A Practical Approach to Stereochemically Defined Tetrahydrofurans from [5+2] Oxidopyrylium-Alkene Cycloadducts

Abstract

The feasibility of the Beckmann fragmentation reaction has been extended to [5+2] cycloadducts derived from the cycloaddition of 3-oxidopyrylium betaine to various olefins. Upon cleavage, these cycloadducts give stereochemically defined tetrahydrofurans in high overall yields as single diastereoisomers.

Key words

cycloaddition - cleavage - Beckmann fission - oxidopyrylium - stereoselectivity

References and Notes

• 1a Harmange JC. Figadere B. Tetrahedron: Asymmetry  1993,  4:  1711 
• 1b Bovin TLB. Tetrahedron  1987,  43:  3309 
• 1c Bartlett PA. Tetrahedron  1980,  36:  2 
• 1d Bartlett PA. Asymmetric Synthesis   Vol. III:  Academic Press; Florida: 1984.  Chap. 6. p.411 
• 1e Semple JE. Jouillie M. Heterocycles  1980,  14:  1825 
• 2a Koert U. Stein M. Wagner H. Chem. Eur. J.  1997,  3:  1170 
• 2b Hoppe R. Scharf HD. Synthesis  1995,  1447 
• For representative recent examples of tetrahydrofuran syntheses, see:
• 3a Friedrichsen W. In Comprehensive Heterocyclic Chemistry II   Vol. 2:  Bird CW. Pergamon Press; Oxford: 1996.  p.351 
• 3b Eames J. Jones RVH. Warren S. Tetrahedron Lett.  1996,  37:  4823 
• 3c Andrey O. Glanzmann C. Landais Y. Parra RL. Tetrahedron  1997,  53:  2835 
• 3d Elliott MC. Williams E. J. Chem. Soc., Perkin Trans. 1  2001,  2303 
• 3e Mascarenas JL. Rumbo A. Castedo L. J. Org. Chem.  1997,  62:  8620 
• 3f Fishwick CWG. Mitchell G. Pang PFW. Synlett  2005,  285 ; and pertinent references therein
• For review, see:
• 4a Carruthers W. Cycloaddition Reactions in Organic Synthesis   Pergamon Press; New York: 1990. 
• 4b Paquette LA. Asymmetric Synthesis   Morrison JD. Academic Press; New York: 1984. 
• 5a Murali Krishna U. Srikanth GSC. Trivedi GK. Deodhar KD. Synlett  2003,  2383 
• 5b Murali Krishna U. Deodhar KD. Trivedi GK. Shaikh M. J. Org. Chem.  2004,  69:  967 
• 5c Murali Krishna U. Trivedi GK. Tetrahedron Lett.  2004,  45:  257 
• 5d Murali Krishna U. Deodhar KD. Trivedi GK. Tetrahedron  2004,  60:  4829 
• 6a Hendrickson JB. Farina JS. J. Org. Chem.  1980,  45:  3361 
• 6b Sammes PG. Street LJ. J. Chem. Soc., Chem. Commun.  1982,  1056 
• 6c Sammes PG. Street LJ. J. Chem. Soc., Perkin Trans. 1  1983,  1261 
• 7a Ohno M. Terasawa I. J. Am. Chem. Soc.  1966,  88:  5683 
• 7b Boaz A. Hassner A. Synthesis  1978,  932 
• 7c Han M. Covey DF. J. Org. Chem.  1996,  61:  7614 
• 7d Wang KJC. Hu Y. Hu H. Covey DF. J. Org. Chem.  2000,  65:  3555 
• 7e Rosenberg MG. Haslinger U. Brinker UH. J. Org. Chem.  2002,  67:  450 
• 7f Iglesias-Arteaga MA. Sandoval-Ramirez J. Mata-Esma MY. Vinas-Bravo O. Bernes S. Tetrahedron Lett.  2004,  45:  4921 
• 7g Blaszczyk K. Koenig H. Mel K. Paryzek Z. Tetrahedron  2006,  62:  1069 
• 8a Petrier C. Luche JL. Tetrahedron Lett.  1987,  28:  2347 
• 8b Alonso F. Yus M. Tetrahedron  1998,  54:  1921 
• 8c Laval G. Holding BT. Synlett  2003,  279 
• 8d Saito S. Yamamoto H. J. Org. Chem.  1996,  61:  2928 
• 8e Belisle CM. Young YM. Singaram B. Tetrahedron Lett.  1994,  35:  5595 
• 9a Khurana JM. Sharma P. Bull. Chem. Soc. Jpn.  2004,  77:  549 
• 9b Ganem B. Osby JO. Chem. Rev.  1986,  86:  763 
• 12a Ishiwata A. Akao H. Ito Y. Org. Lett.  2006,  5525 ; and references cited therein
• 12b Vargeese C. Abushanab C. J. Org. Chem.  1990,  55:  4400 
• 12c Sasmal PK. Maier ME. J. Org. Chem.  2003,  68:  824 
• 12d Wolfe JP. Hay MB. Tetrahedron  2007,  63:  261 

