Preparation and Characterization of New C2- and C1-Symmetric Nitrogen, Oxygen, Phosphorous, and Sulfur Derivatives and Analogs of TADDOL. Part I
| Autor: | Albert K. Beck, Dieter Seebach, Arkadius Pichota, Volker Gramlich |
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| Rok vydání: | 2012 |
| Předmět: |
Aqueous solution
Organic Chemistry Enantioselective synthesis Dithiol Biochemistry Medicinal chemistry Catalysis Inorganic Chemistry chemistry.chemical_compound chemistry Sulfanyl Organocatalysis Drug Discovery Alkoxy group Organic chemistry Physical and Theoretical Chemistry Brønsted–Lowry acid–base theory |
| Zdroj: | Helvetica Chimica Acta. 95:1239-1272 |
| ISSN: | 0018-019X |
| DOI: | 10.1002/hlca.201200146 |
| Popis: | The chloro alcohols 4–6 derived from TADDOLs (=α,α,α′,α′-tetraaryl-1,3-dioxolan-4,5-dimethanols) are used to prepare corresponding sulfanyl alcohols, ethers, and amines (Scheme 1 and Table 1). The dithiol analog of TADDOL and derivatives thereof, 45–49, were also synthesized. The crystal structures of 16 representatives of this series of compounds are reported (Figs. 1–3 and Scheme 2). The thiols were employed in Cu-catalyzed enantioselective conjugate additions of Grignard reagents to cyclic enones, with cycloheptenone giving the best results (er up to 94 : 6). The enantioselectivity reverses from Si-addition with the sulfanyl alcohol to Re-addition with the alkoxy or dimethylamino thiols (Table 4). CuI-Thiolates, 50–53, could be isolated in up to 84% yield (Scheme 2) and were shown to have tetranuclear structures in the gas phase (by ESI-MS), in solution (CH2Cl2, THF; by vapor-pressure osmometry and by NMR pulsed-gradient diffusion measurements; Table 5), and in the solid state (X-ray crystal structures in Scheme 2). The Cu complex 50 of the sulfanyl alcohol is stable in air and in the presence of weak aqueous acid, and it is a highly active catalyst (0.5 mol-%) for the 1,4-additions, leading to the same enantio- and regioselectivities observed with the in situ generated catalyst (6.5 mol-%; Scheme 3). Since the reaction mixtures contain additional metal salts (MgX2, LiX) it is not possible at this stage, to propose a mechanistic model for the conjugate additions. |
| Databáze: | OpenAIRE |
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