33802-05-0Relevant academic research and scientific papers
Highly enantioselective aldol reactions using a tropos dibenz[c,e]azepine organocatalyst
Lygo, Barry,Davison, Christopher,Evans, Timothy,Gilks, James A.R.,Leonard, John,Roy, Claude-Eric
supporting information; scheme or table, p. 10164 - 10170 (2012/01/03)
The four-step synthesis of a chiral primary tertiary diamine salt, possessing a tropos dibenz[c,e]azepine ring is described. It is shown that 3.5-5 mol % of this salt is capable of promoting highly enantioselective crossed-aldol reactions between cyclohexanone and a series of aromatic aldehydes. In all cases, the aldol reactions proceed with high diastereoselectivity for the anti-aldol product. The outcome of crossed-aldol reactions involving other cyclic ketones and acyclic ketones are also described. All examples involving cyclic ketones result in selectivity for the anti-aldol products, whereas acyclic ketones were found to favour the syn-aldol products. A discussion on the role of the chiral primary tertiary diamine salt in the catalysis of the aldol reactions is also presented.
Are oxazolidinones really unproductive, parasitic species in proline catalysis? - Thoughts and experiments pointing to an alternative view
Seebach, Dieter,Beck, Albert K.,Badine, D. Michael,Limbach, Michael,Eschenmoser, Albert,Treasurywala, Adi M.,Hobi, Reinhard,Prikoszovich, Walter,Linder, Bernard
, p. 425 - 471 (2008/02/07)
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.
Lewis base-promoted aldol reaction of dimethylsilyl enolates in aqueous dimethylformamide: Use of calcium chloride as a Lewis base catalyst
Miura, Katsukiyo,Nakagawa, Takahiro,Hosomi, Akira
, p. 536 - 537 (2007/10/03)
In the presence of CaCl2, dimethylsilyl (DMS) enolates smoothly reacted with aldehydes under mild conditions to give aldol adducts in good to high yields. The catalytic activities of various metal and tetrabutylammonium salts have revealed that CaCl2 works as a Lewis base catalyst to activate DMS enolates. The CaCl2-promoted reaction proceeded even in the presence of water or in pure water. This catalytic system was applicable to the aldol reaction with aqueous aldehydes such as formalin. Copyright
