β-Borylation of conjugated carbonyl compounds with silylborane or bis(pinacolato)diboron catalyzed by Au nanoparticles

Article abstract of DOI:10.1039/d0ob01806f

Conjugated aldehydes and ketones undergo reaction with Me2PhSiBpin (pin: pinacolato) catalyzed by Au nanoparticles supported on TiO2 forming exclusively the β-borylation products, via the intermediate formation of the labile silaboration adducts. This chemoselectivity pathway is complementary to the so far known analogous reaction catalyzed by other metals, where β-silylation occurs instead. β-Borylation also occurs with pinBBpin under identical reaction conditions in a variety of conjugated carbonyl compounds, including esters and amides which are unreactive in their attempted Au-catalyzed silaboration. This journal is

Full text of DOI:10.1039/d0ob01806f

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β-Borylation of conjugated carbonyl compounds
with silylborane or bis(pinacolato)diboron
catalyzed by Au nanoparticles†
Cite this: Org. Biomol. Chem., 2020,
18, 8921
Marios Kidonakis,* Michael Fragkiadakis and Manolis Stratakis
*
Conjugated aldehydes and ketones undergo reaction with Me2PhSiBpin (pin: pinacolato) catalyzed by Au
nanoparticles supported on TiO2 forming exclusively the β-borylation products, via the intermediate for-
mation of the labile silaboration adducts. This chemoselectivity pathway is complementary to the so far
known analogous reaction catalyzed by other metals, where β-silylation occurs instead. β-Borylation also
occurs with pinBBpin under identical reaction conditions in a variety of conjugated carbonyl compounds,
including esters and amides which are unreactive in their attempted Au-catalyzed silaboration.
Received 1st September 2020,
Accepted 14th October 2020
DOI: 10.1039/d0ob01806f
rsc.li/obc
reactivity of Me2PhSiBpin with conjugated carbonyl com-
pounds. In our previous study regarding its reaction with
Introduction
Supported gold nanoparticles (Au NPs) and other nano Au(0) simple carbonyl compounds, only aromatic benzaldehydes
materials have emerged as powerful catalytic systems in a
plethora of transformations of organic substrates, beyond
aerobic oxidation or transfer hydrogenation.1 Among them, the
activation and subsequent addition of interelement σ bond lin-
kages (Si–H, Si–Si, B–B, B–Si) to alkynes, allenes and even
strained σ systems represent a practical route for the synthesis
of synthetically attractive organosilicon and organoboron com-
pounds.2 Our group was the first to establish the ability of sup-
ported Au NPs to smoothly activate the Si–B bond of the fairly
stable Me2PhSiBpin (pin: pinacolato) in its reaction with
alkynes.3 Since then, a range of applications appeared using
this silylborane and Au/TiO2 as the catalyst. Thus, we have
additionally shown (Scheme 1) the regioselective silaboration of
allenes,4 the regioselective ring opening of epoxides and oxe-
tanes yielding β- or γ-silyloxy boronates respectively,5 the
pinacol-type reductive dimerization of aryl substituted carbonyl
compounds promoted by the silylborane,6 and more recently,
the silaboration of 2-aryl-substituted cyclopropyl aldehydes, in
which β-boronate silyl enol ethers are formed via ring-opening
rearrangement of an intermediate α-silyloxy cyclopropyl radical.7
and acetophenones exhibited reactivity towards a radical-
initiated dimerization pathway. With the exception of aryl-sub-
stituted cyclopropyl aldehydes which yield rearranged silabora-
tion adducts,7 all simple aliphatic aldehydes or ketones that
were examined did not exhibit any kind of reactivity.6 On the
other hand, the reaction of conjugated carbonyl compounds
with silylboranes in the presence of a proton source is well
known8 under various catalytic protocols, and leads to the
exclusive conjugated addition of the silyl moiety as a nucleo-
phile, forming β-silyl-substituted carbonyl compounds
(Scheme 2). The group of Oestreich was the first to show that
a
cationic Rh(I) complex catalyzes silyl transfer from
Results and discussion
Prompted by our intense interest in the Au NP-catalyzed reac-
tion of silylboranes with organic compounds, we examined the
Department of Chemistry, University of Crete, Voutes 71003, Heraklion, Greece.
