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Angewandte
Communications
(280–370 nm)[8] and a residence time of 120 min, we were
pleased to attain 5H-furanone 4a in 54% isolated yield,
double that given using a conventional photochemical setup.
NMR analysis of crude product mixtures given at various
residence times showed many side products, with the ratio of
product to by-products worsening as the residence times were
increased. In seeking to eliminate side reactions involving the
product, a comparison was made between its UV–visible
spectrum and that of the starting material. Each showed
strong absorbance below 275 nm, with cyclobutenone 1a
exhibiting additional absorbance bands at 295 and 315 nm. A
switch to a 9 W UVB narrow-spectrum lamp giving greatest
intensity in the region 310–320 nm was therefore implicated
and, in the event, this did lead to a modest improvement in
yield to 65%.
Scheme 3. Photochemical rearrangement of (2-pyridyl)-cyclobutenone
1i under continuous flow.
(Scheme 1).[1e] Rather, it suggests that the photoinduced
electrocyclic opening of 1 gives rise to a mixture of (E)- and
(Z)-vinylketenes 2, with (E)-2 giving cyclization to furan 6 en
route to furanone 4 while (Z)-2 reverts back to cyclobutenone
1 unless it too can be captured by an internal nucleophile
(Scheme 4).
The step-change in performance we sought was realized
with a switch of solvent from THF to acetonitrile. Indeed,
through this simple expedient the rearrangement of cyclo-
butenone 1a to furanone 4a was achieved in 97% isolated
yield at 0.05m concentration with a residence time of 1 h.
Interestingly, under irradiation from a UVA lamp (350–
395 nm) the rearrangement was clean but proceeded at
a much slower rate (< 10% conversion after 1 h). The
broad-spectrum UVB lamp (280–370 nm) proved as effective
as the narrow band lamp, while irradiation for 1 h using
a UVC lamp (254 nm) gave complete conversion but the
product 4a was heavily contaminated with by-products which
accounted for around 5% of the total mass balance.[8]
To explore the generality of the method, a range of
4-hydroxycyclobutenones 1b–h were prepared by the addi-
tion of alkyl-, aryl-, alkyny-, and heteroaryl-lithium reagents
to dimethyl squarate.[1–3] Pleasingly, under the aforemen-
tioned conditions, each underwent smooth rearrangement to
the corresponding furanones 4b–h in excellent yield
(Scheme 2).
Scheme 4. Revised mechanism for the photochemical rearrangement
of 4-hydroxycyclobutenones.
To explore this hypothesis we decided to model the
available cyclization pathways for the intermediate (E)- and
(Z)-vinylketenes, 2a and 2i, bearing phenyl- and (2-pyridyl)-
residues, respectively. The method chosen used DFT calcu-
lations at the B3LYP/6-311G(d,p) level to establish the course
of the reaction (Gaussian 09),[9–11] with energies refined for
required points using the coupled cluster method CCSD(T)/6-
31G(d) (GAMESS(US), Schemes 5 and 6).[2,12] Notably, the
calculated barrier for 6p-electrocyclic closure of vinylketene
(Z)-2a to 7 at 258C (16.7 kcalmolꢀ1) exceeded that for 4p-
electrocyclic closure to the starting material 1a (15.8 kcal
molꢀ1), consistent with the recycling of this intermediate. The
situation was reversed for its geometric isomer (E)-2a, where
the calculated barrier for returning cyclobutenone 1a
(20.4 kcalmolꢀ1) exceeded that for cyclization to furan 6a
(12.4 kcalmolꢀ1 [13]) leading to the observed product 4a. For
the thermal rearrangement of cyclobutenone 1a torquoselec-
tive opening was evidenced by the calculated activation
energies for formation of vinylketenes (E)-2a (35.0 kcal
molꢀ1) and (Z)-2a (28.9 kcalmolꢀ1), respectively, at 1508C.
Scheme 2. Photochemically induced cyclobutenone rearrangements of
1a–h [in a flask] and under continuous flow.
Our survey revealed a striking anomaly in respect of the
(2-pyridyl)-cyclobutenone 1i. In this case the photochemical
rearrangement took longer to run to completion and gave
a 1:1 mixture of furanone 4i and quinolizinone 5 (Scheme 3).
This anomalous result casts doubt on the view that rearrange-
ments of 4-hydroxycyclobutenones 1 each proceed by tor-
quoselective opening to a vinylketene, with thermolysis giving
(Z)-2 and photolysis giving its geometric isomer (E)-2
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 4405 –4408