Sniffing Out the Sustainable Future: The Renewability Revolution in Fragrance Chemistry.

In this review, the impact of the transition from today's resource-wasting petrochemical economy towards a 100/100 renewable and biodegradable future is discussed with respect to the fragrance families: "citrus", "green", "fruity", "floral", "floriental", "oriental", "woody", "chypre" and "fougère". After benchmark data on ingredients usage, definitions on biodegradation and sustainability are given. Celebrating the 150 anniversary of synthetic vanillin, its historic synthesis from renewable starting materials serves as introduction.

The Smelling Principle of Vetiver Oil, Unveiled by Chemical Synthesis.

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.

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.

The Serendipitous Discovery of a Rose Odorant.

Serendipity has played a role in many groundbreaking scientific discoveries. Key to their identification and exploitation is the ability to recognize the unexpected and invest time trying to understand it. Like any other field of scientific research, total synthesis requires determination and perseverance.

Evidence for a shape-based recognition of odorants in vivo in the human nose from an analysis of the molecular mechanism of lily-of-the-valley odorants detection in the Lilial and Bourgeonal family using the C/Si/Ge/Sn switch strategy.

We performed an analysis of possible mechanisms of ligand recognition in the human nose. The analysis is based on in vivo odor threshold determination and in vitro Ca2+ imaging assays with a C/Si/Ge/Sn switch strategy applied to the compounds Lilial and Bourgeonal, to differentiate between different molecular mechanisms of odorant detection. Our results suggest that odorant detection under threshold conditions is mainly based on the molecular shape, i.

Synthesis and Olfactory Properties of a 6'-Silasubstituted "Spiro[4.5]-δ-Damascone".

The silicon analogue of the potent spirocyclic δ-damascone odorant 6 was synthesized from allyltrichlorosilane (15) and but-2-en-1-ol (16). The latter was transformed to 3-methylpen-4-enenitrile (11) by Saucy-Marbet reaction with ethoxyethane and subsequent treatment with HONH ⋅HCl. The resulting γ,δ-unsaturated nitrile 11 was silylated with 1-allyl-1-chlorosilolane (14), which was prepared from allyltrichlorosilane (15) and the bis-Grignard reagent of 1,4-dichlorobutane.

Design and enantioselective synthesis of Cashmeran odorants by using "enol catalysis".

Novel Cashmeran odorants were designed by molecular modeling. Their short syntheses involve a novel asymmetric Brønsted acid catalyzed Michael addition of unactivated α-substituted ketones. This key transformation was realized by utilizing a new type of enol activation catalysis and affords different cyclic ketones bearing α-quaternary stereocenters in good to excellent yields and with high enantioselectivity.

Synthesis and olfactory characterization of silicon-containing derivatives of the acyclic lily-of-the-valley odorant 5,7,7-trimethyl-4-methylideneoctanal.

5-Methyl-4-methylidene-6-(trimethylsilyl)hexanal (1b), a sila analog of the acyclic lily-of-the-valley odorant 5,7,7-trimethyl-4-methylideneoctanal (1a), and the Si-containing derivatives 2-6 were prepared in multistep syntheses, starting from Cl3 SiH and Cl2 SiMe2 , respectively. Compounds 1b, 2-6, and their new precursors were characterized by elemental analyses (C, H, N) and NMR spectroscopic studies ((1) H, (13) C, (15) N, and (29) Si). To gain more information about the structureodor correlation in the family of lily-of-the-valley or 'muguet' odorants, C/Si analogs 1a/1b and derivatives 2-6 were evaluated for their olfactory properties.

A novel oxy-oxonia(azonia)-cope reaction: serendipitous discovery and its application to the synthesis of macrocyclic musks.

This brief review, including new experimental results, is the summary of a talk at the GDCh conference 'flavors & fragrances 2013' in Leipzig, Germany, 11th-13th September, 2013. Musk odorants are indispensable in perfumery to lend sensuality to fine fragrances, a nourishing effect to cosmetics, and a comforting feeling to laundry. We have recently found serendipitously a new oxy-oxonia-Cope rearrangement.

Synthesis by ring-closing alkyne metathesis with selective hydrogenation, and olfactory comparison of (7E)- and (7Z)-cyclohexadec-7-enone (Aurelione(®) ).

