Abstract
The mechanism of direct displacement of alkoxy groups in vinylogous and aromatic esters by Grignard reagents, a reaction that is not observed with expectedly better tosyloxy leaving groups, is elucidated computationally. The mechanism of this reaction has been determined to proceed through the inner-sphere attack of nucleophilic alkyl groups from magnesium to the reacting carbons via a metalaoxetane transition state. The formation of a strong magnesium chelate with the reacting alkoxy and carbonyl groups dictates the observed reactivity and selectivity. The influence of ester, ketone, and aldehyde substituents was investigated. In some cases, the calculations predicted the formation of products different than those previously reported; these predictions were then verified experimentally. The importance of studying the actual system, and not simplified models as computational systems, is demonstrated.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6633-6642 |
| Number of pages | 10 |
| Journal | Journal of the American Chemical Society |
| Volume | 135 |
| Issue number | 17 |
| DOIs | |
| State | Published - May 1 2013 |
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ASJC Scopus subject areas
- Chemistry(all)
- Catalysis
- Biochemistry
- Colloid and Surface Chemistry
Cite this
Mechanism of alkoxy groups substitution by Grignard reagents on aromatic rings and experimental verification of theoretical predictions of anomalous reactions. / Jiménez-Osés, Gonzalo; Brockway, Anthony J.; Shaw, Jared T.; Houk, K. N.
In: Journal of the American Chemical Society, Vol. 135, No. 17, 01.05.2013, p. 6633-6642.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Mechanism of alkoxy groups substitution by Grignard reagents on aromatic rings and experimental verification of theoretical predictions of anomalous reactions
AU - Jiménez-Osés, Gonzalo
AU - Brockway, Anthony J.
AU - Shaw, Jared T.
AU - Houk, K. N.
PY - 2013/5/1
Y1 - 2013/5/1
N2 - The mechanism of direct displacement of alkoxy groups in vinylogous and aromatic esters by Grignard reagents, a reaction that is not observed with expectedly better tosyloxy leaving groups, is elucidated computationally. The mechanism of this reaction has been determined to proceed through the inner-sphere attack of nucleophilic alkyl groups from magnesium to the reacting carbons via a metalaoxetane transition state. The formation of a strong magnesium chelate with the reacting alkoxy and carbonyl groups dictates the observed reactivity and selectivity. The influence of ester, ketone, and aldehyde substituents was investigated. In some cases, the calculations predicted the formation of products different than those previously reported; these predictions were then verified experimentally. The importance of studying the actual system, and not simplified models as computational systems, is demonstrated.
AB - The mechanism of direct displacement of alkoxy groups in vinylogous and aromatic esters by Grignard reagents, a reaction that is not observed with expectedly better tosyloxy leaving groups, is elucidated computationally. The mechanism of this reaction has been determined to proceed through the inner-sphere attack of nucleophilic alkyl groups from magnesium to the reacting carbons via a metalaoxetane transition state. The formation of a strong magnesium chelate with the reacting alkoxy and carbonyl groups dictates the observed reactivity and selectivity. The influence of ester, ketone, and aldehyde substituents was investigated. In some cases, the calculations predicted the formation of products different than those previously reported; these predictions were then verified experimentally. The importance of studying the actual system, and not simplified models as computational systems, is demonstrated.
UR - http://www.scopus.com/inward/record.url?scp=84877049847&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877049847&partnerID=8YFLogxK
U2 - 10.1021/ja4015937
DO - 10.1021/ja4015937
M3 - Article
C2 - 23601086
AN - SCOPUS:84877049847
VL - 135
SP - 6633
EP - 6642
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 17
ER -