Journal article
Unified Strategy for 1,5,9- and 1,5,7-Triols via Configuration-Encoded 1,5-Polyol Synthesis: Enantioselective Preparation of γ‑Sulfonyl-α-silyloxyaldehydes and Iterative Julia–Kocienski Coupling
Journal of organic chemistry, Vol.83(22), pp.13636-13649
11/16/2018
DOI: 10.1021/acs.joc.8b02033
PMID: 30365891
Abstract
Diverse classes of natural products contain chiral 1,5-polyols, within which may be stereochemical triads of 1,5,9- and 1,5,7-triols. Biological activities associated with compounds containing these motifs warrant targeted synthetic strategies to access all stereoisomers of a 1,5-polyol family from cheap and easily accessible reagents while avoiding the need to determine configurations at each alcohol stereocenter. Here, we address these problems via design and implementation of an iterative configuration-encoded strategy to access 1,5-polyols with unambiguous stereocontrol; the coupling event exploits Julia–Kocienski reactions of enantiopure α-silyloxy-γ-sulfononitriles. These building blocks, bearing sulfone at one terminus and α-silyloxyaldehyde (in latent form) at the other, were prepared via asymmetric catalysis. An efficient scalable route to these building blocks was developed, leading to enantiopure samples in multigram quantities. Preliminary studies of acetals as the latent aldehyde functionality in the α-silyloxyaldehyde showed that Julia–Kocienski coupling of these building blocks was effective, but iterative application was thwarted during acetal hydrolysis, leading to use of nitrile to perform the latent aldehyde function. A variety of 1,5-polyols, including a 1,5,9,13-tetraol and a differentially protected 1,5,9-triol, were prepared, validating the approach. The accompanying paper describes the application of this configuration-encoded 1,5-polyol synthesis to 1,5,9- and 1,5,7-triols found in tetrafibricin.
Details
- Title: Subtitle
- Unified Strategy for 1,5,9- and 1,5,7-Triols via Configuration-Encoded 1,5-Polyol Synthesis: Enantioselective Preparation of γ‑Sulfonyl-α-silyloxyaldehydes and Iterative Julia–Kocienski Coupling
- Creators
- Ryan M FriedrichGopeekrishnan SreenilayamJacob HackbarthGregory K Friestad
- Resource Type
- Journal article
- Publication Details
- Journal of organic chemistry, Vol.83(22), pp.13636-13649
- DOI
- 10.1021/acs.joc.8b02033
- PMID
- 30365891
- NLM abbreviation
- J Org Chem
- ISSN
- 0022-3263
- eISSN
- 1520-6904
- Publisher
- American Chemical Society
- Grant note
- DOI: 10.13039/100008893, name: University of Iowa
- Language
- English
- Date published
- 11/16/2018
- Academic Unit
- Chemistry
- Record Identifier
- 9983985967802771
Metrics
15 Record Views