Synthesis of arylallenes by palladium-catalyzed retro-propargylation of homopropargyl alcohols

Article abstract of DOI:10.1021/ja800986m

Treatment of tertiary homopropargyl alcohol with aryl halide under palladium catalysis provided arylallenes regioselectively. The reaction includes retro-propargylation, which proceeds in a concerted fashion via a cyclic transition state and transfers the stereochemistry of homopropargyl alcohols through C-C bond cleavage. The present method enables the use of homopropargyl alcohols as allenylmetal equivalents. Copyright

Full text of DOI:10.1021/ja800986m

Published on Web 03/19/2008
Synthesis of Arylallenes by Palladium-Catalyzed
Retro-Propargylation of Homopropargyl Alcohols
Sayuri Hayashi, Koji Hirano, Hideki Yorimitsu,* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Received February 8, 2008; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp; oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Table 1. Palladium-Catalyzed Allenylation of Aryl Bromides 2 with
Homopropargyl Alcohols 1 via Retro-Propargylationa
Allenes are a class of compounds that have interesting
reactivity due to the two orthogonal π-bonds1 and have been
found in many natural products.2 Transition-metal-catalyzed
cross-coupling reaction of aryl halides with allenylmetals is one
of the most convenient ways to prepare arylallenes.3 In the case
of palladium catalysis, allenylzinc and allenylcopper reagents
have been mainly used. These reagents can easily undergo
transmetalation with the arylpalladium halide intermediates
formed in situ through oxidative addition of aryl halides to
palladium. However, the preparation of these allenylmetals
requires multiple steps, and they should be handled carefully
because of their high reactivity. Moreover, they are in equilib-
rium with the corresponding propargylmetals4 so that the control
of regioselectivity in the coupling reaction can be difficult.
Here we report a new allenylation reaction of aryl halides
with homopropargyl alcohols as allenylmetal equivalents. During
our recent studies on palladium-catalyzed regio- and stereospe-
cific allyl transfer from homoallyl alcohols to aryl halides via
retro-allylation,5 we expected the retro-allylation would be
extended to retro-propargylation outlined in Scheme 1. If retro-
propargylation from intermediate B occurs via a cyclic transition
state to provide σ-allenyl(aryl)palladium C and subsequent
reductive elimination proceeds faster than isomerization of C
to π-allenyl- or propargylpalladium, regioselective allenylated
product 3 can be obtained. It is noteworthy that tertiary
homopropargyl alcohols are stable to air and moisture. In
addition, they are readily accessible in short steps.
Treatment of bromobenzene (2a) with homopropargyl alcohol
1a in the presence of N,N-dimethylacetamide (DMA) and
potassium hydroxide under palladium catalysis in refluxing
toluene provided arylallene 3a in good yield (Table 1, entry
1).6 In the reaction, no propargylated product was detected. This
result is strongly suggestive of our hypothesis. A wide range
a A mixture of Pd2(dba)3 (0.010 mmol), P(nOct)3 (0.080 mmol),
DMA (0.28 mmol), KOH (0.80 mmol), 1 (0.48 mmol), and 2 (0.40
mmol) was boiled in toluene (6.0 mL) for 4 h. b Isolated yields. c With
2.0 equiv of 1a. d Xylene was used instead of toluene.
Scheme 1. Working Hypothesis
of p-substituted aryl bromides including electron-deficient as
well as electron-rich ones could be employed (entries 2–7).
Sterically demanding 2h and 2i also participated in the alleny-
lation reaction. Aryl bromides that possess carbonyl groups
except for 2f decomposed under the strongly basic conditions.
Instead, acetal-protected substrates such as 2j and 2k gave good
results (entries 10 and 11). Scope of the substituents at the
alkyne terminus was then examined. Not only primary but also
secondary alkyl groups did not interfere with the reaction (entries
12–14). Notably, allenylation of 2a with 1c proceeded to furnish
3m, leaving the benzyl ether moiety untouched. Unfortunately,
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5048 J. AM. CHEM. SOC. 2008, 130, 5048–5049
10.1021/ja800986m CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Synthesis of Tri- and Tetrasubstituted Arylallenesa
temperature was required, a variety of aryl halides reacted with
4 and 5 to produce the corresponding allenes 6 in moderate to
good yields.
Finally, we attempted diastereoselective synthesis of tetra-
substituted arylallenes as depicted in Scheme 2. Taking advan-
tage of the retro-propargylation that would proceed in a
concerted fashion via a cyclic transition state, the stereochemical
information of homopropargyl alcohols would be transferred
to the corresponding allenes through C-C bond cleavage.8 The
reaction of diastereomerically pure homopropargyl alcohol anti-7
with bromobenzene (2a) provided tetrasubstituted allene 8a in
good yield with perfect anti selectivity (Table 3, entry 1). On
the other hand, syn-8a was obtained as the sole product in the
reaction of syn-7 (entry 2). Other aryl bromides also underwent
the stereospecific allenylation reaction with both diastereomers
(entries 3–8).
In conclusion, we have developed a new method for the
generation of σ-allenylpalladium from homopropargyl alcohols
via retro-propargylation and applied it to the highly regiose-
lective synthesis of gem-di-, tri-, and tetrasubstituted arylallenes.
The details of the reaction mechanism and the development of
other reactions using the retro-propargylation strategy are under
investigation.
entry
alcohol
2
6, yieldb (%)
1
2
3
4
5
6
7
8
9
4
2a
2b
2d
2f
6a, 68
6b, 64
6c, 60
6d, 62
6e, 71
6f, 63
6g, 68
6h, 80
6i, 79
2j
2k
2a
2f
5
2j
a The reaction conditions are the same as those in Table 1 except for
the use of xylene instead of toluene. b Isolated yields.
Scheme 2
Acknowledgment. This work was supported by Grants-in-
Aid for Scientific Research from MEXT, Japan. S.H and K.H.
acknowledge JSPS for financial support.
Supporting Information Available: Experimental details, a
process for optimizing reaction conditions, characterization data
for new compounds, and stereochemical assignments of anti-7 and
anti-8b. This material is available free of charge via the Internet at
http://pubs.acs.org.
Table 3. Stereospecific Synthesis of Tetrasubstituted Arylallenesa, b
References
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(6) Although the exact role of DMA is not clear at this stage, its coordination
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Information for details of reaction optimization studies.
2j
a The reaction conditions were the same as those in Table 2. Both
diastereomers were racemic. b Relative configurations of alcohol 7 and
allene 8 were assigned by X-ray crystallographic analysis. See Suppor-
ting Information. c Isolated yields. Isomeric purity >99:1.
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terminus of which is H, SitBuMe2, or Ph, resulted in no formation of the
desired products.
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the bulky tert-butyl group of 1e suppressed the reaction (entry
15).7
Homopropargyl alcohols having one or two methyl groups
at the propargylic position were converted to tri- or tetrasub-
stituted arylallenes, respectively (Table 2). Although higher
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