Both C=C-bond isomers of cyclohexadec-7-enone (6, Aurelione(®) ) were selectively synthesized via cyclohexadec-7-ynol (16) by ring-closing alkyne metathesis of icosa-2,18-diyn-9-ol (15), employing an in situ-formed catalyst from Mo(CO)6 and 4-(trifluoromethyl)phenol. Pyridinium chlorochromate (PCC) oxidation and subsequent Lindlar hydrogenation afforded the (7Z)-configured isomer (7Z)-6, while hydrosilylation of the intermediate cyclohexadec-7-ynone (17), followed by desilylation, provided the (7E)-configured cyclohexadec-7-enone ((7E)-6). The substrate for the alkyne metathesis was prepared from cycloheptanone (7) by cycloaddition of chloromethylcarbene to its trimethylsilyl enol ether 8, and subsequent ring enlargement of the adduct 9 under rearrangement to 2-methylcyclooct-2-enone (10), which was subjected to Weitz-Scheffer epoxidation and Eschenmoser-Ohloff fragmentation to non-7-ynal (12).

From Cassyrane to cashmeran - the molecular parameters of odorants.

This review, including some new experimental results, is the summary of a talk at the 'flavors & fragrances 2013' conference in Leipzig, organized jointly by the GDCh, the Liebig-Vereinigung, and the EuCheMS. After times of searching for natural odor principles and serendipitous discoveries by chemical inspiration, directed odorant design today offers the highest hit rates for the discovery of new odorants, although serendipity still plays a role. Keeping intact the electronic shape required for a certain olfactophore-binding geometry, one can add or subtract structural elements, rigidify molecular structures, or introduce more structural flexibility.

Disila-galaxolide and derivatives: synthesis and olfactory characterization of silicon-containing derivatives of the musk odorant galaxolide.

A series of silicon-containing derivatives of the polycyclic musk odorant galaxolide (4 a) was synthesized, that is, disila-galaxolide ((4RS,7SR)-4 b/(4RS,7RS)-4 b), its methylene derivative rac-9, and its nor analogue rac-10. The tricyclic title compounds with their 7,8-dihydro-6,8-disila-6 H-cyclopenta[g]isochromane skeleton were prepared in multistep syntheses by using a cobalt-catalyzed [2+2+2] cycloaddition of the mono- yne H2C=CHCH2 OCH2 C≡CB(pin) (B(pin)=4,4,5,5-tetramethyl-1,3,2-di- oxaborolan-2-yl) with the diynes H2C=C[Si(CH3 )2 C≡CH]2 or H2C- [Si(CH3)2 C≡CH]2 as the key step. Employing [Cr(CO)3 (MeCN)3 ] as an auxiliary, the disila-galaxolide diastereomers (4RS,7SR)-4 b and (4RS,7RS)-4 b could be chromatographically separated through their tricarbonylchromium(0) complexes, followed by oxidative decomplexation.

Novel silicon-based patchouli odorants of the trialkyl(1-hydroxy-1-methylethyl)silane type: design, synthesis, and olfactory properties.

tert-Butyl(1-hydroxy-1-methylethyl)dimethylsilane (5), a sila-substituted seco derivative of the recently reported patchouli lead structure (4aR*,8aR*)-1,1,8a-trimethyldecahydronaphthalene-4a-ol (4), and a number of related trialkyl(1-hydroxy-1-methylethyl)silanes and further derivatives, compounds 8-24, with different silicon-bound substituents (Me, Et, iPr, cPr, tBu, iBu, cPent, vinyl, SiMe(3)) were synthesized and studied for their olfactory properties. All of the silanes studied exhibit at least one of the main patchouli odor descriptors 'woody,' 'earthy,' and 'camphoraceous,' and some even exhibit all of them. The silanes MeR(2)SiC(OH)Me(2) (12) and R(3)SiC(OH)Me(2) (14) (R=cyclopropyl) were found to resemble natural patchouli oil most closely, with an even lower odor threshold than the natural lead structure (-)-patchoulol (1).

Woody pretzels: spirocycles from vetiver to patchouli and Georgywood.

This review, including new experimental results, is the summary of a talk at the RSC/SCI conference 'flavours & fragrances 2007' in London, Imperial College, 24-26 September, 2007. Though the third dimension of the receptor models of J. E.

Disila-okoumal: a silicon analogue of the ambergris odorant okoumal.

Two-fold sila-substitution (C/Si exchange) in the saturated ring of the tetrahydronaphthalene skeleton of the ambery odorant okoumal (5) provides disila-okoumal (6). The okoumal isomers 5 a-d were synthesized from 1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)ethanone (7), and the silicon analogues 6 a-d were synthesized from 1-(5,5,8,8-tetramethyl-5,8-disila-5,6,7,8-tetrahydro-2-naphthyl)ethanone (8). Detailed olfactory properties of 5 a-d and 6 a-d are reported, together with the respective threshold values.

'Brain aided' musk design.

This brief review, including new experimental results, is the summary of a talk at the RSC/SCI conference flavours & fragrances 2004 in Manchester, United Kingdom, 12-14 May, 2004. Musk odorants have been a classical domain for computer aided structure-odor relationship (SOR) studies, but, contrary to sandalwood or amber odorants, they belong to structurally very different substance classes, e.g.