Ortho lithiation-in situ borylation of substituted morpholine benzamides

Anna Cederbalk; Morten Lysén; Jan Kehler; Jesper L. Kristensen

doi:10.1016/j.tet.2017.02.002

Ortho lithiation-in situ borylation of substituted morpholine benzamides

Anna Cederbalk, Morten Lysén, Jan Kehler, Jesper L. Kristensen^*

^*Corresponding author for this work

2 Citations (Scopus)

Abstract

Morpholine amides are cheap and safe alternative to Weinreb amides as acylating agents of organometallic species. Herein, the in-situ lithiation/borylation of 18 ortho- meta- and para-substituted morpholine benzamides has been investigated. 10 of the 18 substrates provided the desired boronic esters as the major isomer (>90% regioselectivity) in crude isolated yields ranging from 68 to 93%. The synthetic usability of such building blocks was subsequently illustrated via the synthesis of a kinase inhibitor.

Original language	English
Journal	Tetrahedron
Volume	73
Issue number	12
Pages (from-to)	1576–1582
Number of pages	7
ISSN	0040-4020
DOIs	https://doi.org/10.1016/j.tet.2017.02.002
Publication status	Published - 23 Mar 2017

Keywords

Borylation
Cross coupling
In-situ trapping
Lithiation
Selectivity

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10.1016/j.tet.2017.02.002

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title = "Ortho lithiation-in situ borylation of substituted morpholine benzamides",

abstract = "Morpholine amides are cheap and safe alternative to Weinreb amides as acylating agents of organometallic species. Herein, the in-situ lithiation/borylation of 18 ortho- meta- and para-substituted morpholine benzamides has been investigated. 10 of the 18 substrates provided the desired boronic esters as the major isomer (>90% regioselectivity) in crude isolated yields ranging from 68 to 93%. The synthetic usability of such building blocks was subsequently illustrated via the synthesis of a kinase inhibitor.",

keywords = "Borylation, Cross coupling, In-situ trapping, Lithiation, Selectivity",

author = "Anna Cederbalk and Morten Lys{\'e}n and Jan Kehler and Kristensen, {Jesper L.}",

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doi = "10.1016/j.tet.2017.02.002",

language = "English",

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TY - JOUR

T1 - Ortho lithiation-in situ borylation of substituted morpholine benzamides

AU - Cederbalk, Anna

AU - Lysén, Morten

AU - Kehler, Jan

AU - Kristensen, Jesper L.

PY - 2017/3/23

Y1 - 2017/3/23

N2 - Morpholine amides are cheap and safe alternative to Weinreb amides as acylating agents of organometallic species. Herein, the in-situ lithiation/borylation of 18 ortho- meta- and para-substituted morpholine benzamides has been investigated. 10 of the 18 substrates provided the desired boronic esters as the major isomer (>90% regioselectivity) in crude isolated yields ranging from 68 to 93%. The synthetic usability of such building blocks was subsequently illustrated via the synthesis of a kinase inhibitor.

AB - Morpholine amides are cheap and safe alternative to Weinreb amides as acylating agents of organometallic species. Herein, the in-situ lithiation/borylation of 18 ortho- meta- and para-substituted morpholine benzamides has been investigated. 10 of the 18 substrates provided the desired boronic esters as the major isomer (>90% regioselectivity) in crude isolated yields ranging from 68 to 93%. The synthetic usability of such building blocks was subsequently illustrated via the synthesis of a kinase inhibitor.

KW - Borylation

KW - Cross coupling

KW - In-situ trapping

KW - Lithiation

KW - Selectivity

UR - http://www.scopus.com/inward/record.url?scp=85011957087&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2017.02.002

DO - 10.1016/j.tet.2017.02.002

M3 - Journal article

AN - SCOPUS:85011957087

SN - 0040-4020

VL - 73

SP - 1576

EP - 1582

JO - Tetrahedron

JF - Tetrahedron

IS - 12

ER -

Ortho lithiation-in situ borylation of substituted morpholine benzamides

Abstract

Keywords

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