I. Panov, Pavel Drabina, J. Hanusek
Jan 31, 2011
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Influential Citations
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Journal
Tetrahedron-asymmetry
Abstract
Abstract The acylation of substituted 2-aminopropanamides with (2 S )-Boc-proline, (2 S )-Cbz-proline and (2 S )-Bn-proline was used to prepare substituted 1-protected N -(1-carbamoyl-1,1-dialkyl-methyl)-( S )-prolinamides (74–89%), whose subsequent deprotection gave N -(1-carbamoyl-1,1-dialkyl-methyl)-( S )-prolinamides (94–95%). The enantiomerically pure N -(1-carbamoyl-1,1-dialkyl-methyl)-( S )-prolinamides obtained were tested as organocatalysts for the aldol reaction of cyclohexanone with 4-nitrobenzaldehyde, with yields ranging from 38% to 79% ee. The highest enantioselectivity (89% ee) was achieved by catalysis with N -(1-carbamoyl-cyclopentyl)-( S )-prolinamide (methanol, l0% HCl). By the action of sodium methoxide, Boc -N -(1-carbamoyl-cyclopentyl)-( S )-prolinamide was quantitatively cyclised to 2-(1-Boc-pyrrolidin-2-yl)-1,3-diazaspiro[4.4]non-1-en-4-one, which was accompanied by racemisation at the stereogenic centre of the proline skeleton. Alternatively, the substituted 4,4-dialkyl-2-pyrrolidin-2-yl-4,5-dihydro-1 H -imidazol-5-ones were prepared by oxidation of 4,4-dialkyl-2-((2 S )-1-Boc-pyrrolidin-2-yl)-4,5-dihydro-1 H -imidazolidin-5-ones (54–69%). In an acid medium, 2-pyrrolidin-2-yl-1,3-diazaspiro[4.4]non-1-en-4-one and (4 S )-4-isopropyl-4-methyl-2-pyrrolidin-2-yl-4,5-dihydro-1 H -imidazol-5-one underwent racemisation. Conversely, the free base of (2 S )-2-pyrrolidin-2-yl-1,3-diazaspiro[4.4]non-1-en-4-one very easily underwent oxidation to give the achiral 2-(4,5-dihydro-3 H -pyrrol-2-yl)-1,3-diazaspiro[4.4]non-1-en-4-one.