Subscribe to RSS
DOI: 10.1055/s-2002-34365
A Short, Convenient Synthesis of Enantiomerically Pure N-Protected 2-Azanorbornane-3-carboxaldehydes and Related Amino Alcohols
Publication History
Publication Date:
26 September 2002 (online)
![](https://www.thieme-connect.de/media/synthesis/200214SpecialIssue/lookinside/thumbnails/10.1055-s-2002-34365-1.jpg)
Abstract
The aza-Diels-Alder reaction between cyclopentadiene and the bis(1-phenylethyl)imine of glyoxal provides a short route to the two enantiomerically pure exo-diastereomers of N-(1-phenylethyl)-2-azanorbornane-3-carboxaldehyde. Addition of 1-naphthylmagnesium bromide to these aldehydes followed by reductive removal of the 1-phenylethyl group affords the corresponding amino alcohols with high diastereoselectivity. In the Pt-catalyzed hydrogenation of ethyl pyruvate, 64% ee was obtained when using these amino alcohols as modifiers.
Key words
asymmetric synthesis - amino alcohols - amino aldehydes - aza-Diels-Alder reaction - asymmetric Pt-catalyzed hydrogenation
- 1
Brandt P.Andersson PG. Synlett 2000, 1092 ; and references cited therein -
2a
Stella L.Abraham H.Feneu-Dupont J.Tinant B.Declercq JP. Tetrahedron Lett. 1990, 31: 2603 -
2b
Abraham H.Stella L. Tetrahedron 1992, 48: 9707 -
2c
Bailey PD.Wilson RD.Brown GR. J. Chem. Soc., Perkin Trans 1 1991, 1337 -
2d
Bailey PD.Londesbrough DJ.Hancox TC.Heffernan JD.Holmes AB. J. Chem. Soc., Chem. Commun. 1994, 2543 -
2e
Bailey PD.Millwood PA.Smith PD. Chem. Commun. 1998, 633 -
2f
Waldmann H.Braun M. Liebigs Ann. Chem. 1991, 1045 -
2g
Brandt P.Hedberg C.Lawonn K.Pinho P.Andersson PG. Chem.-Eur. J. 1999, 5: 1692 -
2h
Alonso DA.Guijarro D.Pinho P.Temme O.Andersson PG. J. Org. Chem. 1998, 63: 2749 -
2i
Guijarro D.Pinho P.Andersson PG. J. Org. Chem. 1998, 63: 2530 - For convenient large-scale procedures, see:
-
3a
Tararov VI.Kadyrov R.Kadyrova Z.Dubrovina N.Börner A. Tetrahedron: Asymmetry 2002, 13: 447 -
3b
Ekegren J.Modin SA.Alonso DA.Andersson PG. Tetrahedron: Asymmetry 2002, 13: 25 -
4a
Blaser H.-U.Jalett H.-P.Müller M.Studer M. Catal. Today 1997, 37: 441 -
4b
Blaser H.-U.Jalett H.-P.Lottenbach W.Studer M. J. Am. Chem. Soc. 2000, 122: 12675 -
4c
Pfaltz A.Heinz T. Topics Catal. 1997, 4: 229 -
5a
Nakano H.Kumagai N.Matsuzaki H.Kabuto C.Hongo H. Tetrahedron: Asymmetry 1997, 8: 1391 -
5b
Södergren MJ.Andersson PG. J. Am. Chem. Soc. 1998, 120: 10760 -
6a
Alvaro G.Grepioni F.Savoia D. J. Org. Chem. 1997, 62: 4180 -
6b
Tom Dieck H.Dietrich J. Chem. Ber. 1984, 117: 694 -
6c
Roland S.Mangeney P.Alexakis A. Synthesis 1999, 228 -
6d
The diimine 12, which is unstable at r.t., was freshly prepared and used in the aza-Diels-Alder reaction within 12 h
- 7
Waldmann H. Liebigs Ann. Chem. 1989, 231 -
8a
Alonso DA.Bertilsson SK.Johnsson SY.Nordin SJM.Södergren MJ.Andersson PG. J. Org. Chem. 1999, 64: 2276 -
8b
Bertilsson SK.Ekegren JK.Modin SA.Andersson PG. Tetrahedron 2001, 57: 6399 - 10
Altomare A.Cascarano G.Giacovazzo G.Guagliardi A.Burla MC.Polidori G.Camalli M. J. Appl. Cryst. 1994, 27: 435 - 11
Watkin DJ.Prout CK.Carruthers JR.Betteridge PW.Cooper RI. CRYSTALS Issue 11 Chemical Crystallography Laboratory; Oxford: 2001. - 12
Farrugia LJJ. Appl. Cryst. 1997, 30: 565 - 13
Carruthers W. Acta Cryst. 1979, A35: 698 - 14
Ram S.Spicer LD. Tetrahedron Lett. 1987, 28: 515 - 15
Hurd RE. J. Magn. Reson. 1990, 87: 422 - 16
Bax A.Davis DG. J. Magn. Reson. 1985, 65: 355 - 17
Hwang T.-L.Shaka AJ. J. Am. Chem. Soc. 1992, 114: 3157
References
Crystals of the compound under investigation were mounted on a Nonius KappaCCD diffractometer. Data collection and integration of the dataset was carried out using the Nonius collect suite (COLLECT Software, Nonius BV 1997-2001). The structures were solved using direct methods using the program SIR92. [10] Least squares refinement was carried out using the program CRYSTALS. [11] Plots were produced using Ortep-3 for Windows. [12] Chebychev polynomial weights were used to complete the refinement. [13] Crystallographic data have been deposited with the Cambridge Crystallographic Data Center (deposit number: 187733).