Preparation of alkyltrifluoroborates via Matteson Hydroboration Method

Article abstract of DOI:10.1016/j.jorganchem.2018.03.027

An efficient one-pot method for synthesis of simple alkyltrifluoroborate salts has been developed. Alkyldichloroboranes, prepared by the Matteson Hydroboration Method using in situ generated HBCl₂, were esterified with 2-propanol, treated with

Full text of DOI:10.1016/j.jorganchem.2018.03.027

Accepted Manuscript
Preparation of alkyltrifluoroborates via Matteson Hydroboration Method
David J. Zillman, Thomas E. Cole
PII:
S0022-328X(18)30194-3
10.1016/j.jorganchem.2018.03.027
JOM 20377
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 1 January 2018
Revised Date: 15 March 2018
Accepted Date: 16 March 2018
Please cite this article as: D.J. Zillman, T.E. Cole, Preparation of alkyltrifluoroborates via
Matteson Hydroboration Method, Journal of Organometallic Chemistry (2018), doi: 10.1016/
j.jorganchem.2018.03.027.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Preparation of Alkyltrifluoroborates via Matteson Hydroboration Method
David J. Zillman and Thomas E. Cole*
Department of Chemistry & Biochemistry, San Diego State University, San Diego, California 92182-1030
tcole@mail.sdsu.edu
ABSTRACT
An efficient one-pot method for synthesis of simple alkyltrifluoroborate salts has been developed.
Alkyldichloroboranes, prepared by the Matteson Hydroboration Method using in situ generated HBCl2, were
esterified with 2-propanol, treated with aqueous KHF2 and isolated using standard procedures. The overall
isolated yields were generally greater than 90% when fluoridation was conducted under nitrogen. In contrast,
reactions using “open air” conditions showed oxidation and gave lower yields of the alkyltrifluoroborate salts.
Keywords:
Matteson Hydroboration Method
Hydroboration
Fluoridation
Potassium Alkyltrifluoroborate salts
Alkylboronic acids
1. Introduction
Boronic compounds are very important intermediates for organic synthesis and medicinal
chemistry due to their versatility in synthesizing complex molecules. These reagents have found
extensive use in the metal catalyzed carbon-carbon bond forming reactions such as; Suzuki-Miyaura [1]
and Liebersking-Srogl [2] coupling reactions, conjugate additions [3] and carbon-heteroatom Chan-Lam
couplings [4]. The boronic derivatives can also be used as building blocks to form new types of boronic
compounds using homologation [5] and transformation of pendent functional groups [6].
A number of routes have been developed to prepare alkylboronic compounds using the
hydroboration reaction. Catecholborane is slow to hydroborate most alkenes, therefore, require longer
reaction times and elevated temperatures [7]. The related pinacolborane is even less reactive, requiring
a catalyst to achieve good yields [8]. Catecholborane can also be catalyzed, however, the metal catalyst
may adversely affect regioselectivity [9]. Complexed dihaloboranes have frequently been used to prepare
the alkylboronic derivatives. Unfortunately, the dichloroborane reagents form a mixture of
organoborane products, especially with less reactive alkenes [10]. In contrast, dibromoborane cleanly
forms the corresponding alkyldibromoboranes, but requires 5-20 mol% boron tribromide to catalyze the
Final Version JOMC 12/2017 printed 3/6/18
1

ACCEPTED MANUSCRIPT
hydroboration reaction. Matteson developed a simple and efficient route to alkyldihaloboranes using
boron trihalides and trialkylsilanes, circumventing the limitations of preformed dihaloboranes [11,12].
In addition, the Matteson Hydroboration Method using ligand free HBCl2 is faster, cheaper and less
expensive than other hydroboration reactions. While we had good success in using this method to
prepare alkyldichloroboranes for the conversion to the corresponding alkyldimethylboranes [13],
attempts to convert the alkyldichloroboranes into the boronic acids or esters gave low yields and purity.
It is believed that the trialkylhalosilane side-products interfere with the boronic acid isolation [14,15,16].
Matteson’s solution for the removal of sterically bulky diol ligands from boronic esters using potassium
bifluoride suggested this as a solution to the separation of the boronic and silane materials [17]. The
separation of the potassium alkyltrifluoroborate salt from the silane and other organic products are
expected be straight forward and high yielding. In addition, organotrifluoroborate salts have a number of
desirable properties; they are stable to air and moisture allowing long term storage. The preparation of
organyltrifluoroborates and their application to organic synthesis have been reviewed [18,19]. In
contrast to the boronic acids, they have known compositions and are readily purified. The
tetracoordinate bonding gives extraordinary stability, protecting the boron. Yet, these
organotrifluoroborates can also be readily converted into the corresponding boronic acids and esters
[20,21,22,23]. Literature shows a rather significant variation in the isolated yields in the conversion of
the boronic acids or esters to the corresponding alkyltrifluoroborates, generally between 70-90% yields.
We wished to develop an effective route using the non-coordinated HBCl2 to form the corresponding
potassium alkyltrifluoroborate salts with overall greater than 90% isolated yields.
2. Results and Discussion
Our initial investigation was focused on the fluoridation step, since ligand free HBCl2 gave excellent
selectivity, generally > 98% formation of the alkyldichloroborane. The major variations are attributed to
inefficient conversion of the boronic acids or esters to the trifluoroborate salt; or cleavage of the alkyl
group during treatment with KHF2. Preformed alkylboronic acid was used in preliminary reactions to
avoid potential interference of the silane products formed in the Matteson Hydroboration Method. The n-
decyl group was chosen because of the lower volatility and aqueous solubility of the boronic acid and
possible cleavage products, which would allow for a more accurate determination of the mass balance.
The boronic acid was prepared by hydroboration of 1-decene with dibromoborane dimethyl sulfide with
5 mol% tribromoborane, then hydrolyzed to give the n-decylboronic acid [24]. Fluoridation reaction
conditions were based on the methods reported by Vedejs [25] and Genêt [26]. Decylboronic acid was
first dissolved in methanol then a concentrated aqueous solution of the KHF2 was then added to the open
2

