5-Hydroxyalkyl derivatives of tert-butyl 2-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate: diastereoselectivity of the Mukaiyama crossed-aldol-type reaction.
The title compounds, rac-(1'R,2R)-tert-butyl 2-(1'-hydroxyethyl)-3-(2-nitrophenyl)-5-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate, C(17)H(20)N(2)O(6), (I), rac-(1'S,2R)-tert-butyl 2-[1'-hydroxy-3'-(methoxycarbonyl)propyl]-3-(2-nitrophenyl)-5-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate, C(20)H(24)N(2)O(8), (II), and rac-(1'S,2R)-tert-butyl 2-(4'-bromo-1'-hydroxybutyl)-5-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate, C(13)H(20)BrNO(4), (III), are 5-hydroxyalkyl derivatives of tert-butyl 2-oxo-2,5-dihydropyrrole-1-carboxylate. In all three compounds, the tert-butoxycarbonyl (Boc) unit is orientated in the same manner with respect to the mean plane through the 2-oxo-2,5-dihydro-1H-pyrrole ring. The hydroxyl substituent at one of the newly created chiral centres, which have relative R,R stereochemistry, is trans with respect to the oxo group of the pyrrole ring in (I), synthesized using acetaldehyde. When a larger aldehyde was used, as in compounds (II) and (III), the hydroxyl substituent was found to be cis with respect to the oxo group of the pyrrole ring. Here, the relative stereochemistry of the newly created chiral centres is R,S. In compound (I), O-H...O hydrogen bonding leads to an interesting hexagonal arrangement of symmetry-related molecules. In (II) and (III), the hydroxyl groups are involved in bifurcated O-H...O hydrogen bonds, and centrosymmetric hydrogen-bonded dimers are formed. The Mukaiyama crossed-aldol-type reaction was successful when using the 2-nitrophenyl-substituted hydroxypyrrole, or the unsubstituted hydroxypyrrole, and boron trifluoride diethyl ether as catalyst. The synthetic procedure leads to a syn configuration of the two newly created chiral centres in all three compounds.
Institute of Chemistry, University of Neuchâtel, rue Emile-Argand 11, CH-2009 Neuchâtel, Switzerland.
Olivier
O
Vallat
Ana-Maria
AM
Buciumas
Reinhard
R
Neier
Helen
H
Stoeckli-Evans
D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry*; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000737:chemistry*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D013237:Stereoisomerism
D006573:Heterocyclic Compounds, 1-Ring; D006574:Heterocyclic Compounds, 2-Ring