Practical Stereoselective Synthesis of β-Branched α-Amino Acids through Efficient Kinetic Resolution in the Phase-Transfer-Catalyzed Asymmetric Alkylations

Ooi, Takashi; Kato, Daisuke; Inamura, Koji; Ohmatsu, Kohsuke; Maruoka, Keiji

doi:10.1021/ol701558e

Cited by 40 publications

(13 citation statements)

References 21 publications

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“…This combination involves an efficient kinetic resolution of racemic secondary alkyl halides, thereby giving a straightforward entry to enantiomerically enriched syn-b-alkyl-a-amino acid derivatives, such as 34 (Scheme 22). [33] We also reported the asymmetric alkylation of 7 with alkyl sulfonates, especially with epoxy sulfonates as notable examples, under phase-transfer conditions. The asymmetric reaction of 7 with chiral epoxy triflates furnished g,d-epoxy-aamino acid esters, such as 35, with high stereoselectivity (Scheme 23).…”

Section: Alkylationmentioning

confidence: 91%

Recent Developments in Asymmetric Phase‐Transfer Reactions

2013

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Phase-transfer catalysis has been recognized as a powerful method for establishing practical protocols for organic synthesis, because it offers several advantages, such as operational simplicity, mild reaction conditions, suitability for large-scale synthesis, and the environmentally benign nature of the reaction system. Since the pioneering studies on highly enantioselective alkylations promoted by chiral phase-transfer catalysts, this research field has served as an attractive area for the pursuit of "green" sustainable chemistry. A wide variety of asymmetric transformations catalyzed by chiral onium salts and crown ethers have been developed for the synthesis of valuable organic compounds in the past several decades, especially in recent years.

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Section: Alkylationmentioning

confidence: 91%

Recent Developments in Asymmetric Phase‐Transfer Reactions

2013

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“…For instance, the potential of this reaction has not been applied so far to Michael-type acceptors with aromatic substituents at the b-position (i.e., cinnamates), even though the resulting products would offer unique opportunities for further functionalization. [8] We disclose herein a catalytic enantioselective and diastereoselective method for the synthesis of b-branched a-amino acids (up to 99 % enantiomeric excess (ee) and 99:1 diastereomeric ratio (d.r. )), due to the use of the more reactive gemdiactivated olefins such as alkylidene malonates.…”

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confidence: 99%

Enantiocontrolled Synthesis of β‐Branched α‐Amino Acids by Using Cu^I‐Catalyzed 1,4‐Addition of Glycine Imines to β‐Substituted gem‐Diactivated Olefins

Hernandez‐Toribio

Arrayás

Carretero

2011

Chemistry A European J

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Peptide-based therapies are emerging at an increasingly rapid pace because peptides offer lower toxicity, show higher specificity, and demonstrate fewer toxicology issues compared with small molecule drugs.[1] Modification of these therapeutics with non-natural amino acids of desired structural complexity is instrumental to identify target-specific peptides. Enantiopure b-branched a-amino acids [2] are highly valuable because the incorporation of the b-substituent generally imposes severe conformational restraints, thus allowing the de novo design of peptidic entities with a predetermined three-dimensional structure.[3] Because glutamic acid is the main excitatory amino acid in the central nervous system, its derivatives have attracted great interest as essential components of peptides, as well as potential signal mediators of neurotransmission. [4] The catalytic asymmetric alkylation of Schiff bases of glycine esters is one of the most reliable and straightforward synthetic routes to optically active a-amino acid derivatives. [5] In particular, the asymmetric conjugate addition of glycinate imines to a,b-unsaturated carbonyl compounds [6] (mainly acrylates) is a highly versatile reaction to afford optically active glutamic acid derivatives. However, in contrast to the number of examples able to provide enantioenriched a-amino acid derivatives, the application of this methodology to the synthesis of b-substituted a-amino acids has proven frustratingly elusive. In addition to the difficulty of controlling both diastereo-and enantioselectivity in the two new contiguous stereogenic centers, a major obstacle is the much lower reactivity of b-substituted a,b-unsaturated carbonyl compounds (e.g., crotonates) compared to simple acrylates. The use of strong bases to overcome this limitation has been reported to be detrimental to enantiocontrol.[6a]In a seminal work, the group of Kobayashi recently described, to our knowledge, the only existing general precedent for the catalytic asymmetric 1,4-addition of glycine derivatives to b-substituted acrylic acid derivatives. [6b, 7] High yields and high levels of diastereo-and enantiocontrol were attained with b-alkyl-substituted substrates by using calcium complexes of chiral deprotonated bisoxazoline (Box) ligands as catalysts. In spite of these excellent results, there is room for innovation, especially with regard to the substrate scope of the electrophile component. For instance, the potential of this reaction has not been applied so far to Michael-type acceptors with aromatic substituents at the b-position (i.e., cinnamates), even though the resulting products would offer unique opportunities for further functionalization.[8] We disclose herein a catalytic enantioselective and diastereoselective method for the synthesis of b-branched a-amino acids (up to 99 % enantiomeric excess (ee) and 99:1 diastereomeric ratio (d.r.)), due to the use of the more reactive gemdiactivated olefins such as alkylidene malonates.On the basis of our previous results, which report highly enanti...

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“…An interesting example from Maruokas laboratory allows access to the syn-diastereomers of b-methylphenylalanine in 88% yield with 95% e.e. [206]. Subsequent controlled epimerization yields the anti diastereomers, which lends the method to practical use for obtaining all four stereoisomers of b-methylphenylala- nine.…”

Section: Noncoded Amino Acids By Chemical Modification Of Coded Aminomentioning

confidence: 95%

Methods for the Chemical Synthesis of Noncoded α‐Amino Acids found in Natural Product Peptides

Habay

Park

Kennedy

et al. 2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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Practical Stereoselective Synthesis of β-Branched α-Amino Acids through Efficient Kinetic Resolution in the Phase-Transfer-Catalyzed Asymmetric Alkylations

Cited by 40 publications

References 21 publications

Recent Developments in Asymmetric Phase‐Transfer Reactions

Recent Developments in Asymmetric Phase‐Transfer Reactions

Enantiocontrolled Synthesis of β‐Branched α‐Amino Acids by Using Cu^I‐Catalyzed 1,4‐Addition of Glycine Imines to β‐Substituted gem‐Diactivated Olefins

Methods for the Chemical Synthesis of Noncoded α‐Amino Acids found in Natural Product Peptides

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Practical Stereoselective Synthesis of β-Branched α-Amino Acids through Efficient Kinetic Resolution in the Phase-Transfer-Catalyzed Asymmetric Alkylations

Cited by 40 publications

References 21 publications

Recent Developments in Asymmetric Phase‐Transfer Reactions

Recent Developments in Asymmetric Phase‐Transfer Reactions

Enantiocontrolled Synthesis of β‐Branched α‐Amino Acids by Using CuI‐Catalyzed 1,4‐Addition of Glycine Imines to β‐Substituted gem‐Diactivated Olefins

Methods for the Chemical Synthesis of Noncoded α‐Amino Acids found in Natural Product Peptides

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Enantiocontrolled Synthesis of β‐Branched α‐Amino Acids by Using Cu^I‐Catalyzed 1,4‐Addition of Glycine Imines to β‐Substituted gem‐Diactivated Olefins