Ene reaction of arynes with alkynes

Article abstract of DOI:10.1021/ja058418q

Arynes, generated in situ from ortho-silylaryl triflates, undergo ene reaction with alkynes possessing propargylic hydrogen in the presence of KF/18-crown-6 in THF at room temperature to give substituted phenylallenes. Various terminal and internal alkyne

Full text of DOI:10.1021/ja058418q

Published on Web 01/28/2006
Ene Reaction of Arynes with Alkynes
Thiruvellore Thatai Jayanth, Masilamani Jeganmohan, Mu-Jeng Cheng, San-Yan Chu, and
Chien-Hong Cheng*
Department of Chemistry, Tsing Hua UniVersity, Hsinchu 30013, Taiwan
Received December 12, 2005; E-mail: chcheng@mx.nthu.edu.tw
Arynes are one of the most important classes of organic species
that have received great attention both for the structural aspects as
well as for their use as organic reagents in synthetic organic
chemistry.1 A mild method for the in situ preparation of arynes at
moderate temperatures from ortho-silyl aryltriflates2 has rekindled
the interest, especially in the past 5 years, in employing arynes as
Figure 1. Free energies (kcal/mol) and optimized geometry of the transition
substrates in organic synthesis. As a result, the aryne chemistry
state for the reaction of benzyne and propyne. Activation barrier is in italics,
has been extended to multicomponent assembling reactions,3
and bond lengths are in angstroms.
element-element σ-bond additions,4 and transition-metal-catalyzed
when 3-phenyl-1-propyne (2d) was employed, 1,3-diphenylallene
multicomponent5 and cyclotrimerization reactions.6
(3d) was obtained in 68% yield (entry 4). For the reaction of 1,6-
heptadiyne (2e) with 1a, ene reaction occurred at one of the alkyne
groups to afford product 3e; the other terminal alkyne group
remained intact (entry 5). The reaction was also successfully applied
to propargyl bromide (2f) and propargyl chloride (2g), yielding
1-bromo-3-phenylallene (3f) and 1-chloro-3-phenylallene (3g),
respectively, in good yields (entries 6 and 7). The present reaction
can be further extended to internal alkynes. When 3-hexyne (2h)
was treated with 1b, the corresponding trisubstituted phenylallene
3h was formed in 57% yield (entry 8). However, the reaction of
2-hexyne (2i) with 1a gave a mixture of two regioisomers in
approximately a 1:1 ratio (entry 9).
Apart from the transition-metal-catalyzed reactions, there are very
few reports of reactions involving arynes and alkynes. Guitia´n’s
group has revealed a dehydro Diels-Alder reaction (DDAR) of
1,8-diethynylnaphthalene and benzyne.7 In view of the low-lying
LUMO of aryne, it is expected to be a powerful enophile in the
ene reactions8 with alkynes possessing a propargylic hydrogen to
give phenylallenes. Considering the long history for arynes, we
carefully checked the literature for any report about this reaction.
In 1968, Wasserman et al. had proposed the formation of allenes
from the reaction of benzyne and an alkyne.9 Another report dealing
with a reaction of benzyne with ethynylcyclopropane showed the
formation of a trace amount of allene derivative.10 Other than the
In addition to benzyne 1a, substituted benzynes also underwent
above two reports, this fundamentally important ene reaction of
aryne with alkyne is virtually unknown to us. The failure to isolate
ene products is likely due to the nature of benzyne precursor and
the reaction conditions used.11 The feasibility of the ene reaction
of benzyne and propyne was supported by a DFT calculation.12
The results showed that the reaction proceeds via a concerted
pathway with a barrier of 2.4 kcal/mol and is exothermic by 92.7
kcal/mol. The optimum transition-state geometry is a near planar
cyclic-six-electron framework (four in-plane π electrons and two
σ C-H bond electrons), as shown in Figure 1.
We next tested the above results experimentally employing ortho-
silylaryl triflates as aryne precursors. When 2-(trimethylsilyl)phenyl
triflate (1a) was treated with 1-hexyne (2a) (4 equiv) in the presence
of KF (3 equiv) and 18-crown-6 (3.5 equiv) in THF at room
temperature for 6 h, 1-propyl-3-phenylallene (3a) was formed in
69% yield. Product 3a was thoroughly characterized by 1H NMR,
13C NMR, IR, and mass data. The use of CsF (4 equiv) as the
fluoride source at 35 °C in acetonitrile also worked equally well.
Product 3a appears to further react with benzyne readily during
the reaction, and it is essential to keep 1-hexyne in excess to inhibit
this reaction. To the best of our knowledge, this is the first time
that an alkyne was successfully used in the intermolecular ene
reaction13 and the first detailed account of the synthesis of
phenylallene from a benzyne and an alkyne in good yields under
mild conditions.
