Cation-directed atropselective synthesis of BINOL derivatives
<p>The use of chiral counterions to facilitate enantioselective mono-<em>C</em>-alkylation of enolates has been explored extensively over the past century. We have demonstrated that an alternative mode of reactivity – <em>O</em>-alkylation – predominates if the <em...
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| Other Authors: | |
| Format: | Thesis |
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2017
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| _version_ | 1826316407467409408 |
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| author | Jolliffe, JD |
| author2 | Smith, M |
| author_facet | Smith, M Jolliffe, JD |
| author_sort | Jolliffe, JD |
| collection | OXFORD |
| description | <p>The use of chiral counterions to facilitate enantioselective mono-<em>C</em>-alkylation of enolates has been explored extensively over the past century. We have demonstrated that an alternative mode of reactivity – <em>O</em>-alkylation – predominates if the <em>C</em>-alkylation is impeded. We have applied this concept to the atropselective dynamic kinetic resolution of 1-aryl-2-tetralones, leading to an organocatalytic synthesis of enantio-enriched BINOL derivatives.</p> <p>In this reaction, the chiral counterion plays a key role as both a phase-transfer catalyst and also as the agent to facilitate atropselective alkylation of rapidly interconverting axially chiral enolates. Treatment of 2-tetralones with base in the presence of an ammonium salt leads to intermediate atropisomeric dihydro-BINOL; oxidation with DDQ leads to BINOLs without loss of <em>e.r.</em> This transformation leads to high enantioselectivity and the scope of this reaction is significant: we can insert substituents into any position around the BINOL core, and we can also generate heavily functionalized derivatives without compromising stereochemical integrity.</p> <p>By employing a substoichiometric amount of alkylating agent, we have applied our reaction protocol to the kinetic resolution of MeBINOL with good selectivity.</p> |
| first_indexed | 2024-03-06T21:11:57Z |
| format | Thesis |
| id | oxford-uuid:3e7cb2c5-5f8e-406e-89b0-fc873e552dad |
| institution | University of Oxford |
| last_indexed | 2024-12-09T03:44:36Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | oxford-uuid:3e7cb2c5-5f8e-406e-89b0-fc873e552dad2024-12-07T16:06:04ZCation-directed atropselective synthesis of BINOL derivativesThesishttp://purl.org/coar/resource_type/c_db06uuid:3e7cb2c5-5f8e-406e-89b0-fc873e552dadORA Deposit2017Jolliffe, JDSmith, M<p>The use of chiral counterions to facilitate enantioselective mono-<em>C</em>-alkylation of enolates has been explored extensively over the past century. We have demonstrated that an alternative mode of reactivity – <em>O</em>-alkylation – predominates if the <em>C</em>-alkylation is impeded. We have applied this concept to the atropselective dynamic kinetic resolution of 1-aryl-2-tetralones, leading to an organocatalytic synthesis of enantio-enriched BINOL derivatives.</p> <p>In this reaction, the chiral counterion plays a key role as both a phase-transfer catalyst and also as the agent to facilitate atropselective alkylation of rapidly interconverting axially chiral enolates. Treatment of 2-tetralones with base in the presence of an ammonium salt leads to intermediate atropisomeric dihydro-BINOL; oxidation with DDQ leads to BINOLs without loss of <em>e.r.</em> This transformation leads to high enantioselectivity and the scope of this reaction is significant: we can insert substituents into any position around the BINOL core, and we can also generate heavily functionalized derivatives without compromising stereochemical integrity.</p> <p>By employing a substoichiometric amount of alkylating agent, we have applied our reaction protocol to the kinetic resolution of MeBINOL with good selectivity.</p> |
| spellingShingle | Jolliffe, JD Cation-directed atropselective synthesis of BINOL derivatives |
| title | Cation-directed atropselective synthesis of BINOL derivatives |
| title_full | Cation-directed atropselective synthesis of BINOL derivatives |
| title_fullStr | Cation-directed atropselective synthesis of BINOL derivatives |
| title_full_unstemmed | Cation-directed atropselective synthesis of BINOL derivatives |
| title_short | Cation-directed atropselective synthesis of BINOL derivatives |
| title_sort | cation directed atropselective synthesis of binol derivatives |
| work_keys_str_mv | AT jolliffejd cationdirectedatropselectivesynthesisofbinolderivatives |