Abstract
The double-unsaturated macrocyclic lactones (4E ,8Z )-12-methyloxacyclotetradeca-4,8-dien-2-one and its 7a-homologue (4E ,9Z )-13-methyloxacyclopentadeca-4,9-dien-2-one, designed as new potent musk odorants
by molecular modeling, were synthesized by ring-closing alkyne metathesis in the presence
of 10 mol% of Schrock’s alkylidyne catalyst, and subsequent Lindlar hydrogenation.
Demethylation of citronellol, induced by nitrous acid, afforded the 3-methyloct-6-yn-1-ol
building block. The substrates for the alkyne metathesis were prepared by Steglich
esterification of citronellol with the 3E -configured non-3-en-7-ynoic and dec-3-en-8-ynoic acids, accessible by β,γ-selective
Knoevenagel condensation from the corresponding alkynals hept-5-ynal and oct-6-ynal,
which were synthesized by Eschenmoser-Ohloff fragmentation of the epoxide of 2-methylcyclohex-2-enone,
and methylation of hex-5-yn-1-ol, respectively. Both target structures, (4E ,8Z )-12-methyloxacyclotetradeca-4,8-dien-2-one and its 7a-homologue, emanated most pleasant
and powerful musk odors.
Key words
odorants - macrocycles - metathesis - musks - ring closure
References <A NAME="RT15807SS-1">1 </A>
This work was carried out during a six-month research practical at the Givaudan Schweiz
AG, Fragrance Research. New address: Lehrstuhl für Organische Chemie I, Technische
Universität München, Lichtenbergstraße 4, 85747 Garching, Germany.
<A NAME="RT15807SS-2">2 </A>
Kraft P. In
Chemistry and Technology of Flavors and Fragrances
Rowe DJ.
Blackwell;
Oxford:
2005.
p.143
<A NAME="RT15807SS-3">3 </A>
Voloshina E.
Fleischhauer J.
Kraft P.
Helv. Chim. Acta
2005,
88:
194
<A NAME="RT15807SS-4">4 </A>
Fehr C.
Galindo J.
Etter O.
Eur. J. Org. Chem.
2004,
1953
<A NAME="RT15807SS-5">5 </A>
Kraft P. In
Perspectives in Flavor and Fragrance Research
Kraft P.
Swift KAD.
Wiley-VCH;
Weinheim:
2005.
p.127
<A NAME="RT15807SS-6">6 </A>
Tochtermann W.
Kraft P.
Synlett
1996,
1029
<A NAME="RT15807SS-7">7 </A>
Bunte G.
PhD Thesis
Christian-Albrechts-Universität;
Kiel Germany:
1996.
<A NAME="RT15807SS-8">8 </A>
Fehr C.
Galindo J.
Etter O.
Thommen W.
Angew. Chem. Int. Ed.
2002,
41:
4523 ; Angew. Chem. 2002 , 114 , 4705
<A NAME="RT15807SS-9">9 </A>
Dale J.
Acta Chem. Scand.
1973,
27:
1115
<A NAME="RT15807SS-10">10 </A>
Fürstner A.
Seidel G.
J. Organomet. Chem.
2000,
606:
75
<A NAME="RT15807SS-11">11 </A>
Lacombe F.
Radkowski K.
Seidel G.
Fürstner A.
Tetrahedron
2004,
60:
7315
12a </A>
Fürstner A.
Turet L.
Angew. Chem. Int. Ed.
2005,
44:
3462 ; Angew. Chem. 2005 , 117 , 3528
12b </A>
Fürstner A.
De Souza D.
Turet L.
Fenster MDB.
Parra-Rapado L.
Wirtz C.
Mynott R.
Lehmann CW.
Chem. Eur. J.
2007,
13:
115
<A NAME="RT15807SS-13">13 </A>
Fürstner A.
Larionov O.
Flügge S.
Angew. Chem. Int. Ed.
2007,
46:
5545 ; Angew. Chem. 2007 , 119 , 5641
<A NAME="RT15807SS-14">14 </A>
Ghalit N.
Poot AJ.
Fürstner A.
Rijkers DTS.
Liskamp RMJ.
Org. Lett.
2005,
7:
2961
<A NAME="RT15807SS-15">15 </A>
Fürstner A.
Guth O.
Rumbo A.
Seidel G.
J. Am. Chem. Soc.
1999,
121:
11108
<A NAME="RT15807SS-16">16 </A>
Fürstner A.