ACCEPTED MANUSCRIPT
flask, resulting in an immediate formation of a thick slurry. The reaction was stirred for 15-30 min and
the volatiles, were removed in vacuo until the solid appeared dry. The solid material was dissolved in hot
acetone, inorganic salts were removed by filtration, acetone was removed in vacuo and the solid was then
triturated with ether to afford ca. 76% yield of the potassium decyltrifluoroborate. The 11B NMR
spectrum in acetone-d6, showed a single species at 5.1 ppm, corresponding to the expected potassium
alkyltrifluoroborate salt. The proton, carbon and fluorine NMR spectra were also in agreement with
literature values [27]. The ether trituration liquid was evaporated to dryness yielding a colorless oil. The
11B NMR spectra showed a very weak signal at 32 ppm, indicating the boron acid was a minor constituent
of the oil. However, the amount of this material appeared to account for the majority of the missing mass
balance. This oil was analyzed by capillary gas chromatography. A single major peak corresponding to
the retention time of a C13 compound was seen, but no decene or decane was detected. Proton NMR
spectrum showed a downfield triplet at 3.62 ppm, consistent with a primary alcohol. The 13C NMR
spectrum showed 10 unique resonances with the furthest downfield signal at 63.12 ppm. These spectral
values were in agreement with literature values for 1-decanol [28]. These results indicated oxidation of
the alkylboronic acid, forming the corresponding 1-decanol.
In an effort to determine at which point oxidation occurred, we prepared and isolated a sample of 1-
decylboronic acid by the sodium bicarbonate hydrolysis of potassium n-decyltrifluoroborate under an
inert atmosphere. The 11B NMR spectrum showed single specie at 30.8 ppm with no detectable materials
in the region of the boric acids between 17-20 ppm. The remainder of this boronic acid was dissolved in
a methanol/water mixture (90/10) and stirred in air for 24 h at room temperature. The 11B NMR
spectrum showed a trace amount, ~ 0.1%, of boric acid material indicating very little oxidation even over
an extended period of time. This result is consistent with the air-stability of boronic acids in the presence
of water.
While alkylboronic acids are generally considered to be stable toward oxidation, we have noted
occasional air-sensitivity that is largely dependent on the isolation technique and subsequent handling of
the solid material [29]. Alkylboronic acids isolated from solvent containing water using modestly
reduced pressures at lower temperatures over minimal time, showed no indication of oxidation after
exposure to air as seen in 11B NMR spectra by the absence of boric acid at ca. 18 ppm. This is consistent
with the general agreement that hydrated boronic acids are stable in air. However, exposure of solid
boronic acids to reduced pressure for extended periods of time, or higher temperatures or prolonged
sweeping of flasks with dry nitrogen, leads to a change in appearance from a dull translucent white to a
bright opaque white solid. To illustrate this effect, an ether extract containing decylboronic acid was
pumped down, ca. 5mmHg, using evaporative cooling, < 0 °C, until the ether was just removed and a dull
3

ACCEPTED MANUSCRIPT
translucent white solid remained. This sample was exposed to air for 7 min, then under nitrogen,
dissolved in methanol/water (6:1). The boron NMR spectrum showed in addition to the expected
boronic acid at 30.8 ppm, ~ 3% of boric acid at 18.2 ppm. Repeating the isolation of the decylboronic
acid under essentially identical conditions, but allowing the ether to be removed over a longer period of
time while the sample warmed to room temperature, gave a change in color from dull white to opaque
bright white. Exposure to air for 7 min, followed by transfer to a nitrogen atmosphere and dissolving in
methanol/water mixture gave an increased amount of boric acid to approximately 7%. As a
consequence, all boronic acids used in this study were isolated under conditions that showed reduced
sensitivity to oxidation.
Next, we wanted to study the effects of air on the reaction of KHF2 with decylboronic acid. The
decylboronic acid was dissolved in methanol under a nitrogen atmosphere. This solution was then
exposed to air for 5-7 minutes before a concentrated aqueous solution of KHF2 (2.2 eq) was added and
the mixture stirred for approximately 15 minutes. The volatiles were removed under reduced pressure
to give a dry solid, then under an inert atmosphere and the entire sample was dissolved in a 3:1 mixture
of acetone/D2O. The 11B NMR spectrum showed three species. The largest corresponded to the expected
alkyltrifluoroborate with an area of 74.2%. This amount is in agreement with the earlier isolated yield.
There was a relative small amount of unreacted boronic acid, 7.3%. In addition, there was an upfield
quartet at -0.22 ppm that corresponds to the potassium tetrafluoroborate with 18.5% area. The presence
of this signal indicated oxidation of the boronic acid forming boric acid, which is converted to the
tetrafluoroborate. Since no boric acid was present in the initial decylboronic acid, oxidation had to
occurred during fluoridation since very little oxidation of decylboronic was found in methanol solution
alone. While boronic acids are relative air-stable and organotrifluoroborates are inert to oxygen, the
Scheme 1. Intermediates formed in the fluoridation of boronic acids to give trifluoroborates.
(remove –graphics ChemDraw Helvetica ~ 7 pt, template ACS document 1996, scaled 60%. Planned
width 90 mm, single column. - remove)
intermediates formed in this reaction are air-sensitive. Alkydifluoroboranes, RBF2, are known to be air-
sensitive [30,31], while alkylhydroxyfluoroboronic acids, RB(OH)F, are also expected to be reactive to
oxygen, (Scheme 1). This indicates oxidation of the intermediates can represent a significant loss of
4

