Vetiver oil, produced on a multiton‐scale from the roots of vetiver grass, is one of the finest and most popular perfumery materials, appearing in over a third of all fragrances. It is a complex mixture of hundreds of molecules and the specific odorant, responsible for its characteristic suave and sweet transparent, woody‐ambery smell, has remained a mystery until today. Herein, we prove by an eleven‐step chemical synthesis, employing a novel asymmetric organocatalytic Mukaiyama–Michael addition, that (+)‐2‐epi‐ziza‐6(13)en‐3‐one is the active smelling principle of vetiver oil. Its olfactory evaluation reveals a remarkable odor threshold of 29 picograms per liter air, responsible for the special sensuous aura it lends to perfumes and the quasi‐pheromone‐like effect it has on perfumers and consumers alike.

There has been considerable interest in the stereoselective ring opening of meso-cyclic anhydrides, since the resulting hemiesters are used as versatile intermediates in the construction of many bioactive compounds.1 Especially, the chiral 3-substituted glutaric acid monoesters 2 produced by the alcoholysis of meso-glutaric anhydrides 1 (Scheme 1) are used as key intermediates for the synthesis of a variety of industrially interesting pharmaceutical compounds, e.g., γ-aminobutyric acid (GABA) analogs, 2 selective serotonin receptor antagonists (e.g., Paroxetin·HCl) 3 and potent P2X7 receptor antagonists, 4 etc. Much effort has, therefore, been made to develop efficient enzymatic and non-enzymatic catalytic systems for the alcoholysis of the meso-glutaric anhydrides 1.1 However, the results obtained with meso-glutaric anhydrides as substrates are still unsatisfactory for practical use, whereas alcoholysis with other types of meso-anhydrides, such as bi-, tricyclic and succinic anhydrides, usually gives excellent results. All of the approaches involving the use of meso-glutaric anhydrides as substrates suffer from either a narrow substrate scope and/or very long reaction time and unsatisfactory enantioselectivity. Even enzymatic processes gave very low enantioselectivities. 5Recently, we and another research group employed bifunctional (thio) ureas as organic chiral catalysts for the alcoholytic desymmetrization of meso-glutaric anhydrides.6,7 However, their enantioselectivity (~80% ee) are still unsatisfactory for the synthetic use. Moreover, with this type of catalysts, high ees can be obtained only under conditions of extremely high dilution. We identified the reason for this unusual concentration-dependence in terms of the self-association of the catalyst.6 When considering the reaction time, volume yield, etc., this type of catalysts is highly undesirable for practical use. Thus, it would be highly desirable to develop a new class of highly enantioselective and self-association free organocatalysts for the alcoholytic desymmetrization of meso-glutaric anhydrides I.We have recently developed novel self-association free chiral bis-squaramide catalysts 3, in which the steric bulk of the two alkaloid moieties suppress their self-aggregation. 8Now we report on their use as highly enantioselective catalysts for the alcoholytic desymmetrization of meso-glutaric anhydrides 1. Detailed experimental studies and diffusion ordered spectroscopy (DOSY) data revealed that this type of bifunctional organocatalysts do not self aggregate to any appreciable extent in solution.To examine the catalytic activity and enantioselectivity of 3 we first conducted desymmetrization of 3-OTBDPS glutaric anhydride 1a in presence of the catalysts (10 mol %) and MeOH (10 equiv) in THF. The results are depicted in Table 1, with the data obtained using the monomeric thiourea and † This paper is dedicated to Professor Eun Lee on the occasion of his honourable retirement.Scheme 1 Figure 1. Cinchona-based organocatalysts tested in our study (QN =...

Vetiveröl wird im Multitonnen‐Maßstab aus den Wurzeln des Vetivergrases gewonnen und ist einer der begehrtesten Duftbausteine der modernen Parfümerie. Das exquisite ätherische Öl, das sich in über einem Drittel aller Parfüms findet, ist eine komplexe Mischung aus Hunderten von unterschiedlichen Verbindungen, wobei das riechende Prinzip, das für den charakteristischen sanften und süßen, transparenten, holzig‐ambrierten Geruchscharakter verantwortlich ist, bis heute Rätsel aufgibt. Durch eine elfstufige chemische Synthese mit einer neuartigen asymmetrischen organokatalytischen Mukaiyama‐Michael‐Addition im Zentrum beweisen wir hier, dass (+)‐2‐epi‐Ziza‐6(13)en‐3‐on das riechende Prinzip des Vetiveröls ist. Seine olfaktorische Charakterisierung ergab einen außergewöhnlich tiefen Schwellenwert von 29 Pikogramm pro Liter Luft, der für die sinnliche Aura und die quasi‐pheromonartige Anziehung, die es auf Parfümeure wie Verbraucher gleichermaßen ausübt, verantwortlich ist.

In this account, we provide an overview of the recent achievements through our research programs focusing on sustainable organocatalysis. Our group have unveiled the effectiveness of specific organocatalysts in various environmentally benign conditions. We found that 1) N-heterocyclic carbene and 2) phosphazene superbases exhibit favorable performance in bulk aqueous reaction environments. In addition, 3) using organic superacid catalysts resulted in synergistic effects when hydrogen-bond donor catalysts were assembled under aqueous media. Moreover, we discovered that 4) a neutral organic salt precatalyst can generate a potent silylium Lewis acid catalyst in situ, specifically under solvent-free conditions. These innovative sustainable organocatalytic processes have successfully facilitated the conversion of raw starting materials into valuable compounds, including sulfur (VI) fluoride exchange (SuFEx) click hubs and tetrasubstituted carbon centers incorporating heteroatoms.

Duftstoffchemie In der Zuschrift auf S. 5728 stellen Philip Kraft, Benjamin List et al. eine kurze stereoselektive Totalsynthese von (+)‐2‐epi‐ziza‐6(13)en‐3‐on vor.