Tf20-TMDS combination for the direct reductive transformation of secondary amides to aldimines, aldehydes, and/or amines
The direct partial reduction of highly stable secondary amides to more reactive aldimines and aldehydes is a challenging yet highly demanding transformation. In this context, only three methods have been reported. We report herein an improved ver- sion of the Charette＇s method. Our protocol consists...
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| Published in | 中国科学：化学英文版 Vol. 59; no. 12; pp. 1638 - 1644 |
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| Main Author | |
| Format | Journal Article |
| Language | English |
| Published |
2016
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| Online Access | Get full text |
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| Summary: | The direct partial reduction of highly stable secondary amides to more reactive aldimines and aldehydes is a challenging yet highly demanding transformation. In this context, only three methods have been reported. We report herein an improved ver- sion of the Charette＇s method. Our protocol consists of activation of secondary amides with triflic anhydride/2-fluoropyridine, and partial reduction of the resulting intermediates with 1,1,3,3-tetramethyldisiloxane （TMDS）, which delivered aldimines or aldehydes upon acidic hydrolysis. Aromatic amides were reduced to the corresponding aldimines in 85%-100% NMR yields, and yields （NMR） from aliphatic amides were 72%-86%. Acidic hydrolysis of the aldimine intermediates afforded, in one-pot, the corresponding aldehydes in 80%-96% yields. A simple protocol was established to isolate labile aldimines in pure form in 92%-96% yields. The improved method gave generally higher yields as compared to the known ones, and features the use of cheaper and more atom-economical TMDS as a chemoselective reducing agent. In addition, a convenient extraction protocol has been established to allow the isolation of amines, which constitutes a mild method for the N-deacylation of amides, another highly desirable transformation. The extended method retains the advantages of the original method of Charette in terms of mild conditions, good functional group tolerance, and excellent chemoselectivity. |
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| Bibliography: | secondary amides, amide activation, partial reduction, aldimines, N-deacylation The direct partial reduction of highly stable secondary amides to more reactive aldimines and aldehydes is a challenging yet highly demanding transformation. In this context, only three methods have been reported. We report herein an improved ver- sion of the Charette＇s method. Our protocol consists of activation of secondary amides with triflic anhydride/2-fluoropyridine, and partial reduction of the resulting intermediates with 1,1,3,3-tetramethyldisiloxane （TMDS）, which delivered aldimines or aldehydes upon acidic hydrolysis. Aromatic amides were reduced to the corresponding aldimines in 85%-100% NMR yields, and yields （NMR） from aliphatic amides were 72%-86%. Acidic hydrolysis of the aldimine intermediates afforded, in one-pot, the corresponding aldehydes in 80%-96% yields. A simple protocol was established to isolate labile aldimines in pure form in 92%-96% yields. The improved method gave generally higher yields as compared to the known ones, and features the use of cheaper and more atom-economical TMDS as a chemoselective reducing agent. In addition, a convenient extraction protocol has been established to allow the isolation of amines, which constitutes a mild method for the N-deacylation of amides, another highly desirable transformation. The extended method retains the advantages of the original method of Charette in terms of mild conditions, good functional group tolerance, and excellent chemoselectivity. 11-5839/O6 |
| ISSN: | 1674-7291 1869-1870 |