A Practical, Enantioselective Synthesis of the Fragrances Canthoxal and Silvial^®, and Evaluation of Their Olfactory Activity

Abstract

The fragrances (S)-(+)- and (R)-(–)-canthoxal [(S)-(+)- and (R)-(–)-3-(4-methoxyphenyl)-2-methylpropanal] and (+)- and (–)-Silvial^® [(+)- and (–)-3-(4-isobutylphenyl)-2-methylpropanal] have been synthesized in high enantiopurity via a simple four-step strategy starting from the commercially available 4-substituted benzaldehydes. The key synthetic step is the catalytic asymmetric hydrogenation of the appropriate 3-aryl-2-methylacrylic acid which has been carried out employing an in situ prepared ruthenium/axially chiral phosphine catalyst (up to 98% ee). The olfactory activity of the single enantiomers has been evaluated.

Key words

fragrance synthesis - asymmetric hydrogenation - ruthenium - canthoxal - Silvial^®

• References


Selected references:
• 1a Kraft P, Mannschreck A. J. Chem. Educ. 2010; 87: 598
• 1b Bentley R. Chem. Rev. 2006; 106: 4099
• 1c Abate A, Brenna E, Fuganti C, Gatti FG, Serra S. Chem. Biodiversity 2004; 1: 1888
• 1d Brenna E, Fuganti C, Serra S. Tetrahedron: Asymmetry 2003; 14: 1
• 1e Kraft P, Fráter G. Chirality 2001; 13: 388
• 1f Kraft P, Bajgrowicz JA, Denis C, Fráter G. Angew. Chem. Int. Ed. 2000; 39: 2980
• 2 Chapuis C. Helv. Chim. Acta 2012; 95: 1479

Selected references:
• 3a Schwartz S, Berding V, Matthies M. Chemosphere 2000; 41: 671
• 3b Peck AM, Hornbuckle KC. Atmos. Environ. 2006; 40: 6101
• 3c Niederer M, Bollhalder R, Hohl C. J. Chromatogr., A 2006; 1132: 109

Selected references:
• 4a Rossiter KJ. Chem. Rev. 1996; 96: 3201
• 4b Mannschreck A, Kiesswetter R, von Angerer E. J. Chem. Educ. 2007; 84: 2012
• 5 Schnuch A, Uter W, Geier J, Lessmann H, Frosch PJ. Contact Dermatitis 2007; 57: 1
• 6 Charles AK, Darbre PD. J. Appl. Toxicol. 2009; 29: 422
• 7a Enders D, Dyker H. Liebigs Ann. Chem. 1990; 1107
• 7b Lightfoot A, Schnider P, Pfaltz A. Angew. Chem. Int. Ed. 1998; 37: 2897
• 7c Gualandi A, Emma MG, Giacoboni J, Mengozzi L, Cozzi PG. Synlett 2013; 24: 449
• 7d Stueckler C, Mueller NJ, Winkler CK, Glueck SM, Gruber K, Steinkellner G, Faber K. Dalton Trans. 2010; 39: 8472
• 7e Noonan GM, Fuentes JA, Cobley CJ, Clarke ML. Angew. Chem. Int. Ed. 2012; 51: 2477
• 8 Rosini G, Paolucci C, Boschi F, Marotta E, Righi P, Tozzi F. Green Chem. 2010; 12: 1747
• 9 Bartschat D, Börner S, Mosandl A, Bats JW. Z. Lebensm.-Unters. Forsch. A 1997; 205: 76
• 10 Kawasaki M, Goto M, Hu D, Toyooka N, Kometani T. J. Mol. Catal. B: Enzym. 2013; 96: 27
• 11 Silvial^® is a trademark registered by Givaudan; the odour profile of Silvial is described as a ‘powerful, vibrant muguet ingredient with a slight citrus undertone and a fresh, aldehydic touch’; http://www.givaudan.com. IFF reports that canthoxal is reminiscent of ‘licorice, basil, fennel, anise note with a slight fruity, watery modification’; http://www.iff.com/custom/iff/pdfs/Synthetics_Compendium_A4_Sheets.pdf (accessed Oct 21, 2014).

