Asymmetrische Michael‐Additionen. Stereoselektive Alkylierung chiraler, nicht racemischer Enolate durch Nitroolefine. Herstellung enantiomerenreiner γ‐Aminobuttersäure‐ und Bernsteinsäure‐Derivate

Abstract

Asymmetric Michael-Additions. Stereoselective Alkylation of Chiral, Non-racemic Enolates by Nitroolefins. Preparation of Enantiomerically Pure y-Aminobutyrie and Succinie Acid Derivatives Chiral, non-racemic lithium enolates (E,F,G) of 1,3-dioxolan-4-ones, methyl 1,3-oxazolidin-4-carboxylates, methyl 1,3-oxazolin-4-carboxylates, 1,3-oxazolidin-5-ones, and 1,3-imidazolidin-4-0nes derived from (S)-lactic acid @a), (S)-mandelic acid (2b), and (S)-malic acid (Ze), or from (S)-alanine (lo), (S)-proline (ll), (S)-serine (12), and (S)-threonine (13), are added to nitroolefins. Michael adducts ( S 9 , 14-18) are formed (4&80%) with selectivities generally above 90% ds of one of the four possible stereoisomers. Conversions of these nitroalkylated products furnish the a-branched a-hydroxysuccinic acids 28 and 29, the a-hydroxy-y -amino acid 25, the a,y-diamino acid 32, the substituted y-lactames 19-22, and the pyrrolidine 23. The relative and absolute configuration of the products from dioxolanones and nitropropene are derived by chemical correlation and NOE measurements indicating that the steric course of reaction is to be specified as Ik, ul-1,3. The mechanism is discussed. Einleitung

Asymmetric Michael Additions to Nitroalkenes

“…The addition of the dioxolano enolate 49 to nitroalkenes for example proceeded in good yields giving the addition products 50 in very high diastereomeric excesses as it was shown by Seebach and coworkers. [30] Taking advantage of the versatility of the nitro group, it was possible to convert the Michael adducts 50 into γ-aminobutyric acid 51, pyrrolidine 52, γ-lactam 53 and succinic acid derivatives 54 (Scheme 17). Very good results were also obtained with chiral enolates derived from α-amino acids.…”

“…Very good results were also obtained with chiral enolates derived from α-amino acids. [30] Scheme 17…”

“…( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002) chameleon'' [5] it can serve as masked functionality to be further transformed after the addition has taken place. The Nef reaction, [6] the nucleophilic displacement, [7] the reduction to an amino group, [8] the Meyer reaction, [9] and the conversion into a nitrile oxide [10] are only some examples of the possible transformations that nitro groups can undergo (Scheme 1).…”

A Greener, Efficient Approach to Michael Addition of Barbituric Acid to Nitroalkene in Aqueous Diethylamine Medium

“…These are recognized as versatile synthetic building blocks which can be either transformed into biologically active compounds such as tetrahydropyrans, amino acids, pyrrolidines and lactones [7][8][9], or readily converted into other functionalities such as ketones, amines, carboxylic acids, nitrile oxides, etc. [10][11][12][13]. Extensive studies have been devoted to the development of catalytic systems for Michael additions of various active methines such as pronucleophiles to nitroalkenes including cinchona organocatalysts [14], enzymes [15], various chiral amines [16,17], transition metal-free organocatalysts [18][19][20] and chiral metal complexes [21][22][23][24][25].…”

Highly enantioselective conjugate addition of fluoromalonates to nitroalkenes using bifunctional organocatalysts

“…Michael reaction of nucleophiles to nitroalkenes represents a direct and most appealing approach to chiral nitroalkanes that are versatile intermediates in organic synthesis, which can be transformed into an amine, nitrile oxide, ketone, carboxylic acid, hydrogen, etc. [22][23][24][25]. Recently, several groups presented the catalytic asymmetric conjugate additions of active methine compounds to nitroalkenes in the presence of chiral metal complexes or organocatalysts [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”