1310420-11-1Relevant articles and documents
Stoichiometric reactions of enamines derived from diphenylprolinol silyl ethers with nitro olefins and lessons for the corresponding organocatalytic conversions - A survey
Seebach, Dieter,Sun, Xiaoyu,Ebert, Marc-Olivier,Schweizer, W. Bernd,Purkayastha, Nirupam,Beck, Albert K.,Duschmale, Joerg,Wennemers, Helma,Mukaiyama, Takasuke,Benohoud, Meryem,Hayashi, Yujiro,Reiher, Markus
, p. 799 - 852 (2013/07/19)
The stoichiometric reactions of enamines prepared from aldehydes and diphenyl-prolinol silyl ethers (intermediates of numerous organocatalytic processes) with nitro olefins have been investigated. As reported in the last century for simple achiral and chiral enamines, the products are cyclobutanes (4 with monosubstituted nitro-ethenes), dihydro-oxazine N-oxide derivatives (5 with disubstituted nitro-ethenes), and nitro enamines derived from γ-nitro aldehydes (6, often formed after longer reaction times). The same types of products were shown to be formed, when the reactions were carried out with peptides H-Pro-Pro-Xaa-OMe that lack an acidic H-atom. Functionalized components such as alkoxy enamines, nitro-acrylates, acetamido-nitro-ethylene, or hydroxylated nitro olefins also form products carrying the diphenyl-prolinol silyl ether as a substituent. All of these products must be considered intermediates in the corresponding catalytic reactions; the investigation of their chemical properties provided useful hints about the rates, the conditions, the catalyst resting states or irreversible traps, and/or the limitations of the corresponding organocatalytic processes. High-level DFT and MP2 computations of the structures of alkoxy enamines and thermodynamic data of a cyclobutane dissociation are also described. Some results obtained with the stoichiometrically prepared intermediates are not compatible with previous mechanistic proposals and assumptions. Copyright
Organocatalyzed michael addition of aldehydes to nitro alkenes - Generally accepted mechanism revisited and revised
Patora-Komisarska, Krystyna,Benohoud, Meryem,Ishikawa, Hayato,Seebach, Dieter,Hayashi, Yujiro
experimental part, p. 719 - 745 (2011/06/27)
The amine-catalyzed enantioselective Michael addition of aldehydes to nitro alkenes (Scheme 1) is known to be acid-catalyzed (Fig. 1). A mechanistic investigation of this reaction, catalyzed by diphenylprolinol trimethylsilyl ether is described. Of the 13 acids tested, 4-NO2-C6H 4OH turned out to be the most effective additive, with which the amount of catalyst could be reduced to 1 mol-% (Tables 2-5). Fast formation of an amino-nitro-cyclobutane 12 was discovered by in situ NMR analysis of a reaction mixture. Enamines, preformed from the prolinol ether and aldehydes (benzene/molecular sieves), and nitroolefins underwent a stoichiometric reaction to give single all-trans-isomers of cyclobutanes (Fig. 3) in a [2+2] cycloaddition. This reaction was shown, in one case, to be acid-catalyzed (Fig. 4) and, in another case, to be thermally reversible (Fig. 5). Treatment of benzene solutions of the isolated amino-nitro-cyclobutanes with H2O led to mixtures of 4-nitro aldehydes (the products 7 of overall Michael addition) and enamines 13 derived thereof (Figs. 6-9). From the results obtained with specific examples, the following tentative, general conclusions are drawn for the mechanism of the reaction (Schemes 2 and 3): enamine and cyclobutane formation are fast, as compared to product formation; the zwitterionic primary product 5 of C,C-bond formation is in equilibrium with the product of its collapse (the cyclobutane) and with its precursors (enamine and nitro alkene); when protonated at its nitronate anion moiety the zwitterion gives rise to an iminium ion 6, which is hydrolyzed to the desired nitro aldehyde 7 or deprotonated to an enamine 13. While the enantioselectivity of the reaction is generally very high (>97% ee), the diastereoselectivity depends upon the conditions, under which the reaction is carried out (Fig. 10 and Table 1-5). Various acid-catalyzed steps have been identified. The cyclobutanes 12 may be considered an off-cycle 'reservoir' of catalyst, and the zwitterions 5 the 'key players' of the process (bottom part of Scheme 2 and Scheme 3). Copyright
