Synthesis and Olfactory Properties of a 6′‐Silasubstituted “Spiro[4.5]‐δ‐Damascone”

Abstract

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. Metathetic ring closure employing the Grubbs I catalyst, followed by DIBAL reduction with non-aqueous work up, Grignard reaction with prop-1-en-1-ylmagnesium bromide, and Attenburrow MnO oxidation concluded the synthesis. The target compound was found to be olfactorily related to the spiro[4.5]-δ-damascone lead, but approximately 900 times weaker. In a type of enol Brook rearrangement, it thermally decomposes however to 3,6-dihydro-2H-1,2-oxasilocine (20), which surprisingly is a damascone odorant as well; although, 12 000 times weaker.

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“…[78] Interestingly,t he two hydrophobes of the initial model correspond almost exactly to hydrophobe Ia nd II of the revised model in Figure 13. Thethird hydrophobe is partially cancelled out by an excluded volume but points in the direction of the "magic methyl" group of Nympheal (102). Thed istances to the hydrogen-bond acceptor are 6.3 (hydrophobe I), 10.5 (hydrophobe II), and 5.7 (hydrophobe III), respectively.O utside the excluded volumes, substituents blocking oxidative enzymatic degradation can be placed and the "magic methyl" of Nympheal (102)i s situated in such ap osition ( Figure 13).…”

“…Interestingly,t his compound had only aquite weak, fruity,rosy odor,about 900 times inferior to that of 120.I tw as also unstable and the silaspiro [4.5] system in 121 underwent facile Brook rearrangement into as ilaspiro [4,7]cycle. [102] Recently,t he a'methyl derivative 122 offering an intense floral, dried fruit note was described. [103] Them ethyl group efficiently reduces the restrictive skin sensitization potential of the damascones by significantly lowering the peptide reactivity.…”

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“…Beyond a few exceptional examples on small rings (damascone and galbanone derivatives) [586,587], the RCM has found more application in the synthesis of macrocyclic musky odorants.…”

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“…[78] Interessanterweise entsprechen die beiden hydrophoben Sphären des ursprünglichen Modells beinahe haargenau den hydrophoben Bindungsstellen Iu nd II des revidierten Modells in Abbildung 13. Das dritte Hydrophob wird durch ein Ausschluss-Volumen teilweise aufgehoben, zeigt aber in Richtung der "magischen Methylgruppe" von Nympheal (102). Die Abstände zum Wasserstoffbrückenakzeptor betragen 6.3 (Hydrophob I), 10.5 (Hydrophob II) bzw.…”

“…Zudem war die Verbindung instabil, und das Silaspiro [4,5]-System in 121 durchlief rasch eine Brook-Umlagerung zum Silaspiro [4,7]-Cyclus. [102] Kürzlich wurde das a'-Methylderivat 122 gefunden, das eine intensive blumige und an Tr ockenfrüchte erinnernde Note zeigte. [103] Die Methylgruppe vermindert das Hautsensibilisierungspotential der Damascone deutlich, indem sie die Peptidreaktivitäts ignifikant herabsetzt.…”