An Enantioselective Formal Synthesis of (+)-(R)-α-Lipoic Acid by an l-Proline-Catalyzed Aldol Reaction

Shilei Zhang; Xiaobei Chen; Jiangang Zhang; Wei Wang; Wenhu Duan

doi:10.1055/s-2008-1032022

PAPER

An Enantioselective Formal Synthesis of (+)-(R)-α-Lipoic Acid by an l-Proline-Catalyzed Aldol Reaction

Shilei Zhang^a, Xiaobei Chen^b, Jiangang Zhang^b, Wei Wang*^a,c, Wenhu Duan*^a,b
^a Department of Medicinal Chemistry, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, P. R. of China
^b Shanghai Institute of Materia Medica, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 201203, P. R. of China
^c Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131-0001, USA
Fax: +1(505)2772609; e-Mail: wwang@unm.edu;

Abstract

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Abstract

An efficient, highly stereocontrolled formal synthesis of (+)-(R)-α-lipoic acid was achieved, which utilizes an l-proline-catalyzed highly enantio- and diastereoselective cross-aldol reaction as the key step.

Key words

aldehyde - aldol reaction - ketone - lipoic acid - proline

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References

1a Sigel H. Angew. Chem., Int. Ed. Engl. 1982, 21: 389

1b Yadav JS. Mysorekar SV. Garyali K. J. Sci. Ind. Res. 1990, 49: 400 ; and references cited therein

2 Packer L. Tritschler HJ. Wessel K. Free Rad. Biol. Med. 1997, 22: 359

3 Baur A. Harrer T. Peukert M. Jahn G. Kalden JR. Fleckenstein B. Klin. Wochenschr. 1991, 69: 722 ; Chem. Abstr. 1992, 116, 207360

4 Bingham PM, and Zachar Z. inventors; WO 0024734. ; Chem. Abstr. 2000, 132, 3081921

For examples of racemic syntheses of lipoic acid, see:

5a Segre A. Viterbo R. Parisi G. J. Am. Chem. Soc. 1957, 79: 3503

5b Tsuji J. Yasuda H. Mandai T. J. Org. Chem. 1978, 43: 3606

5c Menon RB. Kumar MA. Ravindranathan T. Tetrahedron Lett. 1987, 28: 5313

5d Crevisy C. Herbage B. Marrel M.-L. Toupet L. Gree R. Eur. J. Org. Chem. 1998, 1949

5e Chavan SP. Shivsankar K. Pasupathy K. Synthesis 2005, 1297

For examples of using chiral auxiliaries or precursors for asymmetric syntheses of lipoic acid, see:

6a Brookes MH. Golding BT. Howes DA. Hudson AT. J. Chem. Soc., Chem. Commun. 1983, 1051

6b Elliott JD. Steele J. Johnson WS. Tetrahedron Lett. 1985, 26: 2535

6c Rama Rao AV. Mysorekar SV. Gurjar MK. Yadav JS. Tetrahedron Lett. 1987, 28: 2183

6d Brookes MH. Golding BT. Hudson AT. J. Chem. Soc., Perkin Trans. 1 1988, 9

6e Silks LA. Peng J. Odom JD. Dunlap RB. J. Chem. Soc., Perkin Trans. 1 1991, 2495

For examples of enzymatic reactions for asymmetric syntheses of lipoic acid, see:

7a Brooks DW. Kellogg RP. Cooper CS. J. Org. Chem. 1987, 52: 192

7b Gopalan AS. Jacobs HK. Tetrahedron Lett. 1989, 30: 5705

7c Dasaradhi L. Fadnavis NW. Bhalerao UT. J. Chem. Soc., Chem. Commun. 1990, 729

7d Gopalan AS. Jacobs HK. J. Chem. Soc., Perkin Trans. 1 1990, 1897

7e Adger B. Bes MT. Grogan G. McCague R. Pedragosa-Moreau S. Roberts SM. Villa R. Wan PWH. Willetts AJ. J. Chem. Soc., Chem. Commun. 1995, 1563

7f Laxmi YRS. Lyengar DS. Synthesis 1996, 594

7g Bezbarua MS. Saikia AK. Barua NC. Kalita D. Ghosh AC. Synthesis 1996, 1289

7h Adger B. Bes MT. Grogan G. McCague R. Pedragosa-Moreau S. Roberts SM. Villa R. Wan PWH. Willetts AJ. Bioorg. Med. Chem. 1997, 5: 253

7i Fadnavis NW. Babu RL. Vadivel SK. Deshpande AA. Bhalerao UT. Tetrahedron: Asymmetry 1998, 9: 4109

For examples of asymmetric syntheses of lipoic acid catalyzed by organometallic reagents, see:

