Strong Hydrogen Bond Donating Solvents Accelerate the Passerini Three-Component Reaction

Claudio Ferdeghini; Minghui Wu; Prabhat Ranjan; Martien A. Wurdemann; Jan Pyschik; Alexander Mitsos; Eelco Ruijter; Romano V. A. Orru; Thomas Hansen; Jordy M. Saya

doi:10.1021/acs.joc.5c00236

Strong Hydrogen Bond Donating Solvents Accelerate the Passerini Three-Component Reaction

Claudio Ferdeghini, Minghui Wu, Prabhat Ranjan, Martien A. Wurdemann, Jan Pyschik, Alexander Mitsos, Eelco Ruijter, Romano V. A. Orru, Thomas Hansen^*, Jordy M. Saya^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

We report enhanced reaction rates of the Passerini reaction (P-3CR) using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a cosolvent. Although alcoholic solvents typically increase the energy barrier of the rate-determining step for the P-3CR, we observed significant rate enhancements even when employing strong hydrogen bond donating (HBD) alcohols as cosolvents. This rate enhancement was observed for most aprotic organic solvents, with the exception of strong hydrogen bond accepting (HBA) solvents such as DMF. Experimental kinetic studies and DFT calculations provided a mechanistic rationale for our observations. An investigation of the substrate scope showed that this rate enhancement generally resulted in a (slight) increase of the overall yield in the P-3CR.

Original language	English
Pages (from-to)	5000-5007
Number of pages	8
Journal	Journal of Organic Chemistry
Volume	90
Issue number	14
DOIs	https://doi.org/10.1021/acs.joc.5c00236
Publication status	Published - 11 Apr 2025

Keywords

MULTICOMPONENT REACTIONS

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title = "Strong Hydrogen Bond Donating Solvents Accelerate the Passerini Three-Component Reaction",

abstract = "We report enhanced reaction rates of the Passerini reaction (P-3CR) using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a cosolvent. Although alcoholic solvents typically increase the energy barrier of the rate-determining step for the P-3CR, we observed significant rate enhancements even when employing strong hydrogen bond donating (HBD) alcohols as cosolvents. This rate enhancement was observed for most aprotic organic solvents, with the exception of strong hydrogen bond accepting (HBA) solvents such as DMF. Experimental kinetic studies and DFT calculations provided a mechanistic rationale for our observations. An investigation of the substrate scope showed that this rate enhancement generally resulted in a (slight) increase of the overall yield in the P-3CR.",

keywords = "MULTICOMPONENT REACTIONS",

author = "Claudio Ferdeghini and Minghui Wu and Prabhat Ranjan and Wurdemann, \{Martien A.\} and Jan Pyschik and Alexander Mitsos and Eelco Ruijter and Orru, \{Romano V. A.\} and Thomas Hansen and Saya, \{Jordy M.\}",

year = "2025",

month = apr,

day = "11",

doi = "10.1021/acs.joc.5c00236",

language = "English",

volume = "90",

pages = "5000--5007",

journal = "Journal of Organic Chemistry",

issn = "0022-3263",

publisher = "American Chemical Society",

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TY - JOUR

T1 - Strong Hydrogen Bond Donating Solvents Accelerate the Passerini Three-Component Reaction

AU - Ferdeghini, Claudio

AU - Wu, Minghui

AU - Ranjan, Prabhat

AU - Wurdemann, Martien A.

AU - Pyschik, Jan

AU - Mitsos, Alexander

AU - Ruijter, Eelco

AU - Orru, Romano V. A.

AU - Hansen, Thomas

AU - Saya, Jordy M.

PY - 2025/4/11

Y1 - 2025/4/11

N2 - We report enhanced reaction rates of the Passerini reaction (P-3CR) using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a cosolvent. Although alcoholic solvents typically increase the energy barrier of the rate-determining step for the P-3CR, we observed significant rate enhancements even when employing strong hydrogen bond donating (HBD) alcohols as cosolvents. This rate enhancement was observed for most aprotic organic solvents, with the exception of strong hydrogen bond accepting (HBA) solvents such as DMF. Experimental kinetic studies and DFT calculations provided a mechanistic rationale for our observations. An investigation of the substrate scope showed that this rate enhancement generally resulted in a (slight) increase of the overall yield in the P-3CR.

AB - We report enhanced reaction rates of the Passerini reaction (P-3CR) using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a cosolvent. Although alcoholic solvents typically increase the energy barrier of the rate-determining step for the P-3CR, we observed significant rate enhancements even when employing strong hydrogen bond donating (HBD) alcohols as cosolvents. This rate enhancement was observed for most aprotic organic solvents, with the exception of strong hydrogen bond accepting (HBA) solvents such as DMF. Experimental kinetic studies and DFT calculations provided a mechanistic rationale for our observations. An investigation of the substrate scope showed that this rate enhancement generally resulted in a (slight) increase of the overall yield in the P-3CR.

KW - MULTICOMPONENT REACTIONS

U2 - 10.1021/acs.joc.5c00236

DO - 10.1021/acs.joc.5c00236

M3 - Article

SN - 0022-3263

VL - 90

SP - 5000

EP - 5007

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 14

ER -

Strong Hydrogen Bond Donating Solvents Accelerate the Passerini Three-Component Reaction

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Keywords

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