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DOI: 10.1055/s-2006-941584
Diastereoselective Conjugate Addition of Cyanide to α,β-Unsaturated Oxazolidinones: Enantioselective Synthesis of ent-Pregabalin and Baclofen
Publication History
Publication Date:
12 June 2006 (online)
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Abstract
Conjugate addition of cyanide to chiral α,β-unsaturated oxazolidinones catalyzed by samarium(III) isopropoxide proceeds with good diastereoselectivity. The addition products can be converted into the biologically active targets ent-pregabalin and baclofen.
Key words
conjugate addition - cyanide - samarium - oxazolidinone
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1a Review of conjugate addition of cyanide:
Nagata W.Nozaki H. Org. React. 1977, 25: 255 -
1b For cyanide group manipulations, see:
North M. Tetrahedron: Asymmetry 2003, 14: 147 ; and references therein -
1c For a review of stereoselective conjugate addition, see:
Armstrong A.Convine NJ. In Comprehensive Organic Functional Group Transformations II Vol. 1:Katritzky AR.Taylor RJK.Cossy J. Elsevier Pergamon; Oxford: 2005. p.287 ; and references therein -
2a
Sammis GM.Jacobsen EN. J. Am. Chem. Soc. 2003, 125: 4442 -
2b
Sammis GM.Danjo H.Jacobsen EN. J. Am. Chem. Soc. 2004, 126: 9928 - 3
Mita T.Sasaki K.Kanai M.Shibasaki M. J. Am. Chem. Soc. 2005, 127: 514 - For selected diastereoselective approaches, see:
-
4a
Dahuron N.Langlois N. Synlett 1996, 51 -
4b
Garcia Ruano JL.Cifuentes Garcia M.Laso NM.Martin Castro AM.Rodriguez Ramos JH. Angew. Chem. Int. Ed. 2001, 40: 2507 -
4c
Acherki H.Alvarez-Ibarra C.Dios A.Quiroga ML. Tetrahedron 2002, 58: 3217 -
4d
Benedetti F.Berti F.Garau G.Martinuzzi I.Norbedo S. Eur. J. Org. Chem. 2003, 1973 -
4e
Steurer S.Podlech J. Eur. J. Org. Chem. 2002, 899 - 5
Kawasaki Y.Fujii A.Nakano Y.Sakaguchi S.Ishii Y. J. Org. Chem. 1999, 64: 4214 - 6
Evans DA.Chapman KT.Bisaha J. J. Am. Chem. Soc. 1988, 110: 1238 -
9a
Hoekstra MS.Sobieray DM.Schwindt MA.Mulhern TA.Grote TM.Huckabee BK.Hendrickson VS.Franklin LC.Granger EJ.Karrick GL. Org. Process Res. Dev. 1997, 1: 26 -
9b
Burk MJ.de Koning PD.Grote TM.Hoekstra MS.Hoge G.Jennings RA.Kissel WS.Le TV.Lennon IC.Mulhern TA.Ramsden JA.Wade RA. J. Org. Chem. 2003, 68: 5731 -
9c
Burk MJ,Goel OP,Hoekstra MS,Mich TF,Mulhern TA, andRamsden JA. inventors; WO01 55090. -
9d
Hoge G. J. Am. Chem. Soc. 2003, 125: 10219 -
9e
Brenner M.Seebach D. Helv. Chim. Acta 1999, 82: 2365 -
9f
See also ref. 2a and 3.
- For selected approaches to (R)-baclofen employing conjugate addition as the key step, see:
-
10a
Corey EJ.Zhang F.-Y. Org. Lett. 2000, 2: 4257 -
10b
Baldoli C.Maiorana S.Licandro E.Perdicchia D.Vandoni B. Tetrahedron: Asymmetry 2000, 11: 2007 -
10c
Licandro E.Maiorana S.Baldoli C.Capella L.Perdicchia D. Tetrahedron: Asymmetry 2000, 11: 975 -
10d
Meyer O.Becht J.-M.Helmchen G. Synlett 2003, 1539 -
10e
Becht J.-M.Meyer O.Helmchen G. Synthesis 2003, 2805 - 11
Olpe H.-R.Demieville H.Baltzer WL.Koella WP.Wolf P.Hass HL. Eur. J. Pharmacol. 1978, 52: 133 - 12
Puetz C, andPrzewosny MT. inventors; WO03 062185. -
13a
Thakur VV.Nikalje MD.Sudalai A. Tetrahedron: Asymmetry 2003, 14: 581 -
13b
Caddick S.Judd DB.de Lewis AKK.Reich MT.Williams MRV. Tetrahedron 2003, 59: 5417
References and Notes
Typical Procedure.
The substrate 3 (1 mmol) in toluene (1 mL) was added to Sm(Oi-Pr)3 (0.1 mmol) under N2 at 0 °C followed by commercial acetone cyanohydrin (2 mmol). The reaction mixture was warmed to r.t. and stirred for the indicated time. Upon completion, wet Et2O (5 mL) was added and the reaction mixture filtered through Celite®, washing with Et2O and CH2Cl2. The filtrate was concentrated in vacuo and the resulting crude material purified by silica flash column chromatography to yield the separated diastereomers of 4. Major diastereomer of 4a (132 mg, 59%) isolated as a colourless oil; [α]D
20 +60 (c 1, CHCl3). IR: νmax = 2965, 2243, 1779, 1703, 1390, 1209 cm-1. 1H NMR (250 MHz, CDCl3): δ = 0.89 (d, J = 7.0 Hz, 3 H, MeCHMe), 0.93 (d, J = 7.0 Hz, 3 H, MeCHMe), 1.41 (d, J = 7.0 Hz, 3 H, Me), 2.41 (sept of d, J = 7.0, 4.0 Hz, 1 H, MeCHMe), 3.07-3.24 (m, 2 H, NCCHCH
2), 3.41 (m, 1 H, NCCHCH
2), 4.25 (dd, J = 9.2, 3.4 Hz, 1 H, OCH
2), 4.31 (dd, J = 9.2, 7.9 Hz, 1 H, OCH
2), 4.46 (dt, J = 7.9, 3.7 Hz, 1 H, NCH). 13C NMR (62.5 MHz, CDCl3): δ = 14.7 (CH3, MeCHMe), 17.7 (CH3), 17.8 (CH3), 21.1 (CH, NCC), 28.3 (CH, MeCHMe), 39.6 (CH2, COCH2), 58.4 (CH, NCH), 63.8 (CH2, OCH2), 122.1 (C, CN), 154.0 [C, NC(O)O], 169.0 (C, COCH2). MS (CI):
m/z (%) = 242 (100) [M + NH4
+]. HRMS: m/z calcd for C11H20N3O3: 242.1505; found: 242.1498.
Details will be provided in a full account of this work. We thank Dr. A. J. P. White, Dept. of Chemistry, Imperial College London, for this structure determination.