Diastereoselective Synthesis of Nitroaldol Derivatives

Abstract

SummaryThree methods are described by which diastereomerically enriched nitroaldols and their O-silylated derivatives can be prepared. threo-Nitroaldols prevail up to 10: 1 over the erythro-isomers if doubly deprotonated nitroaldols 28 are quenched with acetic acid (THF/HMPT or DMPU, -looo) (see Scheme 5 and Table 2). O-Trimethyl-or O-(f-butyl)dimethylsilylated (TBDMSi) erythro-nitroaldols can be obtained by protonation of the corresponding lithium nitronates (35, 39) in THF at low temperature (see Schemes 6 and 7). The erythro-O-TBDMSi-nitroaldol derivatives are also formed in the fluoride catalyzed addition of TBDMSi-nitronates (40-45) to aldehydes (see Schemes 8 and 9). In the latter reaction no 1,2-asymrnetric induction is observed if a-branched silylnitronates or aldehydes are employed (see 48/49 and 50/51). -The stereochemical course of the reactions leading to erythro-O-TBDMSi-nitroaldols follows topological rules of broad applicability (see Scheme 10); possible mechanisms are discussed. -The configuration of erythro/ threo-nitroaldols is determined by chemical correlation (see 24-26) and by I3C-NMR. spectroscopy. -Some examples of the preparation of diastereomerically enriched 1,2-aminoalcohols by reduction of the corresponding nitro compounds without loss of configurational purity are described (see Schemes I 1 and 12).A) Introduction. -The nitroaldol-or Henry reaction is one of the classical C,Cbond forming processes. It furnishes the 1,2-functionalized nitroalcohols 1, precursors of the symmetrical (R' = R2) and unsymmetrical (R' # R2) aminoalcohols 2.Nitroaldols have been extensively reviewed [3] [4], and have frequently been used as intermediates in synthesis. However, the lack of stereoselectivity in the Henry reaction (except in cyclic systems) has hardly been mentioned. This lack of selectivity is due to the reversibility of the reaction and the easy epimerization at the nitro-substituted C-atom. The nitroaldols of type 1 (R',R2#H) occur in two dia-

Enantioselective Preparation of γ ‐Amino Acids and γ ‐Lactams from Nitro Olefins and Carboxylic Acids, with the Valine‐Derived 4‐Isopropyl‐5,5‐diphenyl‐1,3‐oxazolidin‐2‐one as an Auxiliary

“…However, the enantiomer ratio could Helvetica Chimica Acta ± Vol. 82 (1999) 2368 4 ) We have reported on stereoselective protonations of nitronates formed during Henry reactions or by deprotonation of 1,2-dinitro-alcohol derivatives many years ago [9]. These reactions are highly diastereoselective at low temperatures.…”

MgAl-Layered Double Hydroxide Solid Base Catalysts for Henry Reaction: A Green Protocol

“…Noteworthy developments to the Henry reaction have been achieved by using silyl nitronates in the existence of fluoride ion or instead α-α doubly deprotonated primary nitroalkanes [9]. Both of these processes have showed to be valuable for the stereo selective preparation of vicinal amino alcohols under drastic conditions, which reduced diastereoselectivity with aromatic aldehydes.…”

A practical synthesis of L-threo-dihydrosphingosine (safingol), an antineoplastic and antipsoriatic agent

“…Reports on hydrogenations with other reagents such as lithium borohydride or lithium aluminum hydride are not consistent in terms of preservation of the configuration. [15][16][17] Therefore a few attempts of these reactions were performed in order to determine their applicability to our case. We found that during hydrogenation using Raney nickel as catalyst, for larger scale experiments the threo-nitro derivative epimerized under formation of the two amino diastereoisomers, as shown by NMR spectra of the reaction mixtures.…”

“…This classic method is performed under diverse catalytic conditions and has been frequently reviewed. 15,16 The synthesis of 2-nitrooctadecane-1,3-diol starting from 2 and 3 has been described earlier, for both diasteromers and their mixtures. [8][9][10] The mixture of nitrodiol diastereomers (4 + 5 and 7 + 9) was recrystallized from various solvents to give one single isomer.…”