Abstract
Cyclocondensation between acyclic 5-aminopent-2-enoate esters
and aliphatic aldehydes containing an unsubstituted α-methylene
unit affords 1,2,3,4-tetrahydropyridine derivatives in good yields.
The reaction has been applied to a range of aldehydes, showing good
functional group tolerance. Chemoselective hydride reduction of
the enamine double bond provides 3,4-disubstituted tertiary piperidine
derivatives with acceptable to good diastereoselectivities, whereas
catalytic hydrogenation of N-benzyl derivatives leads directly to
the corresponding secondary piperidines.
Key words
condensation - cyclizations - reductions - piperidines - stereoselective synthesis
References
1 Gracia J.
Casamitjana N.
Bonjoch J.
Bosch J.
J. Org. Chem.
1994,
59:
3939
2 Aurrecoechea JM.
Gorgojo JM.
Saornil C.
J.
Org. Chem.
2005,
70:
9640
3 Aurrecoechea JM.
Suero R.
de Torres E.
J.
Org. Chem.
2006,
71:
8767
4 Aurrecoechea JM.
Coy CA.
Patino OJ.
J.
Org. Chem.
2008,
73:
5194
5 Hopper DW.
Kutterer KMK.
Crombie AL.
Clemens JJ. In Progress in Heterocyclic Chemistry
Vol. 20:
Gribble GW.
Joule JA.
Elsevier;
Oxford:
2009.
p.289-332 ; and previous volumes in
the series
6a Bustos F.
Gorgojo JM.
Suero R.
Aurrecoechea JM.
Tetrahedron
2002,
58:
6837
6b Aurrecoechea JM.
Fernandez A.
Gorgojo JM.
Suero R.
Synth.
Commun.
2003,
33:
693
7 Aurrecoechea JM.
Fernandez A.
Gorgojo JM.
Saornil C.
Tetrahedron
1999,
55:
7345
8 This was indicated by the presence
in the crude ¹ H NMR spectrum of new doublets
at ca. δ = 5.3 and 6.8 ppm replacing the characteristic
phenylacetaldehyde signals.
9 Bonjoch J.
Linares A.
Guardià M.
Bosch J.
Heterocycles
1987,
26:
2165
10 Whitesell JK.
Minton MA.
Stereochemical Analysis
of Alicyclic Compounds by C-13 NMR Spectroscopy
Chapman and
Hall;
London:
1987.
11 Yadav V.
Fallis AG.
Can. J. Chem.
1991,
69:
779
12 Stereochemical elucidation based on
NOE measurements was impractical in this case due to signal overlap.
In previous work, we have confirmed the validity of assignments
based on the observation of γ-gauche effects using NOE
studies on related piperidine derivatives (see ref. 3).
13 Also characteristic of the cis -isomers was the room temperature
broadening of some of the ¹³ C NMR resonances,
because of conformational interconversion between two equatorial/axial
conformers, whereas the corresponding signals in the diequatorial trans -isomers were sharp.