E-mail: stratakis@uoc.gr
Scheme 1 Reactivity motifs of silylborane Me2PhSi-Bpin with various
organic compounds catalyzed by Au/TiO2, previously reported by our
group.
†Electronic supplementary information (ESI) available: Copies of the 1H and 13
C
NMR spectra of all products (PDF). See DOI: 10.1039/d0ob01806f
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borane in the absence of the catalyst does not yield any pro-
ducts. Surprisingly in chlorinated solvents, such as 1,2-dichlor-
oethane (DCE), the reaction does not occur. Similarly, conju-
gated cyclic ketones 1b and 1c were also subjected to silabora-
tion forming the corresponding products 3b and 3c in 67%
and 64% yields, respectively. These somehow moderate yields
are rather associated with the instability of the silaboration
adducts under chromatographic conditions. This chemo-
selectivity motif of silaboration is unknown in the literature,
and is complementary to the cases of using Cu or Rh catalysts,
for which β-silylation occurs instead.8
Notably, the reaction of cyclic ketones 1a–1c with bis(pina-
colato)diboron (pinBBpin, 4, pin: pinacolato) also proceeds
smoothly under the same catalytic conditions, and yields the
β-boronate substituted ketones 5a–5c in very good yields
(Scheme 3). Apparently, analogous to the enol silyl ethers 3a–
3c, boron enolates are extremely labile and undergo hydrolysis
under the reaction conditions to yield the single-borylation
products 5a–5c. In the case of borylation of 1a with pinBBpin,
the catalyst was separated after the end of the reaction from
the slurry by filtration, and after washing with an organic
solvent and drying in an oven it was reused without any loss in
its activity. This is a typical characteristic of Au/TiO2 in a series
of reactions involving silylboranes or bis(pinacolato)
diboron.3–7 The activation of the diboron reagent pinBBpin
with nano Au(0) materials has been well established in its reac-
tion with alkynes,18 allenes4 and methylene cyclopropanes.19
The β-borylation of conjugated carbonyl compounds using
pinBBpin as the boron source is also known in the literature
applying several catalytic protocols.20 These include transition
metals such as Rh(I),21 Ni(0),22,23a and Pd(0),23 primarily Cu(I)
catalysts,24 Cu(II),25 Cu NPs or Cu(0),26 as well as organocatalysts.27
In Scheme 4, we propose that after the insertion of
Me2PhSiBpin on Au NPs (denoted as Aun), primarily at its low
coordinated Au atoms (corners and edges)2 to form Me2PhSi–
(Aun)–Bpin species, and coordination of the substrate on
them, the boron and silicon moieties are selectively delivered
on the C and O atoms, respectively, forming the silaboration
Scheme 2 Known chemoselectivity in the metal-catalyzed reaction of
Me2PhSi-Bpin with conjugated carbonyl compounds.
