Metal-Free Direct Deoxygenative Borylation of Aldehydes and Ketones

Article abstract of DOI:10.1021/jacs.0c03813

Direct conversion of aldehydes and ketones into alkylboronic esters via deoxygenative borylation represents an unknown yet highly desirable transformation. Herein, we present a one-step and metal-free method for carbonyl deoxy-borylation under mild conditions. A wide range of aromatic aldehydes and ketones are tolerated and successfully converted into the corresponding benzylboronates. By the same deoxygenation manifold with aliphatic aldehydes and ketones, we also enable a concise synthesis of 1,1,2-tris(boronates), a family of compounds that currently lack efficient synthetic methods. Given its simplicity and versatility, we expect that this novel borylation approach could show great promise in organoboron synthesis and inspire more carbonyl deoxygenative transformations in both academic and industrial settings.

Full text of DOI:10.1021/jacs.0c03813

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Article
Metal-Free Direct Deoxygenative Borylation of Aldehydes and Ketones
Jianbin Li, Haining Wang, Zihang Qiu, Chia-Yu Huang, and Chao-Jun Li
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c03813 • Publication Date (Web): 27 Jun 2020
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Journal of the American Chemical Society
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Metal-Free Direct Deoxygenative Borylation of Aldehydes and Ketones
Jianbin Li, Haining Wang, Zihang Qiu, Chia-Yu Huang, Chao-Jun Li*
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Department of Chemistry and FRQNT Centre for Green Chemistry and Catalysis, McGill University, 801 Sherbrooke
Street W, Montreal, Quebec H3A 0B8, Canada
ABSTRACT: Direct conversion of aldehydes and ketones into alkylboronic esters via deoxygenative borylation represents an
unknown yet highly desirable transformation. Herein, we present a one-step and metal-free method for carbonyl deoxy-
borylation under mild conditions. A wide range of aromatic aldehydes and ketones are tolerated and successfully converted
into the corresponding benzylboronates. By the same deoxygenation manifold with aliphatic aldehydes and ketones, we also
enable a concise synthesis of 1,1,2-tris(boronates), a family of compounds that currently lack efficient synthetic methods.
Given its simplicity and versatility, we expect that this novel borylation approach could show great promise in organoboron
synthesis and inspire more carbonyl deoxygenative transformations in both academic and industrial settings.
Scheme 1. Aliphatic organoboron compound synthesis
1. INTRODUCTION
Alkylboronic acids and their derivatives are valuable re-
agents in organic synthesis,1 as they play indispensable
roles in numerous downstream transformations. Of equal
importance, they are also prevalent in medicinal chemistry,
acting as potent isosteres of bioactive carboxylic acids.2
However, due to their rarity in nature, access to boron com-
pounds mainly relies on chemical synthesis (Scheme 1A).
Traditional approaches to prepare aliphatic organobo-
ron compounds involve the reactions between stoichio-
metric organometallic nucleophiles and boron electrophiles
or hydroboration of olefins.1c, 3 In modern chemistry, the
synthesis of alkylboronates is considerably advanced by
transition-metal-catalyzed C-X (X = H4 or (pseudo)halide5)
borylation. With the contribution by the research groups of
Aggarwal,6 Jiao,7 Paolo,8 Studer9, and many others,10 the
borylation toolkit is further enriched by various metal-free
strategies with different radical precursors. Within the area
[B], boryl group; Ts, tosyl group.
of metal-free borylation, Wang and his co-workers de-
scribed an alternative approach by coupling the bis(pinaco-
lato)diboron (B2pin2) or pinacolborane (HBpin) with to-
sylhydrazones, achieving an indirect deoxygenative hy-
droboration on the carbonyl carbon.11 Despite these
achievements, a simple and reliable synthetic route for al-
kylboronic esters that features the direct usage of abundant
and renewable starting materials in the absence of metal
catalysts remains underexplored.
