Catalytic Asymmetric Epoxidation of α-Methyl α,β-Unsaturated Anilides as Ester Surrogates

Abstract

Catalytic asymmetric epoxidation of α-methyl α,β-unsaturated carboxylic acid derivatives was achieved using anilide as a template. The Pr(Oi-Pr)₃-6,6′-Ph-BINOL complex (10 mol%) with a Ph₃P(O) (30 mol%) additive promoted the epoxidation of anilides in up to 99% yield and 88% ee. For α-methyl-β-Ph α,β-unsaturated anilide, the Gd(Oi-Pr)₃-6,6′-I-BINOL complex (10 mol%) with Ar₃P(O) (30 mol%, Ar = 4-methoxyphenyl) was suitable, giving epoxide in 87% yield and 78% ee.

Key words

asymmetric catalysis - epoxide - anilide - BINOL - rare-earth metal

References and Notes

• Recent general reviews for catalytic asymmetric epoxidation, see:
• 1a Bonini C. Righi G. Tetrahedron  2002,  58:  4981 
• 1b Xia Q.-H. Ge H.-Q. Ye C.-P. Liu Z.-M. Su K.-X. Chem. Rev.  2005,  105:  1603 
• 1c McGarrigle EM. Gilheany DG. Chem. Rev.  2005,  105:  1563 ; and references therein
• Reviews on asymmetric epoxidation of electron deficient C-C double bonds:
• 1d Porter MJ. Skidmore J. Chem. Commun.  2000,  1215 
• 1e Nemoto T. Ohshima T. Shibasaki M. J. Synth. Org. Chem. Jpn.  2002,  60:  94 
• Chiral ketone catalysis:
• 1f Shi Y. Acc. Chem. Res.  2004,  37:  488 ; and references therein
• 1g Yang D. Acc. Chem. Res.  2004,  3:  497 
• Polyamino acid catalysis:
• 1h Lauret C. Roberts SM. Aldrichimica Acta  2002,  35:  47 
• 1i Kelly DR. Roberts SM. Biopolymers  2006,  84:  74 
• 2 α,β-Unsaturated ester: Kakei H. Tsuji R. Ohshima T. Shibasaki M. J. Am. Chem. Soc.  2005,  127:  8962 
• α,β-Unsaturated N-acylimidazole:
• 3a Nemoto T. Ohshima T. Shibasaki M. J. Am. Chem. Soc.  2001,  123:  9474 
• Amide:
• 3b Nemoto T. Kakei H. Gnanadesikan V. Tosaki S.-y. Ohshima T. Shibasaki M. J. Am. Chem. Soc.  2002,  124:  14544 
• N-Acylpyrrole:
• 3c Kinoshita T. Okada S. Park S.-R. Matsunaga S. Shibasaki M. Angew. Chem. Int. Ed.  2003,  42:  4680 
• 3d Matsunaga S. Kinoshita T. Okada S. Harada S. Shibasaki M. J. Am. Chem. Soc.  2004,  126:  7559 
• Amide and anilide:
• 3e Tosaki S.-y. Tsuji R. Ohshima T. Shibasaki M. J. Am. Chem. Soc.  2005,  127:  2147 
• For selected examples of highly enantioselective catalytic epoxidation of α,β-unsaturated ester by other groups:
• 4a Wu X.-Y. She X. Shi Y. J. Am. Chem. Soc.  2002,  124:  8792 ; and references therein
• 4b Seki M. Furutani T. Imashiro R. Kuroda T. Yamanaka T. Harada N. Arakawa H. Kusama M. Hashiyama T. Tetrahedron Lett.  2001,  42:  8201 
• 4c Jacobsen EN. Deng L. Furukawa Y. Martinez LE. Tetrahedron  1994,  50:  4323 ; and references therein
• 4d

  For other examples, see the reviews in ref. 1 and references therein.

