Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to Aldehydes
A library of pinane-based chiral aminodiols, derived from natural (−)-<i>β</i>-pinene, were prepared and applied as chiral catalysts in the addition of diethylzinc to aldehydes. (−)-<i>β</i>-Pinene was reacted to provide 3-methylenenopinone, followed by a reduction of the car...
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MDPI AG
2020-04-01
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| author | Mounir Raji Tam Minh Le Ferenc Fülöp Zsolt Szakonyi |
| author_facet | Mounir Raji Tam Minh Le Ferenc Fülöp Zsolt Szakonyi |
| author_sort | Mounir Raji |
| collection | DOAJ |
| description | A library of pinane-based chiral aminodiols, derived from natural (−)-<i>β</i>-pinene, were prepared and applied as chiral catalysts in the addition of diethylzinc to aldehydes. (−)-<i>β</i>-Pinene was reacted to provide 3-methylenenopinone, followed by a reduction of the carbonyl function to give a key allylic alcohol intermediate. Stereoselective epoxidation of the latter and subsequent ring opening of the resulting oxirane with primary and secondary amines afforded aminodiols. The regioselectivity of the ring closure of the <i>N</i>-substituted secondary aminodiols with formaldehyde was examined and exclusive formation of oxazolidines was observed. Treatment of the allylic alcohol with benzyl bromide provided the corresponding <i>O</i>-benzyl derivative, which was transformed into <i>O</i>-benzyl aminodiols by aminolysis. Ring closure of the <i>N</i>-isopropyl aminodiol derivative with formaldehyde resulted in spirooxazolidine. The obtained potential catalysts were applied in the reaction of both aromatic and aliphatic aldehydes to diethylzinc providing moderate to good enantioselectivities (up to 87% <i>ee</i>). Through the use of molecular modeling at an ab initio level, this phenomenon was interpreted in terms of competing reaction pathways. Molecular modeling at the RHF/LANL2DZ level of theory was successfully applied for interpretation of the stereochemical outcome of the reactions leading to display excellent (<i>R</i>) enantioselectivity in the examined transformation. |
| first_indexed | 2024-03-10T20:12:06Z |
| format | Article |
| id | doaj.art-20ca60a333ae456096adc4f304b78937 |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-10T20:12:06Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Catalysts |
| spelling | doaj.art-20ca60a333ae456096adc4f304b789372023-11-19T22:48:16ZengMDPI AGCatalysts2073-43442020-04-0110547410.3390/catal10050474Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to AldehydesMounir Raji0Tam Minh Le1Ferenc Fülöp2Zsolt Szakonyi3Institute of Pharmaceutical Chemistry, University of Szeged, Interdisciplinary excellent center, H-6720 Szeged, Eötvös utca 6, HungaryInstitute of Pharmaceutical Chemistry, University of Szeged, Interdisciplinary excellent center, H-6720 Szeged, Eötvös utca 6, HungaryInstitute of Pharmaceutical Chemistry, University of Szeged, Interdisciplinary excellent center, H-6720 Szeged, Eötvös utca 6, HungaryInstitute of Pharmaceutical Chemistry, University of Szeged, Interdisciplinary excellent center, H-6720 Szeged, Eötvös utca 6, HungaryA library of pinane-based chiral aminodiols, derived from natural (−)-<i>β</i>-pinene, were prepared and applied as chiral catalysts in the addition of diethylzinc to aldehydes. (−)-<i>β</i>-Pinene was reacted to provide 3-methylenenopinone, followed by a reduction of the carbonyl function to give a key allylic alcohol intermediate. Stereoselective epoxidation of the latter and subsequent ring opening of the resulting oxirane with primary and secondary amines afforded aminodiols. The regioselectivity of the ring closure of the <i>N</i>-substituted secondary aminodiols with formaldehyde was examined and exclusive formation of oxazolidines was observed. Treatment of the allylic alcohol with benzyl bromide provided the corresponding <i>O</i>-benzyl derivative, which was transformed into <i>O</i>-benzyl aminodiols by aminolysis. Ring closure of the <i>N</i>-isopropyl aminodiol derivative with formaldehyde resulted in spirooxazolidine. The obtained potential catalysts were applied in the reaction of both aromatic and aliphatic aldehydes to diethylzinc providing moderate to good enantioselectivities (up to 87% <i>ee</i>). Through the use of molecular modeling at an ab initio level, this phenomenon was interpreted in terms of competing reaction pathways. Molecular modeling at the RHF/LANL2DZ level of theory was successfully applied for interpretation of the stereochemical outcome of the reactions leading to display excellent (<i>R</i>) enantioselectivity in the examined transformation.https://www.mdpi.com/2073-4344/10/5/474(–)-<i>β</i>-pinene3-methylenenopinoneaminodiolsdiethylzincchiral catalyst |
| spellingShingle | Mounir Raji Tam Minh Le Ferenc Fülöp Zsolt Szakonyi Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to Aldehydes Catalysts (–)-<i>β</i>-pinene 3-methylenenopinone aminodiols diethylzinc chiral catalyst |
| title | Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to Aldehydes |
| title_full | Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to Aldehydes |
| title_fullStr | Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to Aldehydes |
| title_full_unstemmed | Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to Aldehydes |
| title_short | Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to Aldehydes |
| title_sort | synthesis and investigation of pinane based chiral tridentate ligands in the asymmetric addition of diethylzinc to aldehydes |
| topic | (–)-<i>β</i>-pinene 3-methylenenopinone aminodiols diethylzinc chiral catalyst |
| url | https://www.mdpi.com/2073-4344/10/5/474 |
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