Aldehydes and ketones are privileged chemical entities
in the synthetic community by virtue of their ubiquity and
chemical versatility.12 These attractive features continu-
ously encourage chemists’ exploration of their novel reac-
tivities and applications. Among these efforts, the deoxy-
genative functionalization is an area of increasing interest.13
In this context, our group disclosed a series of transition-
metal-catalyzed “interrupted Wolff-Kishner reactions” of
hydrazones, which furnished numerous C-C bond-forming
products.14 Our ongoing interest in carbonyl deoxygenation
chemistry led us to consider the possibility of converting
carbonyls into organoboron compounds. Ideally, we
planned to replace the oxygenous moiety of the carbonyl
with the boryl group simply by using readily available bo-
ron reagents. Moreover, it would be preferable to avoid any
pre-functionalization and the usage of precious transition
metal catalysts during this transformation.
Herein, we present a practical method for the synthesis
of alkylboronic acid derivatives from the corresponding al-
dehydes and ketones by using commercially available dibo-
ron reagents (Scheme 1B). This efficient strategy allows the
direct deoxygenative monoboration of aromatic aldehyde
and ketones without pre-functionalization and metal cata-
lysts at mild temperatures. The same borylation manifold
could also enable an unprecedented deoxygenative tribora-
tion reaction, thereby providing a general route for prepar-
ing various synthetically appealing 1,1,2-tris(boronates)
from the corresponding aliphatic aldehydes and ketones.
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With these concerns in mind, we proposed our reaction
Scheme 2. Reaction design and optimization.
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design in Scheme 2B. Initially, the reaction of an aldehyde
with a diboron compound simultaneously forms the C-B
and O-B bonds of Int I. As a pivotal step, the carbonyl bis-
borylation not only gives the desired C-B bond but also re-
duces the C=O bond order.20 Considering its similarity to al-
kene vicinal diboration,3c a highly electrophilic diboron rea-
gent with a compatible basic activator would be beneficial.21
Because of the Lewis acidity of the trivalent boron,1h both
neighboring boron atoms could contribute to the C-O bond
activation in Int I,20g, 20h and consequently, the C-O bond be-
comes cleavable. With another incoming diboron, an 훼,훼-
bisborylated intermediate Int II is formed. At this stage, se-
lective hydrolysis will give the desirable boronic ester as the
final product. 1k, 11a, 22
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In the preliminary study, we envisioned that bis(cate-
cholato)diboron (B2cat2) and N,N-dimethylacetamide
(DMA) could be a feasible combination.6, 9, 10d Delightfully,
when 4-biphenylcarboxaldehyde (1a) was selected as the
model substrate, we obtained the targeted product in the
presence of 3.0 equiv B2cat2 and 10.0 equiv H2O in 0.33 M at
room temperature under argon for 48 hours. For conven-
ient characterization, a simple transesterification was per-
formed to give the 4-phenylbenzylboronic acid pinacol es-
ter (1b) in 62% yield (Scheme 2C). Consistent with our sur-
mise, less electrophilic B2pin2 and B2(OH)4 showed dramat-
ically poor performance (entry 1). Interestingly, in situ for-
mation of B2cat2 by adding B2(OH)4 with catechol (see Sup-
porting information for details) could also promote the de-
sired transformation, although in only 27% yield (entry 2).
We found that changing the solvents did not improve the
yield. Switching the solvent to the analogous N,N-dimethyl-
formamide (DMF) slightly lowered the reaction efficiency
(entry 3); however, acetonitrile (CH3CN), which was com-
monly employed in dehalo-borylation,23 dramatically de-
pressed the yield (entry 4). It was found that a higher pro-
portion of water (20.0 equiv) resulted in a lower yield, pos-
sibly due to the pronounced hydrolysis of B2cat2 (entry 5).
The effect of some other additives was also examined. By
applying 4-phenylpyridine (4-Ph-C5H4N) with sodium
methoxide (NaOMe), which was used in Jiao’s borylation
work,7, 23d only 28% yield of the pinacol ester was afforded;
yet, the borylation was barely affected by acetic acid (en-
tries 6-7). To our delight, at 50 ℃, the reaction time could
be significantly shortened with the same productivity (en-
try 8). Encouraged by this result, by raising the temperature
to 80 ℃, the reaction yield was further improved to 77%.
Under these optimal conditions, the desired 1b was isolated
in 72% yield (entry 9). The control experiment showed that
the reaction still proceeded smoothly under air (entry 10).
