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Synlett 2003(11): 1659-1662
DOI: 10.1055/s-2003-41425
LETTER
© Georg Thieme Verlag Stuttgart · New York

Oxidative Functionalisation of SuperQuat Enamides: Asymmetric Synthesis of Homochiral 1,2 Diols

Stephen G. Davies*, Min-Suk Key, Humberto Rodriguez-Solla, Hitesh J. Sanganee, Edward D. Savory, Andrew D. Smith
The Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QY, UK
e-Mail: steve.davies@chem.ox.ac.uk;
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Publication History

Received 20 June 2003
Publication Date:
22 September 2003 (online)

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Abstract

Homochiral (E)-enamides derived from (S)-4-phenyl-5,5-dimethyl-oxazolidin-2-one undergo highly diastereoselective epoxidation upon treatment with dimethyldioxirane (DMDO). Treatment with m-chloroperbenzoic acid (MCPBA) produces syn-(4S,1′R,2′S)-1′-acyloxy-2′-hydroxy derivatives with high diastereoselectivity, consistent with a mechanism involving initial epoxidation and subsequent in situ SN1 type epoxide opening and trapping with m-chlorobenzoic acid. Reductive cleavage of the isolated 1′-acyloxy-2′-hydroxy derivatives generates 1,2-diols in high yields and in high ee.

Key words

homochiral 1,2-diols - SuperQuat enamides - asymmetric synthesis

9

Experimental procedure for the synthesis (4S,1′E)-3-(2′-phenylethenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (6): Phenylacetaldehyde (0.44 mL, 3.77 mmol) was added to oxazolidinone (S)-5 (600 mg, 3.14 mmol) in toluene (50 mL) and p-TSA (10 mg, 0.06 mmol) and heated under Dean-Stark conditions for three hours before concentration in vacuo. Purification by column chromatography [EtOAc/petroleum ether (40-60), 1:15] gave 6 (780 mg, 85%) as white crystals; mp 144 °C; IR (CH2Cl2) cm-1: 1752 (C=O); [α]23 D +7.8 (c 1, CH2Cl2); Found; C, 78.0; H, 6.5, N, 4.65%; C19H19NO2 requires C, 77.8; H, 6.5, N, 4.8%; δH (400MHz, CDCl3) 7.50-7.12 [11 H, m, ArCH and CH=C(2) ′HPh], 5.51 [1 H, d, J = 14.5 Hz, C(1′)H=CHPh], 4.81 [1 H, s, C(4)H], 1.66 and 1.00 [2 × 3 H, s, C(5)Me 2]; δC (125 MHz, CDCl3) 155.2 (CO), 136.2, 135.0 (Ph:C ipso × 2), 129.3, 129.1, 128.8, 126.8, 125.6 (Ph:CH), 123.4 [C(2′)H], 113.0 [C(1′)H], 82.6 [C(5)], 68.1 [C(4)H], 29.2, 24.0 [C(5)Me 2]; m/z (CI+, NH3) 294 (MH+).

12

Experimental procedure for the synthesis of (4S,1′R,2′S)-3-(1′-m-chlorobenzoate-1′-ethyl-2′-phenyl-2′-hydroxy)-5,5-dimethyl-4-phenyloxazolidin-2-one(8): MCPBA (221 mg, 0.64 mmol) was added to a solution of enamide 6 (150 mg, 0.51 mmol) in CHCl3 (8 mL) at 0 °C and stirred for 30 min before warming to r.t .for 2 h. H2O (2 mL) was then added and the resulting solution concentrated in vacuo and partitioned between CH2Cl2 and sat. aq NaHCO3. The separated organic phase was washed with sat. aq NH4Cl and brine, dried (MgSO4) and the concentrated in vacuo to afford a white solid which was purified by recrystallisation from CH2Cl2/hexanes to give 8 (200 mg, 84%) as white crystals; mp 106 °C; IR cm-1: 1757, 1736 (C=O); [α]25 D +94.0 (c1.0, CHCl3); δH (200 MHz, CDCl3) 7.97-7.04 (14 H, m, ArH), 6.24 [1 H, d, J = 7.8 Hz, C(1′)H], 5.67 [1 H, d, J = 7.8 Hz, C(2′)H], 3.95 [1 H, s, C(4)H], 2.64 (1 H, s, OH), 0.99, 0.83 [2 × 3 H, s, C(5)Me 2]; δC (125 MHz, CDCl3) 164.0 (C=O), 156.7 (NC=O), 139.4 (Ph:C ipso), 135.5 (ArCCl), 134.6 (Ph:C ipso), 133.8, 133.6 (Ph:CH), 131.2 (Ph:C ipso), 130.4, 130.1, 129.9, 129.5, 129.2, 129.0, 128.9, 128.7, 128.4, 128.3, 127.3 (Ph:CH), 82.7 [C(5)Me2], 82.3 [C(1′)H], 72.7 [C(2′)H], 71.4 [C(4)H], 27.9, 23.4 [C(5)Me 2]; HRMS (APCI+) Found: 488.1241, C26H24NO5NaCl+ requires 488.1232.

