Recent Development for Stereoselective Synthesis of 1,3-

Polyol

Ye Zhu

Prof. Burgess’ Group

Aug. 19, 2010

Introduction

The 1,3-polyol structure cluster is present in numerous naturalproducts ranging from antibiotics to marine natural products. A substructuresearch with SciFinder gave 87 and 35 natural products bearing one or more

of 1,3,5,7,9-pentaol(s) and 1,3,5,7,9,11,13-heptaol(s), respectively.

Introduction

Michael, Muller, et al, Synthesis, 2006, 557.

C-C Bond Forming Reactions

Introduction

Asymmetric Alkylation

Knochel, P., et al, Tetrahedron Lett., 1993, 5881.

C-C Bond Forming Reactions

Introduction

Asymmetric Allylation

Leighton, J.L. et al, Angew. Chem. Int. Ed. 2003, 946.

advantage: allylation can be carried out iteratively easily

C-C Bond Forming Reactions

Introduction

Reagent Controlled Aldol Reaction

Mahler, U., et al, Chem. Ber. 1988, 2035.

Stereoselective Reduction

Introduction

Directed Reduction of β-Hydroxyketones

Stereoselective Reduction

Introduction

Asymmetric Hydrogenation

Uchida Y.. et al, Tetrahedron 1993, 1997.

Homoallylic Alcohol As Substrate

Introduction

Asymmetric Silylformylation

Leighton, J.L. et al, J. Am. Chem. Soc. 2000, 122, 8587.

Catalytic Asymmetric Overman Esterification

Kirsch, S.F., et al, Org. Lett., 2009, 5634.

Overman, L.E.; et al, J. Am. Chem. Soc. 2005, 2866. Kirsch, S.F., et al, Chem. Commun.., 2007, 4164.

Kirsch, S.F., et al, Chem. Commun.., 2007, 4164.

1,3-anti-Diols Through Catalytic Hydrogenations

Genet J.P., et al, Org. Lett., 2007, 105.

Iterative Cr-Mediated CatalyticAsymmetric Allylation

Kishi, Y., et al, Org. Lett., 2008, 3073.

Kishi, Y., et al, Org. Lett., 2008, 3077.

Iterative Cr-Mediated CatalyticAsymmetric Allylation

Kishi, Y., et al, Org. Lett., 2008, 3073.

Kishi, Y., et al, Org. Lett., 2008, 3077.

Proline-Catalyzed Sequential α-Aminoxylation and Horner-Wadsworth-

Emmons Olefination of Aldehydes

Kumar, P., et al, Org. Lett., 2009, 2611.

Iridium-Catalyzed Enantioselective Carbonyl Allylation and Iterative Two-Directional Assembly of 1,3-Polyols

Krische, M. J. et al, Angew. Chem. Int. Ed., 2009, 5018.

Elongation of 1,3-Polyols via Iterative Catalyst-Directed Carbonyl Allylation

from the Alcohol Oxidation Level

Krische, M. J. et al, Org. Lett., 2009, 3112.

Elongation of 1,3-Polyols via Iterative Catalyst-Directed Carbonyl Allylation

from the Alcohol Oxidation Level

Krische, M. J. et al, Org. Lett., 2009, 3112.

Elongation of 1,3-Polyols via Iterative Catalyst-Directed Carbonyl Allylation

from the Alcohol Oxidation Level

Iridium-Catalyzed Enantioselective Carbonyl Allylation and Iterative Two-Directional Assembly of 1,3-Polyols

Krische, M. J. et al, Angew. Chem. Int. Ed., 2009, 5018.

Iridium-Catalyzed Enantioselective Carbonyl Allylation and Iterative Two-Directional Assembly of 1,3-Polyols

Krische, M. J. et al, Angew. Chem. Int. Ed., 2009, 5018.

Direct Catalytic Asymmetric Aldol Reactions of Thioamides: Toward a Stereocontrolled

Synthesis of 1,3-Polyols

Shibasaki, M. et al, J. Am. Chem.Soc., 2009, 18244.

Direct Catalytic Asymmetric Aldol Reactions of Thioamides: Toward a Stereocontrolled

Synthesis of 1,3-Polyols

Shibasaki, M. et al, J. Am. Chem.Soc., 2009, 18244.

STEREOCHEMISTRY OF ALTERNATING POLYOL CHAINS: 13C NMR ANALYSIS

OF 1,3-DIOL ACETONIDES

Rycbnovsky, S.D., et al, Tetrahedron Lett., 1990, 945

Rycbnovsky, S.D., et al, Tetrahedron Lett., 1990, 945

Thanks