Mathes C.
Grela K.
Chem. Commun.
2001,
1057
<A NAME="RT15807SS-17">17 </A>
Fürstner A.
Grela K.
Angew. Chem. Int. Ed.
2000,
39:
1234 ; Angew. Chem. 2000 , 112 , 1292
<A NAME="RT15807SS-18">18 </A>
Fürstner A.
Grela K.
Mathes C.
Lehmann CW.
J. Am. Chem. Soc.
2000,
122:
11799
<A NAME="RT15807SS-19">19 </A>
Fürstner A.
Davies PW.
Chem. Commun.
2005,
2307
<A NAME="RT15807SS-20">20 </A>
Hansen EC.
Lee D.
J. Am. Chem. Soc.
2004,
126:
15074 ; and references cited therein
<A NAME="RT15807SS-21">21 </A>
Ragoussis N.
Ragoussis V.
J. Chem. Soc., Perkin Trans. 1
1998,
3529
22a </A>
Weitz E.
Scheffer A.
Ber. Dtsch. Chem. Ges.
1919,
54:
2327
22b </A>
Bailey M.
Staton I.
Ashton PR.
Markó IE.
Ollis WD.
Tetrahedron: Asymmetry
1991,
2:
495
<A NAME="RT15807SS-23">23 </A>
Corey EJ.
Sachdev HS.
J. Org. Chem.
1975,
40:
579
<A NAME="RT15807SS-24">24 </A>
Eschenmoser A.
Felix D.
Ohloff G.
Helv. Chim. Acta
1967,
50:
708
<A NAME="RT15807SS-25">25 </A>
Fürstner A.
Albert M.
Mlynarski J.
Matheu M.
DeClercq E.
J. Am. Chem. Soc.
2003,
125:
13132
<A NAME="RT15807SS-26">26 </A>
Hart H.
Chen B.
Jeffares M.
J. Org. Chem.
1979,
44:
2722
27a </A>
Yan J.
Zhu J.
Matasi JJ.
Herndon JW.
J. Org. Chem.
1990,
55:
786
27b </A>
Matasi JJ.
PhD Thesis
University of Maryland;
USA:
1998.
<A NAME="RT15807SS-28">28 </A>
Quéron E.
Lett R.
Tetrahedron Lett.
2004,
45:
4527
<A NAME="RT15807SS-29">29 </A>
Coutelier O.
Mortreux A.
Adv. Synth. Catal.
2006,
348:
2038
30a </A>
Abidi SL.
Tetrahedron Lett.
1986,
27:
267
30b </A>
Abidi SL.
J. Org. Chem.
1986,
51:
2687
30c </A>
Abidi SL.
J. Chem. Soc., Chem. Commun.
1985,
1222
<A NAME="RT15807SS-31">31 </A>
Corey EJ.
Seibel WL.
Kappos JC.
Tetrahedron Lett.
1987,
28:
4921
<A NAME="RT15807SS-32">32 </A>
Boivin J.
Pillot E.
Williams A.
Roger W.
Zard SZ.
Tetrahedron Lett.
1995,
36:
3333
<A NAME="RT15807SS-33">33 </A>
Neiss B.
Steglich W.
Angew. Chem., Int. Ed. Engl.
1978,
17:
522 ; Angew. Chem., 1978 , 90 , 556
34a </A>
Wengrovius JH.
Sancho J.
Schrock RR.
J. Am. Chem. Soc.
1981,
103:
3932
34b </A>
Schrock RR.
Clark DN.
Sancho J.
Wengrovius JH.
Rocklage SM.
Pedersen SF.
Organometallics
1982,
1:
1645
<A NAME="RT15807SS-35">35 </A>
Fürstner A.
Seidel G.
Angew. Chem. Int. Ed.
1998,
37:
1734 ; Angew. Chem. 1998 , 110 , 1758
36a </A>
Kitamura T.
Mori M.
Org. Lett.
2001,
3:
1161
36b </A>
Mori M.
Sakakibara N.
Kinoshita A.
J. Org. Chem.
1998,
63:
6082
<A NAME="RT15807SS-37">37 </A>
Mortreux A.
Coutelier O.
J. Mol. Catal.
2006,
254:
96
<A NAME="RT15807SS-38">38 </A>
Cram DJ.
Allinger NL.
J. Am. Chem. Soc.
1956,
78:
2518
