A Novel Diazomethane-Mediated Synthesis of Azetidine-Embedded Tetracyclic Ketal Systems

Abstract

Herein, the first diazomethane-mediated synthesis of azetidine-embedded tetracyclic ketal systems is reported. Reactions of norbornyl hemiaminal acetals with diazomethane afford azetidine-embedded tetracyclic ketals in good to excellent yields. The bridgehead-bromo-substituted hemiaminal acetals give higher yields compared to the corresponding bridgehead-chloro-substituted hemiaminal acetals. The hemiaminal acetals are prepared stereoselectively via nucleophilic addition of various amines to norbornyl α-diketones from the exo face.

Key words

diazomethane - azetidines - amines - tetracyclic - acetals

• References

• 1 Present address: G. H. M. Rao, Department of Chemistry, Texila American University, Georgetown, Guyana, South America.
• 2a Honcharenko D. Varghese OP. Plashkevych O. Barman J. Chattopadhyaya J. J. Org. Chem. 2006; 71: 299
• 2b Evans GB. Furneaux RH. Greatrex B. Murkin AS. Schramm VL. Tyler PC. J. Med. Chem. 2008; 51: 948
• 2c Ji J. Bunnelle WH. Li T. Pace JM. Schrimpf MR. Sippy KB. Anderson DJ. Meyer MD. Pure Appl. Chem. 2005; 77: 2041
• 3a Oike H. Washizuka M. Tezuka Y. Macromol. Chem. Phys. 2000; 201: 1673
• 3b Kuo M.-C. Jeng R.-J. Su W.-C. Dai S. Macromolecules 2008; 41: 682
• 3c Wang S.-C. Chen P.-C. Yeh J.-T. Chen K.-N. React. Funct. Polym. 2007; 67: 299
• 4a Almens J. Foubelo F. Yus M. Tetrahedron 1994; 50: 5775
• 4b Banide E. de Talancé VL. Schmidt G. Lubin H. Comesse S. Dechoux L. Hamon L. Kadouri-Puchot C. Eur. J. Org. Chem. 2007; 4517
• 5a Zi GF. Liu RC. Bai XM. Zhang ZB. Appl. Organomet. Chem. 2008; 22: 671
• 5b Couty F. Prim D. Tetrahedron: Asymmetry 2002; 13: 2619

For reviews on the synthesis and chemistry of azetidines, see:
• 6a De Kimpe N. In Comprehensive Heterocyclic Chemistry II . Vol. 1B. Padwa A. Chap 1.18 Elsevier; Oxford: 1996: p 507
• 6b Moore JA. Ayers RS. In Chemistry of Heterocyclic Compounds, Small Ring Heterocycles . Hassner A. Wiley; New York: 1983. Part 3 p 1
• 6c Cromwell NH. Phillips B. Chem. Rev. 1979; 79: 331
• 7a Kobayashi J. Ishibashi M. Heterocycles 1996; 42: 943
• 7b Shuman RT. Rothenberger RB. Campbell CS. Smith GF. Gifford-Moore DS. J. Med. Chem. 1995; 38: 4446
• 8a Ungureanu I. Klotz P. Schoenfelder A. Mann A. Chem. Commun. 2001; 958
• 8b Ungureanu I. Klotz P. Schoenfelder A. Mann A. Tetrahedron Lett. 2001; 42: 6087
• 8c Prasad BA. B. Bisai A. Singh VK. Org. Lett. 2004; 6: 4829
• 9a Van Brabandt W. Mangelinckx S. D’hooghe M. Van Driessche B. De Kimpe N. Curr. Org. Chem. 2009; 13: 827
• 9b Couty F. Evano G. Prim D. Mini-Rev. Org. Chem. 2004; 1: 133
• 10a Vaughan WR. Klonowski RS. McEilhinney RS. Millward BB. J. Org. Chem. 1961; 26: 138
• 10b Hillier MC. Chen C.-Y. J. Org. Chem. 2006; 71: 7885
• 10c de Figueiredo RM. Frölich R. Christmann M. J. Org. Chem. 2006; 71: 4147
• 11a Gaertner VR. Tetrahedron Lett. 1966; 4691
• 11b Gaertner VR. J. Org. Chem. 1967; 29: 2972
• 12a Sulmon P. De Kimpe N. Schamp N. Tinant B. Declercq J.-P. Tetrahedron 1988; 44: 3653
• 12b Sulmon P. De Kimpe N. Schamp N. J. Chem. Soc., Chem. Commun. 1985; 715
• 12c De Kimpe N. De Smaele D. Tetrahedron Lett. 1994; 35: 8023
• 13 Chang HO. Chul YR. Choong HY. Jin RC. Synth. Commun. 2003; 33: 4297
• 14 Sarika M. Upender KN. Synlett 2008; 108
• 15a Dejaegher Y. De Kimpe N. J. Org. Chem. 2004; 69: 5974
• 15b Brabandt WV. Dejaegher Y. Landeghem RV. De Kimpe N. Org. Lett. 2006; 8: 1101
• 16a De Kimpe N. De Smaele D. Tetrahedron 1995; 51: 5465
• 16b Salgado A. Dejaegher Y. Verniest G. Boeykens M. Gauthier C. Lopin C. Tehrani KA. De Kimpe N. Tetrahedron 2003; 59: 2231
• 17 Khan FA. Rao GH. M. Satapathy R. Parasuraman K. Org. Lett. 2007; 9: 1581
• 18 Khan FA. Prabhudas B. Dash J. Sahu N. J. Am. Chem. Soc. 2000; 122: 9558
• 19a Katritzky AR. Physical Methods in Heterocyclic Chemistry . Academic Press; New York: 1971
• 19b Katritzky AR. Handbook of Heterocyclic Chemistry . Pergamon Press; Oxford: 1985: 132
• 19c Fritz SP. Moya JF. Unthank MG. McGarrigle EM. Aggarwal VK. Synthesis 2012; 44: 1584