Substrate scope of monoboration. With the optimal
conditions in hand, we investigated the substrate scope of
this deoxygenative borylation. Aromatic aldehydes bearing
different electronic and steric properties were first evalu-
ated (Scheme 3A). While benzaldehyde (2a) furnished a
similar 75% yield to that of 1a, other derivatives with vari-
ous substituents like methyl, ethyl, tert-butyl, and phenyl
groups, irrespective of their positions, were all effective
substrates (2b to 9b). Notably, a moderate degree of the ste-
ric hindrance could be tolerated in this reaction, as shown
aYields were determined by 1H NMR using 1,3,5-trimethoxybenzene as
the internal standard unless otherwise specified. FG, functional group;
B2X4, diboron compound; rt, room temperature; [Red], reduction; [B],
boryl group; Iso., isolated yield.
2. RESULTS AND DISCUSSION
Reaction design and optimization. Reactions of car-
bon-centered radicals and anions with boron electrophiles
are typical for forming C-B bonds.10a-c However, these reac-
tion modes might not be suitable for the reductive boryla-
tion of aldehyde for two reasons (Scheme 2A). Firstly, as a
consequence of single electron transfer (SET), the ketyl rad-
icals generated from the aldehydes could undergo undesir-
able pinacol couplings or addition to alkenes and alkynes.15
Secondly, 훼-oxy anions that are formed under harsher re-
ducing conditions would be highly reactive towards some
off-target electrophiles (e.g., H+ and carbonyls).13i, 16 These
two species would lower the functional group tolerance and
induce side reactions. Clearly, other reactivity paradigms
are needed to strategize the C-B formation with aldehydes.
Brief reaction analysis revealed that this reductive
borylation requires two key components: a moderate elec-
tron donor and a suitable borylating reagent. As such, we
postulated that diboron reagents could be appropriate can-
didates as they could play both roles as the reductant and
boron source.17 Moreover, these compounds possess dual
philicities, which could activate carbonyls as Lewis acids
and implement borylative nucleophilic attack upon the co-
ordination with Lewis bases.18 Lastly, the formation of ro-
bust B-O bonds could facilitate the C-O bond cleavage.19
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Scheme 3A. Substrate scope of deoxygenative monoboration
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a
See Supporting Information for details. Yields are for isolated products after purification unless otherwise specified. Condition A: reactions were
performed with aromatic aldehyde (0.20 mmol, 1.0 equiv), B2cat2 (0.60 mmol, 3.0 equiv), H2O (2.0 mmol, 10.0 equiv) in DMA (0.60 mL) under argon
at 80 ℃ for 12 hours; then transesterification. bCondition B: same as condition A but performed at room temperature for 72 hours. cCondition C:
reactions were performed with aromatic ketone (0.20 mmol, 1.0 equiv), B2cat2 (0.60 mmol, 3.0 equiv) in DMA (0.60 mL) under argon at 80 ℃ for 72
hours; then transesterification. dReaction yields were determined by NMR due to the volatility or instability of targeted compounds. Based on the
e
recovered starting material. f1,2-bis(boronate) were detected in the GC-MS analysis.
in the case of 2-biphenylcarboxaldehyde (8b). Aldehydes
with large conjugated chromophores such as pyrene were
compatible with our standard conditions and successfully
converted to the desired product (10b), although an ex-
haustive reduction product, 1-methylpyrene, was also iden-
tified in the reaction mixture (see Supporting Information
for details). When our optimal conditions were applied to
the benzaldehydes with weakly withdrawing or donating
groups, such as fluoro, chloro, bromo, acetoxy, tosyloxy as
well as phosphoryloxy groups, moderate yields were given
(11b to 17b). As these disubstituted products contain func-
tional handles with complementary reactivities, they could
serve as useful synthons for cross-couplings in polymer
chemistry. Noticeably, -OCF3 group, a long-sought-after
functionality in medicinal chemistry as it was often linked
to the potency enhancement of drug leads, survived the re-
ductive borylation (18b).24 Regarding substrates with
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Scheme 3B. Substrate scope of deoxygenative triboration
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a
See Supporting Information for details. Yields are for isolated products after purification unless otherwise specified. Condition A: reactions were
performed with aliphatic aldehyde and ketone (0.20 mmol, 1.0 equiv), B2cat2 (0.60 mmol, 3.0 equiv) in DMA (0.60 mL) under argon at 80 ℃ for 12
hours; then transesterification. bLow yield was obtained in the case of acetone probably due to its volatility.
