Efficient Parallel Resolution of Racemic Evans’ Oxazolidinones Using quasi-Enantiomeric Profens

Gregory S. Coumbarides; Marco Dingjan; Jason Eames; Anthony Flinn; Majid Motevalli; Julian Northen; Yonas Yohannes

doi:10.1055/s-2005-922784

LETTER

Efficient Parallel Resolution of Racemic Evans’ Oxazolidinones Using quasi-Enantiomeric Profens

Gregory S. Coumbarides^a, Marco Dingjan^a, Jason Eames*^a, Anthony Flinn^b, Majid Motevalli^a, Julian Northen^b, Yonas Yohannes^a
^a Department of Chemistry, Queen Mary, University of London, Mile End Road, London, E1 4NS, UK
Fax: +44(1482)466410; e-Mail: j.eames@hull.ac.uk;
^b Onyx Scientific Limited, Units 97-98, Silverbriar, Sunderland Enterprise Park East, Sunderland, SR5 2TQ, UK

Abstract

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Abstract

Racemic Evans’ oxazolidinones were efficiently resolved using a combination of quasi-enantiomeric profens. The levels of stereocontrol were high, giving products with predictable configurations.

Key words

chiral auxiliaries - chiral resolution - kinetic resolution - molecular recognition - stereoselectivity

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References

References and Notes

1

New address: Department of Chemistry, University of Hull, Kingston upon Hull, HU6 7RX, UK.

2a Eames J. Angew. Chem. Int. Ed. 2000, 39: 885 ; and references therein

2b Dehli J. Gotor V. Chem. Soc. Rev. 2002, 31: 365

2c Vedejs E. Jure M. Angew. Chem. Int. Ed. 2005, 44: 3974

2d For a review into the separation of enantiomers, see: Fogassy E. Nogradi M. Palovicsc E. Schindlerc J. Synthesis 2005, 20: 1555

3a Brandt J. Jochum C. Ugi I. Jochum P. Tetrahedron 1997, 33: 1353

3b Vedejs E. Rozners E. J. Am. Chem. Soc. 2001, 123: 2428

3c Vedejs E. Daugulis O. Mackay JA. Rozners E. Synlett 2001, 1499

3d Davies SG. Garner AC. Long MJC. Smith AD. Sweet MJ. Withey JM. Org. Biomol. Chem. 2004, 2: 3355

3e Zhang QS. Curran DP. Chem.-Eur. J. 2005, 4866

4 Liao L. Zhang F. Dmitrenko O. Bach RD. Fox JM. J. Am. Chem. Soc. 2004, 126: 4490

5 Vedejs E. Chen X. J. Am. Chem. Soc. 1997, 119: 2584

6 Davies SG. Diez D. El Hammouni MM. Garner AC. Garrido NM. Long MJC. Morrison RM. Smith AD. Sweet MJ. Withey JM. Chem. Commun. 2003, 2410

7 Coumbarides GS. Dingjan M. Eames J. Flinn A. Northen J. Yohannes Y. Tetrahedron Lett. 2005, 46: 2897

8a Coumbarides GS. Eames J. Flinn A. Northen J. Yohannes Y. Tetrahedron Lett. 2005, 46: 849 ; and references therein

8b Yohannes Y. PhD Thesis University of London; UK: 2004.