ACCEPTED MANUSCRIPT
boron materials. The amount of oxidation is likely to be dependent on transfer of oxygen into the
reaction solution.
It remained to be seen whether the presence of the silane products from the Matteson
Hydroboration Method has an adverse effect on the fluoridation. Decyldichloroborane was prepared
using HBCl2 as described in the experimental. The alkyldichloroborane was hydrolyzed under nitrogen,
using an ether/water mixture, washed with brine and the ether removed under vacuum to give the crude
boronic acid/silane mixture. This material was dissolved in methanol in air and a concentrated KHF2
aqueous solution, 2.2 eq, was added and stirred 15 min. Removal of volatiles was complicated with
persistent foaming, resulting in a minor loss of material, eventually forming a dry solid. The crude
alkyltrifluoroborate mixture was dissolved in hot acetone, filtered to remove the insoluble materials.
Acetone was then removed under reduced pressure, to give solid material. This white solid was
triturated with ether, filtered in air, washed with additional ether and then dried as described in the
experimental procedure. The yield of potassium n-decyltrifluoroborate was 78.9%. While there was
some loss of product due to foaming, the isolated yield of the alkyltrifluoroborate salt was in agreement
with the earlier preparations and the general average yields reported in literature. This clearly indicates
the presence of silane materials does not negatively affect the yields. Taking all of these results together;
the lower yields, formation of significant amounts of tetrafluoroborate and presence of the corresponding
alcohol from the alkyl group all indicate oxidation of the boronic derivative likely occurs during
fluoridation in the presence of air. This indicates the necessity of converting boronic acids to the
trifluoroborate under an inert atmosphere. Unfortunately, many of the literature preparations use “open
flask” reaction conditions with plastic ware to avoid etching of glassware with hydrofluoric acid.
Table 1
Effects of inert reaction conditions on fluoridation reactions.
-
Entry
Source
DecylB(OH)2
Reaction
Conditions
KHF2
eq
% Isolated
DecylBF3
% DecylBF3
%
KBF4
%
%
B(OH)3
Comments
1-decanol
-
-
DecylB(OH)2
1
2
3
4
5
a
b
b
c
Air, MeOH/H2O,
0.25 h, RT
Air, MeOH /H2O
(9:1) 24h, RT
Air, MeOH/H2O,
(9:1), 0.25h, RT
Air, MeOH/H2O
(9:1), 0.5h, RT
N2, MeOH/H2O,
(9:1). 0.5 h, RT
2.2
76
0
99.9
7.3
0.1
2.2
2.2
3.3
74.2
18.5
78.9
92.9
d
.
a Prepared from 1-decene and HBBr2 SMe2 + 10 mol% BBr3 and isolated as boronic acid.
b Prepared by NaHCO3 hydrolysis of K DecylBF3.
c Prepared by Matteson Hydroboration Method and hydrolysis of the alkyldichloroborane using ether/water.
d Prepared by Matteson Hydroboration Method followed by THF/i-PrOH.
(remove – Table created in Word, cambria 7 pt. Should be scaled to 190 mm width - remove)
5

ACCEPTED MANUSCRIPT
To verify the importance of an inert atmosphere, the entire synthetic sequence was repeated under
N2 up to the isolation of the product. Decyldichloroborane was directly converted into the corresponding
boronic ester using a mixture of oxygen free THF and isopropanol. The bulk of the solvents were
removed under reduced pressure and the flask refilled with N2. The crude boronic ester was dissolved in
additional i-PrOH, cooled to 0 °C and a concentrated deoxygenated aqueous solution of KHF2 (3.3 eq) was
added dropwise and stirred for 30 min. Volatiles were then removed under reduced pressure. A larger
than normal round-bottomed flask was used to reduce loss of material due to viscous foaming. The
product was isolated in the usual manner giving a 92.9% yield of potassium decyltrifluoroborate (2b).
This reaction demonstrated the importance of carrying out the fluoridation under inert conditions,
resulting in significant increased yields. The NMR analysis showed a pure product, identical to the
potassium n-decyltrifluoroborate salts isolated earlier. Since our initial goal of an isolated yield greater
than 90% were met, this reaction was not further optimized.
Using the general synthetic procedure, 1-hexyldichloroborane was prepared and converted into the
corresponding isopropyl ester. The crude ester was treated with KHF2 (3.0 eq) to give the crude
alkyltrifluoride salt. The potassium 1-hexyltrifluoroborate salt (3) was isolated in the usual manner in a
93.4% yield. The spectral data were in agreement with literature values [17].
Cyclohexene is rapidly hydroborated by HBCl2, selectively forming the cyclohexyldichloroborane.
The 11B NMR spectra showed the cyclohexldichloroborane as the only hydroboration product. This is in
contrast to dibromoborane dimethylsulfide, which is slow to react and must be catalyzed with BBr3 [32].
Hydroborations with coordinated dichloroboranes, undergo extensive disproportionation with these
sterically large alkenes, even when catalyzed with boron trichloride [33]. The Matteson Method is the
superior method for these sterically demanding alkenes. The product was prepared using the general
synthetic procedure. After the reaction with KHF2, removal of solvents was best accomplished using a
larger than normal reaction flask due to the persistent foaming. Also, cyclohexyltrifluoroborate salt was
considerably more soluble in hot acetone than 2b and 3. As a consequence, all of the acetone must be
removed before trituration with ether, otherwise significant loss of product occurs during this step. The
isolated yield for potassium cyclohexyltrifluoroborate (4) was 89.3%. We did not further optimize this
reaction since the yield essentially met our targeted yield. The full spectral analysis was in agreement
with literature or expected values [17,34].
Previously, we have used ligand free HBCl2 to selectively prepare 2-ethylcyclohex-3-
enyldichloroborane from vinylcyclohexene [13]. We selected (S)-(–)-limonene as an example to
demonstrate the selective hydroboration of non-conjugated dienes. The alkyltrifluoroborate was
6

