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Catalysis Science & Technology
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This lack of reactivity could be attributed to conformational
constraints that disfavour the cyclisation.36 The formation of
macrocyclic ketones was next studied. The well-known and
highly desirable civetone and dihydro-civetone fragrances37 9b
and 10d were isolated in pure form with moderate 52% yields.38
A similar moderate 55% yield was observed with the civetone
analog 9c39 featuring an eighteen-membered ring. Finally, our
methodology was also successful in the formation of
macrocyclic carbonate 9d40 and macrolactam 10e41 which were
isolated with 56 and 67% yields respectively in >99% purity.
Angew. Chem. Int. Ed. 2007, 46, 6786.
For recent reviews or book chapterDsOdI:e1a0l.i1n0g39/wCi8tChY0o2l1e1f5inE
metathesis macrocyclization, see: a) F. Grisi, C. Costabile, A.
Grimaldi, C. Viscardi, C. Saturnino and P. Longo, Eur. J. Org.
Chem. 2012, 2012, 5928; b) A. Gradillas and J. Perez-Castells
in Metathesis in Natural Product Synthesis (Eds.: J. Cossy, S.
Arseniyadis, C. Meyer), Wiley-VCH, Weinheim, 2010, p. 149;
c) H. Hagiwara, T. Nakamura, N. Okunaka, T. Hoshi and T.
Suzuki, Helv. Chim. Acta 2010, 93, 175.
a) For instance, see: A. Fürstner and K. Langemann, J. Am.
Chem. Soc. 1997, 119, 9130; b) For instance, see: A. Fürstner
and G. Seidel, J. Organomet. Chem. 2000, 606, 75.
For instance, see: A. Michrowska, P. Wawrzyniak and K. Grela,
Eur. J. Org. Chem. 2004, 2004, 2053.
Selected reviews on macrocyclic musks: a) A. S. Williams,
Synthesis 1999, 1707; b) P. Kraft, J. A. Bajgrowicz, C. Denis and
G. Frater, Angew. Chem. Int. Ed. 2000, 39, 2980; For
toxicological studies on macrocyclic lactones and ketones,
see: c) D. Belsito, D. Bickers, M. Bruze, P. Calow, M. L. Dagli, A.
D. Fryer, H. Greim, Y. Miyachi, J. H. Saura and I. G. Sipes, Food
and Chemical Toxicology 2011, 49, S219; d) D. Belsito, D.
Bickers, M. Bruze, P. Calow, M. L. Dagli, A. D. Fryer, H. Greim,
Y. Miyachi, J. H. Saura and I. G. Sipes, Food and Chemical
Toxicology 2011, 49, S126.
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Conclusions
To conclude, we developed
a set of new ruthenium-
indenylidene complexes bearing two unsymmetrical unsaturated
NHC ligands with a N-cycloalkyl moiety. These low-cost
catalysts42 proved to be highly selective in the macrocyclic ring-
closing metathesis reactions performed in ethylacetate solvent
at low dilution (0.01M) without the requirement of
benzoquinone derivatives to prevent the isomerisation side
reactions. This unprecedented environmentally friendly
catalytic process enabled the synthesis of various macrocyclic
odorant molecules, which were achieved with a remarkable
>99% purity and good isolated yields (up to 78%). As the
isomerization of terminal olefins remains a major obstacle to
numerous industrial applications of olefin metathesis, this
highly selective technology pave the way to a prosperous
future.
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D. McGinty, C. S. Letizia and A. M. Api, Food and Chemical
Toxicology 2011, 49, S207.
D. McGinty, C. S. Letizia and A. M. Api, Food and Chemical
Toxicology 2011, 49, S193.
10 D. McGinty, C. S. Letizia and A. M. Api, Food and Chemical
Toxicology 2011, 49, S152.
11 D. McGinty, C. S. Letizia and A. M. Api, Food and Chemical
Toxicology 2011, 49, S120.
12 a) S. Hübner, J. G. de Vries and V. Farina, Adv. Synth. Catal.
2016, 358, 3; For a seminal review on olefin metathesis at
industrial scale, see b) C. S. Higman, J. A. M. Lummiss and D.