Me2PhSiBpin on cyclic conjugated ketones, obtaining
additionally excellent enantioselectivity if an appropriate
chiral ligand is added.9 This concept was later applied in the
enantioselective conjugate silylation of α,β-unsaturated
esters.10
Hoveyda’s and Procter’s groups reported the same highly
enantioselective transformation in esters, amides, dienones
and dienoates using chiral NHC Cu(I) complexes as catalysts,11
and immediately after a metal-free catalytic version using a
chiral N-heterocyclic carbene.12 A few other catalytic protocols
of β-silylation of α,β-unsaturated carbonyl compounds are also
known, using a Cu(I) complex in the presence of a chiral
amine,13 CuSO4 in the presence of a base,14 and more recently
the Cu(I)-catalyzed reaction of silylborane with N-(2-iodoaryl)
acrylamides forming silane-bearing oxindoles.15 In addition,
trapping of the intermediates in the β-silylation of conjugated
carbonyl compounds with aldehydes generates useful syn-
thetic motifs.16 A common characteristic of the abovemen-
tioned metal-catalyzed procedures is the pre-activation of silyl-
borane upon addition of a base on the B atom, which acceler-
ates transmetallation of the silicon moiety onto the metal
center, which finally delivers the silyl part as a nucleophile on
the enone, in a 1,4-fashion. In general, in all metal-catalyzed
reactions which make use of silylboranes, the silyl moiety
behaves as a pseudo-nucleophile.17
We started the exploration of the possible Au NP-catalyzed
silaboration using cyclic α,β-unsaturated ketones. To our
delight, the treatment of 2-cyclohexen-1-one (1a) with 1.5
equiv. of Me2PhSiBpin (2) in the presence of Au/TiO2 (1 mol%
in Au) in anhydrous benzene at 70 °C for 2 h resulted in the
complete consumption of the enone and the formation of the
β-boronate silyl enol ether 3a as the sole product, in 69% iso-
lated yield (Scheme 3). The treatment of the enone with silyl-
Scheme 3 Silaboration of cyclic enones 1a–1c with Me2PhSi-Bpin, and
their β-borylation with pinB-Bpin catalyzed by Au/TiO2. a A mixture of
diastereomers in a relative ratio of 1.1/1.
Scheme 4 Proposed mechanisms of the Au NP-catalyzed silaboration/
borylation.
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Table 1 β-Borylation of acyclic conjugated aldehydes and ketones with
Me2PhSi-Bpin catalyzed by Au/TiO2
products. Similar arguments have been invoked in the Au NP-
catalyzed silaboration of strained cyclic ethers5 and cyclopropyl
aldehydes7 by our group, with the Bpin part of silylborane
acting as a pseudo-nucleophile. The driving force of this
specific mode of addition is the formation of the thermo-
dynamically stable O–Si and C–B28 bonds, and the fact that
boron is more electronegative compared to silicon. Contrary to
this mode of addition, in all other metal catalyzed reactions as
already mentioned,17 between silylborane and enones, the
silicon moiety acts as a pseudo-nucleophile, being bound on
the metal after an external basic reagent is bonded by the
boron atom of silylborane, breaking therefore the Si–B bond.
Analogous is the proposed mechanistic scenario of using
pinBBpin (Scheme 4). The O–B bond of the diborylation pro-
ducts is extremely labile and via hydrolysis under the reaction
conditions/work up, β-borylated ketones are formed. If in the
borylation of 1a one equiv. of D2O is added along with B2pin2,
>95% single deuteration is observed on the α-carbon (product
5a-d1), indicative of the reaction between the transient boron
enolate and D2O. Note that no D-incorporation was detected
when any of the single borylated products 5a–5c was treated
with D2O under the same reaction conditions. Unfortunately,
any other electrophile added, such as aldehydes or allyl
halides, was inefficient in trapping this putative enol
intermediate.
Following these very interesting results, we extended our
silaboration studies with a series of acyclic α,β-unsaturated
aldehydes and ketones (Table 1). With this kind of substrate
the reaction proceeds smoothly, just as with the cyclic ketones
shown in Scheme 3. Yet, no silaboration products could be
seen. Instead, the corresponding β-borylated carbonyl com-
pounds were isolated in good yields. The acyclic silaboration
adducts can be detected by GC-MS in samples taken directly
from the reaction flask. For example in the silaboration of cro-
tonaldehyde (1l) in benzene-d6, the labile silaboration product
a Mixture of diastereomers in a relative ratio of 1.1/1.
Table 2 β-Borylation of acyclic conjugated carbonyl compounds with
pinB-Bpin catalyzed by Au/TiO2
3
3l was detected having a cis-configuration because the JHH of
the olefinic protons is 6.0 Hz (see page S22 of the ESI†). The
cis-silaboration adducts appear to be more prone towards
hydrolysis under the reaction conditions/workup more poss-
ibly because the Lewis-acidic boron moiety interacts intramole-
cularly with the silyl enol ether facilitating thus its hydrolysis.