10

(a) General procedure for the reduction of cycloadduct 5: To cycloadduct 5 (1 mmol) dissolved in MeOH (12 mL) was added NiCl₂·6H₂O (5 mmol) followed by distilled H₂O (2 mL). NaBH₄ (2 mmol) was then added and the reaction mixture was stirred vigorously at r.t.. The progress of the reaction was monitored by TLC using PE-EtOAc (9:1) and showed the complete disappearance of starting material after 15 min. The reaction was quenched with MeOH (10 mL) and the reaction mixture was filtered through a pad of celite and washed with MeOH. H₂O (50 mL) was added to the combined filtrate, which was extracted with CH₂Cl₂ (3 × 15 mL). The combined CH₂Cl₂ extract was dried over anhyd MgSO₄, decanted through a cotton pad and concentrated in vacuo. The product was purified by column chromatography using silica gel (60-120 mesh) and PE-EtOAc as eluent. (b) General procedure for the synthesis of oxime 6:
The ketone (9 mmol) was dissolved in a solution of NH₂OH·HCl (1 g) and NaOAc (1 g) in H₂O (20 mL) by the addition of EtOH (10 mL). The mixture was heated at reflux for 2 h and then cooled and extracted with CH₂Cl₂. The combined CH₂Cl₂ extract was dried over anhyd MgSO₄, decanted through a cotton pad and concentrated in vacuo. The product was purified by column chromatography using silica gel (60-120 mesh) and PE-EtOAc (9:1) as eluent.

11

Typical procedure: A slight excess of SOCl₂ (1 g, 8.4 mmol) in anhyd CCl₄ (15 mL) at 0 °C was added over a few minutes to a solution of oxime 6 (R = OEt) (1.5 g, 8 mmol) in CCl₄, also at 0 °C. Immediately after the addition, vigorous evolution of H₂ took place, the mixture was allowed to stir for another 10 min and then MeOH (10 mL) was added and the resulting solution was stirred for another 30 min. The solution was quenched with NaHCO₃ and extracted using CH₂Cl₂ (2 × 30 mL). Evaporation of the solvent in vacuo and column chromatography of the residue on silica gel (EtOAc-PE, 1:9) gave tetrahydrofuran 7 (R = OEt) as a pale yellow oil (1.7 g, 90%); IR: 2922, 2243, 1107, 1045 cm^-1; ¹H NMR (500 MHz, CDCl₃): δ = 5.02 (dd, J = 1.5, 3.3 Hz, 1 H), 4.10 (m, 1 H), 4.06 (m, 1 H) 3.55 (m, 1 H), 3.34 (s, 3 H), 3.33 (m, 1 H), 2.60-2.50 (m, 2 H), 2.10 (dddd, J = 3.3, 1.9, 8.4, 0.6 Hz, 1 H), 2.08 (dddd, J = 1.5, 3.6, 8.4, 0.3 Hz, 1 H), 2.05-1.95 (m, 2 H), 1.15 (t, J = 7 Hz, 3 H); ¹³C NMR (75 MHz, CDCl₃): δ = 119.7, 103.8, 78.6, 76.6, 64.9, 55.1, 39.5, 25.1, 15.2, 14.1; HRMS (TOF, ES⁺): m/z [M + Na]⁺ calcd for C₁₀H₁₇NO₃Na: 222.1106; found: 222.1105.