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

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Synlett 2006(1): 0101-0105
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

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Publication History

Received 11 October 2005
Publication Date:
16 December 2005 (online)

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

References and Notes

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

Article in Thieme Connect Google Scholar
2b Dehli J. Gotor V. Chem. Soc. Rev. 2002, 31: 365

Article in Thieme Connect Google Scholar
2c Vedejs E. Jure M. Angew. Chem. Int. Ed. 2005, 44: 3974

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

Article in Thieme Connect Google Scholar
3a Brandt J. Jochum C. Ugi I. Jochum P. Tetrahedron 1997, 33: 1353

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

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

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

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

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

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

Crossref Google Scholar
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

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

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

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

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

Crossref Google Scholar

1

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

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⁺].).