1309664-91-2Relevant academic research and scientific papers
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
Dihydrooxazine oxides as key intermediates in organocatalytic michael additions of aldehydes to nitroalkenes
Sahoo, Gokarneswar,Rahaman, Hasibur,Madarasz, Adam,Papai, Imre,Melarto, Mikko,Valkonen, Arto,Pihko, Petri M.
supporting information, p. 13144 - 13148 (2013/02/26)
The organocatalytic enantioselective Michael addition of aldehydes to nitroalkenes through enamine catalysis has been studied intensively in recent years. Pioneering mechanistic studies by Seebach and Hayashi and co-workers, as well as by the Blackmond group, on reactions catalyzed by diaryl prolinol ethers have identified cyclobutane (CB) species 6a (Scheme 1) as a key intermediate and the resting state of the amine catalyst. Although these studies clearly demonstrated that the rate-determining step in the catalytic cycle takes place after the formation of 6a, and possibly involves the protonation of the iminium nitronate 5a, the detailed mechanism of the rate-determining step was not addressed. More recently, the Blackmond group suggested a modified catalytic cycle where the cyclobutane species 6a is first deprotonated to give the anion 10 a, followed by protonation to form the enamine 8a.
1,2-oxazine N-oxides as catalyst resting states in michael additions of aldehydes to nitro olefins organocatalyzed by α,α-diphenylprolinol trimethylsilyl ether: Preliminary communication
Seebach, Dieter,Sun, Xiaoyu,Sparr, Christof,Ebert, Marc-Olivier,Schweizer, W. Bernd,Beck, Albert K.
scheme or table, p. 1064 - 1078 (2012/09/22)
By combining enamines, derived from aldehydes and diphenylprolinol trimethylsilyl ether (the Hayashi catalyst), with nitroethenes ((D 6)benzene, 4-A molecular sieves, room temperature) intermediates of the corresponding catalytic Michael-addition cycles were formed and characterized (IR, NMR, X-ray analysis; Schemes 3-6 and Fig. 1-3). Besides cyclobutanes 2, 1,2-oxazine N-oxide derivatives 3-6 and 8 have been identified for the first time, some of which are very stable compounds. It may not be a lack of reactivity (between the intermediate enamines and nitro olefins) that leads to failure of the catalytic reactions (Schemes 3-5) but the high stability of catalyst resting states. The central role zwitterions play in these processes is discussed (Schemes 1 and 2). Copyright
Mechanistic rationalization of organocatalyzed conjugate addition of linear aldehydes to nitro-olefins
Bures, Jordi,Armstrong, Alan,Blackmond, Donna G.
supporting information; experimental part, p. 8822 - 8825 (2011/08/04)
Kinetic studies of the conjugate addition of propanal to nitrostyrene catalyzed by diarylprolinol ethers reveal that formation of the product iminium species is rate-determining and is promoted by both the reaction product and acid additives. The beneficial role of a dominant cyclobutane intermediate in maintaining high stereoselectivity is highlighted. This mechanistic understanding led to the design of highly productive reaction protocols.
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
, 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
