872 CHIMIA 2018, 72, No. 12
Chemistry ties Linking Japan to switzerLand
Scheme 5. Ring
opening of benzo-
cyclobutenols to
ortho-methylbenz-
observed, and thus benzaldehydes 3d and
3e were obtained in moderate yield (80%
and 75% respectively) after purification by
MeO
MeO
O
NaOMe (2 eq.)
70 °C, MeOH
OH
R
R
preparative TLC, beside a plethora of polar
byproducts.
aldehydes.
2
3
The impact of the oxygen substitution
pattern [especially at the C(3) position,
vide infra] at the benzene core on the ring
opening of benzocyclobutenones under ba-
sic conditions has been reported.[24] Distal
vs. proximal bond scission strongly de-
pends on the electronic properties of the
benzene moiety, which influences the re-
action pathway (Scheme 6). Furthermore,
Olofson and co-workers reported the clean
formation of arylacetaldehyde 6 from ben-
zocyclobutenone 5 upon NaBH reduc-
tion followed by aqueous acidic 4workup,
whereas other derivatives of 5 gave the re-
MeO
O
MeO
O
MeO
3b, 99%
3c, 99%
MeO
O
MeO
O
MeO
O
MeO
MeO
MeO
3d, 80%
3e, 75%
3f, 99%
spective benzocyclobutenols.[25] The fact
that substrate 2c, cyclobutenol derivative
P. Lek, P. Trapencieris, Synthesis 2012, 44,
2200.
[6] D. L. Comins, J. D. Brown, J. Org. Chem. 1984,
of 5, reacted cleanly (see Scheme 5) led us methyl and the formyl group – disguised
to the assumption, that, in the present case, as the cyclobutenol moiety – onto to the
the reason for the side reactions of benzo- benzene ring with excellent regiocontrol.
cyclobutenols 2d and 2e might be of other
49, 1078.
[7] X. Chen, K. M. Engle, D.-H. Wang, J.-Q. Yu,
Angew. Chem. Int. Ed. 2009, 48, 5094.
Acknowledgements
nature and not dependent on the electronic
[8] X.-Y. Chen, E. J. Sorensen, J. Am. Chem. Soc.
This work is supported by JSPS KAKENHI
properties of the benzene core. Rather the
preferred conformation of the vicinal me-
thoxy groups[26] in substrate 2d (and 2e)
may cause deleterious steric repulsion
with the alkoxide, and thus interfere with
the outward motion of the conrotatory ring
opening (as depicted for anions of 2d [R' =
H] and 2e [R' = OMe]).[27]
2018, 140, 2789.
[9] For selected reviews on aryne chemistry, see:
Grant JP16H06351. M. M. M. greatly acknowl-
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for a postdoctoral fellowship (MA 7096/1).
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O
CH3
O
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O
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O
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Scheme 6. Proximal bond scission of a ben-
zocyclobutenone observed by Olofson and
co-workers.[25] (top); rational for observed
reactivity of substrates 2 with vicinal methoxy-
substitution pattern (bottom).
Alder cycloaddition attempt of a benzocyclobu-
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In summary, we have developed an effi-
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ortho-methylbenzaldehydes via a two-step
procedure, including: (1) a benzyne [2+2]
cycloaddition, and (2) a base-induced
benzocyclobutenol ring opening, starting
from simple, commercially available bro-
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[21] This compound class is of special interest to the
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