As a limitation, the more sterically hindered β,β-disubstituted
conjugated aldehydes and ketones are completely unreactive
against silylborane, as well as a series of the less electron
deficient α,β-unsaturated esters and an amide.
Contrary, however, to the unachieved reaction between
Me2PhSiBpin and conjugated esters or amides (Table 1), their
β-borylation occurs in good to excellent isolated yields using
pinBBpin. In addition, all conjugated aldehydes and ketones
whose reaction with silylborane was studied, as given in
Table 1, afforded the borylated products 5d–5o in slightly
higher yields relative to the use of Me2PhSiBpin. The
additional results from the borylation of the rest of the conju-
gated carbonyl compounds are summarized in Table 2. Amide
1u reacts slowly and requires excess borylating reagent (2–3
equiv.) and a prolonged reaction time (overnight).
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Spectroscopic data of silaboration products
Conclusions
Dimethyl(phenyl)((3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)cyclohex-1-en-1-yl)oxy)silane (3a). Light pale yellow oil
(49.3 mg, 69% yield); 1H NMR (500 MHz, CDCl3): 7.61 (dd, J1 =
7.5 Hz, J2 = 2.0 Hz, 2H), 7.38–7.34 (m, 3H), 4.93 (br m, 1H),
1.96–1.93 (m, 2H), 1.76–1.46 (m, 5H), 1.21 (s, 12H), 0.43 (s,
3H), 0.43 (s, 3H); 13C NMR (125 MHz, CDCl3): 149.1, 138.2,
133.4, 129.5, 127.7, 83.0, 29.7, 24.7, 24.7, 23.6, 23.1, −1.0, −1.1;
MS (EI): 358 (M+, 15%), 135 (100%), 55 (59%), 40 (100%);
HRMS (ESI-Orbit trap) m/z: [M + H]+ calcd for C20H31BO3Si +
H, 359.2214; found 359.2206.
Dimethyl(phenyl)((3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)cyclopent-1-en-1-yl)oxy)silane (3b). Light pale yellow oil
(44.0 mg, 67% yield); 1H NMR (500 MHz, CDCl3): 7.59 (dd, J1 =
7.5 Hz, J2 = 1.5 Hz, 2H), 7.40–7.34 (m, 3H), 4.60 (br q, J = 2.0
Hz, 1H), 2.28–2.25 (m, 2H), 2.09–2.04 (m, 1H), 1.98–1.84 (m,
2H), 1.20 (s, 12H), 0.45 (s, 6H); 13C NMR (125 MHz, CDCl3):
153.9, 137.5, 133.4, 129.6, 127.8, 103.9, 83.0, 33.8, 24.7, 24.7,
23.5, −1.2, −1.3; MS (EI): 344 (M+, 2%), 329 (M+–Me, 1%), 135
(28%), 84 (35%), 40 (100%); HRMS (ESI-Orbit trap) m/z:
[M + H]+ calcd for C19H29BO3Si + H, 345.2057; found 345.2049.
Dimethyl((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)cyclopent-1-en-1-yl)oxy)(phenyl)silane (3c). Light pale
yellow oil (43.7 mg, 64% yield); 1H NMR (500 MHz, CDCl3):
7.61 (dd, J1 = 7.5 Hz, J2 = 1.5 Hz, 2H), 7.39–7.35 (m, 3H),
2.29–2.15 (m, 2H), 1.95–1.77 (m, 3H), 1.56 (d, J = 1.0 Hz, 3H),
1.22 (s, 12H), 0.43 (s, 6H); 13C NMR (125 MHz, CDCl3): 145.7,
138.1, 133.3, 129.6, 127.7, 114.2, 82.9, 33.7, 24.8, 24.8, 22.5,
11.9, −0.7; MS (EI): 358 (M+, 3%), 329 (M+–Me, 1%), 135 (14%),
84 (16%), 40 (100%); HRMS (ESI-Orbit trap) m/z: [M + H]+
calcd for C20H31BO3Si + H, 359.2214; found 359.2206.
