Synthesis 2010(17): 2901-2914  
DOI: 10.1055/s-0030-1258207
SPECIALTOPIC
© Georg Thieme Verlag Stuttgart ˙ New York

Microwave-Assisted Domino Hydroformylation/Cyclization Reactions: Scope and Limitations

Etienne Airiaua, Claire Chemina, Nicolas Girarda, Giacomo Lonzib, André Mann*a, Elena Petriccib, Jessica Salvadorib, Maurizio Taddei*b
a Laboratoire d’Innovation Thérapeutique, UMR 7200 CNRS-Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch, France
e-Mail: andre.mann@pharma.u-strasbg.fr;
b Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy
Fax: +39(0577)234280; e-Mail: taddei.m@unisi.it;
Further Information

Publication History

Received 13 April 2010
Publication Date:
13 August 2010 (online)

Abstract

Hydroformylation of alkenes can be carried out in short time and with low syngas pressure under microwave (MW) dielectric heating. Alkenes, carrying O-, N-, or C-nucleophilic fragments, can be designed for domino reactions, mainly cyclocondensations. Allyl and homoallyl alcohols are excellent substrates for cyclizative hydroformylation to lactols under MW heating. In the presence of NaOAc as an additional nucleophile, a domino reaction occurs giving 2-acetoxytetrahydrofurans, suitable to introduce a C-nucleophile on tetrahydrofuran rings through an oxocarbenium ion. The synthesis of the furanopiperidine substructure of cyclopamine is described as an application. With alkene amides, the domino process collapsed to a transient acyliminium ion that further cyclized with an additional C-nucleophile. To perform domino hydroformylation Pictet-Spengler or aza-Sakurai reactions, an autoclave under conventional heating is essential. Syntheses of (±)-epilupinine and of a homoberberine alkaloid are reported to illustrate each sequence. Although apparently more versatile, hydroformylation of alkenes using MW heating is sensitive to the nature of the nucleophiles present in the substrates, evidencing that the conventional heating process cannot be completely replaced by MW irradiation.