ACCEPTED MANUSCRIPT
prepared according to the general synthetic procedure. The 11B NMR after conversion to the boronic
ester showed no detectable presence of borinic product, indicating clean formation of the
alkyldichloroborane. Unlike the previous reactions, the filtered acetone solution was turbid. After
isolation of the product, the fluorine and boron NMR spectra showed a broad signal without coupling,
indicating fluoride exchange. Repeated purification with hot acetone and trituration with ether did not
give a coupled fluorine or boron NMR spectra, only further loss of product. This problem was solved in
the repeated reaction. The crude product was dissolved in methanol, an additional 5-10 mol% KHF2 was
added and isolation of the product gave a clear acetone filtrate. The potassium trifluoro((R and S)-2-((S)-
4methylcyclohex-3-enyl)propyl)borate (5) was isolated in 93.1% yield. The proton and carbon NMR
spectra showed an equal molar diasteromeric mixture as expected, however, the fluorine and boron
spectra did not resolve into the expected quartets, but remained a broad singlet, albeit better defined
than the initially isolated product.
The hydroboration of allyl chloride was different from the other alkenes studied. Matteson reported
that triethylsilane formed small amounts of the R2BCl product, even when carried out at -78 °C [12]. In
contrast, trimethylsilane exclusively formed the desired alkyldichloroborane. However, use of this more
volatile silane, BP 6.7 °C, is inconvenient and is more difficult to handle in laboratory preparations. In an
effort to minimize the amount of the dialkylchloroborane, a larger excess of BCl3, 10 mol% versus the
usual 5 mol% and a lower reaction temperature of -78 °C was used following the general synthetic
procedure. After the reaction mixture was esterified, the boron NMR spectrum showed 7.8% borinic
ester. The solvents were removed under reduced pressure at 0 °C instead of 30-40 °C to reduce the loss
of this more volatile ester. The potassium 1-chloropropyl-3-trifluoroborate (6) was isolated in a 76.5%
yield. The spectroscopic data is in excellent agreement with literature values [35]. This yield was
considerably lower than previous reactions. Repeated attempts to increase the yield gave essentially the
same result. An interesting relationship is found, the ratio of isolated alkyltrifluoroborate to boronic
ester in all of the previous reactions indicated a ~ 90% conversion. The hydroboration of allyl chloride
give about 84% conversion to the corresponding boronic ester. The isolated 76.5% yield is consistent
with these fluorination reactions. This suggested that the borinic esters are not converted to form the
alkyltrifluoroborate product.
Table 2.
Yields of the alkyltrifluoroborates via Matteson Hydroboration Method and fluorination.
7

ACCEPTED MANUSCRIPT
Entry
Alkene
Product
Isolated
Yield(%)
92.9
1
2
93.4
89.1
3
4
93.1
5
76.5
a
a
Hydroboration done at -78 °C 2 h then warmed to room temperature 2h.
(remove – Table drawn in Word, text Cambria 7 pts, graphics ChemDraw Helvetica ~ 7 pt, template ACS
document 1996, scaled 60%. Proposed width 90 mm - remove)
While diaryldifluoroborate salts have been known for some time [36] a detailed literature search
revealed no examples of dialkyldifluoroborate salts other than the bis(trifluoromethyl)difluoroborate salt
K[(CF3)2BF2]. [37]. This suggests that diorganodifluoroborates may be thermodynamically unstable in
the absence of strongly electron withdrawing groups. In an effort to better understand whether borinic
derivatives undergo fluoridation, we investigated this class of boron compounds. We chose
dicyclohexylborinic ester as our model system as it is readily prepared by hydroboration of cyclohexene
with BMS followed by esterification with an alcohol. A THF solution of dicyclohexylisopropylborinic
ester was prepared and analyzed by 11B NMR. Analysis of the reaction solution showed 2.2% Cy3B,
97.1% Cy2B(OiPr) and 0.7% CyB(OiPr)2. When the remainder of the THF solution was treated with
concentrated KHF2, only a small amount of precipitate formed and the reaction solution separated into
two layers. The solvents were removed under vacuum and the residue was dissolved in Et2O. Analysis of
this solution showed 1.9% Cy3B and 98.1% Cy2BOH; the ratios of Cy3B to the borinic species in the two
experiments were essentially the same. After removal of the Et2O, the remaining solids were exposed to
air, resulting in an exothermic reaction with almost complete conversion of the Cy3B and the borinic
species to boric acid products.
Thus, these finding suggest that the borinic products formed in the hydroboration of allyl chloride do
not react with the KHF2 and remain as the borinic material (Scheme 2). Removal of the solvent after
fluoridation and exposure to air during the hot acetone extraction leads to the complete oxidation of the
borinic materials to form the boric compounds. These materials are not trapped with excess bifluoride,
since water is not present at this point. Oxidation products are removed during product isolation. Thus,
one either accepts a lower yield when working with reactive alkenes such as allyl chloride and
triethylsilane or one uses the somewhat more experimentally demanding liquefied trimethylsilane, (BP
8