13

Data were collected using an Enraf Nonius Kappa CCD diffractometer with graphite monochromated Cu-Kα radiation using standard procedures at room temperature. The structure was solved by direct methods (SIR92), all non-hydrogen atoms were refined with anisotropic thermal parameters. Hydrogen atoms were added at idealised positions. The crystal structure contains a molecule of solvent(pentane) and the chlorine of the m-chlorobenzoic ester fragment was disordered over two sites; Cl(1):Cl(34) 0.80:0.20. The model was refined using CRYSTALS. [25] Crystal Data for 8, C31H35ClNO5, colourless block, M = 536.73, orthorhombic, space group P 21 21 21, a = 9.8350(2) Å, b = 11.0530(2) Å, c = 27.4884(5) Å, U = 2988.2 Å3, Z = 4, µ = 0.165 mm-1, crystal dimensions 0.2 × 0.2 × 0.2 mm, A total of 6376 unique reflections were measured for 1 < θ < 27 and 4518 reflections were used in the refinement. The final parameters were R1 = 0.0510 [I > 3σ(I)] and wR2 = 0.059. Crystallographic data (excluding structure factors) has been deposited with the Cambridge Crystallographic Data Centre (CCDC 213199).

15

Regioselective SN2 opening of epoxide 7 at C(1′) would be expected to furnish anti-(4S,1′S,2′S)-1′-m-chlorobenzoate-20 (Scheme [5] ).

Scheme 5

16

Experimental procedure for the synthesis of (S)-1-phenylethanediol 10: A solution of 8 (100 mg, 0.22 mmol) in MeOH (2 mL) was added to NaBH4 (65 mg, 1.72 mmol) in MeOH (3 mL) and stirred at r.t. for 10 minutes before concentration in vacuo. The residue was dissolved in CH2Cl2 (10 mL) and HCl (1 M, 2 mL) was added and the mixture extracted with CH2Cl2 (3 × 10 ml), dried and concentrated in vacuo. Purification by chromatography [(40-60) petroleum ether/EtOAc, 1:2] gave auxiliary (S)-5 (32mg, 78%) and alcohol 10 (24mg, 81%); [α]22 D +64 (c 0.25, CHCl3), δH (200 MHz, CDCl3) 7.38-7.27 (5 H, m, ArH), 4.82 [1 H, dd, J = 7.9 Hz, J = 3.8 Hz, C(1)H], 3.75-3.67 [2 H, m, C(2)H 2], 2.88 and 2.48 (2 × 1 H, br s, OH).

17

Commercially available from the Aldrich Chemical Company.

19

Chiral gas chromatography of diol 10 was performed on a CE Instruments Trace GC (Thermoquest) machine with an SGE Cydex-β stationary phase (25 m × 0.22 mm) with helium as the carrier gas and a flow rate of 1.5 mL per min using a FID detector. An isocratic temperature of 40 °C was followed for 120 minutes, followed by a temperature ramp of 4 °C to 140 °C for 120 minutes and comparison with an authentic racemic sample. Retention times were 159.25 min (S) and 159.87 min (R).

21

Chiral gas chromatography of the bis-trifluoroacetate derivative of 17 was performed on a CE Instruments Trace GC (Thermoquest) machine with an SGE Cydex-β stationary phase (25 m × 0.22 mm) with helium as the carrier gas and a flow rate of 2 mL per min using a FID detector. An isocratic temperature of 50 °C was followed for 120 minutes, followed by a temperature ramp of 4 °C to 110 °C for 60 minutes and comparison with an authentic racemic sample. Retention times were 139.38 min (S) and 139.89 min (R).

23

Although chromatographic purification led to the separation of diol and auxiliary, the isolated yield of the diol could be increased by acetylation of the crude reaction mixture resulting from reduction, which facilitated chromatographic purification of the bis-acetate derivative of the diol.

24

Chiral gas chromatography of the bis-acetate derivatives was performed on a CE Instruments Trace GC (Thermoquest) machine with an SGE Cydex-β stationary phase (25 m × 0.22 mm) with helium as the carrier gas and a flow rate of 1 mL per min using a FID detector. An isocratic temperature of 40 °C was followed for 30 minutes, followed by a temperature ramp of 5 °C to 60 °C for 30 minutes, another temperature ramp of 20 °C to 190 °C for 2 minutes and comparison with an authentic racemic sample. Retention times for 18-(OAc)2 69.41 min (S) and 69.45 min (R); for 19-(OAc)2 51.00 (R) and 51.07 min (S).