An efficient and general route to reduced polypropionates via Zr-catalyzed asymmetric C—C bond formation
- 8 April 2004
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (16) , 5782-5787
- https://doi.org/10.1073/pnas.0307514101
Abstract
An efficient and general method for the synthesis of reduced polypropionates has been developed through the application of asymmetric carboalumination of alkenes catalyzed by dichlorobis(1-neomenthylindenyl)zirconium [(NMI)2ZrCl2]. In this investigation, attention has been focused on those reduced polypropionates that are α-monoheterofunctional and either ω-ethyl or ω-n-propyl. The reaction of 3-buten-1-ol with triethylaluminum (Et3Al) or tripropylaluminum (nPr3Al) in the presence of (NMI)2ZrCl2 and isobutylaluminoxane gave, after protonolysis, (R)-3-methyl-1-pentanol as well as (R)- and (S)-3-methyl-1-hexanols in 88–92% yield in 90–92% enantiomeric excess in one step. These 3-monomethyl-1-alkanols were then converted to two stereoisomers each of 2,4-dimethyl-1-hexanols and 2,4-dimethyl-1-heptanols via methylalumination catalyzed by (NMI)2ZrCl2 and methylaluminoxane followed by oxidation with O2. The four-step (or three-isolation-step) protocol provided syn-2,4-dimethyl-1-alkanols of ≥98% stereoisomeric purity in ≈50% overall yields, whereas (2S,4R)-2,4-dimethyl-1-hexanol of comparable purity was obtained in 40% overall yield. Commercial availability of (S)-2-methyl-1-butanol as a relatively inexpensive material suggested its use in the synthesis of (2S,4S)- and (2R,4S)-2,4-dimethyl-1-hexanols via a three-step protocol consisting of (i) iodination, (ii) zincation followed by Pd-catalyzed vinylation, and (iii) Zr-catalyzed methylalumination followed by oxidation with O2. This three-step protocol is iterative and applicable to the synthesis of reduced polypropionates containing three or more branching methyl groups, rendering this method for the synthesis of reduced polypropionates generally applicable. Its synthetic utility has been demonstrated by preparing the side chain of zaragozic acid A and the C11–C20 fragment of antibiotics TMC-151 A–F.Keywords
This publication has 46 references indexed in Scilit:
- A New Protocol for the Enantioselective Synthesis of Methyl-Substituted Alkanols and Their Derivatives through a Hydroalumination/Zirconium-Catalyzed Alkylalumination Tandem Process We thank the National Science Foundation (CHE-0080795), the National Institutes of Health (GM36792), and Purdue University for support of this research. We also thank Albemarle and Boulder Chemical for assistance in the procurement of Al and Zr compounds, respectively.Angewandte Chemie International Edition in English, 2002
- Ethylzincation of Monosubstituted Alkenes Catalyzed by EtMgBr−Cl2ZrCp2 and Palladium-Catalyzed Cross Coupling of the Resultant Diisoalkylzinc DerivativesOrganometallics, 2000
- Principle of Activation of Electrophiles by Electrophiles through Dimeric Association—Two Are Better than OneChemistry – A European Journal, 1999
- Enantio- and Diastereoselective Catalytic Carboalumination of 1-Alkenes and α,ω-Dienes with Cationic Zirconocenes: Scope and MechanismOrganometallics, 1998
- Synthesis of Heterocycles Using Zirconium-Catalyzed Asymmetric Diene CyclizationJournal of the American Chemical Society, 1997
- Multiple Mechanistic Pathways for Zirconium-Catalyzed Carboalumination of Alkynes. Requirements for Cyclic Carbometalation Processes Involving C−H ActivationJournal of the American Chemical Society, 1996
- Zirconium-Catalyzed Enantioselective Alkylalumination of Monosubstituted Alkenes Proceeding via Noncyclic MechanismJournal of the American Chemical Society, 1996
- Zirconium-catalyzed enantioselective methylalumination of monosubstituted alkenesJournal of the American Chemical Society, 1995
- Zirconium-catalyzed asymmetric carbomagnesationJournal of the American Chemical Society, 1993
- The role of torsional isomers of planarly chiral nonbridged bis(indenyl)metal type complexes in stereoselective propene polymerizationJournal of the American Chemical Society, 1993