Evolution of a cycloaddition-rearrangement approach to the squalestatins: a quarter-century odyssey
The highs, lows, and diversions of a journey leading to two syntheses of 6,7-dideoxysqualestatin H5 is described. Both syntheses relied on highly diastereoselective n -alkylations of a tartrate acetonide enolate and subsequent oxidation-hydrolysis to provide an asymmetric entry to β-hydrox...
| Egile Nagusiak: | , |
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| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
Thieme Publishing
2020
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| _version_ | 1826301239102537728 |
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| author | Almohseni, HAA Hodgson, DM |
| author_facet | Almohseni, HAA Hodgson, DM |
| author_sort | Almohseni, HAA |
| collection | OXFORD |
| description | The highs, lows, and diversions of a journey leading to two syntheses of 6,7-dideoxysqualestatin H5 is described. Both syntheses relied on highly diastereoselective n -alkylations of a tartrate acetonide enolate and subsequent oxidation-hydrolysis to provide an asymmetric entry to β-hydroxy-α-ketoester motifs. The latter were differentially elaborated to diazoketones which underwent stereo- and regioselective Rh(II)-catalysed cyclic carbonyl ylide formation-cycloaddition and then acid-catalysed transketalisation to generate the 2,8-dioxabicyclo[3.2.1]octane core of the squalestatins/zaragozic acids at the correct tricarboxylate oxidation level. The unsaturated side chain was either protected with a bromide substituent during the transketalisation or introduced afterwards by a stereoretentive Ni-catalyzed Csp 3-Csp 2cross-electrophile coupling. 1 Introduction 2 Racemic Model Studies to the Squalestatin/Zaragozic Acid Core 3 Asymmetric Model Studies to a Keto α-Diazoester 3.1 Dialkyl Squarate Desymmetrisation 3.2 Tartrate Alkylation 3.2.1 Further Studies on Seebach's Alkylation Chemistry4 Failure at the Penultimate Step to DDSQ5 Second-Generation Approach to DDSQ: A Bromide Substituent Strategy5.1 Stereoselective Routes to E -Alkenyl Halides via β-Oxido Phosphonium Ylides5.2 Back to DDSQ Synthesis 6 An Alternative Strategy to DDSQ: By Cross-Electrophile Coupling 7 Alkene Ozonolysis in the Presence of Diazo Functionality: Accessing α-Ketoester Intermediates 8 Summary. |
| first_indexed | 2024-03-07T05:29:23Z |
| format | Journal article |
| id | oxford-uuid:e1b13409-c75b-424c-966c-343f7b4f07ca |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:29:23Z |
| publishDate | 2020 |
| publisher | Thieme Publishing |
| record_format | dspace |
| spelling | oxford-uuid:e1b13409-c75b-424c-966c-343f7b4f07ca2022-03-27T09:56:11ZEvolution of a cycloaddition-rearrangement approach to the squalestatins: a quarter-century odysseyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e1b13409-c75b-424c-966c-343f7b4f07caEnglishSymplectic ElementsThieme Publishing2020Almohseni, HAAHodgson, DMThe highs, lows, and diversions of a journey leading to two syntheses of 6,7-dideoxysqualestatin H5 is described. Both syntheses relied on highly diastereoselective n -alkylations of a tartrate acetonide enolate and subsequent oxidation-hydrolysis to provide an asymmetric entry to β-hydroxy-α-ketoester motifs. The latter were differentially elaborated to diazoketones which underwent stereo- and regioselective Rh(II)-catalysed cyclic carbonyl ylide formation-cycloaddition and then acid-catalysed transketalisation to generate the 2,8-dioxabicyclo[3.2.1]octane core of the squalestatins/zaragozic acids at the correct tricarboxylate oxidation level. The unsaturated side chain was either protected with a bromide substituent during the transketalisation or introduced afterwards by a stereoretentive Ni-catalyzed Csp 3-Csp 2cross-electrophile coupling. 1 Introduction 2 Racemic Model Studies to the Squalestatin/Zaragozic Acid Core 3 Asymmetric Model Studies to a Keto α-Diazoester 3.1 Dialkyl Squarate Desymmetrisation 3.2 Tartrate Alkylation 3.2.1 Further Studies on Seebach's Alkylation Chemistry4 Failure at the Penultimate Step to DDSQ5 Second-Generation Approach to DDSQ: A Bromide Substituent Strategy5.1 Stereoselective Routes to E -Alkenyl Halides via β-Oxido Phosphonium Ylides5.2 Back to DDSQ Synthesis 6 An Alternative Strategy to DDSQ: By Cross-Electrophile Coupling 7 Alkene Ozonolysis in the Presence of Diazo Functionality: Accessing α-Ketoester Intermediates 8 Summary. |
| spellingShingle | Almohseni, HAA Hodgson, DM Evolution of a cycloaddition-rearrangement approach to the squalestatins: a quarter-century odyssey |
| title | Evolution of a cycloaddition-rearrangement approach to the squalestatins: a quarter-century odyssey |
| title_full | Evolution of a cycloaddition-rearrangement approach to the squalestatins: a quarter-century odyssey |
| title_fullStr | Evolution of a cycloaddition-rearrangement approach to the squalestatins: a quarter-century odyssey |
| title_full_unstemmed | Evolution of a cycloaddition-rearrangement approach to the squalestatins: a quarter-century odyssey |
| title_short | Evolution of a cycloaddition-rearrangement approach to the squalestatins: a quarter-century odyssey |
| title_sort | evolution of a cycloaddition rearrangement approach to the squalestatins a quarter century odyssey |
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