Multifactorial optimization enables the identification of a greener method to produce (+)-nootkatone.

The natural aroma compound (+)-nootkatone was obtained in selective conversions of up to 74 mol% from inexpensive (+)-valencene substrate by using a comparatively greener biocatalytic process developed based on modifications of the previously published Firmenich method. Buffer identity and concentration, pH, temperature and downstream work-up procedures were optimized to produce a crude product in which >90 % of (+)-valencene had been converted, with high chemoselectivity observed for (+)-nootkatone production. Interestingly, the biotransformation was carried out efficiently at temperatures as low as 21 ºC. Surprisingly, the best results were obtained when an acidic pH in the range of 3-6 was applied, as compared to the previously published procedure in which it appeared to be necessary to buffer the pH optimally and fixed throughout at 8.5. Furthermore, there was no need to maintain a pure oxygen atmosphere to achieve good (+)-nootkatone yields. Instead, air bubbled continuously at a low rate through the reaction mixture via a submerged glass capillary was sufficient to enable the desired lipoxygenase-catalyzed oxidation reactions to occur efficiently. No valencene epoxide side-products were detected in the organic product extract by a standard GCMS protocol. Only traces of the anticipated corresponding α- and ß-nootkatol intermediates were routinely observed.

A green, economical synthesis of ß-ketonitriles and trifunctionalized building blocks from esters and lactones.

The acylation of the acetonitrile anion with lactones and esters in ethereal solvents was successfully exploited using inexpensive KOt-Bu to obtain a variety of ß-ketonitriles and trifunctionalized building blocks, including useful O-unprotected diols. It was discovered that lactones react to produce the corresponding derivatized cyclic hemiketals. Furthermore, the addition of a catalytic amount of isopropanol, or 18-crown-6, was necessary to facilitate the reaction and to reduce side-product formation under ambient conditions.

(±)-3-Benz-yloxy-1-(4-meth-oxy-benz-yl)piperidine-2-thione.

The title mol-ecule, C20H23NO2S, adopts a twisted conformation in which the two aromatic rings connected to the central piperidine ring are orientated trans to each other. An intra-molecular C-H⋯S contact occurs. In the crystal, C-H⋯π and C-H⋯O inter-actions act to stabilize the structure in three dimensions.

3-Hy-droxy-1-(4-meth-oxy-benz-yl)piperidin-2-one.

The title compound, C13H17NO3, adopts a conformation in which the aromatic ring and the mean plane of the piperidine ring are almost perpendicular to each other [dihedral angle = 79.25 (6)°]. The presence of the carbonyl group alters the conformation of the piperidine ring from a chair to a twisted half-chair conformation. In the crystal, pairs of strong O-H⋯O hydrogen bonds link the mol-ecules into inversion dimers. Weak C-H⋯O inter-actions extend the hydrogen-bonding network into three dimensions.