ACCEPTED MANUSCRIPT
7.6 °C) and neat boron trichloride (BP 12.6 °C) which has been demonstrated to give clean product
formation [12]. However, for the majority of alkenes, there is no significant difference between
triethylsilane and trimethylsilane.
Scheme 2. Hydroboration of allyl chloride and product formation.
(remove – Table drawn in Word Cambria 7 pts, graphics ChemDraw Helvetica ~ 7 pt, template ACS
document 1996, scaled 60%. Proposed width 140 mm - remove)
3. Conclusions
The Matteson Hydroboration Method, using triethylsilane and solutions of 1 M boron trihalides, is a
superior route to the formation of the alkyldihaloboranes for most alkenes. The triethylsilane side
products are effectively removed on conversion to the alkyltrifluoroborate salt, generally giving overall
isolated yields of greater than 90%. The alkyltrifluoroborate salts can be handled and stored for
extended periods of time. They can readily be converted to other boronic derivatives. Importantly, we
have demonstrated the importance of carrying out the fluoridation reactions under an inert atmosphere,
avoiding oxidation seen in “open air” reactions.
4. Experimental
4.1. Instrumentation
1H and 13C NMR spectra were recorded on a Varian VNMR 600 at 599 and 150 MHz respectively
using DMSO-d6 as the solvent and were referenced to the residual proton or carbon signals of DMSO-d6
(1H = 2.50 ppm) and (13C = 39.52 ppm). 13B and 19F NMR spectra were recorded on a Varian VNMR 400 at
128 and 376 MHz respectively and were referenced to an external reference capillary. The external
reference contained 0.56 M BF3∙OEt2 dissolved in C6D6; using neat BF3∙OEt2 (11B = 0.00 ppm) and α,α,α
trifluorotoluene in CDCl3 (19F = -63.72 ppm) as references for the capillary (11B = -0.45 ppm) and (19F = -
9

ACCEPTED MANUSCRIPT
152.80 ppm) respectively. 11B NMR spectra were recorded using, singly or in mixture, MeOH, i-PrOH,
THF, Et2O, D2O or acetone-d6 as the solvent. 19F NMR spectra were recorded using acetone-d6 as the
solvent. Chemical shift and coupling constant data are apparent and reported in units of δ (ppm) and J
(Hz). Infrared spectra were recorded on a Perkin Elmer ATR Spectrum RX-1 FTIR spectrophotometer
and reported in units of cm-1.
4.2 Equipment and reagents
All glassware was dried at 150 °C for at least of 4 hours; the typical reaction apparatus was
assembled hot and cooled by an internal stream of N2. Alkenes were distilled from LiAlH4, allyl chloride
from CaH2, under N2 atmosphere. THF was distilled from sodium benzophenone ketal, MeOH and i-PrOH
from magnesium and CH2Cl2 from CaH2; all under N2. Anhydrous Et2O and acetone were used as
received. Dibromoborane dimethylsulfide was dissolved in CH2Cl2 under N2, forming a solution ca. 2.1 M
in HBBr2•SMe2. Triethylsilane, 1M BBr3 in CH2Cl2 and 1M BCl3 in hexanes were used as received. De-
ionized H2O was boiled and sparged under N2. All alkenes, solvents and liquid reagents were stored
under N2 in storage bottles fitted with Teflon stopcocks.
4.3 General conditions
Hydroboration of alkenes using HBBr2•SMe2 or HBCl2, hydrolysis to the alkylboronic acid,
alcoholysis to the alkylboronic ester and conversion to the potassium alkyltrifluoroborate salts were
conducted based on procedures described in the literature [24,38]. Potassium decyltrifluoroborate was
hydrolyzed to decylboronic acid using aqueous NaHCO3 under N2. Unless otherwise noted, all synthetic
reactions and manipulations were conducted under N2 using standard air-sensitive techniques. Yields of
potassium alkyltrifluoroborate salts derived from alkyldichloroboranes were calculated according to the
limiting reagent of the hydroboration with HBCl2.
4.4 Optimization
4.4.1 (decylboronic acid) (1)
A 100 mL flask was charged with 2.1M HBBr2•Me2S in CH2Cl2 (26.2 mL, ca. 55.0 mmol) and 1-decene
(9.5 mL, 50.0 mmol) was added dropwise to the stirred solution at 20 °C. One molar BBr3 in CH2Cl2 (2.5
mL, 2.5 mmol) was added dropwise while the reaction mixture was cooled to 0 °C; the reaction was
stirred for 15 min; then warmed spontaneously to 20 °C; and stirred for 30 min. The solution of boranes
was hydrolyzed by dropwise transfer to another flask containing a stirred mixture of Et2O (100 mL) and
H2O (20 mL) at 0 °C then stirred for 20 min. The solution was transferred to a separatory funnel with
10

ACCEPTED MANUSCRIPT
minimal exposure to air; the aqueous layer was separated and discarded; the organic phase was washed
with H2O (2 × 30 mL) and brine (2 × 30 mL); dried over MgSO4 and filtered; then concentrated on a
1
rotary evaporator. The yield of free-flowing white powder was 8.71g, 93%. H NMR δ 6.50 (s, 2H), 1.41
(p, J = 7.8, 7.2 Hz, 2H), 1.28 (s, 14H), 0.92 – 0.84 (m, 3H), 0.71 (t, J = 7.8 Hz, 2H). 13C NMR δ 32.55, 32.07,
29.79, 29.73, 29.62, 29.50, 24.53, 23.50, 22.85, 14.28. 11B NMR δ 32.32.
4.4.2 (potassium decyltrifluoroborate) (2)
A 50 mL round bottom flask equipped with a magnetic stir bar was charged with 1-decylboronic
acid (1.489g, 8.00 mmol) and MeOH (4.0, 5.0, 6.0 or 7.0 mL) under air. A concentrated aqueous solution
of KHF2 (1.375 g, 17.6 mmol) was added dropwise and the contents stirred for 15 min. Methanol and H2O
were removed in vacuo for 4 h. The solids were extracted with hot acetone (400 mL) and the solution
was filtered through a Büchner funnel; the solids were washed with acetone the combined organics were
concentrated on a rotary evaporator, leaving a white solid. The solid was triturated with Et2O (20 mL);
filtered onto a tared Büchner funnel and washed with Et2O (2 × 10mL); then dried at 40 °C for 4 h.
Methanol (4.0 mL); isolated yield 1.29 g, 65%. Methanol (5.0 mL); isolated yield 1.36 g, 69%. Methanol
(6.0 mL); isolated yield 1.48 g, 75%. Methanol (7.0 mL); isolated yield 1.51 g, 76%.
4.4.3 (decylboronic acid) (1a)
A 50 mL flask was charged with (2) (0.248 g, 1.00 mmol) and ~ 2 mL of Et2O. The flask was fitted
with a gas inlet valve and most of the Et2O was removed with the aid of reduced pressure; the flask was
refilled with N2. Additional Et2O (4 mL) and 2 mL of 1.1M NaHCO3 were added to the flask; the contents
were vigorously stirred until no solids remained; usually 3.5-4 h. Additional Et2O (4 mL) and H2O (2 mL)
were added to the flask and the contents gently stirred for 10 min; the aqueous layer was carefully
removed; the organic phase was washed with H2O (2 × 4 mL), brine (2 × 4 mL) and H2O (2 × 4 mL).
4.4.4 (potassium decyltrifluoroborate) (2a)
A 50 mL flask was charged with 1M BCl3 (10.0 mL, 10.0 mmol) in hexane and cooled to 0 °C. A 10
mL vial was charged with 1-decene (1.403 g, 10.0 mmol) and triethylsilane (1.163 g, 10 mmol); the
mixture was added dropwise to the vigorously stirred BCl3 over 10 min; with continued stirring at 0 °C
for 4 h. A 100 mL flask was charged with Et2O (20 mL) and H2O (10 mL) and cooled to 0 °C. The contents
in the 50 mL flask were transferred to the 100 mL flask and stirred for 30 min. With minimal exposure to
air, the contents of the 100 mL flask were transferred to a separatory funnel; the aqueous phase was
discarded and the organic phase was washed with H2O (2 × 15 mL), brine (2 × 20 mL) and partially
11

