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

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 S_N1 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.

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

References

1a Adam W. Peters E.-M. Peters K. von Schnering HG. Voerckel V. Chem. Ber.  1992,  125:  1263 

1b Adam W. Ahrweiler M. Paulini K. Reissig H.-U. Voerckel V. Chem. Ber.  1992,  125:  2719 

2a Barton DHR. Motherwell WB. Zard SZ. J. Chem. Soc., Chem. Commun.  1981,  774 

2b Zhang X. Foote CS. J. Am. Chem. Soc.  1993,  115:  8867 

2c Adam W. Ahrweiler M. Sauter M. Schmiedeskamp B. Tetrahedron Lett.  1993,  34:  5247 

2d Adam W. Ahrweiler M. Peters K. Schmiedeskamp B. J. Org. Chem.  1994,  59:  2733 

2e Adam W. Reinhardt D. J. Chem. Soc., Perkin Trans. 2  1994,  1503 

3 Baldwin JE. O’Neil IA. Tetrahedron Lett.  1990,  31:  2047 

4 Baldwin JE. Aldous DJ. Chan C. Harwood LM. O’Neil IA. Peach JM. Synlett  1989,  9 ; and references contained therein

5a Bach J. Bull SD. Davies SG. Nicholson RL. Sanganee HJ. Smith AD. Tetrahedron Lett.  1999,  40:  6677 

5b Bull SD. Davies SG. Nicholson RL. Smith AD. Tetrahedron: Asymmetry  2000,  11:  3475 

5c Davies SG. Nicholson RL. Smith AD. Synlett  2002,  1637 

5d Bach J. Bull SD. Davies SG. Nicholson RL. Sanganee HJ. Smith AD. Org. Biomol. Chem.  2003,  2001 

5e For a related approach see: Gaul C. Scharer K. Seebach D. J. Org. Chem.  2001,  66:  3059 

6a Xiong H. Hsung RP. Berry CR. Rameshkumar C. J. Am. Chem. Soc.  2001,  123:  7174 

6b Rameshkumar C. Xiong H. Tracey MR. Berry CR. Yao LJ. Hsung RP. J. Org. Chem.  2002,  67:  1339 

7a Adam W. Bosio SG. Wolff BT. Org. Lett.  2003,  5:  819 

7b Xiong H. Hsung RP. Shen L. Hahn JM. Tetrahedron Lett.  2002,  43:  4449 

7c For earlier studies regarding the epoxidation of an achiral enamide see: Adam W. Reinhardt D. Reissig H.-U. Paulini K. Tetrahedron  1995,  45:  12257 

7d For a related protocol see: Adam W. Bosio SG. Turro NJ. J. Am. Chem. Soc.  2002,  124:  8814 

8 For preliminary studies in this area see: Sanganee HJ. DPhil Thesis   University of Oxford; UK: 1996. 

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%; δ_H (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]; δ_C (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⁺).

10a Based upon the related protocol for the synthesis of N-alkenyl lactams described in: Zezza CA. Smith MB. Synth. Commun.  1987,  17:  729 

10b For a related protocol see: Akiba T. Tamura O. Hashimoto M. Kobayashi Y. Katoh T. Nakatani K. Kamada M. Hayakawa I. Terashima S. Tetrahedron  1994,  50:  3905 

11 Adam W. Bialas J. Hadjiarapoglou L. Chem. Ber.  1991,  124:  2377 

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); δ_H (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]; δ_C (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 ų, 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).

For related N-acyliminium species see:

14a Marcantoni E. Mecozzi T. Petrini M. J. Org. Chem.  2002,  67:  2989 

14b Mulder JA. Hsung RP. Frederick MO. Tracey MR. Zificsak CA. Org. Lett.  2002,  4:  1383 

15

Regioselective S_N2 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), δ_H (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.

18 Virsu P. Liljeblad A. Kanerva A. Kanerva LT. Tetrahedron: Asymmetry  2001,  12:  2447 

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).

20 Bergstein W. Kleemann A. Martens J. Synthesis  1981,  76 

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).

22 Guette JP. Spassky N. Bull. Soc. Chim. Fr.  1972,  4217 

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).

25 Watkin DJ. Prout CK. Carruthers JR. Betteridge PW. Cooper RI. CRYSTALS   Issue 11:  Chemical Crystallography Laboratory; Oxford UK: 2001.