醛不对称加成反应的进展

综述了近年来醛不对称加成反应的进展,包括加氘还原、与有机金属化合物加成、与有机硼化合物加成、与氰化物加成、与磷酸酯加成和aldol加成等反应。     

Recent advances on copper-catalyzed asymmetric synthesis and their potential biological applications

An asymmetric catalysis is a form of catalytic reaction wherein a chiral catalyst controls the production of a chiral molecule to favour the synthesis of one stereoisomer over another. It's a good way to make stereoisomeric molecules for pharmacological purposes. Among the transition metals, copper is a cost-effective, plentiful, and less poisonous metal. This review focused on the asymmetric transformations in the last fifteen years.     

Stereoselective synthesis of trifluoromethyl-substituted 1,2-diamines by aza-Michael reaction with trans-3,3,3-trifluoro-1-nitropropene

Aza-Michael addition of optically pure 4-phenyl-2-oxazolidinone to 3,3,3-trifluoro-1-nitropropene proceeds smoothly at low temperature with a high yield. Diastereoselectivity of the addition depends on the base used and lithiated species proved to be highly efficient affording 92% de. Optically pure 1,2-diamino-3,3,3-trifluoropropane is prepared in 58% yield from the aza-Michael addition product through a three-step procedure.     

Organocatalytic asymmetric aza-Michael reaction: enantioselective addition of O-benzylhydroxylamine to chalcones

A novel organocatalytic approach for aza-Michael reaction of chalcones using commercial and non-expensive O-benzylhydroxylamine and a readily available organocatalyst is provided. The use of this simple protocol results in β-keto hydroxylamines in up to 60% ee, thus extending the generality of the catalytic enantioselective aza-Michael reaction.     

Stereoselective conjugate addition of nitrogen nucleophiles to 3,3,3-trifluoro-1-nitropropene

In order to access 1,2-diamines incorporating perfluorinated groups, the Michael-like addition of nitrogen nucleophiles to 3,3,3-trifluoro-1-nitropropene has been investigated using racemic and optically pure nucleophiles such as amines, amides, oxazolidin(on)es, and thiazolidin(on)es. Complete diastereoselectivity of the addition was achieved with 4-phenylthiazolidine-2-thione.     

Atropisomeric lactam chemistry: catalytic enantioselective synthesis, application to asymmetric enolate chemistry and synthesis of key intermediates for NET inhibitors

In the presence of (R)-SEGPHOS-Pd(OAc)₂ catalyst, the intramolecular N-arylation of ortho-tert-butyl-NH-anilides possessing an iodophenyl group proceeded in a highly enantioselective manner (89-98% ee) to give optically active atropisomeric lactams having an N-C chiral axis. MPLC purification of the enantio-enriched lactam products using an achiral silica gel column led to a further increase in the enantiomeric purity (>99% ee). The reaction of the lithium enolate prepared from the optically active atropisomeric lactam with various alkyl halides gave α-substituted and α,α-disubstituted lactam products with high diastereoselectivity. α-Alkylated lactam derivatives were efficiently converted to key intermediates for the synthesis of an NET inhibitor.     

Uncatalyzed,green aza-Michael addition of amines to dimethyl maleate

Dimethyl maleate was found to be a very reactive and selective acceptor for the aza-Michael addition in comparison to other commonly used electron-deficient alkenes. It reacts efficiently with a variety of aliphatic amines in complete absence of any catalyst and solvent at room temperature. Under these environmentally-friendly conditions, high yields of selectively mono-adducts were obtained within short reaction times.     

An efficient catalytic asymmetric addition of trimethylsilyl cyanide to aldehydes at room temperature

The BINOL-salen compound (S)-5c in combination with Ti(OⁱPr)₄ is found to catalyze the addition of TMSCN to aldehydes to form chiral cyanohydrins with very good enantioselectivity (75-85% ee). The reactions are carried out in one-pot at room temperature without the need to isolate the chiral Lewis acid catalyst.     

