Highly Diastereoselective Heterogeneously Catalyzed Hydrogenation of Enamines for the Synthesis of Chiral β-Amino Acid Derivatives

Ikemoto, Norihiro; Tellers, David M.; Dreher, Spencer D.; Liu, Jinchu; Huang, Alice E.; Rivera, Nelo R.; Njolito, Eugenia; Hsiao, Yi; McWilliams, J. Christopher; Williams, J. M.; Armstrong, Joseph D.; Sun, Yuhang; Mathre, David J.; Grabowski, Edward J. J.; Tillyer, Richard D.

doi:10.1021/ja038812t

Cited by 63 publications

(36 citation statements)

References 19 publications

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“…However, the preparation of b-amino acids continues to rely principally on the resolution of racemates [105] or on the use of chiral auxilaries. [106] The application of catalytic asymmetric hydrogenation has been hindered by the assumption that protection of the nitrogen atom is required to achieve high levels of selectivity by virtue of the formation of a six-membered ring chelate between the substrate and the metal. Hsiao et al at Merck showed that in the presence of Josiphos ligands 120 and 121, highly selective catalysts generated from [{RhCl(cod)} 2 ] reduced unprotected b-enamine esters 122 and amides 124 to the corresponding bamino acid derivatives 123 and 125, respectively (Scheme 56).…”

Section: A K Yudin and N A Afaghmentioning

confidence: 99%

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

2009

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Achieving high levels of chemoselectivity has been the Achilles' heel of chemical synthesis. The excitement generated by the successful realization of chemoselective strategies underscores the painstaking efforts to define a set of conditions conducive to selection among the available reaction pathways. We discuss in this Review various aspects of chemoselectivity that have been addressed in a range of synthetic methods over the past decade. We have focused on the proposed mechanistic basis of the reactions under consideration in an attempt to categorize them and highlight the key concepts that have been emerging on the basis of these studies. Our overview of recent advances in chemoselective processes suggests that significant progress has been made, but a lot of challenges lie ahead.

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Section: A K Yudin and N A Afaghmentioning

confidence: 99%

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

2009

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“…Treatment of the corresponding β‐ketoester or ‐amide with the chiral auxiliary ( S )‐phenylglycinamide provides the substituted Z ‐enamide 99 . Hydrogen bonding results in a rigid conformation of 99 , with the phenyl substituent on the auxiliary shielding the top face of the molecule, which results in stereoselectivities of up to 200:1 being obtained in the hydrogenation over PtO 2 (Scheme ) 174a. Pretreatment of the catalyst with acetic acid was found to be very important for good catalytic activity.…”

Section: Diastereoselective Heterogeneous Catalysismentioning

confidence: 99%

Asymmetric Heterogeneous Catalysis

2006

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Limited natural resources and an increasing demand for enantiomerically pure compounds render catalysis and especially heterogeneous asymmetric catalysis a key technology. The field has rapidly advanced from the initial use of chiral biopolymers, such as silk, as a support for metal catalysts to the modern research areas. Mesoporous supports, noncovalent immobilization, metal-organic catalysts, chiral modifiers: many areas are rapidly evolving. This Review shows that these catalysts have more to them than facile separation or recycling. Better activities and selectivities can be obtained than with the homogeneous catalyst and novel, efficient reaction mechanisms can be employed. Especially fascinating is the outlook for highly ordered metal-organic catalysts that might allow a rational design, synthesis, and the unequivocal structural characterization to give tailor-made catalysts.

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“…[15] The reduction of (S)-phenylglycine dehydro-β-amino esters or dehydro-β-aminoamides with PtO 2 has been reported on and proceeds in very good ee, but in low overall yield from the starting β-keto esters. [16] Herein, we report on the reductive amination of keto esters 1 with (R)-or (S)-α-MBA to generate amino esters 2 using heterogeneous hydrogenation catalysts (optimally Raney-Ni) with a Brønsted acid (optimally AcOH) for α-and β-keto esters, and with a Lewis acid [optimally Ti(OiPr) 4 ] for a γ-keto ester.…”

Section: Introductionmentioning

confidence: 99%

Selective Synthesis of Unnatural α‐, β‐ and γ‐Amino Esters

Nugent

Ghosh

2007

Eur J Org Chem

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Reductive amination of keto esters 1 with α-methylbenzylamine (α-MBA) in the presence of hydrogen and Raney-Ni allows direct access to diastereomeric amino esters 2 in good to high de (72-94 %). For the α-keto ester 1d and the β-keto esters 1a, 1b and 1c the reaction is optimally performed in the presence of AcOH, while the γ-keto ester 1h requires Ti(OiPr) 4 . The reductive amination product of 1d is an advanced homophenylalanine building block for Angiotensin Converting Enzyme (ACE) inhibitor drugs. The reductive

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Highly Diastereoselective Heterogeneously Catalyzed Hydrogenation of Enamines for the Synthesis of Chiral β-Amino Acid Derivatives

Cited by 63 publications

References 19 publications

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

Asymmetric Heterogeneous Catalysis

Selective Synthesis of Unnatural α‐, β‐ and γ‐Amino Esters

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