In conclusion, we report herein the so far unrecognized ability
of supported Au(0) nanoparticles on TiO2 in catalyzing
the silaboration of conjugated aldehydes and ketones
with Me2PhSiBpin and the quite general β-borylation of
α,β-unsaturated carbonyl compounds with pinBBpin. In con-
trast to all of the known metal-catalyzed analogous reactions
with silylborane, in which the silyl moiety acts as a pseudo-
nucleophile, under our Au NP-catalyzed conditions, the boryl
moiety behaves as
a nucleophile, leading to conjugate
β-borylation. These results, exemplify once more the unique
potency of supported Au nanoparticles in catalyzing organic
transformations of high synthetic utility.
Experimental section
The reactions were monitored by thin-layer chromatography
(TLC) carried out on silica gel plates (60F-254). Benzene was
passed though silica gel and kept over 4 Å molecular sieves.
NMR spectra were recorded on a Bruker Avance-500 instru-
ment. HRMS spectra were recorded on an Agilent Q-TOF mass
spectrometer, G6540B model with the Dual AJS ESI-MS instru-
ment. GC analyses were performed on a Shimadzu GC-17A
model equipped with a 60 m HP-5 capillary column. Flash
column chromatography for the purification of compounds
was carried out on SiO2 (silica gel 60, particle size
0.040–0.063 mm) using mixtures of hexane or petroleum
ether/ethyl acetate as the eluent. Au/TiO2 (1 wt% in Au) was
provided by Strem Chemicals and has an average gold crystal-
lite size of ∼2–3 nm.
Conjugated carbonyl compounds 1a–1c, 1e–1f, 1h, and 1k–
1u are commercially available. Enones 1d, 1g, 1i and 1j were
synthesized as described in the ESI.†
Spectroscopic data of β-borylated products
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohexan-1-
one (5a).27a Colorless oil (35.8 mg, 80% yield); 1H NMR
(500 MHz, CDCl3): 2.38–2.26 (m, 4H), 2.08–2.04 (m, 1H),
1.88–1.84 (m, 1H), 1.77–1.69 (m, 1H), 1.65–1.57 (m, 1H),
1.46–1.43 (m, 1H), 1.22 (s, 12H); 13C NMR (125 MHz, CDCl3):
212.3, 83.4, 42.5, 41.8, 28.4, 26.5, 24.7, 24.7.
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopentan-1-
one (5b).27a Colorless oil (31.1 mg, 79% yield); 1H NMR
(500 MHz, CDCl3): 2.32–2.22 (m, 2H), 2.16–2.07 (m, 3H),
1.89–1.80 (m, 1H), 1.68–1.61 (m, 1H), 1.25 (s, 12H); 13C NMR
(125 MHz, CDCl3): 221.1, 83.5, 40.2, 38.9, 25.2, 24.7.
2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclo-
pentan-1-one (5c, a mixture of diastereomers).29 Colorless oil
(31.3 mg, 70% yield); 1H NMR (500 MHz, CDCl3): 2.39–1.70
(m, 6H from each diastereomer), 1.25 (s, 12H, major diastereo-
mer), 1.22 (s, 12H, minor diastereomer), 1.08 (d, J = 7.5 Hz,
3H, major diastereomer), 1.07 (d, J = 7.5 Hz, 3H, minor diaster-
eomer); 13C NMR (75 MHz, CDCl3): 222.5 and 222.1 (2 diaster-
eomers), 83.4, 46.5 and 45.2 (2 diastereomers), 38.1 and 37.3
(2 diastereomers), 24.8, 24.8, 24.8, 24.7 and 22.7 (2 diastereo-
mers), 22.7 and 22.5 (2 diastereomers), 14.0 and 13.2
(2 diastereomers).
