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Chemoselective reduction of tertiary amides under thermal control for the formation of aldehydes or amines
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
2016 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 55, no 14, 4562-4566 p.Article in journal (Refereed) Published
Abstract [en]

The chemoselective reduction of amides in the presence of other more reactive reducible functional groups is a highly challenging transformation, and successful examples thereof are most valuable in synthetic organic chemistry. Only a limited number of systems have demonstrated the chemoselective reduction of amides over ketones. Until now, the aldehyde functionality has not been shown to be compatible in any catalytic reduction protocol. Described herein is a [Mo(CO)6]-catalyzed protocol with an unprecedented chemoselectivity and allows for the reduction of amides in the presence of aldehydes and imines. Furthermore, the system proved to be tunable by variation of the temperature, which enabled for either C−O or C−N bond cleavage that ultimately led to the isolation of both amines and aldehydes, respectively, in high chemical yields.

Place, publisher, year, edition, pages
2016. Vol. 55, no 14, 4562-4566 p.
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-128695DOI: 10.1002/anie.201600097ISI: 000373133000027OAI: oai:DiVA.org:su-128695DiVA: diva2:916006
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council
Available from: 2016-03-31 Created: 2016-03-31 Last updated: 2016-04-25Bibliographically approved
In thesis
1. Catalytic Amide Reductions under Hydrosilylation Conditions
Open this publication in new window or tab >>Catalytic Amide Reductions under Hydrosilylation Conditions
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis covers the development of catalytic methodologies for the mild and chemoselective reductions of amides. The first part of the thesis describes the use of a Fe(II)/NHC catalyst for the deoxygenation of aromatic tertiary amides to corresponding amines. The protocol is characterized by low catalyst loading, mild reaction conditions and the use of air and moisture stable polymethylhydrosilaxane (PMHS) as the hydride source.

The second part concerns the development of a protocol for the room temperature deoxygenation of a wide range of tertiary amides to amines using catalytic amounts of Et2Zn and LiCl together with PMHS. The system displayed high levels of chemoselectivity tolerating various reducible groups such as nitro, nitrile, and olefin functionalities, and was shown to be applicable for the reduction of aromatic, heteroaromatic and aliphatic tertiary amides.

The attempts to expand the scope of the Fe-based protocol to accommodate benzylic tertiary amides led to the development of a transition metal-free catalytic system based on KOtBu for the formation of enamines. The final products constitute an important class of precursors for a wide range of valuable compounds in organic chemistry. Moreover, avoiding the use of transition metals in the protocol allowed the desired products to be obtained without the hazardous metal contaminants.

The last chapter of the thesis describes the Mo(CO)6-catalyzed hydrosilylation of amides. The Mo-based catalyst was proven to mediate the deoxygenation of α,β-unsaturated tertiary and secondary amides to the corresponding allylamines without reduction of the olefinic bonds. Further development of the catalytic system revealed an unprecedented chemoselectivity in the hydrosilylation of aromatic and certain aliphatic tertiary amides in the presence of a variety of reducible groups along with aldehydes and imines that were tolerated for the first time. Moreover, it was possible to control the reaction outcome by variation of the reaction temperature to obtain either amines or aldehydes as the major products. The synthetic utility of the developed Mo(CO)6-catalyzed protocols was further demonstrated in the synthesis of the pharmaceuticals Naftifine and Donepezil.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University, 2016. 71 p.
Keyword
Hydrosilylation, amides, reduction, chemoselectivity
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-129028 (URN)978-91-7649-406-6 (ISBN)
Public defence
2016-06-03, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:00 (English)
Opponent
Supervisors
Available from: 2016-05-11 Created: 2016-04-13 Last updated: 2016-04-27Bibliographically approved

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Tinnis, FredrikVolkov, AlexeySlagbrand, ToveAdolfsson, Hans
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