Robust and scalable synthesis of Soai aldehydes via improved Barbier-type halogen−lithium exchange

Ryan T. Kenny; Fei Liu

doi:10.1002/ajoc.202100787

Robust and scalable synthesis of Soai aldehydes via improved Barbier-type halogen−lithium exchange

Ryan T. Kenny, Fei Liu^*

^*Corresponding author for this work

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

1 Citation (Scopus)

79 Downloads (Pure)

Abstract

A robust synthesis of Soai-type pyrimidine aldehydes proceeds in good to high yields by controlled formation and quenching of a lithiated pyrimidine intermediate. The alkyne-substituted bromopyrimidine, furnished by Sonogashira cross-coupling, underwent a Barbier-type halogen-lithium exchange to form a transient pyrimidinyl lithium species. The rate of n-BuLi addition was optimized to better synchronize with the addition to ethyl formate, in order to achieve consistently high yields of 2-alkylpyrimdinecarboxaldehydes for use in autocatalysis or as functionalized synthons.

Original language	English
Article number	e202100787
Pages (from-to)	1-6
Number of pages	6
Journal	Asian Journal of Organic Chemistry
Volume	11
Issue number	7
Early online date	27 Jan 2022
DOIs	https://doi.org/10.1002/ajoc.202100787
Publication status	Published - Jul 2022

Bibliographical note

Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

asymmetric autocatalysis
barbier-type lithiation
metalated pyrimidines
pyrimidine carboxaldehyde preparation
transient intermediate capturing

Access to Document

10.1002/ajoc.202100787

Publisher version (open access)Final published version, 4.13 MBLicence: CC BY-NC

Cite this

@article{6ca9af0b80624edbb806117c6fd3bc34,

title = "Robust and scalable synthesis of Soai aldehydes via improved Barbier-type halogen−lithium exchange",

abstract = "A robust synthesis of Soai-type pyrimidine aldehydes proceeds in good to high yields by controlled formation and quenching of a lithiated pyrimidine intermediate. The alkyne-substituted bromopyrimidine, furnished by Sonogashira cross-coupling, underwent a Barbier-type halogen-lithium exchange to form a transient pyrimidinyl lithium species. The rate of n-BuLi addition was optimized to better synchronize with the addition to ethyl formate, in order to achieve consistently high yields of 2-alkylpyrimdinecarboxaldehydes for use in autocatalysis or as functionalized synthons.",

keywords = "asymmetric autocatalysis, barbier-type lithiation, metalated pyrimidines, pyrimidine carboxaldehyde preparation, transient intermediate capturing",

author = "Kenny, \{Ryan T.\} and Fei Liu",

note = "Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher. ",

year = "2022",

month = jul,

doi = "10.1002/ajoc.202100787",

language = "English",

volume = "11",

pages = "1--6",

journal = "Asian Journal of Organic Chemistry",

issn = "2193-5807",

publisher = "John Wiley \& Sons",

number = "7",

}

TY - JOUR

T1 - Robust and scalable synthesis of Soai aldehydes via improved Barbier-type halogen−lithium exchange

AU - Kenny, Ryan T.

AU - Liu, Fei

N1 - Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2022/7

Y1 - 2022/7

N2 - A robust synthesis of Soai-type pyrimidine aldehydes proceeds in good to high yields by controlled formation and quenching of a lithiated pyrimidine intermediate. The alkyne-substituted bromopyrimidine, furnished by Sonogashira cross-coupling, underwent a Barbier-type halogen-lithium exchange to form a transient pyrimidinyl lithium species. The rate of n-BuLi addition was optimized to better synchronize with the addition to ethyl formate, in order to achieve consistently high yields of 2-alkylpyrimdinecarboxaldehydes for use in autocatalysis or as functionalized synthons.

AB - A robust synthesis of Soai-type pyrimidine aldehydes proceeds in good to high yields by controlled formation and quenching of a lithiated pyrimidine intermediate. The alkyne-substituted bromopyrimidine, furnished by Sonogashira cross-coupling, underwent a Barbier-type halogen-lithium exchange to form a transient pyrimidinyl lithium species. The rate of n-BuLi addition was optimized to better synchronize with the addition to ethyl formate, in order to achieve consistently high yields of 2-alkylpyrimdinecarboxaldehydes for use in autocatalysis or as functionalized synthons.

KW - asymmetric autocatalysis

KW - barbier-type lithiation

KW - metalated pyrimidines

KW - pyrimidine carboxaldehyde preparation

KW - transient intermediate capturing

UR - https://www.scopus.com/pages/publications/85123778879

U2 - 10.1002/ajoc.202100787

DO - 10.1002/ajoc.202100787

M3 - Article

AN - SCOPUS:85123778879

SN - 2193-5807

VL - 11

SP - 1

EP - 6

JO - Asian Journal of Organic Chemistry

JF - Asian Journal of Organic Chemistry

IS - 7

M1 - e202100787

ER -

Robust and scalable synthesis of Soai aldehydes via improved Barbier-type halogen−lithium exchange

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this