strong electron-donating groups including methoxy, pro-
pargyloxy, methylthio and dimethylamino groups, unal-
tered reaction efficiencies were generally observed, afford-
ing the boronic esters in yields ranging from 47% to 63%
(19b to 22b). Although unsaturated functional groups (e.g.,
triple bond) were susceptible to borylation in the presence
of diboron,3c we were pleased to see that borylation oc-
curred chemoselectively at the aldehyde site with the al-
kyne remaining intact (20b). Encouragingly, the reaction of
carboxaldehyde with heteroaromatic core such as dibenzo-
furan was also successful (23b). However, aromatic alde-
hydes with strongly withdrawing groups were ineffective
under our conditions (see Supporting Information for de-
tails).13i Although the reasons behind these failed examples
remain unclear, we thought that the diminished basicity of
carbonyl oxygens of these reactants might cause their inef-
ficient coordination towards B2cat2, therefore, the poor re-
activities. Pleasingly, aromatic ketones were also applicable
with our deoxy-monoboration method, providing a series of
훼-substituted benzylboronates. As lower conversion was
not uncommon for ketones under previous conditions, pro-
longed reaction time was necessary. For alkyl aryl ketones,
their deoxy-hydroboration could give the expected prod-
ucts successfully with similar performance (24b and 25b).
Despite the bulky geminal groups of diarylketones, their
borylation could also proceed smoothly (26b and 27b).
In addition to the pinacol esters, other boronates could
be conveniently accessed simply through the transesterifi-
cation of catechol ester intermediate. As such, various five-
and six-membered ring boronic acid derivatives were pre-
pared in 54% to 90% yields (1c to 1g), including the (+)-
pinanediol ester, whose congeners were frequently encoun-
tered in the stereoselective synthesis.25 Other than the
above-mentioned boronates, by reacting with N-methylim-
inodiacetic acid (MIDA), the tetravalent MIDA boronate
could also be assembled successfully (1h).
For convenient diversifications, installing the boryl
group on compounds with high molecular complexity
would be advantageous for their post-synthetic modifica-
tion. With this consideration, aldehydes bearing tri-
phenylphosphine, ibuprofen and (-)-menthol moieties were
subjected to our deoxygenative borylation conditions. De-
lightfully, all of them could furnish the corresponding boro-
nate products (28b to 30b). Substrates with phosphino
groups are often problematic in the metal-catalyst-involved
process. By leveraging our metal-free conditions, the phos-
phine group remained untouched, which allowed the easy
diversification of phosphine-based ligands and catalysts.
Substrate scope of triboration. In the synthetic com-
munity, multi-borylated alkanes are valuable targets due to
their essential roles as conjunctive reagents and bioactive
agents.1h, 26 Among them, 1,1,2-tris(boronate) is a unique
subset as it allows multiple deborylative transformations
on two neighboring carbons selectively and sequentially.26c,
26f, 26g Surprisingly, an in-depth investigation of its reactivity
and application remains rare, which was possibly attributed
to the limited methods for its preparation.
During our investigation in deoxy-borylation of aliphatic
aldehydes and ketones, an exclusive 훼,훼,훽-triboration oc-
curred instead of the regular monoboration (Scheme 3B). A
brief survey of the substrate scope indicated that linear and
branched (훼- or 훽-substituted) aldehydes underwent the
deoxygenative triboration smoothly (31b to 33b), so did
the cyclic and non-cyclic ketones (34 and 35b). Due to its
simplicity and efficiency, we believe that such a deoxygena-
tion method could become a practical route to access this
class of valuable organoboron compounds.
Synthetic application. To demonstrate the utility of
our new borylation method, we submitted the benzyl-
boronate products for further diversification (Scheme 4A).
