The purpose of this paper is to give an overview of our intense synthetic efforts that have been expended in the quest for novel fragrance ingredients. Carbon-carbon bond formation is at the heart of organic synthesis. Several examples will be presented, which will highlight the utility of diverse synthetic reactions such as Diels-Alder, Mannich, ene reactions, etc. that have been used to uncover highly desirable aroma chemicals (Iso E Super, Lyral, Triplal [or Aldehyde AA], Isocyclocitral and so forth; F-1). Some recent synthetic work will illustrate how these powerful reactions provide substrates that can be elaborated into novel polycyclic structures with interesting odor profi les. In the course of this research investigation, three new proprietary fragrance molecules were discovered and commercialized: Cassiffi x, a fresh herbal, long-lasting cassis note; Prismantol, a woody, spicy, ginger, cardamom note; and Prismylate, a woody, amber, vetivert odorant. These are presented in F-2.
Background Research in Pursuit of Cassiffix
The Diels-Alder reaction was discovered in 1928 while Kurt Alder was working with Otto Diels. They showed that when butadiene, a diene, is allowed to react with acrolein, a dienophile, under thermal conditions, it produces a (4 + 2) cycloaddition product — 3-cyclohexene carboxaldehyde (F-3) — in high yields, thus offering a simple way to prepare cyclic structures. This reaction played a crucial role in the synthesis of reserpine, morphine and cantharedine, to name a few. Since its discovery, the Diels-Alder reaction has been used in the synthesis of numerous complex natural products. In fact, the Nobel Prize in chemistry was awarded to Kurt Alder and Otto Diels in 1950 because of the enormous utility of their discovery.
Diels–Alder Adducts as Templates
As stated above, the Diels-Alder adducts were employed as templates for further elaboration into new chemicals. This can be achieved easily by fi rst reducing these adducts with an appropriate reducing agent, such as sodium borohydride, followed by cyclization with an acid to furnish a cyclic ether. A series of novel cyclic ethers were prepared for odor evaluation. F-4 also shows how these adducts can be used to prepare new structures by functional group transformation.