General procedure of the Au/TiO2-catalyzed β-borylation
To a tube containing a solution of 0.2 mmol of the conju-
gate carbonyl compound in benzene (0.5 mL) were added
0.30 mmol of Me2PhSiBpin or 0.24 mmol of pinBBpin fol-
lowed by the addition of 47.3 mg of Au/TiO2 (1.0 mol% in
Au) and the mixture was heated to 70 °C for a certain period
of time until the reaction was complete (TLC and GC-MS).
The slurry was filtered with the aid of dichloromethane
under a low pressure through a short pad of silica gel and
the filtrate was evaporated. The desired product was isolated
after column chromatography, using petroleum ether/ethyl
acetate (typically ∼15/1). The borylation was also performed
on a larger scale using 96.1 mg (1.0 mmol) of enone 1a,
305 mg of bis(pinacolato)diboron (4, 1.2 mmol), 3 mL of
benzene and 236.4 mg of Au/TiO2 (2.4 mg of Au, as the cata-
lyst contains 1 w/w% Au). After 2 h at 70 °C the reaction was
complete and following the above workup, compound 5a
was isolated in 76% yield (170 mg) after column chromato-
graphy, using petroleum ether/ethyl acetate = 15/1 as an
eluent.
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1-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)butanal (5l).23b
propan-1-one (5d).30 Colorless oil (33.2 mg, 72% yield); 1H Colorless oil (32.2 mg, 83% yield); H NMR (500 MHz, CDCl3):
NMR (500 MHz, CDCl3): 7.97 (dd, J1 = 7.5 Hz, J2 = 1.5 Hz, 2H), 9.75 (s, 1H), 2.58 (dd, J1 = 18.0 Hz, J2 = 7.0 Hz, 1H), 2.50 (dd,
7.54 (t, J = 7.0 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 3.16 (d, J = 7.0 J1 = 18.0 Hz, J2 = 6.5 Hz, 1H), 1.39–1.35 (m, 1H), 1.23 (s, 6H),
Hz, 2H), 1.25 (m, 12H), 1.07 (d, J = 7.0 Hz, 2H); 13C NMR 1.23 (s, 6H), 1.00 (d, J = 7.5 Hz, 3H); 13C NMR (125 MHz,
(125 MHz, CDCl3): 200.6, 137.0, 132.7, 128.4, 128.0, 83.1, 33.7, CDCl3): 202.8, 83.3, 47.7, 24.7, 24.6, 15.1.
1
24.8.
2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pro-
1-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan- panal (5m).31 Colorless oil (28.1 mg, 75% yield); 1H NMR
1-one (5e).27b Colorless oil (31.5 mg, 70% yield); 1H NMR (500 MHz, CDCl3): 9.63 (d, J = 0.5 Hz, 1H), 2.59–2.52 (m, 1H),
(500 MHz, CDCl3): 7.97 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz, 2H), 7.53 1.24 (s, 6H), 1.23 (s, 6H), 1.14 (d, J = 7.0 Hz, 3H), 1.05 (dd,
(t, J = 7.5 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 3.11 (d, J = 7.0 Hz, J1 = 16.0 Hz, J2 = 7.0 Hz, 1H), 0.82 (dd, J1 = 16.0 Hz, J2 = 7.5 Hz,
2H), 1.48–1.40 (m, 1H), 1.26 (s, 6H), 1.24 (s, 6H), 1.05 (d, J = 1H); 13C NMR (125 MHz, CDCl3): 205.2, 83.3, 42.6, 24.7,
7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3): 200.2, 137.1, 132.7, 15.6.
128.4, 128.0, 83.0, 42.9, 24.7, 24.6, 15.1.