Firstly, the boronates were subjected to protodeboronation,
deborylative iodination as well as Suzuki-Miyaura coupling,
giving the corresponding C-H, C-I and C-C bond-forming
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Scheme 4. Applications
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a
See Supporting Information for details. Yields are of isolated products after purification unless otherwise specified. Condition A: reactions were
performed with 4-iodobenzaldehyde (0.10 mmol, 1.0 equiv), B2pin2 (0.20 mmol, 2.0 equiv), TMDAM (0.10 mmol, 1.0 equiv) in CH3CN (1.0 mL) under
argon at room temperature and irradiated by >250 nm light. bCondition B: reactions were performed with aldehyde (0.20 mmol, 1.0 equiv), B2cat2
(0.60 mmol, 3.0 equiv), H2O (2.0 mmol, 10.0 equiv) in DMA (0.60 mL) under argon at 80 ℃ for 12 hours; then transesterification. cCondition C: same
as condition C but performed at room temperature for 72 hours. FG, functional group; TMDAM, N,N,N’,N’-tetramethyldiaminomethane; t-Bu, tert-
butyl; hν, photon; ∆, heating.
products, respectively. Later, the benzylboronic ester was
shown to be amenable in the radical processes meditated by
silver (I). Using the protocol developed by Shen’s group,27
we realized the catalytic radical difluoromethylthiolation
with 1b, successfully converting the -Bpin into -SCF2H
group (1l). Interestingly, the oxidative mono-fluorination
conditions that were reported by Li and his colleagues28
gave us an unexpected benzylic difluorination product
(1m). This finding not only showcased the uniqueness of
benzylboronic esters but also opened up a new approach to
prepare the difluorotoluenes. Secondly, given the apprecia-
ble chemoselectivity of our method, the sequential boryla-
tion of the bifunctional 4-iodobenzaldehyde (37a) becomes
conceivable (Scheme 4B). Although iodide has been vali-
dated as an excellent leaving group in both metal-catalyzed
and metal-free borylations,10a-c our carbonyl-selected
borylation protocol could still afford the 4-iodobenzyl-
boronic ester as the major product (37b). On the contrary,
based on our previous work23b and others’,18b, 29 photo-in-
duced deiodo-borylation of 37a was also realized, leaving
the -CHO functionality in 4-formylphenylboronic ester
(38a) for subsequent deoxy-borylation (38b).
Mechanistic study. To better understand this process, a
series of experiments were performed. Firstly, the possibil-
ity of involving open-shell intermediates was evaluated
with radical quenchers 2,2,6,6-tetramethyl-1-piperidi-
nyloxy (TEMPO), butylated hydroxytoluene (BHT) and 1,1-
diphenylethylene (1,1-DPE). Yields of targeted boronic es-
ter 1b mostly remained unaffected except in the case of
TEMPO (Scheme 5A). Further experiments explained that
the decreased yield was mainly caused by the direct reac-
tion between TEMPO and B2cat2 (see Supporting Infor-
mation for details). Additionally, the deoxy-borylation of 2-
allyloxybenzaldehyde (39a) was found to generate the acy-
clic boronic ester as the only product in 64% yield (39b).
Combining the results from inter- and intramolecular trap-
ping experiments, the involvement of radical or carbene in-
termediates seems unlikely in this transformation.
Secondly, the requirement of amide solvents suggested
the importance of a basic and coordinating environment for
B2cat2 to promote the desired transformation.6, 9, 10d There-
fore, 11B nuclear magnetic resonance (NMR) spectra of
B2cat2 were recorded in DMA and the control solvent di-
chloromethane (DCM), respectively. In line with the litera-
ture reports,6a, 10d broadened and upfield 11B NMR signal
was observed in DMA (25.8 ppm) relative to DCM (30.8
ppm), suggesting the loose complexation of B2cat2 with the
former solvent. This interaction seemed crucial to enable
the deoxy-borylation reaction, as no targeted product was
detected in the non-coordinating DCM. Interestingly, the ad-
dition of 4-dimethylaminopyridine (DMAP) or DMA could
retrieve some desired reactivities (Scheme 5B).
