Carreira Alkynylations with Paraformaldehyde. A Mild and Convenient Protocol for the Hydroxymethylation of Complex Base-SensitiveTerminal Acetylenes via Alkynylzinc Triflates

Karl J. Hale, Ziyue Xiong, Liping Wang, Soraya Manaviazar, Ryan Mackle

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Abstract

A new synthetic protocol for the hydroxymethylation of terminal acetylenes is described that involves stoichiometric Carreira alkynylation with solid paraformaldehyde (HO[CH2O]nH) in PhMe at 60 oC. Significantly, the method can be successfully applied on acetylenes that possess base-sensitive ester functionality and heterocyclic rings that readily undergo metallation. While N-methylephedrine (NME) is generally the best Zn(OTf)2-coordinating ligand for promoting hydroxymethylation, TMEDA can serve as a replacement.
Original languageEnglish
Pages (from-to)198-201
Number of pages4
JournalOrganic Letters
Volume17
Issue number2
Early online date24 Dec 2014
DOIs
Publication statusPublished - 16 Jan 2015

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Alkynes
acetylene
esters
Esters
Ligands
ligands
rings
paraform
N-methylephedrine
phenyllithium

Keywords

  • Alkyne Hydroxymethylation with Paraformaldehyde
  • Carreira Alkynylation
  • Hale O-Directed Alkyne Free Radical Hydrostannation

Cite this

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title = "Carreira Alkynylations with Paraformaldehyde. A Mild and Convenient Protocol for the Hydroxymethylation of Complex Base-SensitiveTerminal Acetylenes via Alkynylzinc Triflates",
abstract = "A new synthetic protocol for the hydroxymethylation of terminal acetylenes is described that involves stoichiometric Carreira alkynylation with solid paraformaldehyde (HO[CH2O]nH) in PhMe at 60 oC. Significantly, the method can be successfully applied on acetylenes that possess base-sensitive ester functionality and heterocyclic rings that readily undergo metallation. While N-methylephedrine (NME) is generally the best Zn(OTf)2-coordinating ligand for promoting hydroxymethylation, TMEDA can serve as a replacement.",
keywords = "Alkyne Hydroxymethylation with Paraformaldehyde, Carreira Alkynylation, Hale O-Directed Alkyne Free Radical Hydrostannation",
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TY - JOUR

T1 - Carreira Alkynylations with Paraformaldehyde. A Mild and Convenient Protocol for the Hydroxymethylation of Complex Base-SensitiveTerminal Acetylenes via Alkynylzinc Triflates

AU - Hale, Karl J.

AU - Xiong, Ziyue

AU - Wang, Liping

AU - Manaviazar, Soraya

AU - Mackle, Ryan

PY - 2015/1/16

Y1 - 2015/1/16

N2 - A new synthetic protocol for the hydroxymethylation of terminal acetylenes is described that involves stoichiometric Carreira alkynylation with solid paraformaldehyde (HO[CH2O]nH) in PhMe at 60 oC. Significantly, the method can be successfully applied on acetylenes that possess base-sensitive ester functionality and heterocyclic rings that readily undergo metallation. While N-methylephedrine (NME) is generally the best Zn(OTf)2-coordinating ligand for promoting hydroxymethylation, TMEDA can serve as a replacement.

AB - A new synthetic protocol for the hydroxymethylation of terminal acetylenes is described that involves stoichiometric Carreira alkynylation with solid paraformaldehyde (HO[CH2O]nH) in PhMe at 60 oC. Significantly, the method can be successfully applied on acetylenes that possess base-sensitive ester functionality and heterocyclic rings that readily undergo metallation. While N-methylephedrine (NME) is generally the best Zn(OTf)2-coordinating ligand for promoting hydroxymethylation, TMEDA can serve as a replacement.

KW - Alkyne Hydroxymethylation with Paraformaldehyde

KW - Carreira Alkynylation

KW - Hale O-Directed Alkyne Free Radical Hydrostannation

U2 - 10.1021/ol503222j

DO - 10.1021/ol503222j

M3 - Article

VL - 17

SP - 198

EP - 201

JO - Organic Letters

JF - Organic Letters

SN - 1523-7060

IS - 2

ER -