Angewandte
Forschungsartikel
Chemie
In the field of transition metal catalysis, ligand photod-
1,4-selective hydroboration and protonation. Previous studies
issociation has been shown as a method to switch a reaction
between on and off states by revealing ligation sites at a metal
centre. One such example is the 18 electron earth-abundant
transition-metal complex, CoH[PPh(OEt)2]4 which und-
ergoes photodissociation with visible light to generate 16
electron complex, CoH[PPh(OEt)2]3.[25,26]
have established that this cobalt complex is able to isomerise
alkenes under light irradiation.[25]
As we had shown that light was able to switch the reaction
outcome on a range of linear substrates, we therefore then
turned to more challenging cyclic a,b-unsaturated ketone
substrates. The inability of these substrates to undergo 1,4
selective hydroboration to initially form the boron enolate,
had been highlighted as a restriction in previous me-
thodologies.[14,29,30] With 4,4-dimethylcyclohex-2-en-1-one,
1k, as the starting material in benzene, using pinacolborane in
the dark, we observed 1,2-selective reduction product 3k
upon quenching with water—selectivity that has been repor-
ted for a broad range of catalysts.[5,8] Upon carrying out the
identical reaction in the light, however, we were delighted to
obtain the product 2k from conjugate reduction. This unusual
control of regioselectivity using only light as an external sti-
mulus appeared to offer an excellent route to the desired
boron enolates. Furthermore, this showcases the concept of
using light to control the catalytic pathway and thus the se-
lectivity of a hydridic reagent, rather than stoichiometric
quantities of additives which generate significant waste.
Further optimisation (see the Supporting Information for
details) demonstrated that in the light, the saturated ketone
was obtained with even higher yield when the reaction was
carried out in THF.
It can be seen from the optimised structures[27] that any
coordinative interaction of a substrate with the metal centre
of CoH[PPh(OEt)2]4 appears improbable, whereas in con-
trast, the corresponding complex generated upon light irra-
diation, CoH[PPh(OEt)2]3, has a vacant coordination site
(Scheme 1d). Despite this, we have recently reported a cata-
lytic system based on the use of CoH[PPh(OEt)2]4 in con-
junction with pinacolborane for alkene isomerisation, in-
dicating the potential for a different mechanistic scenario.[28]
We therefore hypothesised that if two different mechanistic
pathways, controlled only by the presence or absence of light,
are operative, this may lead to contrasting selectivity in the
context of catalytic hydroboration of a,b-unsaturated carbo-
nyls. In addition, this divergent mechanistic control may ob-
viate the requirement of s-cis conformation to perform 1,4-
hydroboration, leaving a single catalytic platform able to
carry out both 1,2 and 1,4-hydroboration of linear and, the
previously unsolved, cyclic unsaturated ketones.
We carried out a scope of the light-switchable reduction
under the optimised conditions. Starting material 1l, contai-
ning an ester group, showed complete selectivity for enone
reduction under both sets of conditions, yielding either 3l or
2l selectively. Cyclohexenone rings substituted at the g-posi-
tion (1m & 1n) were also suitable substrates for these reac-
tions (albeit showing a mixture of diastereomers in the dark).
Carvone, 1o, is a challenging substrate to selectively hy-
droborate due to the presence of the electron rich alkene.
Previously reported methods which rely on more reactive
alkylboranes would also hydroborate this functionality, ho-
wever under our conditions, this handle remains untouched to
yield either 2o or 3o in the light or dark, respectively. We also
sought to see if this reactivity was also applicable to a,b-un-
saturated aldehydes, however, substrate 1p gave only the 1,2-
reduced product in the dark with this also being the major
product in the light.
Our next step sought to build upon the new reactivity
discovered in the light by reacting the boron enolates with
other electrophiles. Lipshutz and Papa have reported a one-
pot reductive aldol reaction using air-sensitive Strykerꢀs rea-
gent and in situ generated diethyl borane which leads to anti-
selective aldol products for cyclic substrates.[15] Similarly,
there are limited reports on precious metal hydride catalysis
for reductive aldol reactions which are applicable to cyclic
enone substrates, though these again favour the anti-pro-
ducts.[31]
Results and Discussion
Our investigations began using 5 mol% of CoH[PPh-
(OEt)2]4 in conjunction with pinacolborane for the reduction
of chalcone 1a. In benzene solvent and in the dark, product
2a was obtained upon quenching the reaction with water,
selectivity in line with previous reports of hydroboration with
catechol borane.[14] Interestingly, upon irradiating the reaction
with blue light, a complete switch in selectivity was noted,
yielding the allylic alcohol, 3a. A scope of this reaction was
then carried out to probe the generality of this light con-
trolled, regioselective reduction procedure (Scheme 2).
Chalcones containing both electron rich (1b) and electron
poor arenes (1c–1 f) were selectively reduced under light or
dark reaction conditions, displaying precise control over se-
lectivity. Notably, the ester functionality of 1c was untouched
despite using excess pinacolborane. Upon changing from
a phenyl ketone to a methyl ketone with b-phenyl substitu-
tion, the selectivity unexpectedly changed in the dark to yield
the allylic alcohol, 2g in good yield which we initially at-
tributed to the conformational preference of the starting
material. However, substrates 1h and 1i gave a mixture of
products under the „dark conditions“. In contrast, substrate
1g underwent non-selective hydroboration in the light whe-
reas substrates 1h and 1i gave selective, although contrasting
1,4- and 1,2-products, respectively.
Starting material 1j, with a methylene group between the
alkene and ketone functionality, was reduced in a 1,2 fashion
in the dark to give 3j as the major product. Notably we ob-
tained product 2j when the reaction was carried out in the
light which we believe arises from the following sequence:
isomerisation of the olefin to give the a,b-unsaturated ketone,
Unlike for linear substrates, where control of enolate ge-
ometry is the major factor for controlling aldol stereoselec-
tivity, cyclic substrates require a change of enolate. Methods
to generate the syn-aldol products have relied on tin,[32] zir-
conium[33] or titanium[34] enolates, however there have also
been previous reports that enolborates favour syn-aldol pro-
Angew. Chem. 2020, 132, 2 – 9
ꢀ 2020 Die Autoren. Verçffentlicht von Wiley-VCH GmbH
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