Reversible C-F bond formation and the Au-catalyzed hydrofluorination of alkynes

Article abstract of DOI:10.1021/ja0723784

The gold(I) fluoride complex [(SIPr)AuF] [SIPr = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene] reacts reversibly with 3-hexyne to form a (β-fluorovinyl)gold(I) species. The more stable fluorovinyl complex trans-{(SIPr)Au[(Ph)C=C(F)CH₃]}, formed by addition of [(SIPr)AuF] across 1-phenyl-1-propyne, has been characterized crystallographically. Both the protonolysis of a (fluorovinyl)gold complex and the reaction of a cationic (alkyne)gold(I) complex with the mild HF source Et₃N?3HF result in fluoroalkene formation. Electrophilic gold(I) complexes, supported by N-heterocyclic carbene ligands and generated in situ, catalyze the trans-hydrofluorination of internal alkynes at room temperature. This catalysis represents a new, selective, and potentially versatile method for the synthesis of fluoroalkenes. Copyright

Full text of DOI:10.1021/ja0723784

Published on Web 06/05/2007
Reversible C-F Bond Formation and the Au-Catalyzed Hydrofluorination of Alkynes
Jennifer A. Akana, Koyel X. Bhattacharyya, Peter Mu¨ller, and Joseph P. Sadighi*
Department of Chemistry, Massachusetts Institute of Technology,
77 Massachusetts AVenue, Cambridge, Massachusetts 02139
Received April 4, 2007; E-mail: jsadighi@mit.edu
Scheme 1
Organofluorine compounds have found widespread and growing
use in the pharmaceutical, materials, and other industries.1 Transition
metals offer great potential improvements in the scope, selectivity,
and convenience of fluorination chemistry. Their use in C-F bond
formation, however, has only begun to be explored.2 Examples to
date include electrophilic fluorinations of arene2a and enol2b,c C-H
bonds, the reductive elimination of aryl2d or acyl2e C-F bonds,
and nucleophilic halide displacement reactions.2f,g
Recent years have seen a resurgence in gold catalysis,3 notably
in the formation of C-C,4 C-N,5 and C-O6 bonds from alkynes.
We now report the reversible addition of a gold(I) fluoride across
an unactivated alkyne. This addition is a likely key step in a new
days but is stable in the solid state for roughly 2 weeks at ambient
temperature.12
Treatment of 3 with an organic-soluble fluoride source,
hydrofluorination of alkynes under mild conditions, using gold(I)
[(Me2N)3P]2N+F-, results in predominant displacement of alkyne
precatalysts and a relatively benign HF source.
by fluoride, re-establishing the equilibrium between 1 and 2a. In
The gold(I) fluoride complex (SIPr)AuF (1; SIPr ) 1,3-bis(2,6-
contrast, the reaction of 3 with Et3N•3HF (1 equiv, Scheme 1), a
diisopropylphenyl)imidazolin-2-ylidene)7 reacts with excess 3-hex-
fluoride source that is both nucleophilic and mildly acidic,13 results
yne (150 equiv) in CH2Cl2 solution at 20 °C. After 10 min, the
in hydrofluorination of the coordinated alkyne to form (Z)-3-fluoro-
reaction mixture displays a new triplet resonance (δ -95.5 ppm, J
) 21 Hz), representing >95% of the original peak area of 1 (relative
to C6H5F internal standard), in its 19F NMR spectrum. This
resonance is assigned to the â-(fluorovinyl)gold complex 2a, formed
by addition of fluoride and gold(I) across the alkyne (Scheme 1).
Removal of solvent and excess alkyne from 2a, over a period of
30 min, results in quantitative regeneration of 1. Rapid (e5 min)
concentration affords mixtures of 1 and 2a, which regain equilib-
rium within 2 h after redissolution in CD2Cl2.
Analysis of mixtures formed from different concentrations of 1
and 3-hexyne at 20 °C gives an equilibrium constant of 2.7 (
0.2 M-1 for the addition process, corresponding to ∆G° ) -0.58
( 0.04 kcal/mol (Table S1, Supporting Information). Certain
[CoIII]X complexes react with acetylene reversibly, forming trans-
â-halovinyl products,8 but fluoride addition was not observed. The
addition of AgF across an alkyne is known but requires a highly
