∕ mol) leading to enantiomerically enriched products are not easily rationalized. Additionally, these methods generally depend on a detailed understanding of the parent chiral catalyst structure. Furthermore, kinetic analyses of asymmetric catalytic reactions often reveal the general complexities of catalysis and highlight the importance of the Curtin-Hammett principle (11, 12), but do not often expose the key catalyst structural features responsible for enantioselection. These issues highlight an underlying challenge in the field of asymmetric catalysis: how does one design a ligand for a given reaction type without engaging in a longterm, empirical investigation of multiple ligand classes?A goal of our program has been to utilize classic linear free energy relationships (LFER) to predict the enantioselective outcomes of new catalytic systems (13). We have recently disclosed the use of steric parameters originally developed by Taft and modified by Charton (14-17) to quantitatively ...

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“…[5] This study was extended to the allylation of ketones with analogues of ligand 3 affording enantioselectivities up to 92 %. [6] We previously reported the synthesis of tridentate bis-(oxazoline) ligands 4 and their application in the enantioselective Nozaki-Hiyama-Kishi (NHK) allylation, crotylation and methallylation of a range of aromatic and aliphatic aldehydes. [7][8][9] The ligands were prepared by means of a palladium-catalysed aryl amination between the corresponding anilino-oxazoline and bromo-oxazoline.…”

Section: Introductionmentioning

confidence: 99%

New Proline–Oxazoline Ligands and Their Application in the Asymmetric Nozaki–Hiyama–Kishi Reaction

2007

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Sixteen members of a new ligand class incorporating an oxazoline ring linked by an amide bond to a chiral protected proline unit were prepared in a high‐yielding four‐step synthesis from readily available chiral amino alcohols and N‐protected proline. The ligands were applied in the enantioselective Nozaki–Hiyama–Kishi allylation of benzaldehyde and gave enantioselectivities of up to 57 %. Diastereomeric ligand pairs were prepared to determine the role of each chiral centre in enantioselection.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Design and Synthesis of Modular Oxazoline Ligands for the Enantioselective Chromium-Catalyzed Addition of Allyl Bromide to Ketones

Cited by 121 publications

References 11 publications

A Novel Proline‐Valinol Thioamide Small Organic Molecule for a Highly Enantioselective Direct Aldol Reaction

A Novel Proline‐Valinol Thioamide Small Organic Molecule for a Highly Enantioselective Direct Aldol Reaction

Predicting and optimizing asymmetric catalyst performance using the principles of experimental design and steric parameters

New Proline–Oxazoline Ligands and Their Application in the Asymmetric Nozaki–Hiyama–Kishi Reaction

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