Efficient Synthesis of Enantiopure β-Amino-γ-Keto Acids from<scp>l</scp>-Homoserine

Sharma, Anil Kumar; Hergenrother, Paul J.

doi:10.1021/ol0345327

Cited by 21 publications

(3 citation statements)

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“…In contrast, the analogous γ-oxo-β-amino esters, although equally useful, are far less accessible. To the best of our knowledge, no catalytic methods for the synthesis of γ-oxo-β-amino esters have been developed to date, and the multistep transformations of aspartic acid or homoserine are the current synthetic methods of choice for this class of compounds . Herein we disclose the first example of a highly regio- and stereoselective catalytic method that enables access to highly functionalized α-vinylated γ-oxo-β-amino esters 4 from readily available 1-alkynes 1 , sulfonyl azides 2 , and γ-hydroxy α,β-unsaturated esters 3 (Scheme b).…”

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confidence: 99%

Cu^I/Rh^II-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of γ-Oxo-β-amino Esters

et al. 2015

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The first example of a highly regio- and stereoselective catalytic method for the three-component one-pot synthesis of highly functionalized α-vinylated γ-oxo-β-amino esters is disclosed. In this catalytic triad, the Cu(I)-catalyst selectively catalyzes the cycloaddition of the 1-alkyne and sulfonyl azide first resulting in the corresponding 1-sulfonyl-1,2,3-triazole. An α-imino Rh(II)-carbene is generated from an open-chain α-imino diazo of the triazole, and this species reacts with γ-hydroxy α,β-unsaturated esters to form allylic (Z)-amino vinyl ethers. Rapid deconjugative [3,3]-sigmatropic rearrangement affords the α-vinyl γ-oxo-β-amino esters in high yields with high levels of diastereoselectivity.

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confidence: 99%

Cu^I/Rh^II-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of γ-Oxo-β-amino Esters

et al. 2015

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“…[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] New discoveries that can address this challenge will be of significant value, both for the discovery and development of new therapeutics, and as diagnostic tools in chemical biology. Herein, we describe one contribution toward that goal: a copper-catalyzed transformation of peptidic thiol esters and boronic acids into peptidyl ketones, [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] which are important compounds in the development of molecular therapeutics. [44,[61][62][63][64][65][66][67][68][69][70][71]…”

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confidence: 99%

A Copper‐Catalyzed, pH‐Neutral Construction of High‐Enantiopurity Peptidyl Ketones from Peptidic S‐Acylthiosalicylamides in Air at Room Temperature

Liebeskind

Yang

2009

Angew Chem Int Ed

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Described herein is a Cu-catalyzed transformation of peptidic thiol esters and boronic acids into peptidyl ketones that takes place at room temperature in DMF or in DMF/H 2 O open to air and uses only catalytic quantities of a Cu carboxylate to mediate the reaction. This aerobic transformation occurs only at a thiol ester capable of coordinating to Cu through its S-appendage and is hampered neither by racemization of the reactants or products, nor by the presence of disulfides or of unprotected phenols, alcohols, or indoles. KeywordsC-C coupling; Cross-coupling; Synthetic methods; Copper; Peptidomimetics; Protein modifications In recent decades great strides have been made in uncovering novel methods for the metalcatalyzed construction of C-C and C-X bonds from organic halides/sulfonates/ phosphonates [1][2][3][4][5][6][7][8][9][10][11] and through C-H functionalization. [12][13][14][15][16][17][18][19][20][21][22][23][24] The great majority of these metal-catalyzed couplings are now carried out using mild organic transfer agents such as boronic acids, organostannanes, and organosilanes. The synthetic power and breadth of impact of these modern methods for the efficient and selective generation of a variety of bond types in a vast array of target molecules is unquestioned. And, yet, significant unmet challenges remain for the synthetic scientist to address. One holy grail is the highly chemoselective, nonenzymatic formation of a C-C or C-X bond at a specific site on a functionally complex biomolecule under biologically relevant conditions (i.e., minimal or no protecting groups, ambient temperatures, neutral pH reaction conditions, aerobic or anaerobic conditions, compatibility with protic solvents). [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] NIH Public Access In probing the value of Cu-catalyzed, aerobic, desulfitative coupling for the construction of peptidyl ketones, a control experiment using tryptophan-derived thiol esters validated the importance of the nature of the thiol ester S-pendant on the substrate reactivity (Scheme 1): at 50 °C in DMF with 5 mol % Cu I 3-methylsalicylate (CuMeSal) the reaction occurred only with the tryptophan derived thiophenyl ester bearing an ortho CONHt-Bu group and not with the simple thiophenyl ester.This result clearly confirmed that a coordinating moiety on the pendant group of the thiol ester is a requisite condition for this Cu-catalyzed, aerobic reaction. As described in the initial manuscript disclosing the "second generation" desulfitative coupling,[73] the reaction is rendered catalytic in Cu under aerobic conditions through "scavenging" of the thiolate residue with a second sacrificial equivalent of the boronic acid. A Cu-centered transmetalation/ reductive elimination sequence generates a thioether thus removing thiolate from the reaction system and regenerating Cu I for subsequent reaction with O 2 and continuation of the catalytic cycle.A brief study of the influence of the nature of the ortho-positioned amide group on the obs...

