Mechanistic insights into the gold-catalyzed cycloisomerization of bromoallenyl ketones: Ligand-controlled regioselectivity

Article abstract of DOI:10.1021/ja802144t

Through computational and experimental studies, the mechanisms of gold-catalyzed cycloisomerization of bromoallenyl ketones in toluene have been elucidated. The divergent 1,2-migrations for the Au(I)- and Au(III)-catalyzed reactions have been investigated

Full text of DOI:10.1021/ja802144t

Published on Web 05/08/2008
Mechanistic Insights into the Gold-Catalyzed Cycloisomerization of
Bromoallenyl Ketones: Ligand-Controlled Regioselectivity
Yuanzhi Xia,†,‡ Alexander S. Dudnik,§ Vladimir Gevorgyan,§ and Yahong Li*,†,‡
Key Laboratory of Organic Synthesis of Jiangsu ProVince, Department of Chemistry and Chemical Engineering,
Suzhou UniVersity, Suzhou 215006, China, Qinghai Institute of Salt Lakes, Chinese Academy of Sciences, Xining
810008, China, and Department of Chemistry, UniVersity of Illinois at Chicago, Chicago, Illinois 60607-7061
Received March 23, 2008; E-mail: liyahong@suda.edu.cn
Scheme 1. Regiodivergent Au(III)- and Au(I)-Catalyzed
In recent years, the homogeneous catalysis by gold complexes
received increasing attention. Particularly, cyclizations of alkynes and
allenes mediated by gold complexes have been widely explored.1
Along this line, the Gevorgyan group has recently reported a gold-
catalyzed regiodivergent cycloisomerization of bromoallenyl ketones
a into isomeric bromofurans b and c (Scheme 1).2 According to the
originally proposed mechanism, products b and c result from different
activation modes of the substrate by gold complexes.2 It was thought
that more oxophilic Au(III) catalyst3 coordinates to the carbonyl oxygen
(d), which, via halirenium intermediate e, produces the 3-bromofuran
b, a product of 1,2-Br migration. Alternatively, the more π-philic Au(I)
catalyst coordinates to the distal double bond of the allene (f), leading
to the gold carbenoid intermediate g. Subsequent 1,2-hydride shift in
the latter forms 2-bromofuran c (Scheme 1).2 Great interest has been
aroused by this important discovery, since it not only opens an
unprecedented access to different types of halofurans but also represents
the very first example of reaction, in which employment of gold catalyst
in different oxidation states leads to different products.1b,c,4–6 A more
detailed mechanistic investigation of origins of the observed regiose-
lectivity of this cycloisomerization, properties of the key intermediates,
as well as profiles of the overall catalytic cycles, may give better
understanding on the important transition metal-catalyzed chemistry
of alkynes and allenes. This in turn, may provide a guide for future
design of new catalytic transformations. Herein, we wish to report our
theoretical and experimental results on the mechanism of Au(III)- and
Au(I)-catalyzed cycloisomerization of bromoallenyl ketones, with the
emphasis on the origins of the regiochemistry of 1,2-migrations. Our
study indicates that the 1,2-H migration could be assisted by the ligand
L of the Au(PR′3)L complex, thus, the regioselectivity of 1,2-migrations
can be controlled by ligands at Au-complexes.
Thus, DFT calculations to investigate the above-mentioned cycloi-
somerization have been performed.7,8 The computed energy surfaces
for the AuCl3 and Au(PH3)Cl-catalyzed cycloisomerizations of bro-
moallenyl ketone 1 are provided in Figure 1. Results of the Au(III)-
catalyzed reaction (I, Figure 1) indicate that the gold catalyst, upon
coordination to the distal double bond of the allene 1,9 instantly gives
the cyclic intermediate 2 via a barrierless and highly exergonic process
with relative free energies of 32.6 and 33.6 kcal/mol, in the gas phase
and in toluene solution, respectively. Next, intermediate 2 undergoes
more favorable 1,2-Br migration via the transition state TS1 to generate
the product complex 3 rather than 1,2-H shift through TS2 to give 4.
Thus, the computed free energy barriers difference of 14.3 kcal/mol
for the latter processes is in good agreement with the experimentally
observed nearly exclusive 1,2-Br migration.2 Although, the formation
of the complex 3 from intermediate 2 is endergonic (Figure 1), the
latter will be transformed into the product b irreversibly via a highly
Cycloisomerizations of Bromoallenyl Ketones
exergonic (30.3 kcal/mol) ligand exchange process of 3 with another