    References

  • 1a Caddick S. Fitzmaurice R. Tetrahedron  2009,  65:  3325 
  • 1b Jindal R. Bajaj S. Curr. Org. Chem.  2008,  12:  836 
  • 1c Coquerel Y. Rodriguez J. Eur. J. Org. Chem.  2008,  1125 
  • 1d Solinas A. Taddei M. Synthesis  2008,  2409 
  • 1e Hayes BL. Aldrichimica Acta  2004,  37:  66 
  • 1f Kappe CO. Angew. Chem. Int. Ed.  2004,  43:  6250 
  • 2 Kappe CO. Stadler A. Microwaves in Organic and Medicinal Chemistry   Wiley-VCH; Weinheim: 2005.  p.153 
  • 3 Kappe CO. Dallinger D. Nature Rev. Drug Discovery  2006,  5:  51 
  • 4a Chaudhari RV. Curr. Opin. Drug Discovery Dev.  2008,  11:  820 
  • 4b Breit B. Top. Curr. Chem.  2007,  279:  139 
  • 4c Breit B. Seiche W. Synthesis  2001, 
  • 5 Petricci E. Mann A. Rota A. Schoenfelder A. Taddei M. Org. Lett.  2006,  8:  3725 
  • 8 Petricci E. Mann A. Salvadori J. Taddei M. Tetrahedron Lett.  2007,  48:  8501 
  • 10a Dübon P. Farwick A. Helmchen G. Synlett  2009,  1413 
  • 10b Kemme ST. Smejkal T. Breit B. Adv. Synth. Catal.  2008,  350:  989 
  • 10c Chiou W.-H. Mizutani N. Ojima I. J. Org. Chem.  2007,  72:  1871 
  • 10d Padwa A. Bur SC. Tetrahedron  2007,  63:  5341 
  • 10e Teoh E. Campi EM. Jackson WR. Robinson AJ. Chem. Commun.  2002,  978 
  • 10f Hoffmann RW. Brückner D. Gerusz VJ. Heterocycles  2000,  52:  121 
  • 10g Bergmann DJ. Campi EM. Jackson WR. Patti AF. Chem. Commun.  1999,  1279 
  • 10h Eilbracht P. Rzychon LB. Kranemann CL. Rische T. Roggenbuck R. Schmidt A. Chem. Rev.  1999,  99:  3329 
  • 10i Ojima I. Tzamarioudaki M. Eguchi M. J. Org. Chem.  1995,  60:  7078 
  • 11a Schmidt B. Biernat A. Synlett  2007,  2375 
  • 11b Morinaka BI. Skepper CK. Molinski TF. Org. Lett.  2007,  9:  1975 
  • 12a da Silva JG. Barros HJV. dos Santos EN. Gusevskaya EV. Appl. Catal., A  2006,  309:  169 
  • 12b Nozaki K. Li W.-G. Horiuchi T. Takaya H. Tetrahedron Lett.  1997,  38:  4611 
  • 12c For stereoselective hydroformylation of allylic alcohol derivatives, see: Breit B. Acc. Chem. Res.  2003,  36:  264 
  • 13 Heretsch P. Rabe S. Giannis A. Org. Lett.  2009,  11:  5410 
  • 14 Larsen CH. Ridgway BH. Shaw JT. Woerpel KA. J. Am. Chem. Soc.  1999,  121:  12208 
  • 15 Du Y. Linhardt RJ. Vlahov IR. Tetrahedron  1998,  54:  9913 
  • 16 Boukouvalas J. Radu I.-I. Tetrahedron Lett.  2007,  48:  2971 
  • 17a D’Aniello F. Taddei M. J. Org. Chem.  1992,  57:  5247 
  • 17b D’Aniello F. Mattii D. Taddei M. Synlett  1993,  119 
  • 18 Giannis A. Heretsch P. Sarli V. Stößel A. Angew. Chem. Int. Ed.  2009,  48:  7911 
  • For some recent literature, see:
  • 19a Airiau E. Spangenberg T. Girard N. Breit B. Mann A. Org. Lett.  2010,  12:  528 
  • 19b Spangenberg T. Breit B. Mann A. Org. Lett.  2009,  11:  261 
  • 19c Spangenberg T. Airiau E. BuiTheThuong M. Donnard M. Billet M. Mann A. Synlett  2008,  2859 
  • 19d Vieira TO. Alper H. Chem. Commun.  2007,  2710 
  • 19e Wittmann K. Wisniewski W. Mynott R. Leitner W. Kranemann CL. Rische T. Eilbracht P. Sander S. Ernsting JM. Chem. Eur. J.  2001,  7:  4584 
  • 20 Royer J. Bonin M. Micouin L. Chem. Rev.  2004,  104:  2311 
  • 21a Youn SW. Org. Prep. Proced. Int.  2006,  38:  205 
  • 21b Larghi EL. Kaufman TS. Synthesis  2006,  187 
  • 21c Larghi EL. Amongero M. Bracca ABJ. Kaufman TS. ARKIVOC  2005,  (xii):  98 
  • 22a Kulkarni A. Abid M. Török B. Huang X. Tetrahedron Lett.  2009,  50:  1791 
  • 22b Kusurkar RS. Alkobati NAH. Gokule AS. Puranik VG. Tetrahedron  2008,  64:  1654 
  • 22c Liu F. You Q.-D. Synth. Commun.  2007,  37:  3933 
  • 22d Lesma G. Danieli B. Lodroni F. Passarella D. Sacchetti A. Silvani A. Comb. Chem. High Throughput Screening  2006,  9:  691 
  • 22e Kuo F.-M. Tseng M.-C. Yen Y.-H. Chu Y.-H. Tetrahedron  2004,  60:  12075 
  • 22f Campiglia P. Gomez-Monterrey I. Lama T. Novellino E. Grieco P. Mol. Diversity  2004,  8:  427 
  • 22g Wu C.-Y. Sun C.-M. Synlett  2002,  4826 
  • 23a Bondzic BP. Eilbracht P. Org. Biomol. Chem.  2008,  6:  4059 
  • 23b Airiau E. Girard N. Mann A. Salvadori J. Taddei M. Org. Lett.  2009,  11:  5314 
  • 24 Wakchaure PB. Easwar S. Argade NP. Synthesis  2009,  1667 ; and references cited therein
  • 25 Itoh T. Nagata K. Yokoya M. Miyazaki M. Kameoka K. Nakamura S. Ohsawa A. Chem. Pharm. Bull.  2003,  51:  951 
  • 26 Airiau E. Spangenberger T. Girard N. Schoenfelder A. Salvadori J. Taddei M. Mann A. Chem. Eur. J.  2008,  14:  10938 
6

http://www.cem.com/page163.html.

7

http://www.anton-paar.com/001/en/60/262.

9

In a 10 mL vial, the gas present under the reaction conditions is roughly 3 mmol for 1 mmol of substrate.