Henry reaction diastereoselectivity

The diastereoselectivity is observed in the Henry reaction using optical active niti o compounds or a-heteroatom substituted aldehydes. Lor example, the reaction of O-benzyl-D-lactal-dehyde with methyl 3-niti opropionate in the presence of neubal alumina leads to a mixture of three niti o-aldol products from which D-ribo isomer is isolated by direct crystallization. D-Ribo... 

They react with a wide range of aliphatic and aromatic aldehydes in the presence of catalytic amounts of tetrabutylammonium fluoride (TBAF) to give the trialkylsilyl ethers of P-nitro alcohols with high anti-selectivity (98%). The diastereoselective Henry reaction is summarized in Table 3.2. The products are reduced to P-amino alcohols using Raney Ni-H2 with retention of the configuration of P-nitro alcohols (Scheme 3.12). 

The classical Henry reaction conditions (base catalyzed addition) have some drawbacks sometimes the nitro alcohols are obtained in low yields and diastereoselectivities are not always high. To improve these results, a number of modifications were introduced. One of them is the Seebach s silyl nitronate method,25 that involves a reaction between an aldehyde with a silyl nitronate prepared by metalation of the corresponding nitro alkane with LDA, followed by reaction of the resulting nitronate with tert-butyldimethylsilyl chloride.26... 

Scheme 6.75 Proposed mechanism of the enantio- and diastereoselective aza-Henry reaction between N-Boc-protected aldimines and nitroalkanes in the presence of biflinctional catalyst 12 and catalyzed epimerization of the syn-adduct at increased temperature.

Since a-branched aldehydes gave rather higher asymmetric induction (Scheme 6.166), Nagasawa et al. extended the biphasic strategy to the diastereoselective Henry reaction of nitromethane with enantiomerically pure (S)-configured N,N -dibenzyl protected a-amino aldehydes and a-hydroxy aldehydes protected as silyl ethers. The screening reaction (Scheme 6.169) demonstrated a match/mismatch... 

Scheme 6.169 Screening reaction to identify (R,R)-configured guanidine-thiourea 186 as matching catalyst for the anti-diastereoselective and enantioselective Henry reaction of (S)-a-amino aldehydes with nitromethane.

Enantiomerically pure /3-nitroamines of enolizable aldimines and ketimines have been accessed via a diastereoselective aza-Henry reaction of A-sulfinylimines and nitromethane.37 The reaction is catalysed by sodium hydroxide, but also by tetrabuty-lammonium fluoride, the latter species giving an inversion of stereochemistry. An CT -+N contact ion pair is proposed in the ammonium-catalysed route. 

Bulbule, V. J., Deshpande, V. H., Velu, S., Sudalai, A., Sivasankar, S. and Sathe, V. T. (1999). Heterogeneous Henry reaction of aldehydes diastereoselective synthesis of nitroalcohol derivatives over Mg-Al hydrotalcites. Tetrahedron 55, 9325. 

In a similar study, Schaus extended the scope of this reaction to include nitroethane [30]. The hydroquinine-derived thiourea catalyst 95 efficiently promotes the aza-Henry reaction of nitroethane with the acyl imines 96, affording the syn-(3-nitroamines 97 in good yields with enantioselectivities of 90-98% ee and syn-diastereoselectivities of up to 97% (Scheme 8.31). 

By employing the primary amine catalyst 160, Zhong and coworkers developed the tandem Michael-Henry reaction of ketones with nitroalkenes to provide highly functionalized chiral hexanes and pentanes with high diastereo- and enantioselec-tivity [49]. The selected examples depicted in Scheme 9.56 show that, in the presence of 160 (10-15 mol%), various Michael donors and nitroalkenes smoothly underwent the tandem reaction with almost quantitative yield and extremely high enantios-electivity with the complete diastereoselectivity of the products. Further details of this reaction can be seen in Section 10.4. 

Keywords HeterobimetaUic lanthanoid catalysts. Asymmetric nitroaldol reaction, Henry reaction, Enantioselective and diastereoselective reactions, syn-Selectivity... 

First encouraging results for a stereoselective synthesis in general were reported by Seebach in 1982, who investigated the syn/anti-diastereoselectivity starting from achiral aldehydes and nitroalkanes [4,5]. Barrett et al. examined the influence of nonchiral Lewis acids on the syn/anti diastereoselectivity [6]. Stoichiometric amounts of an enantiomerically pure aldehyde were used in a di-astereoselective reaction with 3-nitropropionate by Hanessian et al. [7]. However, an approach to enantioselective synthesis of nitroalcohols via the route of the asymmetric Henry reaction could not be carried out until almost one hundred years after the discovery of the nitroaldol reaction. 

Diastereomeric mixtures of vicinal nitro alcohols obtained by a classical Henry reaction with low dia-stereoselectivity can be easily silylated to give the corresponding mixture of 0-f-butyldimethylsilyl ethers. The latter undergoes an enrichment of the erythro isomer (54 up to >95 5) by treatment with LDA and successive protonation of the corresponding lithium salts (Scheme 8), which occurs with high diastereoselectivity. 

A stereoselective Henry reaction has also been observed between bicyclic trimethylsilyl nitronates and benzaldehyde with fluoride ion as the catalyst. The reaction results in the formation in high yield of a cyclic hemiacetal (equation 20) and is highly diastereoselective (95% ds)P-... 

Ma, D., Pan, Q. and Han, R (2002) Diastereoselective Henry reactions of iV,iV-dihenzyl a-amino aldehydes with nitromethane catalysed hy enantiopure guanidines. Tetrahedron Letters, 43, 9401-9403. 

Most recently, Xu et al. have demonstrated the first example of a diastereo-and enantioselective aza-MBH-type reaction by the asymmetric synthesis of p-nitro-y-enamines via a (li ,2i )-diaminocyclohexane thiourea derivative (182) mediated tandem Michael addition and aza-Henry reaction in good yields (up to 95%) with high enantioselectivities (up to 91% ee) and diastereoselectivities (up to 1 99 dr) (Scheme 2.90) easily prepared A -tosylimines and nitroalkene are employed as the starting materials. ... 

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