molecule of substrate, thus, completing the catalytic cycle.10
Remarkably, it was found that the AuCl3-catalyzed cycloisomer-
ization of 1 in wet toluene11 leads to the decreased ratio of 1,2-Br vs
1,2-H migration products. This implies that the H-shift could be
catalyzed by a trace amount of water present in the system, analogously
to the recently reported H2O-assisted formal 1,2-H shift in the Au+-
catalyzed carbocyclization.8c This hypothesis was unambiguously
confirmed by the calculations and further by reactions performed in
the presence of D2O.10 Thus, DFT calculations revealed the H2O-
assisted H-shift from 2 to 4 is a stepwise H-abstraction/donation process
with an activation free energy of 17.8 kcal/mol in toluene, which is
only about 1.4 kcal/mol higher than that for the 1,2-Br migration.10
The energy surface for the reaction catalyzed by Au(I) (II, Figure
1) is quite different from that for Au(III). Coordination of the less
electrophilic Au(PH3)Cl to the distal double bond of 1 gives π-complex
5 with the free energy increased by 20.8 kcal/mol in toluene solution.
The latter, via the TS3 with 10.5 kcal/mol activation energy barrier,
transforms into the zwitterionic intermediate 6. From intermediate 6,
the reaction may proceed through the direct 1,2-migration steps to
generate complexes 7 and 8. Calculations showed that the activation
barrier for the direct 1,2-H shift (TS5) is 30.1 kcal/mol, while that for
the 1,2-Br migration (TS4) is only 14.6 kcal/mol, thus contradicting
with the experimental results on the observed predominant 1,2-H shift.2
However, the major 1,2-H migration pathway can reasonably be
rationalized in terms of the stepwise ligand-assisted H-shift process.
Thus, as shown in II (Figure 1), 6 rotamerizes to a relatively more
stable intermediate 9. Geometries of 6 and 9 revealed the remarkably
prolonged Au-Cl distances, implying quite weak Au-Cl interac-
tions.12 Consequently, the weakly coordinated chloride is now capable
of hydrogen abstraction at C2 via TS6 with a barrier of 6.3 kcal/mol
only to give intermediate 10. Notably, the HCl moiety is associated
with the gold-substituted furan through Cl-H-C3 hydrogen-bonding
interaction.10 Gas phase calculations showed that the formation of 10
is slightly exergonic, though a solvation by toluene substantially
destabilizes this intermediate. Protiodeauration of 10 at C3 via TS7
leads to the product complex 8. The activation free energy of this step
is 15.7 and 8.7 kcal/mol in the gas phase and in toluene, respectively.
Dissociation of 8 is quite favorable with an exergonicity of 26.3 kcal/
† Suzhou University.
‡ Qinghai Institute of Salt Lakes, Chinese Academy of Sciences.
§ University of Illinois at Chicago.
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10.1021/ja802144t CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
and Au(III) complexes,14,15 different catalytic performance of Au-
complexes in different oxidation states, and particularly the ligand
effect, which has received only limited attention.1c,8d,16
Acknowledgment. This work was supported by Hundreds of
Talents Program of CAS, Natural Science Foundation of Jiangsu
Province (BK2005030), and NIH of the U.S. (Grant GM-64444). We
thank Prof. Z.-X. Yu of Peking University for helpful discussion.
Supporting Information Available: Computational and experimental
details. This material is available free of charge via the Internet at http://
pubs.acs.org.
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-
free energy of only 9.6 kcal/mol , whereas those for BF4- and SbF6
are much higher (20.2 and 29 kcal/mol, respectively), which is in a
good agreement with the experiments.
In summary, the mechanism of Au-catalyzed cycloisomerization
of bromoallenyl ketones has been investigated through DFT compu-
tational and experimental studies. It was found that both Au(I) and
Au(III) catalysts13 activate the distal double bond of the allene to
produce cyclic zwitterionic intermediates, which undergo a kinetically
favored 1,2-Br migration. However, in the cases of Au(PR3)L (L )
Cl, OTf) catalysts, the counterion-assisted H-shift is the major process,
indicating that the regioselectivity of the Au-catalyzed 1,2-H vs 1,2-
Br migration is ligand dependent. The present study may provide better
understanding of the reactions of allenes and alkynes activated by Au(I)
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