Synthesis of 2,6-trans-tetrahydropyrans using a palladium-catalyzed oxidative heck redox-relay strategy

Holly E. Bonfield; Colin M. Edge; Marc Reid; Alan R. Kennedy; David D. Pascoe; David M. Lindsay; Damien Valette

doi:10.1021/acs.orglett.3c03866

Synthesis of 2,6-trans-tetrahydropyrans using a palladium-catalyzed oxidative heck redox-relay strategy

Holly E. Bonfield, Colin M. Edge, Marc Reid, Alan R. Kennedy, David D. Pascoe, David M. Lindsay, Damien Valette

Pure And Applied Chemistry

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

25 Downloads (Pure)

Abstract

The C-aryl-tetrahydropyran motif is prevalent in nature in a number of natural products with biological activity; however, this challenging architecture still requires novel synthetic approaches. We demonstrate the application of a stereoselective Heck redox-relay strategy for the synthesis of functionalized 2,6-trans-tetrahydropyrans in excellent selectivity in a single step from an enantiopure dihydropyranyl alcohol, proceeding through a novel exo-cyclic migration. The strategy has also been applied to the total synthesis of a trans-epimer of the natural product centrolobine in excellent yield and stereoselectivity.

Original language	English
Pages (from-to)	2857-2861
Number of pages	5
Journal	Organic Letters
Volume	26
Issue number	14
Early online date	10 Jan 2024
DOIs	https://doi.org/10.1021/acs.orglett.3c03866
Publication status	Published - 12 Apr 2024

Funding

The authors thank the GSK/University of Strathclyde Collaborative PhD Programme and the EPSRC for funding via Prosperity Partnership EP/S035990/1.

Keywords

alcohols
aldehydes
chemical synthesis
molecular structure
redox reactions

Access to Document

10.1021/acs.orglett.3c03866Licence: CC BY 4.0

Bonfield-etal-ACS-OL-2024-Synthesis-of-2-6-trans-tetrahydropyrans-using-a-palladium-catalyzed-oxidative-heck-redox-relay-strategyFinal published version, 1.35 MBLicence: CC BY 4.0

Accelerated Discovery and Development of New Medicines: Prosperity Partnership for a Healthier Nation
Kerr, W. (Principal Investigator), Brown, C. (Co-investigator), Florence, A. (Co-investigator), Jamieson, C. (Co-investigator), Johnston, B. (Co-investigator), Murphy, J. (Co-investigator), Palmer, D. (Co-investigator) & Tomkinson, N. (Co-investigator)
EPSRC (Engineering and Physical Sciences Research Council)
1/01/19 → 30/09/24
Project: Research

Cite this

@article{923316dc80f04196a8100ad41115738b,

title = "Synthesis of 2,6-trans-tetrahydropyrans using a palladium-catalyzed oxidative heck redox-relay strategy",

abstract = "The C-aryl-tetrahydropyran motif is prevalent in nature in a number of natural products with biological activity; however, this challenging architecture still requires novel synthetic approaches. We demonstrate the application of a stereoselective Heck redox-relay strategy for the synthesis of functionalized 2,6-trans-tetrahydropyrans in excellent selectivity in a single step from an enantiopure dihydropyranyl alcohol, proceeding through a novel exo-cyclic migration. The strategy has also been applied to the total synthesis of a trans-epimer of the natural product centrolobine in excellent yield and stereoselectivity.",

keywords = "alcohols, aldehydes, chemical synthesis, molecular structure, redox reactions",

author = "Bonfield, {Holly E.} and Edge, {Colin M.} and Marc Reid and Kennedy, {Alan R.} and Pascoe, {David D.} and Lindsay, {David M.} and Damien Valette",

year = "2024",

month = apr,

day = "12",

doi = "10.1021/acs.orglett.3c03866",

language = "English",

volume = "26",

pages = "2857--2861",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society",

number = "14",

}

TY - JOUR

T1 - Synthesis of 2,6-trans-tetrahydropyrans using a palladium-catalyzed oxidative heck redox-relay strategy

AU - Bonfield, Holly E.

AU - Edge, Colin M.

AU - Reid, Marc

AU - Kennedy, Alan R.

AU - Pascoe, David D.

AU - Lindsay, David M.

AU - Valette, Damien

PY - 2024/4/12

Y1 - 2024/4/12

N2 - The C-aryl-tetrahydropyran motif is prevalent in nature in a number of natural products with biological activity; however, this challenging architecture still requires novel synthetic approaches. We demonstrate the application of a stereoselective Heck redox-relay strategy for the synthesis of functionalized 2,6-trans-tetrahydropyrans in excellent selectivity in a single step from an enantiopure dihydropyranyl alcohol, proceeding through a novel exo-cyclic migration. The strategy has also been applied to the total synthesis of a trans-epimer of the natural product centrolobine in excellent yield and stereoselectivity.

AB - The C-aryl-tetrahydropyran motif is prevalent in nature in a number of natural products with biological activity; however, this challenging architecture still requires novel synthetic approaches. We demonstrate the application of a stereoselective Heck redox-relay strategy for the synthesis of functionalized 2,6-trans-tetrahydropyrans in excellent selectivity in a single step from an enantiopure dihydropyranyl alcohol, proceeding through a novel exo-cyclic migration. The strategy has also been applied to the total synthesis of a trans-epimer of the natural product centrolobine in excellent yield and stereoselectivity.

KW - alcohols

KW - aldehydes

KW - chemical synthesis

KW - molecular structure

KW - redox reactions

U2 - 10.1021/acs.orglett.3c03866

DO - 10.1021/acs.orglett.3c03866

M3 - Article

SN - 1523-7060

VL - 26

SP - 2857

EP - 2861

JO - Organic Letters

JF - Organic Letters

IS - 14

ER -

Synthesis of 2,6-trans-tetrahydropyrans using a palladium-catalyzed oxidative heck redox-relay strategy

Abstract

Funding

Keywords

Access to Document

Fingerprint

Projects

Accelerated Discovery and Development of New Medicines: Prosperity Partnership for a Healthier Nation

Cite this