8c Fukuzawa S.-I. Chino Y. Yokoyama T. Tetrahedron: Asymmetry 2002, 13: 1645

9

Experimental Section: Representative Procedure for the Parallel Kinetic Resolution of Oxazolidinone ( rac )-1 Using quasi -Enantiomeric Profen Esters ( S )-17 and ( R )-25.
n-BuLi (0.61 mL, 2.5 M in hexane, 1.52 mmol) was added to a stirred solution of oxazolidinone (rac)-1 (0.18 g, 1.08 mmol) in THF (2 mL) at -78 °C. After stirring for 1 h, a solution of active esters (S)-17 (0.22 g, 0.55 mmol) and (R)-25 (0.20 g, 0.55 mmol) in THF (2 mL) were slowly added. The resulting solution was stirred for a further 2 h at -78 °C. The reaction was quenched with H₂O (10 mL) and extracted with Et₂O (2 × 20 mL). The combined organic layers were dried (over MgSO₄) and evaporated under reduced pressure. The residue was purified by flash column chromatography eluting with light PE (40-60 °C)-Et₂O (1:1) to give oxazolidinone syn-21 (101 mg, 49%) as a white solid and oxazolidinone syn-26 (99 mg, 52%) as a white solid.
Oxazolidinone syn-21: mp 168-170 °C; R _f = 0.19 [light PE (40-60 °C)-Et₂O (1:1)]; [α]_D ²⁴ +166.2 (c 1.5, CHCl₃). IR (CHCl₃): ν_max = 1780 and 1706 (CO), 1632, 1605 and 1500 (Ar) cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 7.64 (1 H, d, J = 7.7 Hz, CH, Ar), 7.52 (1 H, d, J = 7.7 Hz, CH, Ar), 7.35 (1 H, br s, CH, Ar), 7.30-7.05 (5 H, m, 6 × CH, Ar and Ph), 6.88 (2 H, d, J = 7.7 Hz, 2 × CH, Ar), 5.46 (1 H, dd, J = 9.2, 5.2 Hz, CHN), 5.20 (1 H, q, J = 6.9 Hz, CHCO), 4.63 (1 H, t, J = 8.9 Hz, CH _AH_BO), 4.05 (1 H, dd J = 8.9, 5.2 Hz, CH_A H _BO), 3.92 (3 H, s, CH ₃, CH ₃O), 1.44 (3 H, d, J = 6.9 Hz, CH ₃CH). ¹³C NMR (100.6 MHz, CDCl₃): δ = 173.3 (C=O), 157.7 (C=O), 153.1 (i-COCH₃, Ar), 138.2 (i-C, Ar), 135.2 (i-C, Ar), 133.7, 129.4, 128.9, 128.5, 127.4, 127.1, 126.4, 126.0, 118.8 and 105.5 (10 × C, Ar and Ph), 69.6 (CHN), 57.9 (CH₂O), 55.3 (CH₃O), 43.9 (CHCO), 18.8 (CH₃). MS: m/z calcd for C₂₃H₂₂NO₄: 376.1549; found: 376.1553 [MH⁺].
Oxazolidinone syn-26: mp 97-99 °C; R _f = 0.47 [light PE (40-60 °C)-Et₂O (1:1)]; [α]_D ²⁴ -99.1 (c 0.4, CHCl₃). IR (CHCl₃): ν_max = 1779 and 1705 (CO), 1514 (Ar) cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 7.28-7.15 (3 H, m, 3 × CH, Ph), 7.0 (4 H, s, 4 × CH, Ar), 6.90 (2 H, d, J = 7.9 Hz, 2 × CH, Ph), 5.44 (1 H, dd, J = 9.2, 5.2 Hz, CHN), 5.09 (1 H, q, J = 6.9 Hz, CHCO), 4.63 (1 H, t, J = 9.2 Hz, CH _AH_BO), 4.06 (1 H, dd, J = 8.9, 5.2 Hz, CH_A H _BO), 2.43 (2 H, d, J = 7.4 Hz, CH ₂CHCH₃), 1.89-1.79 [1 H, m, CH(CH₃)₂], 1.38 (3 H, d, J = 6.9 Hz, CH ₃CHCO), 0.90 [6 H, d, J = 6.7 Hz, 2 × CH₃, (CH ₃)₂CH)]. ¹³C NMR (100.6 MHz, CDCl₃): δ = 174.3 (C=O), 153.3 (C=O), 140.7, 139.4 and 137.4 (3 × i-C, Ar and Ph), 129.3, 129.2, 128.7, 127.9, 125.8 (5 × CH, Ar and Ph), 69.7 (NCH), 58.1 (CH₂O), 45.1 (CHCO), 42.7 (CH₂Ar), 30.2 [CH(CH₃)₂], 22.4 [CH(CH₃)₂], 19.4 [CH₃CH]. MS: m/z calcd for C₂₂H₂₆NO₃: 352.1913; found: 352.1909 [MH⁺].).