ene reaction with alkynes smoothly. Under the standard reaction
conditions, an unsymmetrical 1,3-diarylallene 3k was obtained from
1c, a 1,3-benzodioxole derivative, and 2d (entry 10). Similarly,
benzyne precursor 1b with two methyl groups on the phenyl ring
furnished allene product 3l in 70% yield, and indanyl derivative,
1d, afforded 3m in 68% yield (entries 11 and 12). The reaction of
benzyne precursor 1c with 2j (entry 13) gave the corresponding
allene, 3n, in 62% yield. Further, the difluoro-substituted benzyne
precursor 1e gave allene 3o in 66% yield (entry 14). In the case of
benzyne precursor 1f, the ene reaction gave a mixture of regio-
isomers (entry 15) as expected for a reaction using unsymmetrical
4-methylbenzyne as a substrate. When methoxy-substituted aryne
precursor 1g was used, the meta-isomer 3q was the exclusive
product (entry 16).
The experimental support for the mechanism was obtained from
two labeling experiments. The use of 1-deuterium-1-hexyne (2k)
as the ene reagent resulted in the deuterium incorporation on the
allene double bond (entry 17). Conversely, the reaction of 1c with
R,R-dideuteriobenzylethyne (2l) possessing two propargylic deu-
teriums led to allene 3k-d2, in which a deuterium is on the allenyl
moiety and the other is on the benzodioxole ring ortho to the allenyl
moiety, as expected for an ene reaction (entry 18).
We also examined the reactivity of an alkyne without propargylic
hydrogen toward benzyne. Thus, when tert-butylacetylene (2m) was
treated with benzyne precursor 1a under the standard conditions,
we were surprised to see two products (Scheme 1). Product 4 was
from the direct addition of the acetylenic C-H bond across benzyne,
while phenanthrene derivative 5 in less than 5% yield is presumably
from the dehydro Diels-Alder addition reaction (DDAR) of 4 and
This ene reaction was smoothly extended to various alkylalkynes
(Table 1). Thus, treatment of 4-methyl-1-pentyne (2b) and 3-cyclo-
pentyl-1-propyne (2c) with 1a gave the corresponding phenylallenes
in 68 and 65% yields, respectively (entries 2 and 3). Similarly,
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J. AM. CHEM. SOC. 2006, 128, 2232-2233
10.1021/ja058418q CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Results of the Ene Reaction of Arynes 1 with Alkynes 2a
Scheme 1
reactions. These reactions provide simple and efficient routes for
the synthesis of various phenanthrene, phenylallene, and phenyl-
alkyne derivatives. A deeper understanding of these reactions and
the application toward organic synthesis as well as a comprehensive
theoretical study on the mechanistic details are of fundamental
importance to the development of aryne chemistry. Further work
toward this end is in progress in our laboratory.
Acknowledgment. We thank the National Science Council of
the Republic of China (NSC 94-2113-M-007-011) for support of
this research.
Supporting Information Available: General experimental proce-
1
dures, spectral data for all compounds, H and 13C NMR spectra for
all compounds, and complete ref 12. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
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(11) All the early reports of reactions of alkynes and benzynes involve
benzenediazonium carboxylate as benzyne precursor. (a) Stiles, M.;
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(12) Frisch, M. J.; et al. Gaussian 98, revision A.3; Gaussian, Inc.: Pittsburgh,
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optimized with analytic gradients at the B3LYP/6-31G* level. Harmonic
vibrational frequency calculations and thermal corrections were then
performed at stationary points. Quoted energies include a correction for
zero-point energies (see Supporting Information).
a Reaction conditions: 0.50 mmol of aryne precursor 1, 2.0 mmol of
alkyne 2, 1.50 mmol of KF, and 1.75 mmol of 18-crown-6 under nitrogen
in 2.0 mL of THF at room temperature for 6 h. b Isolated yields. c Mixture
of meta- and para-regioisomers (1:1).
(13) Reported intramolecular ene reaction of alkynes occurred only at very
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(14) (a) Alkynes having acetylenic carbon-hydrocarbon linkage. Alkynes
having acetylenic carbon-heteroatom linkage might react in a different
way. (b) For reaction of alkynylmetals with arynes, see: Du, C.-J. F.;
Hart, H. J. Org. Chem. 1997, 62, 4896.
1a. The same reaction with 2 equiv of benzyne relative to alkyne
2m gave 5 in 92% yield. To the best of our knowledge, this is the
first time that an acetylenic C-H addition across benzyne was
observed.
At present, it appears that there are three basic reactions for the
alkynes14 with arynes: DDAR, ene, and acetylenic C-H addition
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