Abstract
Given the widespread importance of amides in biochemical and chemical systems, an efficient synthesis that avoids wasteful use of stoichiometric coupling reagents or corrosive acidic and basic media is highly desirable. We report a reaction in which primary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen (the only products) in high yields and high turnover numbers. This reaction is catalyzed by a ruthenium complex based on a dearomatized PNN-type ligand [where PNN is 2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine], and no base or acid promoters are required. Use of primary diamines in the reaction leads to bis-amides, whereas with a mixed primary-secondary amine substrate, chemoselective acylation of the primary amine group takes place. The proposed mechanism involves dehydrogenation of hemiaminal intermediates formed by the reaction of an aldehyde intermediate with the amine.
| Original language | English |
|---|---|
| Pages (from-to) | 790-792 |
| Number of pages | 3 |
| Journal | Science |
| Volume | 317 |
| Issue number | 5839 |
| DOIs | |
| Publication status | Published - Aug 10 2007 |
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Direct synthesis of amides from alcohols and amines with liberation of H2 . / Gunanathan, Chidambaram; Ben-David, Yehoshoa; Milstein, David.
In: Science, Vol. 317, No. 5839, 10.08.2007, p. 790-792.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Direct synthesis of amides from alcohols and amines with liberation of H2
AU - Gunanathan, Chidambaram
AU - Ben-David, Yehoshoa
AU - Milstein, David
PY - 2007/8/10
Y1 - 2007/8/10
N2 - Given the widespread importance of amides in biochemical and chemical systems, an efficient synthesis that avoids wasteful use of stoichiometric coupling reagents or corrosive acidic and basic media is highly desirable. We report a reaction in which primary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen (the only products) in high yields and high turnover numbers. This reaction is catalyzed by a ruthenium complex based on a dearomatized PNN-type ligand [where PNN is 2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine], and no base or acid promoters are required. Use of primary diamines in the reaction leads to bis-amides, whereas with a mixed primary-secondary amine substrate, chemoselective acylation of the primary amine group takes place. The proposed mechanism involves dehydrogenation of hemiaminal intermediates formed by the reaction of an aldehyde intermediate with the amine.
AB - Given the widespread importance of amides in biochemical and chemical systems, an efficient synthesis that avoids wasteful use of stoichiometric coupling reagents or corrosive acidic and basic media is highly desirable. We report a reaction in which primary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen (the only products) in high yields and high turnover numbers. This reaction is catalyzed by a ruthenium complex based on a dearomatized PNN-type ligand [where PNN is 2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine], and no base or acid promoters are required. Use of primary diamines in the reaction leads to bis-amides, whereas with a mixed primary-secondary amine substrate, chemoselective acylation of the primary amine group takes place. The proposed mechanism involves dehydrogenation of hemiaminal intermediates formed by the reaction of an aldehyde intermediate with the amine.
UR - http://www.scopus.com/inward/record.url?scp=34547896611&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547896611&partnerID=8YFLogxK
U2 - 10.1126/science.1145295
DO - 10.1126/science.1145295
M3 - Article
AN - SCOPUS:34547896611
VL - 317
SP - 790
EP - 792
JO - Science
JF - Science
SN - 0036-8075
IS - 5839
ER -