ACCEPTED MANUSCRIPT
concentrated with the aid of reduced pressure; then transferred to a 50 mL round-bottom flask and the
rest of the solvents removed with the aid of reduced pressure. In the presence of air, the contents of the
flask were dissolved with MeOH (8.0 mL) and a concentrated aqueous solution of KHF2 (1.72 g, 22 mmol)
was added dropwise and stirred for 15 min. Methanol and H2O were removed in vacuo for 4 h at 40 °C.
The solids were extracted with hot acetone (400 mL), the solution was filtered and the solids were
washed with acetone (20 mL); the combined organics were concentrated on a rotary evaporator, leaving
an oily white solid. The solid was triturated with Et2O (20 mL), filtered onto a tared Büchner funnel and
washed with Et2O (2 × 10mL); then dried at 40 °C for 4 h. The yield was 1.90 g, 78.9%.
4.5 General synthetic procedure
A 100 mL flask was charged with 1M BCl3 (21.0 mL, ~21 mmol) in hexane (BCl3) and cooled to 0 °C
in an ice/H2O bath. A 10 mL serum vial was charged with an alkene (20 mmol) and triethylsilane (2.33 g,
20 mmol). The alkene-Et3SiH mixture was added dropwise with stirring over a period of 8-10 min and
stirred at 0 °C for 2 h then spontaneously warmed to 25 °C; total time of reaction was 4 h. A 20 mL vial
was charged with oxygen free THF (~11 mL) and i-PrOH (4 mL, ~54 mmol); the mixture was transferred
to the stirred contents of the reaction flask and stirred for 30 min. The hexane-THF solution of esters was
transferred to a N2 flushed graduated cylinder and the volume was recorded; an aliquot was withdrawn
for analysis by 11B NMR. The solution in the cylinder was transferred to a 250 mL flask and the bulk of
the hexane, THF and i-PrOH were removed with the aid of reduced pressure; the flask was refilled with
N2 and isopropanol (20 mL) was added to the flask. A solution of KHF2 (4.68 g, 60 mmol) prepared in
oxygen free H2O (11.8 mL) was added dropwise to the vigorously stirred contents of the 250 mL flask and
stirred for an additional 15 min. The solvents were removed with the aid of reduced pressure for 12 h.
The flask was connected to vacuum line and volatiles further removed in vacuo at 40 °C for 4 h. The crude
product was quantitatively transferred to an Erlenmeyer flask and dissolved in sufficient boiling acetone
to dissolve the alkyltrifluoroborate salt. The hot acetone solution was filtered through a Büchner funnel
and the salts were washed with hot acetone (2 × 10 mL); the combined organics were concentrated on a
rotary evaporator. The remaining solids were triturated with Et2O (100 mL) and filtered onto a tared
Büchner funnel then washed with Et2O (4 × 15 mL) and dried at 40 °C for 4 h. To calculate the yield: the
cooled Büchner funnel was weighed, the tare weight was subtracted and the difference multiplied by the
quotient of the initial and final volume of the graduated cylinder.
4.5.1 (potassium decyltrifluoroborate) (2b)
12

