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Synlett 2007(6): 0989-0991  
DOI: 10.1055/s-2007-973866
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Arun A. Yadav, Prajakta S. Sarang, Girish K. Trivedi*, Manikrao M. Salunkhe*
Department of Chemistry, The Institute of Science, 15 Madam Cama Road, Mumbai 400032, India
Fax: +91(22)22816750; e-Mail: mmsalunkhe@hotmail.com; snehgkt@yahoo.com;
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Publication History

Received 18 September 2006
Publication Date:
26 March 2007 (online)

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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

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(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.

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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.