E. Fogg, Angew. Chem. Int. Ed. 2016, 55, 3552.
13 a) T. M. Trnka, J. P. Morgan, M. S. Sanford, T. E. Wilhem, M.
Scholl, T.-L. Choi, S. Ding, M. W. Day and R. H. Grubbs, J. Am.
Chem. Soc. 2003, 125, 2546; b) M. B. Dinger, J. C. Mol, Eur. J.
Inorg. Chem. 2003, 2003, 2827; c) S. H. Hong, M. W. Day and
R. H. Grubbs, J. Am. Chem. Soc. 2004, 126, 7414; d) B. Schmidt,
J. Mol. Catal. A: Chem. 2006, 254, 53; e) N. J. Beach, K. D.
Camm and D. E. Fogg, Organometallics 2010, 29, 5450; f) N. J.
Beach, J. A. M. Lummins, J. M. Bates and D. E. Fogg,
Organometallics 2012, 31, 2349 ; g) S. Manzini, D. J. Nelson, T.
Lebl, A. Poater, L. Cavallo, A. M. Z. Slawin and S. P. Nolan,
Chem. Commun. 2014, 50, 2205; for mechanistic studies, see:
h) I. W. Ashworth, I. H. Hillier, D. J. Nelson, J. M. Percy and M.
A. Vincent, Eur. J. Org. Chem. 2012, 2012, 5673.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This work was supported by the Association Nationale de la
Recherche et de la Technologie and DEMETA company (grant to
A.D.; CIFRE N°2014/0702), the Région Bretagne (AAP-IMA-
2105-15006528-BIOFRAGRANCES; grant to G.F.) and the FASO
(grant to IC; Z-SELECT). SCR, OB and MM acknowledge the Ecole
Nationale Supérieure de Chimie de Rennes (ENSCR) and the
Centre National de la Recherche Scientifique (CNRS) for
financial supports. Umicore AG & Co is acknowledged for a
generous gift of M and M ruthenium complexes.
14 a) A. Fürsner, O. R. Thiel, L. Ackermann, H.-J. Schanz and S. P.
Nolan, J. Org. Chem. 2000, 65, 2204; b) D. Bourgeois, A.
Pancrazi, S. P. Nolan and J. Prunet, J. Organomet. Chem. 2002,
643-644, 242.
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15 a) For the pioneer use of benzoquinones, acids or oxidants to
prevent isomerisation during Olefin Metathesis, see: S. H.
Hong, D. P. Sanders, C. W. Lee and R. H. Grubbs, J. Am. Chem.
Soc. 2005, 127, 17160; For acidic treatments, see also: b) N.
Gimeno, P. Formentin, J. H. G. Steinke and R. Vilar, Eur. J. Org.
Chem. 2007, 2007, 918.
16 For macrocyclic-RCM involving low catalyst loading, see: a) C.
Shu, X. Zeng, M.-H. Hao, X. Wei, N. K. Yee, C. A. Busacca, Z.
Han, V. Farina and C. H. Senanayake, Org. Lett. 2008, 10, 1303;
b) R. Kadyrov, Chem. Eur. J. 2013, 19, 1002; c) R. Gawin, A.
Tracz, M. Chwalba, A. Kozakiewicz, B. Trzaskowski, K.
Skowerski, ACS Catal. 2017, 7, 5443.
Notes and references
1
Selected comprehensive books and reviews on olefin
metathesis: a) R. H. Grubbs, A. G. Wenzel, D. J. O’Leary, E.
Khosravi, (Eds.) Handbook of Metathesis, 2nd Edition; Wiley-
VCH: Weinheim, Germany, 2015; b) K. Grela (Ed.), Olefin
Metathesis: Theory and Pratice, Wiley-VCH: Weinheim,
Germany, 2014; c) G. C. Vougioukalakis and R. H. Grubbs,
Chem. Rev. 2010, 110, 1746.
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a) A. Parenty, X. Moreau, G. Niel and J.-M. Campagne, Chem.
Rev. 2006, 106, 911; b) A. Parenty, X. Moreau, G. Niel and J.-
M. Campagne, Chem. Rev. 2013, 113, PR1.
17 a) M. Jordaan, P. van Helden, C. van Sittert and H. C. M.
Vosloo, J. Mol. Catal. A: Chem. 2006, 254, 145 ; see also : B. J.
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