Wieland-Miescher ketone analogues

The absolute configuration of Wieland-Miescher ketone analogues bearing an angular protected hydroxymethyl group was unambiguously determined after regio- and stereoselective reduction of the saturated ketone function to cis -alcohols and application of the exciton chirality method to bicyclic enone-benzoate chromophoric systems 155-158352. 

The first total synthesis of barbacenic acid, a bisnorditerpene containing five contiguous stereocenters, was achieved by A. Kanazawa et. al. They started out from a Wieland-Miescher ketone analogue that could be synthesized with high yield and excellent enantioselectivity by the procedure of S. Takahashi. According to this procedure, the Michael addition product 2-methyl-2-(3-oxo-pentyl)-cyclohexane-1,3-dione was cyclized in the presence of (S)-(-)-phenylalanine and D-camphorsulfonic acid. 

D. B. Ramachary, M. Kishor, J. Org. Chem. 2007, 72, 5056-5068. Organocatalytic sequential one-pot double cascade asymmetric synthesis of Wieland-Miescher ketone analogues from a Knoevenagel/hydrogenation/Robinson annulation sequence scope and apphcations of organocatalytic biomi-metic reductions. 

Draw the structures of the bicyclo[3.1.0]hex-2-ene-2-carboxaldehyde, cis-jasmone, the Wieland-Miescher ketone and the bis-nor-analogue -which you may find through the "Subject index"- and ... 

The key intermediate in the synthesis of the derivatives of 19-F3-androstane is the trifluoro analogue of the Wieland-Miescher ketone. Its preparation involves a Diels-Alder reaction between a trifluoromethyi ketone and a siloxy diene. Another original step is the regioselective reduction of a diketone only the ketone function in P of CF3 (probably activated by this substituent) is reduced (Figure 4.6). " Then, a succession of classical reactions leads to derivatives of androstane from the trifluoro analogue of the Wieland-Miescher ketone (Figure 4.7). ... 

Figure 4.6 Synthesis of the trifluoro analogue of the Wieland-Miescher ketone. ...

In addition of sesquiterpenes, several bioactive diterpenes have also been synthesized from the Wieland-Miescher ketone (1) and its methyl analogues. The syntheses of some of these diterpenes are described below. 

Bradshaw B, Etxebarria-Jardi G, Bonjoch J, Viozquez SF, Guillena G, Najera C (2009) Efficient Solvent-Free Robinson Armulation Protocols for the Highly Enantioselective Synthesis of the Wieland-Miescher Ketone and Analogues. Adv Synth Catal 351 2482... 

A comparative study of the efficiency of chiral bimorpholine- and bipiperidine-type organocatalysts for asymmetric aldolisations was reported by Kanger et al. These chiral tertiary amines were investigated for both the aldolisation of acetone with para-nitrobenzaldehyde and the intramolecular aldolisation of triketones. In both cases of aldolisations, the bimorpholine derivatives were found to be more reactive as well as more selective than the corresponding bipiperidine derivatives, as summarised in Scheme 2.44. The intramolecular aldolisations yielded the Wieland-Miescher ketone and its analogue in enantioselectivities of up to 95% ee by using the bimorpholine-type catalyst combined with an additive such as TfOH, while the aldol product from acetone was isolated in the same conditions with enantioselectivities of up to 88% ee. 

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