Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jul 14;132(27):9480-7.
doi: 10.1021/ja1038598.

Structural basis for regioisomerization in the alkali-metal-mediated zincation (AMMZn) of trifluoromethyl benzene by isolation of kinetic and thermodynamic intermediates

David R Armstrong  1 , Victoria L Blair, William Clegg, Sophie H Dale, Joaquin Garcia-Alvarez, Gordon W Honeyman, Eva Hevia, Robert E Mulvey, Luca Russo
Affiliations
Free PMC article

Structural basis for regioisomerization in the alkali-metal-mediated zincation (AMMZn) of trifluoromethyl benzene by isolation of kinetic and thermodynamic intermediates

David R Armstrong et al. J Am Chem Soc. .
Free PMC article

Abstract

Performed with a desire to advance knowledge of the structures and mechanisms governing alkali-metal-mediated zincation, this study monitors the reaction between the TMP-dialkylzincate reagent [(TMEDA)Na(TMP)((t)Bu)Zn((t)Bu)] 1 and trifluoromethyl benzene C(6)H(5)CF(3) 2. A complicated mixture of products is observed at room temperature. X-ray crystallography has identified two of these products as ortho- and meta-regioisomers of heterotrianionic [(TMEDA)Na(TMP)(C(6)H(4)-CF(3))Zn((t)Bu)], 3-ortho and 3-meta, respectively. Multinuclear NMR data of the bulk crystalline product confirm the presence of these two regioisomers as well as a third isomer, 3-para, in a respective ratio of 20:11:1, and an additional product 4, which also exhibits ortho-zincation of the aryl substrate. Repeating the reaction at 0 degrees C gave exclusively 4, which was crystallographically characterized as [{(TMEDA)(2)Na}(+){Zn(C(6)H(4)-CF(3))((t)Bu)(2)}(-)]. Mimicking the original room-temperature reaction, this kinetic product was subsequently reacted with TMP(H) to afford a complicated mixture of products, including significantly the three regioisomers of 3. Surprisingly, 4 adopts a solvent-separated ion pair arrangement in contrast to the contacted ion variants of 3-ortho and 3-meta. Aided by DFT calculations on model systems, discussion focuses on the different basicities, amido or alkyl, and steps, exhibited in these reactions, and how the structures and bonding within these isolated key metallic intermediates (prior to any electrophilic interception step), specifically the interactions involving the alkali metal, influence the regioselectivity of the Zn-H exchange process.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
Scheme 2
Scheme 2
Scheme 3
Scheme 3
Figure 1
Figure 1
Aromatic region of 1H NMR spectra for deuterated benzene solutions of (a) crystals obtained from the reaction of [(TMEDA)Na(TMP)(tBu)Zn(tBu)] (1) with 1 equiv of trifluoromethyl benzene (2) at room temperature; (b) isolated crystals of 4, obtained by reaction of [(TMEDA)Na(TMP)(tBu)Zn(tBu)] (1) with 1 equiv of trifluoromethyl benzene (2) at 0 °C; (c) isolated crystals of 4 on the addition of 1 equiv of TMP(H) after 2 h; (d) trifluoromethyl benzene (2).
Figure 2
Figure 2
Molecular structures of (a) 3-ortho and (b) 3-meta. Hydrogen atoms and other disorder components are omitted for clarity.
Figure 3
Figure 3
Molecular structure of 4. Hydrogen atoms and minor disorder components are omitted for clarity.
Scheme 4
Scheme 4
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Knochel P.; Leuser H.; Gong L.-Z.; Perrone S.; Kneisel F. F. In Handbook of Functionalised Organometallics; Knochel P., Ed.; Wiley-VCH: Weinheim, 2005.
    1. The chemistry of organozinc compounds; Rappoport Z., Marek I., Eds.; Patai Series; Wiley: Chichester, U.K., 2006.

    1. For recent reviews on the applications of alkali-metal zincates in deprotonative metalation reactions see:

    2. Mulvey R. E. Organometallics 2006, 25, 1060.
    3. Mulvey R. E.; Mongin F.; Uchiyama M.; Kondo Y. Angew. Chem., Int. Ed. 2007, 46, 3802. - PubMed
    4. Mulvey R. E. Acc. Chem. Res. 2009, 42, 743. - PubMed
    1. Kondo Y.; Shilai M.; Uchiyama M.; Sakamoto T. J. Am. Chem. Soc. 1999, 121, 3539.
    2. Uchiyama M. M.; Matsumoto Y.; Nobuto D.; Furuyama T.; Yamaguchi K.; Morokuma K. J. Am. Chem. Soc. 2006, 128, 8748. - PubMed
    3. Clegg W.; Dale S. H.; Hevia E.; Honeyman G. W.; Mulvey R. E. Angew. Chem., Int. Ed. 2006, 45, 2370. - PubMed
    1. Andrikopoulos P. C.; Armstrong D. R.; Barley H. R. L.; Clegg W.; Dale S. H.; Hevia E.; Honeyman G. W.; Kennedy A. R.; Mulvey R. E. J. Am. Chem. Soc. 2005, 127, 6184. - PubMed