Communication
doi.org/10.1002/chem.202102536
Chemistry—A European Journal
and the excited state (S1), resulting in a bathochromic shift in
the absorption. As a counterpart of this strategy based on a
Lewis acid activation, we conjectured that the plausible
coordination of a Lewis base to the Lewis acidic p-orbital of a
boronate attached to the alkene might give rise to a transient
chromophore species and lower the S0!S1 transition (Sche-
me 2A). Then, its irradiation would permit the contra-thermody-
namic E!Z isomerization. The viability of this scenario is
subjected to 1) a stronger light absorption of the coordinated
(E)-boronate than the (Z)-isomer, 2) a reversible coordination of
the Lewis base to the boron center, and finally 3) the
irreversibility of the isomerization process. In other words, the
quantum yield (Φ) of the E!Z isomerization (ΦE!Z) of the
chromophore species formed in situ should be higher than the
Z!E isomerization quantum yield (ΦZ!E) of both coordinated
and uncoordinated boronate species. To assess whether our
conjecture could lead to the isomerization of α-substituted
styryl boronate, we elected (E)-1 as the model substrate and
several catalysts, based on a binaphthyl backbone, were
screened (Scheme 2B).[14] The first attempt using rac-BINAP gave
a promising 80:20 Z/E ratio (entry 1). The BINAM and the bis-
thiolated derivatives gave lower isomerization ratios (entries 3
and 4), while the best results were obtained with binaphthol
derivatives (entries 2, 5–7), C3 being the best one providing a
93:7 Z/E ratio (entry 2). The lower ratio obtained with biphenol
clearly highlighted the importance of the binaphthyl backbone
(entry 8). Finally, a screening of the reaction conditions revealed
that CH3CN was the best solvent and pleasingly a decrease of
the catalyst loading to 5 mol% did not alter the efficiency of the
isomerization process (entries 9 and 10). Note, that control
experiments revealed that the E!Z isomerization did not
proceed in the absence of light or catalyst, was not promoted
under thermal conditions and did not required an inert
atmosphere nor a degassed solvent.[14] Finally, to showcase the
versatility and reproducibility of this E!Z isomerization proto-
col, a sensitivity assessment regarding the reaction parameters
was conducted (Scheme 2B).[15] The reaction proved to be
robust and insensitive toward temperature, oxygen, scale and
light intensity. A slight impact of moisture was witnessed and a
decrease of the Z/E ratio was measured in the presence of water
(15% drop).
With these optimized reaction conditions in hand, we
evaluated the scope of this E!Z isomerization process
(Scheme 3). The introduction of an ethyl substituent ((Z)-2) in
place of the methyl substituent gave an excellent 96:4 Z/E ratio,
while the (E)-β-pinacolborane styrene furnished a modest 65:35
ratio in favor of (Z)-3. This result, clearly highlight the
importance of the substituent at the α-position to drive the
photostationary state toward the (Z)-isomer. Then, the influence
of a methyl substituent at the para, meta and ortho positions of
the aromatic ring was evaluated ((Z)-4 to (Z)-6). Substitution at
the para- and the meta position were well tolerated and did not
impact the E!Z isomerization, whereas the ortho substitution
inhibited the isomerization process. The steric hinderance that
prevents the conjugation of the olefin could explain this result.
This observation is in line with previous reports, which high-
lighted the crucial role of the conjugation of the alkene with
the aromatic ring.[12] Then, various electron-donating groups
were introduced on the aromatic ring, giving excellent Z/E
ratios from 96:4 to 90:10 ((Z)-7 to (Z)-10). The TBDMS-
protected primary alcohol (Z)-11 was also tested and gave an
excellent 95:5 ratio. Pleasingly, the aryl bearing the
trifluoromethoxy substituent, an important motif in drug
discovery program,[16] was smoothly reacted, furnishing a 92:8
Z/E ratio ((Z)-12). Halogen atoms, including the redox and light
sensitive iodide, and the CF3 group were also well tolerated and
provided Z/E ratio from 92:8 to 95:5 ((Z)-13–(Z)-17). The
introduction of thiophene, a five-membered heterocycle, was
detrimental ((Z)-18). Indeed, the Z/E ratio dropped to 63:37 due
to a minimization of the 1,3-allylic strain in the Z isomer, which
could explain the observed photostationary composition. The
presence of electron-withdrawing groups on the aromatic ring
like ketone (Z)-19 and ester (Z)-20 did not affect the outcome of
the process and fairly decent Z/E ratios were obtained (up to
92:8). Finally, the reaction was attempted with BMIDA and
Bdan derivatives. As expected, no isomerization of the BMIDA
derivative (E)-21 was observed. The intramolecular lone pair
donation of the amino group to the boron preventing the
coordination of the catalyst to the boron center.[17]
The Bdan derivative (Z)-22 furnished a low 44:56 Z/E ratio,
probably due to the lower Lewis acidity of the boron center,
resulting from the lone pair donation of the nitrogen to the p
orbital of the boron,[18] which disfavored the coordination of the
Scheme 2. A) Prerequisites for the E!Z isomerization. B) Optimization of the reaction and sensitivity test.
Chem. Eur. J. 2021, 27, 1–6
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