Asymmetric Michael Addition of Arylthiols to α,β-Unsaturated Carbonyl Compounds Catalyzed by Bifunctional Organocatalysts

Abstract

Bifunctional chiral organocatalysts comprising thiourea and tertiary amine groups were synthesized. They act as efficient catalysts for asymmetric Michael addition of arylthiols to α,β-unsaturated carbonyl compounds. Enantioselectivity up to 85% has been achieved. Asymmetric α-protonation reaction (up to 60% ee) can be obtained in the presence of the bifunctional catalyst.

Key words

bifunctional organocatalyst - thiourea - hydrogen bonding - asymmetric Michael addition - asymmetric protonation

References

• For recent reviews on organocatalysis involving hydrogen bonding, see:
• 1a Pihko PM. Angew. Chem. Int. Ed.  2004,  43:  2062 
• 1b Dalko PI. Moisan L. Angew. Chem. Int. Ed.  2004,  43:  5138 
• For recent reviews on organocatalysis by proline and proline derivatives, see:
• 2a List B. Acc. Chem. Res.  2004,  37:  548 
• 2b Notz W. Tanaka F. Barbas CF. Acc. Chem. Res.  2004,  37:  580 
• 2c List B. Tetrahedron  2002,  58:  5573 
• 3a Huang Y. Rawal VH. J. Am. Chem. Soc.  2002,  124:  9662 
• 3b Huang Y. Unni AK. Thadani AN. Rawal VH. Nature  2003,  424:  146 
• 3c McDougal NT. Schaus SE. J. Am. Chem. Soc.  2003,  125:  12094 
• 3d Thadani AN. Stankovic AR. Rawal VH. Proc. Natl. Acad. Sci., U.S.A.  2004,  101:  5839 
• 3e Uraguchi D. Sorimachi K. Terada M. J. Am. Chem. Soc.  2004,  126:  11804 ; and references therein
• 4a Vachal P. Jacobsen EN. J. Am. Chem. Soc.  2002,  124:  10012 
• 4b Wenzel AG. Jacobsen EN. J. Am. Chem. Soc.  2002,  124:  12964 
• 4c Wenzel AG. Jacobsen EN. Synlett  2003,  1919 
• 4d Joly GD. Jacobsen EN. J. Am. Chem. Soc.  2004,  126:  4102 
• For a review, see:
• 5a Schreiner PR. Chem. Soc. Rev.  2003,  32:  289 
• 5b For thiourea as ligand in transition metal-catalyzed reactions, see: Yang D. Chen Y.-C. Zhu N.-Y. Org. Lett.  2004,  6:  1577 ; and references therein
• 6a Okino T. Hoashi Y. Takemoto Y. J. Am. Chem. Soc.  2003,  125:  12672 
• 6b Okino T. Nakamura S. Furukawa T. Takemoto Y. Org. Lett.  2004,  6:  625 
• 6c Okino T. Hoashi Y. Furukawa T. Xu X. Takemoto Y. J. Am. Chem. Soc.  2005,  127:  119 
• 6d Achiral F-C alkylation with nitroolefin, see: Dessole G. Herrera RP. Ricci A. Synlett  2004,  2374 
• 7a Sohtome Y. Tanatani A. Hashimoto Y. Nagasawa K. Chem. Pharm. Bull.  2004,  52:  477 
• 7b Sohtome Y. Tanatani A. Hashimoto Y. Nagasawa K. Tetrahedron Lett.  2004,  45:  5589 
• For a review on enantioselective 1,4-addition of thiol to activated olefin, see:
• 8a Fehr C. Angew. Chem., Int. Ed. Engl.  1996,  35:  2566 
• 8b For recent examples, see: Nishimura K. Ono M. Nagaoka Y. Tomioka K. J. Am. Chem. Soc.  1997,  119:  12974 
• 8c Emori E. Arai T. Sasai H. Shibashaki M. J. Am. Chem. Soc.  1998,  120:  4043 
• 8d Kanemasa S. Oderaotoshi Y. Wada E. J. Am. Chem. Soc.  1999,  121:  8675 
• 8e Kobayashi S. Ogawa C. Kawamura M. Sugiura M. Synlett  2001,  983 
• 8f McDaid P. Chen Y. Deng L. Angew. Chem. Int. Ed.  2002,  41:  338 
• 8g Nishimura K. Tomioka K. J. Org. Chem.  2002,  67:  431 
• 8h Matsumoto K. Watanabe A. Uchida T. Ogi K. Katsuki T. Tetrahedron Lett.  2004,  45:  2385 
• 9a For a recent review on asymmetric catalysis with modified cinchona alkaloids, see: Tian S.-K. Chen Y. Hang J. Tang L. McDaid P. Deng L. Acc. Chem. Res.  2004,  37:  621 
• 9b For late examples, see: Zhu C. Shen X. Nelson SG. J. Am. Chem. Soc.  2004,  126:  5352 
• 9c Li H. Wang Y. Tang L. Deng L. J. Am. Chem. Soc.  2004,  126:  9906 
• 9d Saaby S. Bella M. Jørgensen KA. J. Am. Chem. Soc.  2004,  126:  8120 
• 9e Acocella MR. Mancheno OG. Bella M. Jørgensen KA. J. Org. Chem.  2004,  69:  8165 
• 10 Brunner H. Bügler J. Nuber B. Tetrahedron: Asymmetry  1995,  6:  1699 
• 11a Goodman SN. Jacobsen EN. Adv. Synth. Catal.  2002,  344:  953 
• 11b For enantioselective 1,4-addition with unsaturated imide, see: Sammis GM. Danjo H. Jacobsen EN. J. Am. Chem. Soc.  2004,  126:  9928 ; and references therein
• 11c

