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Synthesis 2008(3): 383-386
DOI: 10.1055/s-2008-1032022
DOI: 10.1055/s-2008-1032022
PAPER
© Georg Thieme Verlag Stuttgart · New York
An Enantioselective Formal Synthesis of (+)-(R)-α-Lipoic Acid by an l-Proline-Catalyzed Aldol Reaction
Further Information
Received
12 September 2007
Publication Date:
10 January 2008 (online)
Publication History
Publication Date:
10 January 2008 (online)
![](https://www.thieme-connect.de/media/synthesis/200803/lookinside/thumbnails/10.1055-s-2008-1032022-1.jpg)
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
-
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, andZachar 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