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Synthesis and evaluation of bicyclic 1,3-diols (BODOLs) as ligands for asymmetric catalysis

Sarvary, Ian LU (2002)
Abstract
Several ligands based upon 2-substituted bicyclic[2.2.2]octane-2,6-diols (BODOLs) were synthesized and evaluated in two catalytic reactions: I) the Ti(IV)-mediated catecholborane asymmetric reduction of prochiral ketones and II) as catalysts in the asymmetric addition of diethylzinc to aromatic aldehydes. The ligands were prepared by baker's yeast mono-reduction of bicyclo[2.2.2]octane-2,6-dione, followed by protection of the alcohol and then a sidearm was introduced in the 2-position by nucleophilic addition to the carbonyl group. Subsequent deprotection then gave the optically active 1,3-diols. In general, ligands with modifications of the bicyclic framework, and monocyclic analogues, did not produce as good enantioselectivities as... (More)
Several ligands based upon 2-substituted bicyclic[2.2.2]octane-2,6-diols (BODOLs) were synthesized and evaluated in two catalytic reactions: I) the Ti(IV)-mediated catecholborane asymmetric reduction of prochiral ketones and II) as catalysts in the asymmetric addition of diethylzinc to aromatic aldehydes. The ligands were prepared by baker's yeast mono-reduction of bicyclo[2.2.2]octane-2,6-dione, followed by protection of the alcohol and then a sidearm was introduced in the 2-position by nucleophilic addition to the carbonyl group. Subsequent deprotection then gave the optically active 1,3-diols. In general, ligands with modifications of the bicyclic framework, and monocyclic analogues, did not produce as good enantioselectivities as ligands with the unmodified bicyclic[2.2.2]octane framework. The influence of steric and electronic properties of ortho-substituted aromatic groups positioned at the 2-position of the bicyclic framework were also examined and the steric effect was found to be important in the Ti(IV) catalyzed reductions, whereas heteroatoms (oxygen and sulfur) attached to the aromatic sidearm was of little (or no) importance. On the contrary, electronegative atoms (nitrogen or oxygen) incorporated in the sidearm were of importance in the additions of diethylzinc to benzaldehyde. The complexes formed in situ between Ti(OiPr)4 and BODOL ligands were studied by NMR spectroscopy and DFT computations. The complexes were found to be C2-symmetric µ-oxo bridged dimers in all of the studied cases; in particular the mixed complex between anisyl-BODOL and phenyl-BODOL indicated a dimeric composition. This, combined with a positive non-linear effect, suggested that the observed complexes may be the actual catalysts since the monomeric species were disfavored, according to both NMR- and computational- studies. When screening a library of yeast strains (for the asymmetric mono-reduction of bicyclo[2.2.2]octane-2,6-dione) it was observed that several strains gave different stereoselectivities, compared to that of the previously known baker's yeast, allowing the isolation of the diastereomeric keto-alcohol (+)-exo-6-hydroxy-2-oxo-bicyclo[2.2.2]octane. This compound formed an infinite helical supramolecular structure in the solid state, implying that structures based upon bicyclo[2.2.2]octane framework may be used as supramolecular building blocks for crystal engineering. (Less)
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author
supervisor
opponent
  • Gautun, Odd R., Department of Chemistry, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Organisk kemi, Organic chemistry, yeast reductions, supramolecular chemistry, diethylzinc, computation, structure of Ti-diolates, diol ligands, titanates, asymmetric catalysis, asymmetric synthesis
pages
143 pages
publisher
Department of Organic Chemistry, Lund University
defense location
Kemicentrum sal C
defense date
2002-05-17 10:15:00
ISBN
91-628-5259-0
language
English
LU publication?