ACCEPTED MANUSCRIPT
BCl3 (19.7 mL, 19.7 mmol), 1-decene (2.588 g, 18.45 mmol) and Et3SiH (2.152 g, 18.51 mmol); yield
1
4.254 g, 92.9%. H NMR δ 1.34 – 1.03 (m, 16H), 0.85 (t, J = 6.9 Hz, 3H), -0.05 (dt, J = 9.1, 6.3 Hz, 2H). 13C
NMR δ 33.16, 31.31, 29.47, 29.27, 29.16, 28.76, 25.54, 22.08, 20.00, 13.87. 11B NMR (Acetone-d6) δ 5.79
(q, J = 64 Hz). 19F NMR δ -141.00 (m). IR 2954, 2915, 2849, 1232, 1094, 1020, 917, 722 cm-1.
4.5.2 (potassium hexyltrifluoroborate) (3)
BCl3 (21 mL, ~21 mmol), 1-hexene (1.716 g, 20.39 mmol) and Et3SiH (2.405 g, 20.68 mmol); yield
3.658 g, 93.4%. 1H NMR δ 1.37 – 1.01 (m, 8H), 0.84 (t, J = 7.0 Hz, 3H), -0.05 (h, J = 6.5 Hz, 2H). 13C NMR δ
32.8, 31.7, 25.5 (q, J = 2.3 Hz), 22.2, 20.09 (bs), 14.1. 13B NMR (Acetone-d6) δ 4.36 (q, J = 63.5 Hz). 19F
NMR δ -140.04 (m). IR 2953, 2914, 2847, 1221, 1091, 1068, 908, 724 cm-1.
4.5.3 (potassium cyclohexyltrifluoroborate) (4)
BCl3 (19.5 mL, ~19.5 mmol), cyclohexene (1.583 g, 19.27 mmol) and Et3SiH (2.244 g, 19.30 mmol);
1
yield 3.269 g, 89.3%. H NMR δ 1.65 – 1.54 (m, 3H), 1.53 – 1.43 (m, 2H), 1.20 – 0.98 (m, 3H), 0.90 (qd, J =
12.3, 2.7 Hz, 2H), -0.01 (dtq, J = 11.8, 7.7, 3.8 Hz, 1H). 13C NMR δ 29.58 (br), 28.78 (q, J = 1.4 Hz), 28.17,
27.44. 11B NMR (Acetone-d6) δ 4.84 (q, J = 61.6). 19F NMR δ -147.99 (m). IR 2929, 2849, 1221, 1089, 911,
879, 725 cm-1.
4.5.4 (potassium trifluoro((R and S)-2-((S)-4-methylcyclohex-3-enyl)propyl)borate (5)
BCl3 (19.5 mL, ~19.5 mmol), (S)(-) limonene (2.60 g, 19.11 mmol) and Et3SiH (2.21 g, 18.98 mmol);
1
yield 4.314 g, 93.1%. H NMR δ 5.34 (ddt, J = 4.0, 2.5, 1.3 Hz, 1H), 2.01 – 1.80 (m, 3H), 1.79 – 1.62 (m, 1H),
1.62 – 1.56 (m, 3H), 1.50 (ddp, J = 13.9, 6.3, 3.5 Hz, 1H), 1.30 (dddd, J = 16.8, 8.4, 7.0, 4.1 Hz, 1H), 1.24 –
1.10 (m, 1H), 0.84 (dd, J = 6.8, 2.2 Hz, 3H), 0.31 (h, J = 6.2 Hz, 1H), 0.07 – -0.11 (m, 1H). 13C NMR δ 132.78,
132.77, 121.73, 121.71, 40.56, 40.41, 33.96 (q, J = 2.0 Hz), 33.80 (q, J = 1.97 Hz), 30.83, 30.73, 28.90,
27.35, 26.79, 25.20, 24.31, 23.29, 18.78, 18.40. 11B NMR (Acetone-d6) δ 5.66. 19F NMR δ -137.89. IR 2963,
2915, 2881, 2852, 1262, 1075, 931, 903, 716 cm-1.
4.5.5 (potassium 1-chloropropyl-3-trifluoroborate) (6)
BCl3 (21.0 mL, ~21.0 mmol), Et3SiH (2.377 g, 20.44 mmol) and 3-chloropropene (1.527 g, 19.95
1
mmol); yield 2.815 g, 76.5%. H NMR δ 3.49 (t, J = 7.5 Hz, 2H), 1.60 (p, J = 7.7 Hz, 2H), 0.04 (h, J = 6.5 Hz,
2H). 13C NMR δ 48.95, 29.90 (q, J = 2.4 Hz), 17.36. 11B NMR δ 4.90 (q, J = 61.1 Hz). 19F NMR δ -141.41
(m). IR 2963, 2939, 2914, 2851, 1271, 1080, 920, 718 cm-1.
13

ACCEPTED MANUSCRIPT
4.5.6 (potassium dicyclohexyldifluoroborate) (7)
The 50 mL flask was charged with BMS (0.7597 g, 10 mmol) and THF (10 mL) then cooled to 0 °C.
Cyclohexene (2.0 mL, ca. 20 mmol) was added dropwise over 7 min and stirred for 2 h at 0 °C.
Isopropanol (1.3 mL, ca. 15.4 mmol) was added (very carefully-H2 gas evolution) and stirred for 15 min;
the flask warmed to room temperature and stirred for 1 h. An aliquot of the esters was withdrawn for
NMR analysis. 11B NMR (THF- i-PrOH) δ 80.25 (bs, 2.21%), 49.68 (s, 97.06%) 31.76 (s, 0.73%). A
concentrated solution of KHF2 (1.72 g, 22 mmol) was added dropwise to the vigorously stirred solution of
esters and stirred for an additional 10 min; and the solvents were removed in vacuo 12 h. The dried
reaction products were dissolved in THF (10 mL) and an aliquot withdrawn for NMR analysis. 11B NMR
(Et2O-MeOH, 6:1 v:v) δ 80.30 (bs, 1.88%), 51.71 (s, 98.12%).
Acknowledgements
We thank the San Diego Foundation, Blasker Foundation and San Diego State University for
Financial support of this project. We also thank Dr. LeRoy Lafferty for his valuable assistance in the NMR
characterizations.
References
[1] A. Suzuki, Angew. Chem. Int. Ed. 50 (2011) 6723-6733.
[2] H. Prokopcová, C.O. Kappe, Angew. Chem. Int. Ed. 48 (2008) 2276-2286.
[3] G. Berthon-Gelloz, T. Hayashi, Rhodium- and palladium-catalyzed asymmetric conjugate additions
of organoboronic acids, Chapter 5 in: D.G. Hall (Ed.), Boronic Acids, 2nd ed., Wiley-VCH Verlag Gmbh
& Co. KGaA, Weinheim, Germany, 2011, pp 263-314.
[4] J.X. Qiao, P.Y.S. Lam, Synthesis 6 (2011) 829-856.
[5] D.S. Matteson, (α-Haloalkyl)boronic esters in asymmetric synthesis, Chapter 8 in: D.G. Hall (Ed.),
Boronic Acids, Wiley-VCH Verlag Gmbh & Co. KGaA, Weinheim, Germany, 2005, pp 305-342.
[6] G.A. Molander, L. Jean-Gérard, Organotrifluoroborates: Organoboron reagents for the twenty-first
century, Chapter 11, Vol 2 in: D.G. Hall (Ed.), Boronic Acids, 2nd ed., Wiley-VCH Verlag Gmbh & Co.
KGaA, Weinheim, Germany, 2011, pp 507-550.
[7] H.C. Brown, J. Chandrasekharan, J. Org. Chem. 48 (1983) 5080-5082.
[8] Y. Yamamoto, R. Fujikawa, T. Umemoto, N. Miyaura, Tetrahedron 60 (2004) 10695-10700.
[9] K. Burgess, W.A. van der Donk, S.A. Westcott, T.B. Marder, R.T. Baker, J.C. Calabrese, J. Am. Chem.
Soc. 114 (1992) 9350-9349.
[10] M. Zaidlewicz, J.V.B. Kanth, H.C. Brown, J. Org. Chem. 65 (2000) 6697-6702.
[11] R. Soundararajan, D.S. Matteson, J. Org. Chem. 55 (1990) 2274-2275.
[12] R. Soundararajan, D.S. Matteson, Organomet. 14 (1995) 4157-4166.
[13] D.J. Zillman, G.C. Hincapié, M.R. Savari, F.G. Mizori, T.E. Cole, Tetrahedron Lett. 51 (2010) 3033-
3036.
[14] E.W. Abel, A. Singh, J. Chem. Soc. 1959, 690-693.
14

