Rapid Synthesis of Weinreb Amides via Titanium‐Mediated Direct Amidation at Room Temperature

Reported herein is a mild, rapid, and operationally simple protocol for the direct synthesis of N ‐methoxy‐ N ‐methylamides (Weinreb amides) from carboxylic acids in the presence of TiCl 4 . The reaction proceeds under ambient conditions, overcoming the challenges encountered by existing amidation methodologies. The protocol accommodates a broad range of substrates, delivering both aliphatic and aromatic Weinreb amides in good to excellent yields. Notably, the simple workup procedure eliminates the need for column chromatography, further enhancing the practical appeal.

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Publication Details

Journal
European Journal of Organic Chemistry
Published
2026-08-17
DOI
https://doi.org/10.1002/ejoc.70788
Primary Topic
Advanced Synthetic Organic Chemistry
Type
article
Field-Weighted Citation Impact
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article

Rapid Synthesis of Weinreb Amides via Titanium‐Mediated Direct Amidation at Room Temperature

Aman Singh, Henry J. Hamann, P. Veeraraghavan Ramachandran
European Journal of Organic Chemistry
Advanced Synthetic Organic Chemistry
article

Rapid Synthesis of Weinreb Amides via Titanium‐Mediated Direct Amidation at Room Temperature

Aman Singh, Henry J. Hamann, P. Veeraraghavan Ramachandran
article en

Abstract

Reported herein is a mild, rapid, and operationally simple protocol for the direct synthesis of N ‐methoxy‐ N ‐methylamides (Weinreb amides) from carboxylic acids in the presence of TiCl 4 . The reaction proceeds under ambient conditions, overcoming the challenges encountered by existing amidation methodologies. The protocol accommodates a broad range of substrates, delivering both aliphatic and aromatic Weinreb amides in good to excellent yields. Notably, the simple workup procedure eliminates the need for column chromatography, further enhancing the practical appeal.

European Journal of Organic Chemistry
Purdue University West Lafayette (US)
Openalex Percentile: Top 18%
Advanced Synthetic Organic Chemistry
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