Being aware of the electrophilic character of B2cat2 and
the high chemoselectivity of this reaction, we surmised that
B2cat2 could ligate with the carbonyl oxygen of aldehyde in
a similar way to DMA. Accordingly, we proposed that a ter-
nary species B1 was formed reversibly,6a, 30 activating both
the carbonyl and diboron, and bringing them in close prox-
imity (Scheme 5C). To get more insight, NMR and ultravio-
let-visible (UV-Vis) spectra were used to characterize the al-
dehyde, B2cat2 as well as their mixture in DMA. Indeed,
changes in the spectroscopic behavior of their mixture com-
pared to the individual component were observed,6a which
substantiated the formation of B1 in low concentration.
Similar to copper-catalyzed vicinal diboration of carbon-
yls,20a-i an intramolecular boryl group migration to the
formyl carbon of B1 might occur, resulting in an alcoholate.
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Scheme 5. Mechanistic study.
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See Supporting Information for details. Catecholatoboronates are converted into pinacol esters and their yields are determined by 1H NMR using
1,3,5-trimethoxybenzene as the internal standard unless otherwise specified. Condition A: reactions were performed with aldehyde or its equiva-
lence (0.20 mmol, 1.0 equiv), B2cat2 (0.60 mmol, 3.0 equiv), H2O (2.0 mmol, 10.0 equiv) in DMA (0.60 mL) under argon at 80 ℃ for 12 hours. Condition
B: same as the Condition A but without H2O. ND, not detected; Ar, aryl group; TMS, trimethylsilyl group.
To trap this potential alkoxide intermediate, we performed
a reaction with methyl 2-formylbenzoate (40a, Scheme 5D).
Interestingly, a lactone product 40o, which might result
from the hydrolysis of 40b’, was identified. Moreover, the
competition experiment showed that the borylation prefer-
entially occurred with less hindered benzaldehyde over
acetophenone. Both results evidenced the nucleophilic ad-
dition of diboron towards the carbonyl.31
Next, the mechanism of breaking the key C-O bond in the
alcohol-related intermediates was investigated. Control ex-
periments showed that neither the free alcohols 1o and 33o
nor their O-Bpin derivatives 1o’ and 33o’ were viable inter-
mediates (Scheme 5E, eq. 1 and 2). Like our original design,
we hypothesized that the C,O-bisborylated species was the
key intermediate for this deoxy-borylative transformation.
In this case, a catecholato 훼 -boryl- 훼 -(boryloxy)toluene-
type compound would be well-suited; however, because of
its synthetic difficulty,32 the analogous benzyl silyl ethers, a
type of compounds recently reported by Ito’s and Glorius’s
groups, were considered instead.20d, 20f, 33 As expected, the
targeted mono-boronate 19b was obtained under our opti-
mal conditions, which possibly resulted from the boro-sub-
stitution of C-OTMS bond in 19b-OTMS and the subsequent
hydrolysis of 19b’ (Scheme 5E, eq. 3).20g, 20h In terms of the
triboration, we envisioned that a similar C,O-bisborylated
intermediate B7 was also involved. Since B7 was prece-
dented to eliminate the hydroxyborate under either acidic
or basic conditions,34 the elimination product vinylboronate
was rationalized as another key species. Unsurprisingly,
when the independently synthesized 41b’ was subjected to
the triboration conditions, we could obtain the desired
tris(boronate) in 80% yield (Scheme 5E, eq. 4). Although B7
has the propensity for C-O borylation as well,20g the reason
for such divergent reactivities remained uncertain.
In the proposed monoboration mechanism, the final
product derives from a protodeboronation step. In princi-
ple, lower temperatures and more congested substituents
around the boron centers might decelerate the hydrolysis of
the gem-bisborylated species. By subjecting mesitaldehyde
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Scheme 6. Proposed mechanism.
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(42a) to the deoxy-borylation at room temperature, the bis-
tively. The exploration of more mechanistic details is ongo-
ing in our laboratory, and current efforts are focusing on in-
vestigating the formation of B3 and B8 via computation.