Recent advances and applications of iridium-catalysed asymmetric allylic substitution

Since their discovery in 1997, iridium-catalysed asymmetric allylic substitutions have been developed into a broadly applicable tool for the synthesis of chiral building blocks via C-C and C-heteroatom bond formation. The remarkable generality of these reactions and the high levels of regio- and enantioselectivity that are usually obtained in favour of the branched products have been made possible by a thorough investigation of the catalyst system and its mode of action. Therefore, today the Ir-catalysed asymmetric allylic substitution is a powerful reaction in the organic chemist's repertoire and has been used extensively for several applications. This article aims to provide an overview of the development of iridium catalysts derived from an Ir salt and a chiral phosphoramidite and their application to the enantioselective synthesis of natural products and biologically relevant compounds.     

Asymmetric catalyzed intramolecular aza-Michael reaction mediated by quinine-derived primary amines

An intramolecular organocatalytic enantioselective aza-Michael reaction of carbamates, sulfonamides and acetamides to a,b-unsaturated ketones was developed. This process is promoted by 9-amino-9-deoxy-epi-quinine and diphenyl hydrogen phosphate to afford a straightforward and expeditious synthesis of several synthetically useful five-and six-membered heterocycles with excellent enantioselectivity(92%–97.5% ee) and very good yields(up to 99%).     

Elucidating the mechanism of the asymmetric aza-Michael reaction

The mechanism of the palladium-catalysed asymmetric aza-Michael addition of aniline to alpha,beta-unsaturated N-imide was examined from several aspects using a combination of techniques, including X-ray crystallography, mass spectrometry, NMR, UV/Vis spectroscopy, and kinetic studies. The binding of aniline to the dicationic palladium(II) metal centre was found to occur in two consecutive steps: The binding of the first aniline is fast and reversible, whereas the binding of the second aniline is slower and irreversible. This occurs in competition with the binding of the N-imide, which forms a planar six-membered chelate ring with the metal centre; coordinating through the 1,3-dicarbonyl moiety. Isotopic labelling revealed that the addition of N-H occurs in a highly stereoselective manner, allowing the synthesis of optically active beta(2)- and beta(2,3)-amino acid derivatives. The stereochemistry of the addition is postulated to be syn. In situ kinetic studies provided evidence for product inhibition. The binding of the N-imide to the catalyst was found to be the rate-limiting step. Aniline was found to be an inhibitor of the pre-catalyst. The study culminated in the design of a new reaction protocol. By maintaining a low concentration of the aniline substrate during the course of the reaction, significant enhancement of yield and enantioselectivity can be achieved.     

Highly diastereoselective radical addition to glyoxylate imines of chiral amines without additional heteroatoms

The diastereoselective addition of alkyl radicals to glyoxylate imines of α-alkylbenzylamines has been investigated and it was found that diastereoselectivity improved as the size of the alkyl group increased.     

From targeted aza-Michael addition to linked azaheterocyclic scaffolds

A straightforward method for the synthesis of spaced, phenyl-linked bis(thiohydantoin) derivatives and (thio)hydantoins spiro-fused to pyrroline ring has been developed. All the synthetic strategies here presented rely on initial aza-Michael addition followed by acylation/regioselective ring-closure step involving DD, primary amine and iso(thio)cyanate in a 3-CR providing 1,3,5-trisubstituted (thio)hydantoins. The choice of opportune acyclic reagents in the sequential 3-CR followed by 1,4-nucleophilic addition/intramolecular ring closing and 1,3-dipolar cycloaddition permits a number of C–N and C–C formation that realizes different kind of linkage between several pharmacophores.     

A stereoselective formal total synthesis of (+)-hyperaspine via a tandem aza-Michael reaction

A stereoselective formal total synthesis of (+)-hyperaspine via a tandem aza-Michael reaction as the key step in good yield is reported.     

Recent advances in asymmetric reactions catalyzed by chiral phosphoric acids

The very recent advances in chiral phosphoric acids (CPAs) catalyzed asymmetric reactions are discussed.