Structure‐Odor Correlation XVII. Synthesis and Olfactory Properties of further Theaspirane Analogs

Abstract

Alkylation of ethyl geranate (5) with the bromo esters 7 and 8 gave the P,y-unsaturated esters 10 and 11, which could be isomerized to 13 and 14 by treatment with DBU. The u,p-unsaturated esters 12 -14 were cyclized to 15-17, and subsequent reduction of 15 -17 led to the diols 18 -20. Final cyclization afforded the spiro ethers 2-4. -The olfactive properties (intensity and quality) of the theaspirane analogs 1 -4 are determined by the conformational flexibility of the respective molecule. Thus, the rigid 1 and 2 have strong camphoraceous odors. Augmenting flexibility (-3, -4) results in weaker, fruity-woody notes.Recently, we investigated the structure-odor correlation of various theaspirane analogs [']. We found that the odor of the theaspirane derivatives A-C in strength and quality is strongly dependent on the size of the heterocyclic ring. The odor intensity is rapidly decreasing from strong (A) to medium (B) and weak (C), and the quality varies from dominating camphoraceous with a herbaceous undertone (A) to camphoraceous-herbaceous green with a fruity undertone (B) and to floral-woody-fruity (C). We explained these results with the large difference of conformational flexibility of the heterocyclic four-, five-or six-membered ring. Since A -C possess both similar shapes and polarities, rigidity should be responsible for the strong camphoraceous-herbaceous odor, flexibility for the weak fruity-floral-woody tonality.This hypothesis should be supported by the synthesis and olfactory evaluation of the analogs 1-4. The odor of the rigid molecules 1 and 2 should be similar to that of A, and the increasing flexiblity of 3 and 4 should be expressed by an olfactory similarity to B and C. In other words, our Scheme 1. The atom numbering in the schemes is used for comparison purposes of the NMR data in Tables 1 -3 and does The alkylation of 5 with the halo esters 6-8 in THF in the presence of LDA/HMPT leads primarily to the P,y-diesters 9-11 in moderate (9, 11) to very good (10) yield. The

Design, Synthesis and Olfactory Properties of 2-Substituted 2-tert-Butyl-5-­methyl-2,5-dihydrofurans: seco-Derivatives of Theaspiranes

“…As detailed in Scheme 1, the synthesis of the parent secotheaspiranes 7 and 8 followed the general route developed by Weyerstahl et al [8][9][10] employing the alkyne Grignard reagent 14, which was prepared by reaction of but-3-yn-2ol with two equivalents of ethylmagnesium bromide. Reaction of 14 with 2,2-dimethylhexan-3-one (13) afforded the crude alkyne diol 15 in 90% yield, sufficiently pure for further transformations.…”

“…It emanates a fresh, fruity odor with a strong blackcurrant impact and an additional camphoraceous tonality. Despite extensive research in this family, [6][7][8][9][10] no seco-structures have yet been prepared. From the spiro-systems studied, it was only known that a 2-Me group was crucial, 7,8 and that a C 3 =C 4 double-bond could intensify the blackcurrant odor.…”

Structure−Odor Relationships

“…In 1992, Weyerstahl discovered that the macrocyclic spiroethers ( 115a − c , Figure ) possess a dominating woody character reminiscent of cedar, while the corresponding saturated compounds still smell woody, but are relatively weak. Further investigations into the structure−activity relationships of spiroethers revealed that the size of the heterocyclic ring has a strong influence on the odor of the theaspirane derivatives ( 116 − 118 , Figure ) . The odor intensity rapidly decreases from strong ( 116 ) to medium ( 117 ) and weak ( 118 ), and the quality varies from dominating camphoraceous ( 116 ) to camphoraceous-herbaceous green ( 117 ) to floral-woody and fruity ( 118 ).…”

“…Further investigations into the structure-activity relationships of spiroethers revealed that the size of the heterocyclic ring has a strong influence on the odor of the theaspirane derivatives (116-118, Figure 59). 223 The odor intensity rapidly decreases from strong (116) to medium (117) and weak (118), and the quality varies from dominating camphoraceous (116) to camphoraceous-herbaceous green (117) to floral-woody and fruity (118).…”

Odor and Structure

“…If the conformational flexibility is in the fact the determining factor for the either strong, camphoraceous or weak, fruity, floral character, then these alterations should be more or less independent on the position of the oxygen in the heterocyclic ring. Therefore, we synthesized compounds 49-51, and we found that also in the series 49 + 50 + 51 the odor strength decreases drastically, and that the tonality proceeds also from camphoraceous to fruity [62]. 43 Several furans such as rose luran (63) and naginata ketone (64) are important constituents of essential oils.…”