Abstract
Investigation of titanium-centered metallacycle-mediated cross-coupling between unsymmetrical internal alkynes has led to the discovery that TMSCl significantly accelerates the [Formula presented] bond forming event. We report a collection of results that compare the efficiency of this reaction employing Ti(Oi-Pr)4/2n-BuLi in PhMe with and without TMSCl, demonstrating in every case that the presence of TMSCl has a profound impact on efficiency. While relevant in the context of developing this fundamental bond-forming process as an entry to more complex organometallic transformations, these modified reaction conditions allow coupling processes to be run at >10 times the concentrations previously possible [in 2.4 M n-BuLi (hexanes)], without the requirement of additional solvent. Finally, we demonstrate the effectiveness of these modified reaction conditions for the annulative cross-coupling between TMS-alkynes and 1,6-enynes leading to the formation of angularly substituted hydrindanes with, now well appreciated, high levels of regio- and stereoselection.
| Original language | English |
|---|---|
| Pages (from-to) | 3848-3850 |
| Number of pages | 3 |
| Journal | Tetrahedron Letters |
| Volume | 57 |
| Issue number | 34 |
| DOIs | |
| Publication status | Published - Jan 1 2016 |
| Externally published | Yes |
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Keywords
- 1,3-Dienes
- Directed reactions
- Metallacycle-mediated cross-coupling
- Titanium isopropoxide
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry
Cite this
Acceleration of metallacycle-mediated alkyne–alkyne cross-coupling with TMSCl. / Cassidy, James S.; Mizoguchi, Haruki; Micalizio, Glenn C.
In: Tetrahedron Letters, Vol. 57, No. 34, 01.01.2016, p. 3848-3850.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acceleration of metallacycle-mediated alkyne–alkyne cross-coupling with TMSCl
AU - Cassidy, James S.
AU - Mizoguchi, Haruki
AU - Micalizio, Glenn C.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Investigation of titanium-centered metallacycle-mediated cross-coupling between unsymmetrical internal alkynes has led to the discovery that TMSCl significantly accelerates the [Formula presented] bond forming event. We report a collection of results that compare the efficiency of this reaction employing Ti(Oi-Pr)4/2n-BuLi in PhMe with and without TMSCl, demonstrating in every case that the presence of TMSCl has a profound impact on efficiency. While relevant in the context of developing this fundamental bond-forming process as an entry to more complex organometallic transformations, these modified reaction conditions allow coupling processes to be run at >10 times the concentrations previously possible [in 2.4 M n-BuLi (hexanes)], without the requirement of additional solvent. Finally, we demonstrate the effectiveness of these modified reaction conditions for the annulative cross-coupling between TMS-alkynes and 1,6-enynes leading to the formation of angularly substituted hydrindanes with, now well appreciated, high levels of regio- and stereoselection.
AB - Investigation of titanium-centered metallacycle-mediated cross-coupling between unsymmetrical internal alkynes has led to the discovery that TMSCl significantly accelerates the [Formula presented] bond forming event. We report a collection of results that compare the efficiency of this reaction employing Ti(Oi-Pr)4/2n-BuLi in PhMe with and without TMSCl, demonstrating in every case that the presence of TMSCl has a profound impact on efficiency. While relevant in the context of developing this fundamental bond-forming process as an entry to more complex organometallic transformations, these modified reaction conditions allow coupling processes to be run at >10 times the concentrations previously possible [in 2.4 M n-BuLi (hexanes)], without the requirement of additional solvent. Finally, we demonstrate the effectiveness of these modified reaction conditions for the annulative cross-coupling between TMS-alkynes and 1,6-enynes leading to the formation of angularly substituted hydrindanes with, now well appreciated, high levels of regio- and stereoselection.
KW - 1,3-Dienes
KW - Directed reactions
KW - Metallacycle-mediated cross-coupling
KW - Titanium isopropoxide
UR - http://www.scopus.com/inward/record.url?scp=84979650189&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979650189&partnerID=8YFLogxK
U2 - 10.1016/j.tetlet.2016.07.045
DO - 10.1016/j.tetlet.2016.07.045
M3 - Article
AN - SCOPUS:84979650189
VL - 57
SP - 3848
EP - 3850
JO - Tetrahedron Letters
JF - Tetrahedron Letters
SN - 0040-4039
IS - 34
ER -