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)hexanal (5n).32
1
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-one Colorless oil (24.4 mg, 67% yield); H NMR (500 MHz, CDCl3):
(5f).23b Colorless oil (30.4 mg, 77% yield); H NMR (500 MHz, 9.76 (t, J = 1.0 Hz, 1H), 2.58 (dd, J1 = 19.0 Hz, J2 = 8.0 Hz, 1H),
1
CDCl3): 2.58 (t, J = 7.0 Hz, 2H), 2.12 (s, 3H), 1.23 (s, 12H), 0.90 2.51 (dd, J1 = 19.0 Hz, J2 = 7.0 Hz, 1H), 1.46–1.44 (m, 1H),
(t, J = 7.0 Hz, 2H); 13C NMR (125 MHz, CDCl3): 209.2, 83.1, 1.36–1.31 (m, 1H), 1.24 (s, 16H), 1.22 (s, 16H), 0.89 (t, J = 7.0
38.4, 29.3, 24.7.
Hz, 3H); 13C NMR (75 MHz, CDCl3): 203.0, 83.2, 45.8, 32.7,
24.8, 24.6, 21.9, 14.2.
2-Methyl-1-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)propan-1-one (5g). Colorless oil (32.4 mg, 74% yield); 1H
2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butanal
NMR (500 MHz, CDCl3): 7.95 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz, 2H), (5o, mixture of diastereomers).31 Colorless oil (24.7 mg, 68%
7.53 (t, J = 7.5 Hz, 1H), 7.44 (t, J = 8.0 Hz, 2H), 3.70–3.63 (m, yield); 1H NMR (500 MHz, CDCl3): 9.65 (d, J = 1.0 Hz, 1H,
1H), 1.23 (t, J = 7.5 Hz, 3H) 1.23 (s, 6H), 1.21 (s, 6H), 1.19 (dd, minor diastereomer), 9.60 (d, J = 1.5 Hz, 1H, major diastereo-
J1 = 16.0 Hz, J2 = 7.0 Hz, 1H), 0.97 (dd, J1 = 16.0 Hz, J2 = 8.0 Hz, mer), 2.50–2.43 (m, 1H from each diastereomer), 1.38–1.31 (m,
1H); 13C NMR (125 MHz, CDCl3): 204.9, 136.3, 132.5, 128.4, 1H from one diastereomer), 1.30–1.27 (m, 1H from one diaster-
128.4, 83.1, 37.3, 24.8, 24.7, 19.8; HRMS (ESI-Orbit trap) m/z: eomer), 1.24 (s, 6H), 1.23 (s, 12H), 1.23 (s, 6H), 1.18 (d, J = 6.5
[M + H]+ calcd for C16H23BO3 + H, 275.1819; found 275.1816.
Hz, 3H from one diastereomer), 1.11 (d, J = 6.5 Hz, 3H from
5-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan- one diastereomer), 0.96 (d, J = 7.5 Hz, 3H from major diaster-
2-one (5h).31 Colorless oil (35.0 mg, 79% yield); 1H NMR eomer), 0.94 (d, J = 7.5 Hz, 3H from minor diastereomer); 13C
(500 MHz, CDCl3): 2.62 (dd, J1 = 18.0 Hz, J2 = 11.0 Hz, 1H), NMR (125 MHz, CDCl3): 205.8 and 205.6 (2 diastereoisomers),
2.51 (dd, J1 = 18.0 Hz, J2 = 5.0 Hz, 1H), 2.12 (s, 3H), 1.74–1.66 83.3 and 83.2 (2 diastereoisomers), 48.8 and 48.6 (2 diastereo-
(m, 1H), 1.25 (s, 6H), 1.21 (s, 6H), 1.19–1.68 (m, 1H), 0.93 (d, isomers), 24.7, 24.7, 24.5, 12.3, 11.8 and 11.7 (2
J = 7.0 Hz, 3H), 0.91 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, diastereoisomers).
CDCl3): 209.5, 83.0, 43.8, 29.7, 28.9, 24.9, 24.7, 22.1, 21.6.
Methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nonan-3-one (5p).33 Colorless oil (34.0 mg, 81% yield); H NMR (500 MHz,
(5i). Colorless oil (34.7 mg, 74% yield); 1H NMR (500 MHz, CDCl3): 3.65 (s, 3H), 2.44 (t, J = 7.5 Hz, 2H), 1.24 (s, 2H), 1.02
CDCl3): 2.55 (t, J = 7.0 Hz, 2H), 2.37 (t, J = 7.5 Hz, 2H), (t, J = 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): 175.1, 83.2,
1.58–1.52 (m, 2H), 1.27–1.24 (m, 6H), 1.22 (s, 12H), 0.89 (t, J = 51.5, 28.6, 24.7.