Considering the simplicity and versatility of this deoxygen-
ation borylation strategy, we envisioned that this approach
could enrich the current toolkit of alkylboronate synthesis
and inspire more research endeavors on carbonyl deoxy-
genative transformation.
borylated 42b’ was obtained as the major product, while a
reversed product distribution was observed at 80 ℃
(Scheme 5F). As further evidence for the intermediacy of
the gem-diboronate,11a, 22b benzyldiboronate 2b’ was inde-
pendently prepared and submitted to our optimal condi-
tions. As anticipated, 2b’ was fully converted into the mono-
protodeboronated product 2b under our standard condi-
tions (see Supporting Information for details). Finally, two
deuteration experiments were conducted to probe the role
of water, the results of which unambiguously determined
that one of the benzylic hydrogens of 1b came from water,
and the other originated from the aldehyde.
Putting all the information together, we depicted a tenta-
tive mechanism in Scheme 6. Firstly, DMA, B2cat2 and alde-
hyde were engaged as a three-membered complex B1,
which simultaneously activated the diboron and aldehyde.
Then, through a DMA-mediated intramolecular boryl group
transfer, a 1,2-bis(catecholato)boronate intermediates B3
and B7 were formed for aromatic and aliphatic substrates,
respectively. For the monoboration, B3 was subjected to the
C-O cleavage with the assistance of another B2cat2. After this
metathesis process, the resulted benzylic 훼,훼-diboronate
B4 could undergo a protodeboronation/transesterification
sequence to furnish the desired boronate B6. Concerning
the triboration, removal of HO-Bcat in B7 resulted in the vi-
nylboronate intermediate B8, which was bisborylated and
transesterified to give tris(boronate) B10.
ASSOCIATED CONTENT
The supporting information is available free of charge via the
Internet at http://pubs.acs.org.
Experimental procedures, spectroscopic data and
computational methods
AUTHOR INFORMATION
Corresponding Author
*cj.li@mcgill.ca
Notes
The authors declare no competing financial interest.
Author Contributions
All the authors contributed to the discussion of experimental
results. The manuscript was written through the contributions
of all authors. All authors have approved the final version of the
manuscript.
Funding Sources
3. CONCLUSIONS
We are grateful to the Canada Research Chair Foundation (to
C.-J.L.), the Canada Foundation for Innovation, the FQRNT Cen-
ter in Green Chemistry and Catalysis, the Natural Sciences and
Engineering Research Council of Canada, and McGill University
for supporting our research.
We have established a step-economic and metal-free ap-
proach for direct conversion of carbonyls into organoboron
compounds. A series of monoboronates and tris(boronates)
could be prepared from the corresponding aldehydes and
ketones in a single step with the commercially available
B2cat2 in wet DMA. The deoxy-borylation was performed
under mild conditions, featuring a broad substrate scope
and high chemoselectivity. Compared to the earlier litera-
ture methods, this approach does not require pre-function-
alization, and it is capable of cleaving the strong C=O bond
in the absence of metal catalysts. Preliminary mechanistic
studies revealed the role of each reaction component and
elucidated the key intermediacy of gem-diboronate and vi-
nylboronate. These important intermediates would lead to
the desired monoboronates and tris(boronates), respec-
ACKNOWLEDGEMENT
We would like to acknowledge the McGill Chemistry Character-
ization Facility for their contribution to the compound charac-
terization in this work, specifically, Robin Stein on the NMR,
Nadim Saadé and Alexander Wahba on HRMS. We are indebted
to Siting Ni (McGill University) for our access to the spectro-
scopic facilities. Also, we would like to thank our group mem-
bers and colleagues, especially Zhang-Pei Chen (McGill Univer-
sity) and Wenbo Liu (University of Michigan), for their gener-
ous help on polishing the manuscript.
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R.; Martin, R., Ipso-Borylation of Aryl Ethers via Ni-Catalyzed C–OMe
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Enantioselective Preparation and Chemoselective Cross-Coupling of
1,1-Diboron Compounds. Nat. Chem. 2011, 3, 894-899; (b) Feng, X.;
Jeon, H.; Yun, J., Regio‐ and Enantioselective Copper(I)‐Catalyzed
Hydroboration of Borylalkenes: Asymmetric Synthesis of 1,1‐
Diborylalkanes. Angew. Chem., Int. Ed. 2013, 52, 3989-3992; (c)
Coombs, J. R.; Zhang, L.; Morken, J. P., Enantiomerically Enriched
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Sun, C.; Potter, B.; Morken, J. P., A Catalytic Enantiotopic-Group-
Selective Suzuki Reaction for the Construction of Chiral
Organoboronates. J. Am. Chem. Soc. 2014, 136, 6534-6537; (e)
Mlynarski, S. N.; Schuster, C. H.; Morken, J. P., Asymmetric Synthesis
from Terminal Alkenes by Cascades of Diboration and Cross-coupling.