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“…Thus, although there are some very efficient asymmetric metal-catalyzed protocols for the addition of enolate reagents to N -aryl imines, N -acyl imines, N -acyl hydrazones, and N -phosphinoyl imines, 4d-e, the use of sulfonyl imines as electrophiles is limited mainly to the case of the highly electronically activated α-tosyliminoesters . However, as a result of their great synthetic availability, stability, and structural variety, aryl, alkenyl, and alkyl N -sulfonyl imines are very appealing N -protected electrophiles in Mannich-type reactions . To the best of our knowledge, there are only two precedents concerning the use of nonactivated N- sulfonyl imines, in particular tosylimines, both involving the participation of a particular type of nucleophile partner: enolates of glycine Schiff bases and N -(2-hydroxyacetyl)pyrrole …”

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Copper(I)-Fesulphos Lewis Acid Catalysts for Enantioselective Mannich-Type Reaction of N-Sulfonyl Imines

2006

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[reaction: see text] Copper(I) complexes of Fesulphos ligands are efficient chiral Lewis acid catalysts in the Mannich-type addition of silyl enol ethers of ketones, esters, and thioesters to N-(2-thienyl)sulfonyl aldimines. The corresponding optically active beta-amino carbonyl derivatives were obtained in good yields (58-91%) and with moderate to good enantioselectivity (61-93% ee). Removal of the N-activating group was achieved under mild conditions by simple treatment of the products with Mg in methanol.

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Efficient Synthesis of Enantiopure β-Amino-γ-Keto Acids froml-Homoserine

Cited by 21 publications

References 29 publications

Cu^I/Rh^II-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of γ-Oxo-β-amino Esters

Cu^I/Rh^II-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of γ-Oxo-β-amino Esters

A Copper‐Catalyzed, pH‐Neutral Construction of High‐Enantiopurity Peptidyl Ketones from Peptidic S‐Acylthiosalicylamides in Air at Room Temperature

Copper(I)-Fesulphos Lewis Acid Catalysts for Enantioselective Mannich-Type Reaction of N-Sulfonyl Imines

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Efficient Synthesis of Enantiopure β-Amino-γ-Keto Acids froml-Homoserine

Cited by 21 publications

References 29 publications

CuI/RhII-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of γ-Oxo-β-amino Esters

CuI/RhII-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of γ-Oxo-β-amino Esters

A Copper‐Catalyzed, pH‐Neutral Construction of High‐Enantiopurity Peptidyl Ketones from Peptidic S‐Acylthiosalicylamides in Air at Room Temperature

Copper(I)-Fesulphos Lewis Acid Catalysts for Enantioselective Mannich-Type Reaction of N-Sulfonyl Imines

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Cu^I/Rh^II-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of γ-Oxo-β-amino Esters

Cu^I/Rh^II-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of γ-Oxo-β-amino Esters