1
7.0 Hz, 2H), 0.85 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz,
Methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butanoate
CDCl3): 211.7, 83.0, 42.3, 37.4, 31.6, 28.9, 24.7, 24.1, 22.5, 14.0; (5q).24 Colorless oil (33.3 mg, 79% yield); H NMR (500 MHz,
1
HRMS (ESI-Orbit trap) m/z: [M + H]+ calcd for C15H29BO3 + H, CDCl3): 3.65 (s, 3H), 2.46–2.35 (m, 2H), 1.39–1.35 (m, 1H), 1.24
269.2288; found 269.2280.
2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)octan-4-one (125 MHz, CDCl3): 174.3, 83.2, 51.3, 37.5, 24.7, 24.6, 15.1.
(s, 6H), 1.23 (s, 6H), 0.99 (d, J = 7.5 Hz, 3H); 13C NMR
(5j). Colorless oil (32.2 mg, 70% yield); 1H NMR (500 MHz,
Methyl 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
CDCl3): 2.52 (d, J = 7.0 Hz, 2H), 2.41–2.31 (m, 2H), 1.57–1.51 yl)propanoate (5r).33 Colorless oil (28.7 mg, 73% yield); 1H
(m, 2H), 1.33–1.26 (m, 4H), 1.23 (s, 6H), 1.22 (s, 6H), 0.94 (d, J NMR (500 MHz, CDCl3): 3.65 (s, 3H), 2.72–2.65 (m, 1H), 1.24
= 7.5 Hz, 3H), 0.89 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, (s, 6H), 1.23 (s, 6H), 1.19 (d, J = 7.0 Hz, 3H), 1.12 (dd, J1 = 16.0
CDCl3): 211.4, 82.9, 46.7, 42.3, 26.2, 24.7, 24.6, 22.3, 15.0, 13.8; Hz, J2 = 7.5 Hz, 1H), 0.93 (dd, J1 = 16.0 Hz, J2 = 7.0 Hz, 1H); 13
C
HRMS (ESI-Orbit trap) m/z: [M + H]+ calcd for C14H27BO3 + H, NMR (125 MHz, CDCl3): 117.7, 83.2, 51.5, 35.3, 24.8, 24.7,
255.2131; found 255.2122.
19.4.
t-Butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)propanal (5k).23b
Colorless oil (29.5 mg, 81% yield); H NMR (500 MHz, CDCl3): (5s).33 Colorless oil (29.5 mg, 67% yield); H NMR (500 MHz,
9.79 (t, J = 1.0 Hz, 1H), 2.60 (dd, J1 = 7.0 Hz, J2 = 1.0 Hz, 2H), CDCl3): 2.35 (t, J = 7.5 Hz, 2H), 1.43 (s, 9H), 1.23 (s, 12H), 0.96
1.24 (s, 12H), 0.97 (t, J = 7.0 Hz, 2H); 13C NMR (125 MHz, (t, J = 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): 174.0, 83.1,
1
1
CDCl3): 202.8, 83.3, 38.8, 24.7.
79.8, 29.9, 28.1, 24.8.
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Organic & Biomolecular Chemistry
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47, 3818.
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J2 = 8.0 Hz, 1H), 0.96 (dd, J1 = 16.0 Hz, J2 = 7.5 Hz, 1H);
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Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
The research work was supported by the Hellenic Foundation
for Research and Innovation (HFRI) and the General
Secretariat for Research and Technology (GSRT), under the
HFRI PhD fellowship grant (GA No 31449). M. K. ProFI
(FORTH, Heraklion, Greece) is acknowledged for obtaining the
HRMS spectra of the unknown compounds.
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