A method for the deprotection of alkylpinacolyl boronate esters

Article abstract of DOI:10.1021/jo200250y

A two-step procedure for deprotection of alkylpinacolyl boronate esters via transesterification with diethanolamine followed by hydrolysis was successfully developed with the advantages of tolerance to various functional groups, short reaction time, and ease of product isolation.

Full text of DOI:10.1021/jo200250y

NOTE
pubs.acs.org/joc
A Method for the Deprotection of Alkylpinacolyl Boronate Esters
Jing Sun, Michael T. Perfetti, and Webster L. Santos*
Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, United States
S Supporting Information
b
ABSTRACT: A two-step procedure for deprotection of alkylpi-
nacolyl boronate esters via transesterification with diethanola-
mine followed by hydrolysis was successfully developed with the
advantages of tolerance to various functional groups, short
reaction time, and ease of product isolation.
Scheme 1. Attempted Deprotection of 1e
oronic acids are important in organic synthesis because of
their versatility as synthetic intermediates in the prepara-
B
tion of complex molecules. Their utility is exemplified by the
powerful carbonꢀcarbon bond-forming SuzukiꢀMiyaura cou-
pling reaction.1,2 As inhibitors of serine proteases, boronic acids
inhibit therapeutically relevant proteases including chymotrypsin,
thrombin, dipeptidyl peptidase, HCV NS3 protease, and the
proteasome.3 Indeed, the first boron-containing drug, bortezomib
(Velcade), was approved by the FDA for the treatment of multiple
myeloma and mantle cell lymphoma. Thus, methods for synthesiz-
ing boronic acids are vital in harnessing their full potential in a
variety of applications.
Introduction of the boronyl moiety has been a subject of
intense investigation. Traditionally, arylboronic acids can be
obtained from electrophilic borate trapping of arylmetal inter-
mediates from aryl halides,4 transmetalation of arylsilanes and
stannanes,5 transition-metal-catalyzed coupling between aryl
halides/triflates and diboron reagents,6 and direct boration by
transition-metal-catalyzed aromatic CꢀH activation.7,8 Some
boronic acids are unstable and incompatible to reaction condi-
tions during functional group transformations; therefore, they
are converted to air- and chromatography-stable boronate esters
using diols such as pinanediol,9 cathecol,10,11 neopentyl glycol,12ꢀ16
and pinacol.17,18 Although these groups are usually benign to
various reaction conditions, their removal has been troublesome
and unpredictable.19 Recently, trifluoroborate,20 N-methylimi-
nodiacetic acid,21ꢀ23 and 1,8-diaminonaphthalene24,25 units
were introduced as alternative protecting groups for boronic
acids. Organotrifluoroborate salts undergo hydrolysis in the
presence of silica gel to afford the corresponding boronic acids,26
and more recently, a direct route to arylboronic acids was
reported.27
Alternatively, a solid-phase process that utilizes polystyre-
neꢀboronic acid has been developed for arylpinacolyl boronic
esters.35 However, this method requires acidic conditions, is
time-consuming, and relies on the commercial availability of the
resin. Recently, Hutton and co-workers36 reported a two-step
deprotection of the pinacol group via fluorinated intermediates37
that is followed by trimethylsilyl chloride38 or lithium hydroxide.
In the course of our work on the development of N-terminal
peptidic boronic acids as protease inhibitors,39 we were faced
with the difficulty of removing the pinacolyl group during the
initial phase of our study. The boronyl moiety in all of these
cases was directly attached to alkyl groups. For example, when
β-boronopinacolyl-β-phenyl benzyl ester 1e was subjected to
various deprotection conditions, either the starting material
decomposed or no reaction occurred, and thus β-boronic acid
3e was not obtained (Scheme 1).
In order to circumvent this issue, we investigated a transester-
ification procedure with diethanolamine (DEA) to form an sp3-
hybridized boron DEA adduct, which is then hydrolyzed to yield
3
a boronic acid derivative. Indeed, a few examples of pinacol
deprotection with DEA have been reported, but most of these are
arylboronic esters.40ꢀ42 To date, only two examples of successful
alkylpinacolyl boronate ester deprotection involving transester-
ification and hydrolysis to produce boron-containing amino acid
analogues have been disclosed.43,44 In some cases, an acidic resin,
long reaction time, or distillation was necessary to effectively
provide the boronic acid moiety. Because there has not been a
Several deprotection methods for the removal of cyclic boro-
nate esters are available. These include oxidative cleavage with
sodium periodate,28 biphasic transesterification with other boro-
nic acids,28,29 transborylation with boron trichloride,30ꢀ32 and
acidic hydrolysis.33,34 The yield and purity of these deprotection
procedures vary greatly, notwithstanding issues that can arise
from functional group incompatibilities and purification problems.
Received: February 7, 2011
Published: March 30, 2011
r
2011 American Chemical Society
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NOTE
Scheme 2. Two-Step Protocol for the Boronic Ester
Deprotection
comprehensive investigation of the boryl pinacolate deprotec-
tion with DEA, we explored the generality of a two-step protocol
in the deprotection of alkylpinacolyl boronate esters. Herein, we
