Abstract
An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.
| Original language | English |
|---|---|
| Pages (from-to) | 5313-5325 |
| Number of pages | 13 |
| Journal | European Journal of Organic Chemistry |
| Volume | 2019 |
| Issue number | 31-32 |
| Early online date | 25 Apr 2019 |
| DOIs | |
| Publication status | Published - 1 Sep 2019 |
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Bibliographical note
Special Issue: Heterocyclic ChemistryKeywords
- Argatroban
- Multicomponent reactions
- Pharmaceuticals
- Pipecolic amides
- Stereoselectivity
Cite this
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Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides. / van der Heijden, Gydo; van Schaik, Timo B.; Mouarrawis, Valentinos; de Wit, Martin J.M.; Velde, Christophe M.L.Vande; Ruijter, Eelco; Orru, Romano V.A.
In: European Journal of Organic Chemistry, Vol. 2019, No. 31-32, 01.09.2019, p. 5313-5325.Research output: Contribution to Journal › Article › Academic › peer-review
TY - JOUR
T1 - Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides
AU - van der Heijden, Gydo
AU - van Schaik, Timo B.
AU - Mouarrawis, Valentinos
AU - de Wit, Martin J.M.
AU - Velde, Christophe M.L.Vande
AU - Ruijter, Eelco
AU - Orru, Romano V.A.
N1 - Special Issue: Heterocyclic Chemistry
PY - 2019/9/1
Y1 - 2019/9/1
N2 - An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.
AB - An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.
KW - Argatroban
KW - Multicomponent reactions
KW - Pharmaceuticals
KW - Pipecolic amides
KW - Stereoselectivity
UR - http://www.scopus.com/inward/record.url?scp=85066616787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066616787&partnerID=8YFLogxK
U2 - 10.1002/ejoc.201900399
DO - 10.1002/ejoc.201900399
M3 - Article
VL - 2019
SP - 5313
EP - 5325
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
SN - 1434-193X
IS - 31-32
ER -