  We failed to get the desired Michael addition product using cinnamoyl-2-oxazolidinone as the receptor.

• 12 Schreiner PR. Wittkopp A. Org. Lett.  2002,  4:  217 
• 13 Kaik M. Gawroñski J. Tetrahedron: Asymmetry  2003,  14:  1559 
• 16a Okino T. Hoashi Y. Takemoto Y. Tetrahedron Lett.  2003,  44:  2817 
• 16b Wittkopp A. Shreiner PR. Chem.-Eur. J.  2003,  9:  407 
• For catalytic asymmetric protonation in Michael additions of thiols, see:
• 17a Pracejus VH. Wilcke F.-W. Hanemann K. J. Prakt. Chem.  1977,  319:  219 
• 17b Kumar A. Salunkhe RV. Rane RA. Dike SY. J. Chem. Soc., Chem. Commun.  1991,  485 ; also see ref. 7c
• 17c For catalytic protonation of enolate, see: Ishihara K. Nakashima D. Hiraiwa Y. Yamamoto H. J. Am. Chem. Soc.  2003,  125:  24 ; and references therein
• 17d Hamashima Y. Somei H. Shimura Y. Tamura T. Sodeoka M. Org. Lett.  2004,  6:  1861 

14

HRMS data of new organocatalysts: 1a, 564.1770 (calcd 564.1782); 1b, 564.1781 (calcd 564.1782); 1f, 501.1853 (calcd 501.1861); 1g, 701.1728 (calcd 701.1734).

15

General Experimental Procedure for ( S , S )-1d-Catalyzed Asymmetric Michael Addition. Phenylthiol (12 µL, 0.11 mmol) was added to the stirred solution of α,β-unsaturated imide 7a (25.1 mg, 0.1 mmol) and 1d (4.2 mg, 0.01 mmol) in 0.5 mL CH₂Cl₂ at -40 °C. The reaction was stirred for 72 h. Flash chromatography eluting with petroleum ether-EtOAc (10:1) gave the product as a white solid (35.3 mg, 98%). ¹H NMR (400 MHz, CDCl₃): δ = 9.47 (s, NH), 7.78-7.76 (m, 2 H), 7.62-7.59 (m, 1 H), 7.51-7.47 (m, 2 H), 7.36-7.32 (m, 4 H), 7.29-7.19 (m, 6 H), 4.85 (dd, J = 1.6, 8.4 Hz, 1 H), 3.77 (dd, J = 8.4, 15.6 Hz, 1 H), 3.62 (dd, J = 8.4, 15.6 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 173.3, 165.6, 140.8, 133.9, 133.3, 133.1, 132.4, 128.9, 128.8, 128.4, 127.8, 127.7, 127.6, 127.4, 48.2, 43.8. ESI-MS: m/z = 360.1 [M - H]^-; ee was determined by HPLC on Daicel Chiralcel OD (20% 2-propanol in hexane, 0.5 mL/min, t _S = 10.8 min, t _R = 12.1 min, 75% ee).

18

The absolute configuration was determined by the rotation after conversion to ethyl ester.^8c