Applications of N-Phosphinoyloxaziridines in the Conversion of Alkenes to Epoxides and Esters to α-Hydroxyesters

Abstract

N-Phosphinoyloxaziridines possessing an activating 3-CF₃ substituent oxidise alkenes to epoxides at 35-45 °C. Esters can be oxidised to α-hydroxyesters via their lithium enolates by various 3-subsituted N-phosphinoyloxaziridines. Stereoselectivity is observed in both these oxidations.

oxaziridines - α-hydroxyesters - epoxidation - enolate oxidation - stereoselective oxidation

References

1 Boyd DR. Malone JF. McGuckin MR. Jennings WB. Rutherford M. Saket BM. J. Chem Soc., Perkin Trans. 2  1988,  1145 

2 Cook SD. Hamor TA. Jennings WB. Tebbutt AA. Watson SP. Boyd DR. J. Chem Soc., Perkin Trans. 2  1991,  1281 

3 Jennings WB. O’Shea JH. Schweppe A. Tetrahedron Lett.  2001,  42:  101 

4

The yields quoted in Scheme [1] are isolated yields following flash column chromatography on silica gel except for the volatile cyclohexene epoxide where it refers to the observed conversion as established by ¹H NMR analysis of the reaction product. A 10% excess of oxaziridine was employed. A problem encountered with the trifluoromethyl oxaziridine (1b) is that the N-phosphinoylimine byproduct is somewhat unstable and decomposes to several unidentified products, which can complicate product purification. This problem can be largely overcome by adding a couple of drops of water to the stirred epoxidation solution at the beginning of the reaction. The water hydrolyses the reactive imine byproduct to the volatile 1,1,1-trifluoroacetone and the relatively insoluble diphenylphosphinic amide. Obviously this procedure is not appropriate in enolate oxidations.

5 Lusinchi X. Hanquet G. Tetrahedron  1997,  53:  13727 

6 Davis FA. Ulatowski TG. Haque MS. J. Org. Chem.  1987,  52:  5288 

7 Davis FA. Reddy RT. Reddy RE. J. Org. Chem.  1992,  57:  6387 

8 Bunnage ME. Chernega AN. Davies SG. Goodwin CJ. J. Chem Soc., Perkin Trans. 1  1994,  2373 

9 Bunnage ME. Davies SG. Goodwin CJ. J. Chem Soc., Perkin Trans. 1  1994,  2385 

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Experimental Procedure: A solution of the β-aminoester(6) (300 mg, 0.75 mmol) in anhyd THF (5mL) was cooled to 0 °C and LHMDS (1.1 mmol, 1.1 mL) added dropwise via a syringe. After stirring at 0 °C for 40 min, the yellow enolate solution was cooled to -78 °C and the N-phosphinoyloxaziridine (1.5 mmol) was added in a small amount of dry THF. The mixture was then stirred at -78 °C for 2.5 h, warmed slowly to 0 °C (1 h) and quenched by the careful addition of aq NH₄Cl. After concentration on a rotary evaporator the residue was diluted with water (15 mL) and extracted with CH₂Cl₂ (3 × 20 mL). Rotary evaporation of the dried combined CH₂Cl₂ extracts afforded the crude product which was purified by flash chromatography on silica gel using hexane:diethyl ether (2:1) as eluent to afford the product as a diastereoisomeric mixture identified by
¹H and ¹³C NMR. The preparation of oxaziridines 1a-c has been previously reported. [1-3]

11

The anti/syn relative stereochemistry at C-2/C-3 in 7a and 7b respectively was assigned from the ¹H NMR data for the corresponding methyl and tert-butyl esters (See ref. [8] above). In particular, the more widely separated AB system with the largest J _AB coupling for the central OCH-CHN moiety [δ (CDCl₃) = 4.50 (d, J _AB = 9.6 Hz, OCH and 3.95 (d, J _AB = 9.6 Hz, CHN)] can be assigned to the syn isomer 7b. The anti isomer 7a gives a closer AB system with a much smaller coupling constant [δ (CDCl₃) = 4.43 (d, J _AB = 3.4 Hz, OCH) and 4.23 (d, J _AB = 3.4 Hz, CHN)].