An iron-catalysed C-C bond-forming spirocyclization cascade providing sustainable access to new 3D heterocyclic frameworks

Kirsty Adams, Anthony K. Ball, James Birkett, Lee Brown, Ben Chappell, Duncan M. Gill, P. K.Tony Lo, Nathan J. Patmore, Craig R. Rice, James Ryan, Piotr Raubo, Joseph B. Sweeney

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Heterocyclic architectures offer powerful creative possibilities to a range of chemistry end-users. This is particularly true of heterocycles containing a high proportion of sp3 -carbon atoms, which confer precise spatial definition upon chemical probes, drug substances, chiral monomers and the like. Nonetheless, simple catalytic routes to new heterocyclic cores are infrequently reported, and methods making use of biomass-accessible starting materials are also rare. Here, we demonstrate a new method allowing rapid entry to spirocyclic bis-heterocycles, in which inexpensive iron(III) catalysts mediate a highly stereoselective C-C bond-forming cyclization cascade reaction using (2-halo)aryl ethers and amines constructed using feedstock chemicals readily available from plant sources. Fe(acac) 3 mediates the deiodinative cyclization of (2-halo)aryloxy furfuranyl ethers, followed by capture of the intermediate metal species by Grignard reagents, to deliver spirocycles containing two asymmetric centres. The reactions offer potential entry to key structural motifs present in bioactive natural products.

LanguageEnglish
Pages396-401
Number of pages6
JournalNature Chemistry
Volume9
Issue number4
Early online date12 Dec 2016
DOIs
Publication statusPublished - 1 Apr 2017

Fingerprint

Ethers
Cyclization
Iron
Metalloids
Chemical bonds
Biological Products
Feedstocks
Amines
Biomass
Carbon
Monomers
Atoms
Catalysts
Metals
Pharmaceutical Preparations

Cite this

Adams, Kirsty ; Ball, Anthony K. ; Birkett, James ; Brown, Lee ; Chappell, Ben ; Gill, Duncan M. ; Lo, P. K.Tony ; Patmore, Nathan J. ; Rice, Craig R. ; Ryan, James ; Raubo, Piotr ; Sweeney, Joseph B. / An iron-catalysed C-C bond-forming spirocyclization cascade providing sustainable access to new 3D heterocyclic frameworks. In: Nature Chemistry. 2017 ; Vol. 9, No. 4. pp. 396-401.
@article{9ee2df7c308a4fe58ba255f09869f79b,
title = "An iron-catalysed C-C bond-forming spirocyclization cascade providing sustainable access to new 3D heterocyclic frameworks",
abstract = "Heterocyclic architectures offer powerful creative possibilities to a range of chemistry end-users. This is particularly true of heterocycles containing a high proportion of sp3 -carbon atoms, which confer precise spatial definition upon chemical probes, drug substances, chiral monomers and the like. Nonetheless, simple catalytic routes to new heterocyclic cores are infrequently reported, and methods making use of biomass-accessible starting materials are also rare. Here, we demonstrate a new method allowing rapid entry to spirocyclic bis-heterocycles, in which inexpensive iron(III) catalysts mediate a highly stereoselective C-C bond-forming cyclization cascade reaction using (2-halo)aryl ethers and amines constructed using feedstock chemicals readily available from plant sources. Fe(acac) 3 mediates the deiodinative cyclization of (2-halo)aryloxy furfuranyl ethers, followed by capture of the intermediate metal species by Grignard reagents, to deliver spirocycles containing two asymmetric centres. The reactions offer potential entry to key structural motifs present in bioactive natural products.",
keywords = "Catalysis, Chemical synthesis",
author = "Kirsty Adams and Ball, {Anthony K.} and James Birkett and Lee Brown and Ben Chappell and Gill, {Duncan M.} and Lo, {P. K.Tony} and Patmore, {Nathan J.} and Rice, {Craig R.} and James Ryan and Piotr Raubo and Sweeney, {Joseph B.}",
year = "2017",
month = "4",
day = "1",
doi = "10.1038/nchem.2670",
language = "English",
volume = "9",
pages = "396--401",
journal = "Nature Chemistry",
issn = "1755-4330",
publisher = "Nature Publishing Group",
number = "4",

}

An iron-catalysed C-C bond-forming spirocyclization cascade providing sustainable access to new 3D heterocyclic frameworks. / Adams, Kirsty; Ball, Anthony K.; Birkett, James; Brown, Lee; Chappell, Ben; Gill, Duncan M.; Lo, P. K.Tony; Patmore, Nathan J.; Rice, Craig R.; Ryan, James; Raubo, Piotr; Sweeney, Joseph B.

In: Nature Chemistry, Vol. 9, No. 4, 01.04.2017, p. 396-401.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An iron-catalysed C-C bond-forming spirocyclization cascade providing sustainable access to new 3D heterocyclic frameworks

AU - Adams, Kirsty

AU - Ball, Anthony K.

AU - Birkett, James

AU - Brown, Lee

AU - Chappell, Ben

AU - Gill, Duncan M.

AU - Lo, P. K.Tony

AU - Patmore, Nathan J.

AU - Rice, Craig R.

AU - Ryan, James

AU - Raubo, Piotr

AU - Sweeney, Joseph B.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Heterocyclic architectures offer powerful creative possibilities to a range of chemistry end-users. This is particularly true of heterocycles containing a high proportion of sp3 -carbon atoms, which confer precise spatial definition upon chemical probes, drug substances, chiral monomers and the like. Nonetheless, simple catalytic routes to new heterocyclic cores are infrequently reported, and methods making use of biomass-accessible starting materials are also rare. Here, we demonstrate a new method allowing rapid entry to spirocyclic bis-heterocycles, in which inexpensive iron(III) catalysts mediate a highly stereoselective C-C bond-forming cyclization cascade reaction using (2-halo)aryl ethers and amines constructed using feedstock chemicals readily available from plant sources. Fe(acac) 3 mediates the deiodinative cyclization of (2-halo)aryloxy furfuranyl ethers, followed by capture of the intermediate metal species by Grignard reagents, to deliver spirocycles containing two asymmetric centres. The reactions offer potential entry to key structural motifs present in bioactive natural products.

AB - Heterocyclic architectures offer powerful creative possibilities to a range of chemistry end-users. This is particularly true of heterocycles containing a high proportion of sp3 -carbon atoms, which confer precise spatial definition upon chemical probes, drug substances, chiral monomers and the like. Nonetheless, simple catalytic routes to new heterocyclic cores are infrequently reported, and methods making use of biomass-accessible starting materials are also rare. Here, we demonstrate a new method allowing rapid entry to spirocyclic bis-heterocycles, in which inexpensive iron(III) catalysts mediate a highly stereoselective C-C bond-forming cyclization cascade reaction using (2-halo)aryl ethers and amines constructed using feedstock chemicals readily available from plant sources. Fe(acac) 3 mediates the deiodinative cyclization of (2-halo)aryloxy furfuranyl ethers, followed by capture of the intermediate metal species by Grignard reagents, to deliver spirocycles containing two asymmetric centres. The reactions offer potential entry to key structural motifs present in bioactive natural products.

KW - Catalysis

KW - Chemical synthesis

UR - http://www.scopus.com/inward/record.url?scp=85016234249&partnerID=8YFLogxK

U2 - 10.1038/nchem.2670

DO - 10.1038/nchem.2670

M3 - Article

VL - 9

SP - 396

EP - 401

JO - Nature Chemistry

T2 - Nature Chemistry

JF - Nature Chemistry

SN - 1755-4330

IS - 4

ER -