ACCEPTED MANUSCRIPT
[15] S.K. Mehrotra, G. Srivastava, R.C. Mehrotra, J. Organomet. Chem. 73 (1974), 277-296.
[16] M. Beckett, P. Owen, K.S. Varma, J. Organomet. Chem. 588 (1999) 107-112.
[17] D. S. Matteson, G.Y. Kim, Org. Lett. 4 (2002) 2153-2155.
[18] H.A. Stefani, R. Cella, A.S. Vieira, Tetrahedron 63 (2007) 3623-3658.
[19] S. Darses, J.-P. Genêt, Chem. Rev. 108 (2008) 288-325.
[20] B.J. Kim, D.S. Matteson, Angew. Chem. Int. Ed. 43 (2004) 3056-3056.
[21] G.A. Molander, L.N. Cavalcanti, B. Canturk, P.-S. Pan, L.E. Kennedy, J. Org. Chem. 74 (2009) 7364-
7369.
[22] G.W. Kabalka, V. Coltuclu, Tetahedron Letters 50 (2009) 6271-6272.
[23] Q.I. Churches, J.F. Hopper, C.A. Hutton, J. Org. Chem. 80 (2015) 5428-5435.
[24] H.C. Brown, J. Chandrasekharan,. Organometallics 2 (1983) 1261-1263.
[25] E. Vedejs, R.W. Chapman, S.C. Fields, S. Lin, M.R. Schrimpf, J. Org. Chem 60 (1995) 3020-3037.
[26] S. Darses, J.-P. Genêt, J.-L. Brayer, J.-P. Demoute, Tetrahedron Lett. 38 (1998) 4393-4396.
[27] J.-J. Dai, W.-M. Zhang, Y.-J. Shu, Y.-Y. Sun, J. Xu, Y.-S. Feng, H.-J. Xu, Chem. Comm. 52 (2016) 6793-
6796.
[28] J.D. Roberts, F.J. Weigert, J.I. Kroschwitz, H.J. Reich, J. Am. Chem. Soc. 92 (1970) 92, 1338-1347.
[29] D.G. Hall, Structure, properties, and preparation of boronic acids, Chapter 1, Vol 1 in: D.G. Hall (Ed.),
Boronic Acids, 2nd ed., Wiley-VCH Verlag Gmbh & Co. KGaA, Weinheim, Germany, 2011, pp 1-133.
[30] P.A. McCusker, L.J. Glunz, J. Am. Chem. Soc. 77 (1955) 4253-4255
.
[31] P.A. McCusker, H.S. Makowski, J. Am. Chem. Soc. 79 (1957) 5185-5188.
[32] H.C. Brown, J. Chandrasekharan, J. Org. Chem. 53 (1988) 4811-4814.
[33] J.V. Kanth, H.C. Brown, J. Org. Chem. 66 (2001) 5359-5365.
[34] C. Cazorla, E. Métay, M. Lemaire, Tetrahedron 67 (2011) 8615-8621.
[35] G.A. Molander, C.-S. Yun, M. Ribagorda, B. Biolatto, J. Org. Chem. 68 (2003) 5534-5539.
[36] D. Thierig, F. Umland, Naturwissenschaften 54 (1967), 563.
[37] G. Pawelke, F. Heyder, H. Bürger, J. Organomet. Chem. 178 (1979) 1-4.
[38] H.C. Brown, N.G. Bhat, V. Somayaji, Organometallics 2 (1983) 1311-1316.
15

ACCEPTED MANUSCRIPT
Highlights:
•
Matteson Hydroboration Method using ligand free HBCl2 is fast and highly
selective
•
Fluoridation of boronic compounds require oxygen-free conditions to
prevent loss
•
•
•
Isolated yields of alkyltrifluoroborates generally greater than 90%
Alkene to alkyltrifluoroborate conversion without isolation of intermediates
Dialkylborinic derivatives do not form fluoroborate salts