• For examples of highly enantioselective asymmetric epoxidation of α,β-unsaturated aldehydes, see:
• 5a Marigo M. Franzén J. Poulsen TB. Zhuang W. Jørgensen KA. J. Am. Chem. Soc.  2005,  127:  6964 
• 5b Sundén H. Ibrahem I. Córdova A. Tetrahedron Lett.  2006,  47:  99 
• Rare-earth-metal-BINOL complex for asymmetric epoxidation of enones:
• 6a Bougauchi M. Watanabe T. Arai T. Sasai H. Shibasaki M. J. Am. Chem. Soc.  1997,  119:  2329 
• 6b Nemoto T. Ohshima T. Yamaguchi K. Shibasaki M. J. Am. Chem. Soc.  2001,  123:  2725 
• 6c See also: Daikai K. Kamaura M. Inanaga J. Tetrahedron Lett.  1998,  39:  7321 
• 8a For an elegant catalytic asymmetric 1,4-addition of amine nucleophile to α,β-disubstituted α,β-unsaturated carboxylic acid derivatives using imide as a template, see: Sibi MP. Prabagaran N. Ghorpade SG. Jasperse CP. J. Am. Chem. Soc.  2003,  125:  11796 
• 8b For use of imides in asymmetric catalysis, see also: Goodman SN. Jacobsen EN. Adv. Synth. Catal.  2002,  344:  953 ; and references therein
• 9 For use of anilide activated with Boc group as a template, see: Saito S. Kobayashi S. J. Am. Chem. Soc.  2006,  128:  8704 
• 10 THF-toluene mixed solvent gave better results than THF alone in related asymmetric epoxidation. Matsunaga S. Qin H. Sugita M. Okada S. Kinoshita T. Yamagiwa N. Shibasaki M. Tetrahedron  2006,  62:  6630 
• For catalyst tuning of rare-earth-metal-BINOL complexes by various phosphine oxides, see:
• 11a Yamagiwa N. Tian J. Matsunaga S. Shibasaki M. J. Am. Chem. Soc.  2005,  127:  3413 ; and references therein
• 11b

  See also ref. 6c.

• 12a Grehn L. Gunnarsson K. Ragnarsson U. J. Chem. Soc., Chem. Commun.  1985,  1317 
• 12b

  For a different strategy to convert anilides into carboxylic acids, see ref. 9.

• 14a

  Relative configurations of epoxide 3e, 3f, and 3k were confirmed to be trans by NOE. Absloute configuration of epoxide 3i was determined to be 2R,3S after conversion into known compound 8i by comparing sign of optical rotation. Absolute configuration of epoxide 3l was determined to be 2R,3S by comparing sign of optical rotation of 7l with reported data.

• 14b Compound 8i: Jung ME. D’Amico DC. J. Am. Chem. Soc.  1995,  117:  7379 
• 14c Compound 7l: Lee M. Kim DH. Bioorg. Med. Chem.  2000,  8:  815 
• 14d

  Relative and absolute configurations of other products were tentatively assigned by analogy.

7

Shi and co-workers realized highly enantioselective catalytic epoxidation of an acyclic (Z)-α-methyl α,β-unsaturated ester using chiral ketone catalyst. Use of (E)-α-substituted α,β-unsaturated ester was limited to a cyclic substrate. See, ref. 5a. We also succeeded in asymmetric epoxidation of cyclic α-substituted α,β-unsaturated amides (two examples). See ref. 3e.

13

General Procedure of Catalytic Asymmetric Epoxidation of Anilide 2.
MS 4 Å (300 mg, powdered) in a flask was flame-dried prior to use under vacuum (0.7 kPa) for 5 min. To a stirred suspension of Ph₃P(O) (25.0 mg, 0.09 mmol), (S)-6,6′-Ph-BINOL (13.2 mg, 0.03 mmol) and MS 4 Å in dry THF (1.5 mL) and toluene (1.5 mL) at 25 °C was added Pr(Oi-Pr)₃ (0.15 mL, 0.03 mmol, 0.2 M in THF). The mixture was stirred for 10 min at 25 °C and tert-butyl hydroperoxide (TBHP; 90 µL, 0.36 mmol, 4 M in toluene) was added. After 10 min, 2e (65.5 mg, 0.3 mmol) was added. After 4 h, the reaction was quenched with 2% aq citric acid. The mixture was extracted with CH₂Cl₂ (3×). Then, the combined organic layers were washed with brine and dried over MgSO₄. The solvent was evaporated under reduced pressure and the resulting crude residue was purified by flash silica gel column chromatography (acetone-hexane = 1:20 to 1:5) to afford 3e (92% yield, 87% ee).

15

α-Substituents other than methyl are still problematic at present. For example, α-ethyl β-methyl α,β-unsaturated anilide gave epoxide in 39% yield and 73% ee. Studies to improve reactivity and enantioselectivity are in progress.