Are Oxazolidinones Really Unproductive, Parasitic Species in Proline Catalysis? – Thoughts and Experiments Pointing to an Alternative View
| العنوان: | Are Oxazolidinones Really Unproductive, Parasitic Species in Proline Catalysis? – Thoughts and Experiments Pointing to an Alternative View |
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| المؤلفون: | Bernard Linder, Albert K. Beck, Dieter Seebach, Michael Limbach, Albert Eschenmoser, Reinhard Hobi, Adi M. Treasurywala, D. Michael Badine, Walter Prikoszovich |
| المصدر: | Helvetica Chimica Acta. 90:425-471 |
| بيانات النشر: | Wiley, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Bicyclic molecule, Stereochemistry, Organic Chemistry, Cyclohexanone, Iminium, Chloral, Biochemistry, Catalysis, Pyrrolidine, Enamine, Inorganic Chemistry, chemistry.chemical_compound, chemistry, Aldol reaction, Drug Discovery, Electrophile, Physical and Theoretical Chemistry |
| الوصف: | The N,O-acetal and N,O-ketal derivatives (oxazolidinones) formed from proline, and aldehydes or ketones are well-known today, and they are detectable in reaction mixtures involving proline catalysis, where they have been considered ‘parasitic dead ends’. We disclose results of experiments performed in the early 1970's, and we describe more recent findings about the isolation, characterization, and reactions of the oxazolidinone derived from proline and cyclohexanone. This oxazolidinone reacts (THF, room temperature) with the electrophiles β-nitrostyrene and chloral (=trichloroacetaldehyde), to give the Michael and aldol adduct, respectively, after aqueous workup (Scheme 5). The reactions occur even at −75° when catalyzed with bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or EtN(i-Pr)2 (DIPEA) (10%; Table 1). It is shown by NMR (Figs. 1 and 3) and IR analysis (Figs. 2 and 4) that the primarily detectable product (before hydrolysis) of the reaction with the nitro-olefin is again an oxazolidinone. When dissolved in hydroxylic solvents such as MeOH, ‘hexafluoroisopropanol’ ((CF3)2CHOH; HFIP), AcOH, CF3COOH, or in LiBr-saturated THF, the ring of the oxazolidinone from cyclohexanone and proline opens up to the corresponding iminium ion (Tables 2–4), and when treated with strong bases such as DBU (in (D8)THF) the enamino-carboxylate derived from proline and cyclohexanone is formed (Scheme 8). Thus, the two hitherto putative participants (iminium ion and enamine) of the catalytic cycle (Scheme 9) have been characterized for the first time. The commonly accepted mechanism of the stereoselective C,C- or C,X-bond-forming step (i.e., A–D) of this cycle is discussed and challenged by thoughts about an alternative model with a pivotal role of oxazolidinones in the regio- and diastereoselective formation of the intermediate enamino acid (by elimination) and in the subsequent reaction with an electrophile (by trans-addition with lactonization; Schemes 11–14). The stereochemical bias between endo- and exo-space of the bicyclo[3.3.0]octane-type oxazolidinone structure (Figs. 5 and 6) is considered to possibly be decisive for the stereochemical course of events. Finally, the remarkable consistency, with which the diastereotopic Re-face of the double bond of pyrrolidino-enamines (derived from proline) is attacked by electrophiles (Schemes 1 and 15), and the likewise consistent reversal to the Si-face with bulky (Aryl)2C-substituents on the pyrrolidine ring (Scheme 16) are discussed by invoking stereoelectronic assistance from the lone pair of pyramidalized enamine N-atoms. |
| تدمد: | 1522-2675 0018-019X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::867408ec8100dc7e29d26626a7c2a765 https://doi.org/10.1002/hlca.200790050 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........867408ec8100dc7e29d26626a7c2a765 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15222675 0018019X |
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