yes
additional info
Article: I. Asymmetric reduction of ketones with catecholborane using 2,6-BODOL complexes of titanium(IV) as catalystsIan Sarvary, Fredrik Almqvist and Torbjörn Frejd.Chem. Eur. J., 2001, 7, 2158-66. Article: II. Novel, cyclic and bicyclic 1,3-diols as catalysts for the diethylzinc addition to aldehydesIan Sarvary, Yiqian Wan and Torbjörn Frejd.J. Chem. Soc., Perkin Trans. 1, 2002, 645-651. Article: III. Stereostructures in 1,3-diol synthesis: (1R,3S)-1-(2-Methoxyphenyl)-2,2-dimethyl-1,3-cyclohexanediol and (1S,3S)-1-(2-Methoxyphenyl)-3-(tert-butyldimethylsilyloxy)-2,2-dimethyl-1,3-cyclohexanediolIan Sarvary, Yiqian Wan, Christer Svensson and Torbjörn Frejd.Submitted. Article: IV. New Ti-BODOLates Tested as Catalysts in the Asymmetric Reduction of Acetophenone with Catecholborane.Ian Sarvary and Torbjörn Frejd.Manuscript. Article: V. Reduction of bicyclo[2.2.2]octane-2,6-dione with resting cells of different yeast strainsAdriana L. Botes, Daniel Harvig, Martha S. van Dyk, Ian Sarvary, Torbjörn Frejd, Mikael Katz, Bärbel Hahn-Hägerdal and Marie F. Gorwa-Grauslund.J. Chem. Soc., Perkin Trans. 1, 2002, In Press. Article: VI. Self-assembly of chiral bicyclic keto-alcohols into supramolecular helixes in the solid stateIan Sarvary, Maria H. Johansson and Torbjörn Frejd.Submitted.VII. Structure investigation of Ti(IV)BODOLates involved in the catalytic asymmetric reduction of ketones using catecholboraneIan Sarvary, Per-Ola Norrby and Torbjörn Frejd.Manuscript. The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)
id
73c302a1-6ff3-43d9-bc29-f20bfa419b9d (old id 464590)
date added to LUP
2016-04-04 10:54:05
date last changed
2018-11-21 21:01:28
@phdthesis{73c302a1-6ff3-43d9-bc29-f20bfa419b9d,
  abstract     = {Several ligands based upon 2-substituted bicyclic[2.2.2]octane-2,6-diols (BODOLs) were synthesized and evaluated in two catalytic reactions: I) the Ti(IV)-mediated catecholborane asymmetric reduction of prochiral ketones and II) as catalysts in the asymmetric addition of diethylzinc to aromatic aldehydes. The ligands were prepared by baker's yeast mono-reduction of bicyclo[2.2.2]octane-2,6-dione, followed by protection of the alcohol and then a sidearm was introduced in the 2-position by nucleophilic addition to the carbonyl group. Subsequent deprotection then gave the optically active 1,3-diols. In general, ligands with modifications of the bicyclic framework, and monocyclic analogues, did not produce as good enantioselectivities as ligands with the unmodified bicyclic[2.2.2]octane framework. The influence of steric and electronic properties of ortho-substituted aromatic groups positioned at the 2-position of the bicyclic framework were also examined and the steric effect was found to be important in the Ti(IV) catalyzed reductions, whereas heteroatoms (oxygen and sulfur) attached to the aromatic sidearm was of little (or no) importance. On the contrary, electronegative atoms (nitrogen or oxygen) incorporated in the sidearm were of importance in the additions of diethylzinc to benzaldehyde. The complexes formed in situ between Ti(OiPr)4 and BODOL ligands were studied by NMR spectroscopy and DFT computations. The complexes were found to be C2-symmetric µ-oxo bridged dimers in all of the studied cases; in particular the mixed complex between anisyl-BODOL and phenyl-BODOL indicated a dimeric composition. This, combined with a positive non-linear effect, suggested that the observed complexes may be the actual catalysts since the monomeric species were disfavored, according to both NMR- and computational- studies. When screening a library of yeast strains (for the asymmetric mono-reduction of bicyclo[2.2.2]octane-2,6-dione) it was observed that several strains gave different stereoselectivities, compared to that of the previously known baker's yeast, allowing the isolation of the diastereomeric keto-alcohol (+)-exo-6-hydroxy-2-oxo-bicyclo[2.2.2]octane. This compound formed an infinite helical supramolecular structure in the solid state, implying that structures based upon bicyclo[2.2.2]octane framework may be used as supramolecular building blocks for crystal engineering.},
  author       = {Sarvary, Ian},
  isbn         = {91-628-5259-0},
  language     = {eng},
  publisher    = {Department of Organic Chemistry, Lund University},
  school       = {Lund University},
  title        = {Synthesis and evaluation of bicyclic 1,3-diols (BODOLs) as ligands for asymmetric catalysis},
  year         = {2002},
}