electrophilic substrate.9,10 Reversible metal-mediated C-F bond
rupture has been demonstrated intramolecularly in R-fluoride
elimination from Ru and Os trifluoromethyl complexes.11
Addition product 2b, formed from 1 and 1-phenyl-1-propyne,
proved more amenable than 2a to isolation and crystallization.
Dissolution of 1 in a 1:1 mixture of 1-phenyl-1-propyne and
CH2Cl2, followed by vapor diffusion of n-pentane at -40 °C,
afforded crystals of 2b suitable for X-ray diffraction. The resulting
structure (Figure 1) displays a 1,1-arrangement of the phenyl group
and gold and confirms the trans-arrangement of gold and fluorine
about the vinylic CdC bond.
3-hexene14 (64%, relative to BF4-, by 19F NMR). The same
fluoroalkene is observed in >95% yield (19F NMR, relative to
internal standard) when 2a is treated with CF3CO2H.
This observation of tandem C-F and C-H bond formation led
us to seek conditions for a catalytic transformation of alkynes to
fluoroalkenes using Et3N•3HF. Alkynes react directly with the more
harshly acidic reagent pyridine/HF (70% HF), and although
fluoroalkenes may be observed as byproducts in some cases, only
gem-difluoroalkanes are isolated in useful yields.15 Alkynes acti-
vated by highly electron-withdrawing groups undergo trans-
hydrofluorination on reaction with [H2F3]- salts16,17 or by heating
with CsF in wet DMF.18 Generally, however, fluoroalkenes are
obtained indirectly,19 and control over the stereochemistry often
requires careful strategy.20 Given the interest in fluoroalkenes for
medicinal chemistry,21 stereoselective addition of HF to alkynes
under mild conditions could be important synthetically.
Initial catalytic screening reactions between 3-hexyne and
Et3N•3HF, using 3 as precatalyst, afforded fluoroalkene in yields
up to 53% as judged by 19F NMR relative to internal standard.
Product yields were not significantly improved by an increase in
catalyst loading from 1 to 5 mol %. Reasoning that decreasing
acidity, as HF was consumed,22 caused the reactions to stall before
complete conversion was attained, we examined the effects of acidic
additives on the reaction efficiencies. The presence of powdered
KHSO4, in conjunction with the CH2Cl2-soluble acid cocatalyst
PhNMe2•HOTf (10 mol %), resulted in greatly increased yields of
fluoroalkene.
The trans-addition of fluoride and gold(I) across the triple bond
could proceed via displacement of fluoride from 1 by alkyne,
followed by nucleophilic addition of fluoride to the resulting cationic
gold(I)-alkyne complex. Abstraction of chloride from (SIPr)AuCl
by AgBF4 in the presence of 3-hexyne affords an independent route
to the cationic complex 3, {(SIPr)Au[η2-(3-hexyne)]}+[BF4]-. This
complex decomposes in CH2Cl2 solution over a period of several
Both SIPr and its imidazolylidene analogue IPr are moderately
effective supporting ligands for the catalytic hydrofluorination
of 6-dodecyne. Very similar results were obtained using
(SIPr)AuOt-Bu or (SIPr)AuCl/AgBF4 as precatalysts. The use of
less sterically demanding NHCs, or triphenylphosphine, led to poor
catalytic conversions (see Table S2, Supporting Information), with
rapid precipitation of gold metal. Complete consumption of
9
7736
J. AM. CHEM. SOC. 2007, 129, 7736-7737
10.1021/ja0723784 CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
for their generous support; MIT NMR facilities are supported in
part by NSF Awards CHE-9808061 and DBI-9729592.
Supporting Information Available: Experimental details and
characterization data for new compounds; comparison of different
precatalysts. Crystallographic data for 2b are provided as a CIF. This
material is available free of charge via the Internet at http://pubs.acs.org.
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Acknowledgment. We thank the NSF (Grant No. CHE-
0349204), Corning, Inc., and the MIT Department of Chemistry
JA0723784
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