Role of base assisted proton transfer in N-heterocyclic carbene-catalyzed intermolecular Stetter reaction

Manjaly J. Ajitha; Cherumuttathu H. Suresh

doi:10.1016/j.tetlet.2013.10.116

Role of base assisted proton transfer in N-heterocyclic carbene-catalyzed intermolecular Stetter reaction

Manjaly J. Ajitha, Cherumuttathu H. Suresh^*

^*Corresponding author for this work

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

16 Scopus citations

Abstract

The mechanism of the NHC-catalyzed intermolecular Stetter reaction between benzaldehyde and cyclopropene has been investigated using the PCM-M062X/6-311++G(3df,2p)//M062X/6-31+G(d,p) level of DFT. Compared to the direct reaction, a substantial reduction in the activation free energy by 10.6-14.4 kcal/mol is observed when the reaction is performed in the presence of water, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU). The bases promote the proton transfer step of the reaction to yield the Breslow intermediate. An early concerted transition state has been located for the stereocontrolling C-C bond formation step (ΔG^# = 26.6 kcal/mol) which is used to explain the diastereomeric ratio observed in the experiment.

Original language	English (US)
Pages (from-to)	7144-7146
Number of pages	3
Journal	Tetrahedron Letters
Volume	54
Issue number	52
DOIs	https://doi.org/10.1016/j.tetlet.2013.10.116
State	Published - Dec 25 2013

Keywords

Breslow intermediate
Density functional theory
N-Heterocyclic carbene
Organocatalysis
Stetter reaction

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1016/j.tetlet.2013.10.116

Cite this

@article{60ee40f88faf4db299d022b547d6042e,

title = "Role of base assisted proton transfer in N-heterocyclic carbene-catalyzed intermolecular Stetter reaction",

abstract = "The mechanism of the NHC-catalyzed intermolecular Stetter reaction between benzaldehyde and cyclopropene has been investigated using the PCM-M062X/6-311++G(3df,2p)//M062X/6-31+G(d,p) level of DFT. Compared to the direct reaction, a substantial reduction in the activation free energy by 10.6-14.4 kcal/mol is observed when the reaction is performed in the presence of water, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU). The bases promote the proton transfer step of the reaction to yield the Breslow intermediate. An early concerted transition state has been located for the stereocontrolling C-C bond formation step (ΔG# = 26.6 kcal/mol) which is used to explain the diastereomeric ratio observed in the experiment.",

keywords = "Breslow intermediate, Density functional theory, N-Heterocyclic carbene, Organocatalysis, Stetter reaction",

author = "Ajitha, {Manjaly J.} and Suresh, {Cherumuttathu H.}",

note = "Funding Information: We thank the support from the Council of Scientific and Industrial Research (CSIR), Government of India through the project CSC0129 . A.M.J. is thankful to UGC, Government of India for a fellowship. ",

year = "2013",

month = dec,

day = "25",

doi = "10.1016/j.tetlet.2013.10.116",

language = "English (US)",

volume = "54",

pages = "7144--7146",

journal = "Tetrahedron Letters",

issn = "0040-4039",

publisher = "Elsevier Ltd",

number = "52",

}

TY - JOUR

T1 - Role of base assisted proton transfer in N-heterocyclic carbene-catalyzed intermolecular Stetter reaction

AU - Ajitha, Manjaly J.

AU - Suresh, Cherumuttathu H.

N1 - Funding Information: We thank the support from the Council of Scientific and Industrial Research (CSIR), Government of India through the project CSC0129 . A.M.J. is thankful to UGC, Government of India for a fellowship.

PY - 2013/12/25

Y1 - 2013/12/25

N2 - The mechanism of the NHC-catalyzed intermolecular Stetter reaction between benzaldehyde and cyclopropene has been investigated using the PCM-M062X/6-311++G(3df,2p)//M062X/6-31+G(d,p) level of DFT. Compared to the direct reaction, a substantial reduction in the activation free energy by 10.6-14.4 kcal/mol is observed when the reaction is performed in the presence of water, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU). The bases promote the proton transfer step of the reaction to yield the Breslow intermediate. An early concerted transition state has been located for the stereocontrolling C-C bond formation step (ΔG# = 26.6 kcal/mol) which is used to explain the diastereomeric ratio observed in the experiment.

AB - The mechanism of the NHC-catalyzed intermolecular Stetter reaction between benzaldehyde and cyclopropene has been investigated using the PCM-M062X/6-311++G(3df,2p)//M062X/6-31+G(d,p) level of DFT. Compared to the direct reaction, a substantial reduction in the activation free energy by 10.6-14.4 kcal/mol is observed when the reaction is performed in the presence of water, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU). The bases promote the proton transfer step of the reaction to yield the Breslow intermediate. An early concerted transition state has been located for the stereocontrolling C-C bond formation step (ΔG# = 26.6 kcal/mol) which is used to explain the diastereomeric ratio observed in the experiment.

KW - Breslow intermediate

KW - Density functional theory

KW - N-Heterocyclic carbene

KW - Organocatalysis

KW - Stetter reaction

UR - http://www.scopus.com/inward/record.url?scp=84888134754&partnerID=8YFLogxK

U2 - 10.1016/j.tetlet.2013.10.116

DO - 10.1016/j.tetlet.2013.10.116

M3 - Article

AN - SCOPUS:84888134754

SN - 0040-4039

VL - 54

SP - 7144

EP - 7146

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 52

ER -

Role of base assisted proton transfer in N-heterocyclic carbene-catalyzed intermolecular Stetter reaction

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this