Selected references:
• 12a Shang G, Li W, Zhang X In Catalytic Asymmetric Synthesis . 3rd ed.; Ojima I. Wiley; Hoboken: 2010: 343
• 12b Shimizu H, Nagasaki I, Matsumura K, Sayo N, Saito T. Acc. Chem. Res. 2007; 40: 1385
• 12c Saudan LA. Acc. Chem. Res. 2007; 40: 1309
• 12d Blaser H.-U, Malan C, Pugin B, Spindler F, Steiner H, Studer M. Adv. Synth. Catal. 2003; 345: 103
• 12e Chapuis C, Jacoby D. Appl. Catal. A: Gen. 2001; 221: 93
• 13 Maryanoff BE, Reitz AB. Chem. Rev. 1989; 89: 863
• 14a Matteoli U, Ciappa A, Bovo S, Bertoldini M, Scrivanti A. Tetrahedron: Asymmetry 2007; 18: 797
• 14b Takaya H, Ohta T, Sayo N, Kumobayashi H, Akutagawa S, Inoue S, Kasahara I, Noyori R. J. Am. Chem. Soc. 1987; 109: 1596
• 14c Sun Y, Wang J, LeBlond C, Reamer RA, Laquidara J, Sowa JR. Jr, Blackmond DG. J. Organomet. Chem. 1997; 548: 65
• 15a Cheng X, Xie J.-H, Li S, Zhou Q.-L. Adv. Synth. Catal. 2006; 348: 1271
• 15b Tang W, Zhang X. Chem. Rev. 2003; 103: 3029
• 15c Bruneau C, Renaud J.-L, Jerphagnon T. Coord. Chem. Rev. 2008; 252: 532
• 15d Zhang W, Chi Y, Zhang X. Acc. Chem. Res. 2007; 40: 1278

Selected references on ferrocenyl ligands for the asymmetric hydrogenation of α,β-unsaturated carboxylic acids and esters:
• 16a Matteoli U, Beghetto V, Scrivanti A, Aversa M, Bertoldini M, Bovo S. Chirality 2011; 23: 779
• 16b Spindler F, Malan C, Lotz M, Kesselgruber M, Pittelkow U, Rivas-Nass A, Brielb O, Blaser H.-U. Tetrahedron: Asymmetry 2004; 15: 2299

Selected references:
• 17a Scrivanti A, Bovo S, Ciappa A, Matteoli U. Tetrahedron Lett. 2006; 47: 9261
• 17b Forman GS, Ohkuma T, Hems WP, Noyori R. Tetrahedron Lett. 2000; 41: 9471
• 17c Grasa GA, Zanotti-Gerosa A, Ghosh S, Teleha CA, Kinney WA, Maryanoff BE. Tetrahedron Lett. 2008; 49: 5328
• 18 Hoffmann RW, Schopfer U, Müller G, Brandl T. Helv. Chim. Acta 2002; 85: 4424
• 19 Pawson BA, Cheung H.-C, Gurbaxani S, Saucy G. J. Am. Chem. Soc. 1970; 92: 336
• 20 Nozawa M, Takahashi K, Kato K, Akita H. Chem. Pharm. Bull. 2000; 48: 272
• 21 Armarego WL. F, Perrin DD. Purification of Laboratory Chemicals . 4th ed. Butterworth-Heinemann; Oxford: 1996
• 22 Bennett MA, Smith AK. J. Chem. Soc., Dalton Trans. 1974; 233
• 23 Roush WR, Sciotti RJ. J. Am. Chem. Soc. 1998; 120: 7411
• 24 Cheng X, Zhang Q, Xie JH, Wang LX, Zhou QL. Angew. Chem. Int. Ed. 2005; 44: 1118
• 25 Wang Z.-G, Chen L, Chen J, Zheng J.-F, Gao W, Zeng Z, Zhou H, Zhang X.-K, Huang P.-Q, Su Y. Eur. J. Med. Chem. 2013; 62: 632
• 26 Harada N.-a, Nishikata T, Nagashima H. Tetrahedron 2012; 68: 3243