Biomimetic Synthesis of Nor-Cedrene and Nor-Isozizaene Sesquiterpenoids and Exploration of Their Olfactive Properties.

We report the preparation of nor-bisabolyl epoxide 13 and its use as a common biomimetic intermediate for the synthesis of nor-sesquiterpenoids. Through a cationic cyclization cascade pathway, we prepared nor-isozizaenol 25, ultimately constituting an eight-step access to this complex sesquiterpenoid from inexpensive and abundant starting materials. Using a radical cyclization cascade pathway, we prepared nor-cedryl alcohol 26 from the same intermediate. Derivatization of these two products led to the discovery of two potent woody odorants of interest in perfumery.

What's Hot, What's Not: The Trends of the Past 20 Years in the Chemistry of Odorants.

This review is the sequel to the 2000 report on the recent advances in the chemistry of odorants and it summarizes the developments in fragrance chemistry over the past 20 years. Following the olfactory spectrum set out in that report, trendsetting so-called captive odorants (patent-protected ingredients unavailable to the market) are presented according to the main odor families: "fruity", "marine", "green", "floral", "spicy", "woody", "amber", and "musky". The design of odorants, their chemical synthesis, and their use in modern perfumery are illustrated with prominent examples. Featured are new fruity odorants that provide signature in the top note, as well as precursor technology. In the green domain, focus is on leafy notes and green pear. New benzodioxepines and benzodioxoles have modernized the marine family and required a revision of the existing olfactophore models. The replacement of Lilial and Lyral kept the industry busy in the floral domain with a plethora of new "muguets". There was continued activity in the domain of rose odorants, especially in the area of rose ketones. Biotechnology became significant, for example, with Clearwood and Ambrofix, and the principal odorants of vetiver oil in the woody family have been found. Fourth and fifth families of musk odorants were also discovered and populated. Thus, new avenues for further explorations into fragrance chemistry have been opened.

An eight-step synthesis of epicolactone reveals its biosynthetic origin.

Epicolactone is a recently isolated fungal metabolite that is highly complex for its size, and yet racemic. With its array of quaternary stereocentres, high degree of functionalization and intricate polycyclic structure, it poses a considerable challenge to synthesis, a challenge that can be met by understanding its biosynthetic origin. If drawn in a certain way, epicolactone reveals a pattern that resembles purpurogallin, the archetype of ubiquitous natural colourants formed via oxidative dimerization. Based on this insight, we designed a biomimetic synthesis of epicolactone that proceeds in only eight steps from vanillyl alcohol. We have isolated a key intermediate that supports our biosynthetic hypothesis and anticipate that an isomer of epicolactone stemming from our synthetic efforts could also be found as a natural product.

Biomimetic synthesis of the calcineurin phosphatase inhibitor dibefurin.

Dibefurin is a Ci -symmetric natural product that acts as an inhibitor of calcineurin phosphatase. A six-step synthesis of this compound is reported, which features an oxidative dimerization of the aromatic polyketide epicoccine as the key step. Dibefurin is proposed to be related to epicolactone, a complex yet racemic fungal metabolite that has recently been discovered. Attempts to access epicolactone from epicoccine and epicoccone B resulted in an unusual dimer that is formed through a hetero-Diels-Alder reaction of a para-quinone methide with an ortho-quinone.

Autotandem catalysis with ruthenium: remote hydroesterification of allylic amides.

A one-pot tandem sequence involving olefin isomerization and hydroesterification has been developed that enables the incorporation of a C1-unit at the remote terminal position of allylic amides. Key observations suggest that generation of an active ruthenium hydride, formed by addition of acetic acid, allows both processes to take place under mild conditions in an autotandem catalytic, cascading fashion, which is characterized by the use of a single catalytic entity capable of promoting multiple distinct steps without operator intervention.

Ruthenium-catalyzed intramolecular hydrocarbamoylation of allylic formamides: convenient access to chiral pyrrolidones.

An attractive strategy for the synthesis of saturated nitrogen-containing heterocycles is described herein, involving the implementation of ruthenium-catalyzed intramolecular hydrocarbamoylation of olefins. The process proceeds by formal C-H bond cleavage of an allylic formamide followed by construction of a new C-C bond in a reaction that is characterized by complete atom-economy. The method is particularly valuable in conjunction with the numerous efficient strategies available for the preparation of optically active allylic formamides.

Mild electrophilic trifluoromethylation of secondary and primary aryl- and alkylphosphines using hypervalent iodine(iii)-CF(3) reagents.

A direct, mild and efficient trifluoromethylation of primary and secondary phosphines is achieved with easily accessible, cheap hypervalent iodine compounds acting as electrophilic CF(3)-transfer reagents.