Novel Routes to the Kainates: Stereoselectivity in Addition Reactions to ­Pyrrole [1,2c]-oxazol-3-one

Abstract

This paper describes the addition of a range of electrophiles to 1. An unusual and unpredicted stereochemistry of addition has been observed in line with our original photochemical observations.

Key words

electrophilic attack - photochemical addition - kainates - oxazolidinone - ab initio calculations - molecular modelling

References

• 1 Greenwood ES. Parsons PJ. Tetrahedron  2003,  18:  3307 
• 2 Davis AS. Gates NJ. Lindsay KB. Tang M. Pyne SG. Synlett  2004,  49 
• 3 Murray A. Third Year Report   University of Sussex; UK: 2002. 
• 4 Greenwood ES. D. Phil Thesis   University of Sussex; UK: 2001. 
• 5a Schumacher KK. Jiang J. Joullie MM. Tetrahedron: Asymmetry  1998,  9:  47 
• 5b Abraham DJ. Mokotoff M. Sheh L. Simmons JC. J. Med. Chem.  1983,  26:  549 
• 5c Zhao H. Thurkauf A. Synlett  1999,  1280 
• 7 Asouti A. Hadjiarapoglou LP. Synlett  2001,  1847 
• 8 Andrau L. Lebreton J. Viazzo P. Alphand V. Furstoss R. Tetrahedron Lett.  1997,  38:  825 
• 9a Cieplak AS. J. Am. Chem. Soc.  1981,  103:  4540 
• 9b Katagiri N. Ito Y. Kitano K. Toyota A. Kaneko C. Chem. Pharm. Bull.  1994,  42:  2653 
• 9c Mahmodian M. Baines BS. Dawson MJ. Lawrence GC. Enzyme Microb. Technol.  1992,  14:  911 
• 11 Modification of the procedure described in: Shi Y. Whang Z. Froha M. J. Org. Chem.  1998,  63:  6425 

6

Typical Experimental Procedure: [11]
(5 R ,6 S ,7 R )-1-aza-3-oxa-6,7-epoxybicyclo[3,3, O ]-octan-2-one ( 6) . To a stirred solution of oxazolidinone 1 (4.00 g, 32 mmol) in dimethoxymethane (130 mL) and MeCN (260 mL) were added tetrabutylammonium hydrogen sulfate (0.43 g, 1.28 mmol), acetone (71 mL, 960 mmol) and K₂CO₃ (0.1 M in water, 64 mL). A solution of EDTA (4 × 10^-4 M in water, 341 mL) acidified with enough HOAc to dissolve the insoluble solid was added to oxone^® (78.7 g, 992 mmol). The resulting solution and a solution of K₂CO₃ (87.2 g, 631.5 mmol) in water (341 mL) were concomitantly added to the initial solution of oxazoline 1 over 5 h. The reaction mixture was then extracted with EtOAc (3 × 100 mL) and washed with brine (100 mL) and water (100 mL). The combined organic extracts were dried over MgSO₄ and concentrated under reduced pressure. The resulting oil was purified by flash column chromatography (60% EtOAc-petroleum ether) to give epoxide 6 as a white crystalline solid (3.60 g, 80%); mp (uncorrected) 60-63 °C; [α]²³ _D -8.6 (c = 1.91, CHCl₃). IR (film): 3059, 2922, 1748 (s), 1410 (s), 1199, 1075 (s) cm^-1. ¹H NMR (500 MHz, C₆D₆): δ = 3.95 (dd,
J = 8.7, 3.6 Hz, 1 H), 3.87 (apparent t, J = 8.7 Hz, 1 H), 3.80 (d, J = 13.2 Hz, 1 H), 3.08 (dd, J = 8.7, 3.6 Hz, 1 H), 2.97 (d, J = 2.8 Hz, 1 H), 2.91 (d, J = 2.8 Hz, 1 H), 2.50 (d, J = 13.2 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 163.2, 64.5, 58.4, 55.7, 55.5, 48.9. HRMS: m/z [M⁺] calcd for C₆H₇NO₃: 141.0426; found: 141.0420.

10

The addition of 2-propenylmagnesium bromide in the presence of Cu(I) gave a 6:1 mixture of regioisomers in favour of desired alcohol 10 as determined by high field NMR (500 MHz).