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Q., Base-Controlled Highly Selective Synthesis of Alkyl 1,2-
Bis(boronates) or 1,1,2-Tris(boronates) from Terminal Alkynes. Green
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Muranaka, A.; Uchiyama, M., Quadruple Borylation of Terminal
Alkynes. J. Am. Chem. Soc. 2019, 141, 9819-9822; (h) Liu, X.; Ming, W.;
Zhang, Y.; Friedrich, A.; Marder, T. B., Copper-Catalyzed Triboration:
Straightforward, Atom-Economical Synthesis of 1,1,1-Triborylalkanes
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(19) Luo, Y.-R., Comprehensive Handbook of Chemical Bond Energies.
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(20) For selected examples: (a) Laitar, D. S.; Tsui, E. Y.; Sadighi, J. P.,
Catalytic Diboration of Aldehydes via Insertion into the Copper−Boron
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of Aldehydes Catalyzed by Copper(I) Boryl Complexes. J. Am. Chem. Soc.
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Catalyzed Enantioselective Nucleophilic Borylation of Aldehydes: An
Efficient Route to Enantiomerically Enriched α-Alkoxyorganoboronate
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Nishiura, M.; Hou, Z., Synthesis of Lithium Boracarbonate Ion Pairs by
Copper-Catalyzed Multi-Component Coupling of Carbon Dioxide,
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(f) Kubota, K.; Osaki, S.; Jin, M.; Ito, H., Copper(I)-Catalyzed
Enantioselective Nucleophilic Borylation of Aliphatic Ketones:
Synthesis of Enantioenriched Chiral Tertiary α-Hydroxyboronates.
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W.; He, Z.; Xia, C.; Lan, Y.; Liu, C., C–O Functionalization of α-
Oxyboronates:
A
Deoxygenative gem-Diborylation and gem-
(27) Zhu, D.; Shao, X.; Hong, X.; Lu, L.; Shen, Q., PhSO2SCF2H: A Shelf-
Stable, Easily Scalable Reagent for Radical Difluoromethylthiolation.
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(28) Li, Z.; Wang, Z.; Zhu, L.; Tan, X.; Li, C., Silver-Catalyzed Radical
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2014, 136, 16439-43.
(31) Ming, W.; Liu, X.; Friedrich, A.; Krebs, J.; Budiman, Y. P.; Huang, M.;
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Multicomponent Coupling of Salicylaldehydes, Amines, and B2(OH)4.
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(33) Ye, J.-H.; Quach, L.; Paulisch, T.; Glorius, F., Visible-Light-Induced,
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(34) (a) Guan, W.; Michael, A. K.; McIntosh, M. L.; Koren-Selfridge, L.;
Scott, J. P.; Clark, T. B., Stereoselective Formation of Trisubstituted
Vinyl Boronate Esters by the Acid-Mediated Elimination of α-
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(29) For selected examples: (a) Chen, K.; Zhang, S.; He, P.; Li, P., Efficient
Metal-Free Photochemical Borylation of Aryl Halides under Batch and
Continuous-Flow Conditions. Chem. Sci. 2016, 7, 3676-3680; (b) Mfuh,
A. M.; Nguyen, V. T.; Chhetri, B.; Burch, J. E.; Doyle, J. D.; Nesterov, V. N.;
Arman, H. D.; Larionov, O. V., Additive- and Metal-Free, Predictably 1,2-
and 1,3-Regioselective, Photoinduced Dual C-H/C-X Borylation of
Haloarenes. J. Am. Chem. Soc. 2016, 138, 8408-8411; (c) Mfuh, A. M.;
Schneider, B. D.; Cruces, W.; Larionov, O. V., Metal- and Additive-Free
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610.
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metal free C-C bond cleavage/borylation of cycloketone oxime esters.
Chem. Sci. 2019, 10, 161-166.
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