Intramolecular Aza-[4+3] Cycloaddition Reactions of α-Halohydroxamates

This article is dedicated in honor of Professor Scott Denmark’s 60^th birthday.

Abstract

Polyheterocyclic scaffolds were prepared by intramolecular aza-[4+3] cycloaddition reactions of aza-oxyallylic cations with cyclic dienes. The aza-oxyallylic cation was generated in situ by the dehydrohalogenation of α-halohydroxamates. The highly functionalized heterocyclic products undergo a variety of reactions that provide useful scaffolds for target-directed synthesis, including macrocyclic furans and polyhydroxylated azepanes.

Key words

cycloaddition - nitrogen - azasugars - heterocycles - macrocycles

• References

• 1a O’Connor CJ, Beckmann HS, Spring DR. Chem. Soc. Rev. 2012; 41: 4444
• 1b Marson CM. Chem. Soc. Rev. 2011; 40: 5514; and references cited therein
• 2a Jeffrey CS, Barnes KL, Eickhoff JA, Carson CR. J. Am. Chem. Soc. 2011; 133: 7688
• 2b Jeffrey CS, Anumandla D, Carson CR. Org. Lett. 2012; 14: 5764
• 3 For a review on the reactivity and synthetic applications of stabilized nitrenium ions, see: Kikugawa Y. Heterocycles 2009; 78: 571; and references cited therein

For examples of recent applications of stabilized nitrenium ions in organic synthesis, see:
• 4a Wardrop DJ, Bowen EG, Forslund RE, Sussman AD, Weerasekera SL. J. Am. Chem. Soc. 2009; 132: 1188
• 4b Bowen EG, Wardrop DJ. Org. Lett. 2010; 12: 5330
• 4c Wardrop DJ, Bowen EG. Org. Lett. 2011; 13: 2376
• 4d Wardrop DJ, Yermolina MV, Bowen EG. Synthesis 2012; 44: 1199
• 5a Lohse AG, Hsung RP. Chem. Eur. J. 2011; 17: 3812
• 5b Harmata M. Chem. Commun. 2010; 8904
• 5c Harmata M. Chem. Commun. 2010; 8886
• 5d Huan J, Hsung RP. ChemTracts 2005; 18: 207
• 5e Harmata M. Adv. Synth. Catal. 2006; 348: 2297
• 5f Harmata M. Acc. Chem. Res. 2001; 34: 595
• 5g Cha JK, Oh J. Curr. Org. Chem. 1998; 2: 217
• 5h Harmata M In Advances in Cycloaddition . Vol. 4. Lautens M. JAI Press; Greenwich (CT, USA): 1997: 41-86
• 5i West FG In Advances in Cycloaddition . Vol. 4. Lautens M. JAI Press; Greenwich (CT, USA): 1997: 1-40
• 5j Harmata M. Tetrahedron 1997; 53: 6235
• 5k Padwa A, Schoffstall A In Advances in Cycloaddition . Vol. 2. Curran DP. JAI Press; Greenwich (CT, USA): 1990: 1-89
• 5l Harmata M. Recent Res. Dev. Org. Chem. 1997; 1: 523
• 5m Rigby JH, Pigge FC. Org. React. 1997; 51: 351
• 5n Mann J. Tetrahedron 1986; 42: 4611
• 5o Hoffmann HM. R. Angew. Chem., Int. Ed. Engl. 1984; 23: 1
• 5p Hoffmann HM. R. Angew. Chem., Int. Ed. Engl. 1973; 12: 819
• 6a Föhlisch B, Herter R. Chem. Ber. 1984; 117: 2580
• 6b Grainger RS, Owoare RB, Tisselli P, Steed JW. J. Org. Chem. 2003; 68. 7899
• 7 Föhlisch B, Gehrlach E, Herter R. Angew. Chem., Int. Ed. Engl. 1982; 21: 137
• 8 Herter R, Föhlisch B. Synthesis 1982; 976

Hexafluoroisopropanol improves the yield of reactions proceeding through reactive oxyallyl cationic intermediates, see:
• 9a Harmata M, Huang C, Rooshenas P, Schreiner PR. Angew. Chem. Int. Ed. 2008; 47: 8696
• 9b Myers AG, Barbay JK. Org. Lett. 2001; 3: 425
• 10 For a review on the synthesis and biological activity of polyhydroxylated aza-heterocycles, see: Wardrop DJ, Waidyarachchi SL. Nat. Prod. Rep. 2010; 27: 1431; and references cited therein
• 11 Cicchi S, Goti A, Brandi A, Guarna A, De Sarlo F. Tetrahedron Lett. 1990; 31: 3351