8a Page PCB. Rayner CM. Sutherland IO. J. Chem. Soc., Chem. Commun. 1986, 1408

8b Page PCB. Rayner CM. Sutherland IO. J. Chem. Soc., Perkin Trans. 1 1990, 1615

8c Zimmer R. Hain U. Berndt M. Gewald R. Reissig H.-U. Tetrahedron: Asymmetry 2000, 11: 879

8d Upadhya TT. Nikalje MD. Sudalai A. Tetrahedron Lett. 2001, 42: 4891

8e Zimmer R. Peritz A. Czerwonka R. Schefzig L. Reissig H.-U. Eur. J. Org. Chem. 2002, 3419

8f Chavan SP. Praveen C. Ramakrishna G. Kalkote UR. Tetrahedron Lett. 2004, 45: 6027

8g Bose DS. Fatima L. Rajender S. Synthesis 2006, 1863

For selected recent reviews of organocatalysis, see:

9a Dalko PI. Moisan L. Angew. Chem. Int. Ed. 2001, 40: 3726

9b Dalko PI. Moisan L. Angew. Chem. Int. Ed. 2004, 43: 5138

9c List B. Tetrahedron 2002, 58: 5573

9d Notz W. Tanaka F. Barbas CF. Acc. Chem. Res. 2004, 37: 580

9e Jarvo ER. Miller SJ. Tetrahedron 2002, 58: 2481

9f Special issue on Asymmetric Organocatalysis: Acc. Chem. Res. 2004, 37: 487

For l-proline-promoted aldol reactions, see:

10a List B. Lerner RA. Barbas CF. J. Am. Chem. Soc. 2000, 122: 2395

10b Northrup AB. MacMillan DWC. J. Am. Chem. Soc. 2002, 124: 6798

10c Enders D. Grondal C. Angew. Chem. Int. Ed. 2005, 44: 1210

10d Casas J. Engqvist M. Ibrahem I. Kaynak B. Córdova A. Angew. Chem. Int. Ed. 2005, 44: 1343

10e Pan Q. Zou B. Wang Y. Ma D. Org. Lett. 2004, 6: 1009

10f Northrup AB. MacMillan DWC. Science 2004, 305: 1752

10g Suri JT. Ramachary DB. Barbas CF. Org. Lett. 2005, 7: 1383

For selected examples of aldol reactions catalyzed by proline derivatives, see:

11a Mase N. Tanaka F. Barbas CF. Angew. Chem. Int. Ed. 2004, 43: 2420

11b Sakthivel K. Notz W. Bui T. Barbas CF. J. Am. Chem. Soc. 2001, 123: 5260

11c Nakadai M. Saito S. Yamamoto H. Tetrahedron 2002, 58: 8167

11d Tang Z. Jiang F. Yu L.-T. Cui X. Gong L.-Z. Mi A.-Q. Jiang Y.-Z. Wu Y.-D. J. Am. Chem. Soc. 2003, 125: 5262

11e Mangion IK. Northrup AB. MacMillan DWC. Angew. Chem. Int. Ed. 2004, 43: 6722

11f Krattiger P. Kovasy R. Revell JD. Ivan S. Wennemers H. Org. Lett. 2005, 7: 1101

11g Torii H. Nakadai M. Ishihara K. Saito S. Yamamoto H. Angew. Chem. Int. Ed. 2004, 43: 1983

11h Cobb AJA. Shaw DM. Longbottom DA. Ley SV. Org. Biomol. Chem. 2005, 3: 84

11i Wang W. Li H. Wang J. Tetrahedron Lett. 2005, 46: 5077

11j Hayashi Y. Sumiya T. Takahashi J. Gotoh H. Urushima T. Shoji M. Angew. Chem. Int. Ed. 2006, 45: 958

11k Dziedzic P. Zou W. Hafren J. Córdova A. Org. Biomol. Chem. 2006, 4: 38

11l Chimni SS. Mahajan D. Babu VVS. Tetrahedron Lett. 2005, 46: 5617

11m Bellis E. Vasilatou K. Kokotos G. Synthesis 2005, 2407

11n Chen J.-R. Lu H.-H. Li X.-Y. Cheng L. Wan J. Xiao W.-J. Org. Lett. 2005, 7: 4543

12a Zhang S.-L. Duan W.-H. Wang W. Adv. Synth. Catal. 2006, 348: 1228 ; and other examples using l-proline-catalyzed aldol reactions in natural product synthesis for total synthesis

12b Mangion IK. MacMillan DWC. J. Am. Chem. Soc. 2005, 127: 3696

12c Pihko PM. Erkkila A. Tetrahedron Lett. 2003, 44: 7607

13 Molander GA. McKie JA. J. Org. Chem. 1993, 58: 7216

14 Akita H. Chen CY. Kato K. Tetrahedron 1998, 54: 11011