report a simple and efficient deprotection method of pinacolyl
boronate esters.
Figure 1. X-ray crystal structure of 2b.
We initially employed an arylboronic ester as our test case
(Scheme 2). Treatment of pinacolylphenylboronic ester with
DEA in ether afforded the DEA boronate product, which was
filtered and subsequently treated with 0.1 M HCl for 20 min to
provide phenylboronic acid in 99% yield. Having established the
deprotection procedure, we investigated whether a one-pot
deprotection method was possible with pinacolyl boronate ester
substrates.45 However, none of these studies (changing solvents,
biphasic solutions, sequential addition of reagents, etc.) was
successful. Thus, we elected to pursue the two-step transester-
ification/hydrolysis using a variety of pinacolyl-β-alkylboronic
esters. As shown in Table 1, transesterification of the pinacol
group with DEA efficiently proceeded in up to 97% isolated yield.
It should be noted that not only did this reaction occur in a short
amount of time (<30 min) but the purification was a simple
filtration as the DEA boronate product precipitated in the ethereal
solution. For example, unhindered substrates containing benzyl
or methyl esters provided compounds 2a,b in good yields
(entries 1 and 2). Introduction of substituents on the β-position
with a phenyl or methyl group was also effective (entries 3ꢀ7). In
addition, cyclic and acyclic ketones as well as nitriles underwent
the transesterification smoothly (entries 8ꢀ11). All the isolated
compounds 2aꢀl were white solids, stable to atmospheric
conditions, and had long shelf lives. These compounds were
characterized by 1H, 13C, and 11B NMR and high-resolution mass
spectroscopy. Introduction of DEA produced desirable effects:
the formation of a “boronꢀate” species that is stable to oxidation
and an adduct that is insoluble in ether. sp3-hybridized boron
complexes are reported to be stable and resistant to air
oxidation.20,22 To further confirm the tetracoordination on boron,
the single-crystal X-ray diffraction data for 2b was solved. As
shown in Figure 1, boron adopts a tetrahedral geometry similar to
Scheme 3. Rapid Hydrolysis and Subsequent Trapping of 2
under acidic aqueous conditions as previously observed, and the
unstable alkylboronic acids 3 are subsequently trapped as the
boron pinacolyl esters 1 (Scheme 3). Indeed, when the in situ
hydrolysis-trapping protocol was performed, the pinacol boro-
nate esters were achieved in excellent yields (Table 1).
In conclusion, a two-step deprotection protocol for alkyl
pinacolyl boronic esters via DEA-protected boronates was suc-
cessfully developed with the advantages of tolerance to various
functional groups, short reaction time, and ease of product
isolation. Moderate to excellent yields were achieved for stable
boronic acid products.
’ EXPERIMENTAL SECTION
General Procedure for the Synthesis of DEA-Protected
Boronic Esters 2aꢀl. To a solution of pinacolyl boronic ester 1 (1.7
mmol) in ether was added diethanolamine (0.199 g, 1.9 mmol). After a
few minutes, a white precipitate formed, and the reaction was allowed to
continue until the starting material was completely consumed as
monitored by TLC (∼30 min). The precipitate was then filtered,
washed with ether, and dried to afford the desired product 2.
8-(3-(Benzyloxy)-3-oxopropyl)hexahydro-1,3,2-oxazaborolo-
[2,3-b]-1,3,2-oxazaborol-4-ium-8-uide (2a): white solid (0.305 g,
85% yield); mp 159.7ꢀ161.6 °C; 1H NMR (500 MHz, CDCl3)
δ 7.43ꢀ7.27 (m, 5H), 6.16 (s, 1H), 5.08 (s, 2H), 3.95 (m, 2H), 3.81 (m,
2H), 3.15ꢀ3.00 (m, 2H), 2.76ꢀ2.65 (m, 2H), 2.60ꢀ2.48 (m, 2H),
0.81ꢀ0.56 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 179.3, 136.1, 128.7,
128.3, 128.0, 66.3, 63.3, 51.3, 29.8; the signal for the carbon directly attached
to boron was not observed due to quadrupolar relaxation; 11B NMR
(160 MHz, CDCl3) δ 11.26; HRMS (ESIþ) calcd for C14H21BO4
[M þ H]þ 278.1558, found 278.1532.
what is observed in aryl DEA boronates.
3
With the diethanolamine derivatives in hand, hydrolysis to the
corresponding boronic acids was performed using a biphasic
solution of 0.1 M HCl and ether. As expected, the boronic acid
products were readily formed within minutes. For example,
esters 3a,b, amides 3f,g, ketone 3i, and nitrile 3j were isolated
as white solids in moderate to excellent yields (Table 1). How-
ever, in some cases, we experienced difficulty in isolating the
desired alkylboronic acids. This was not surprising as some
boronic acids are known to be unstable, undergoing facile
decomposition in polar protic media via protodeboronation,
oxidation, and/or polymerization.46ꢀ49 To test whether boronic
acids were formed but decomposed during the reaction and/or
workup, the DEA boronates were subjected to a biphasic solution
of 0.1 M HCl and hexanes in the presence of 2 equiv of pinacol.
We hypothesized that DEA boronates 2 undergo rapid hydrolysis
8-(3-Methoxy-3-oxopropyl)hexahydro-1,3,2-oxazaborolo-
[2,3-b]-1,3,2-oxazaborol-4-ium-8-uide (2b): white solid; 72%
1
yield; mp 147.3ꢀ148.4 °C; H NMR (500 MHz, CD3Cl) δ 6.39 (s,
1H), 4.00 (td, J = 5.3, 9.6, 2H), 3.92ꢀ3.81 (m, 2H), 3.65 (s, 3H),
3.26ꢀ3.14 (m, 2H), 2.86ꢀ2.73 (m, 2H), 2.53ꢀ2.45 (m, 2H),
0.77ꢀ0.60 (m, 2H); 13C NMR (125 MHz, CD3Cl) δ 180.1, 63.3,
51.71, 51.3, 29.4; 11B NMR (160 MHz, CD3Cl) δ 11.25; HRMS (ESIþ)
calcd for C8H17BNO4 [M þ H]þ 202.1245, found 202.1243.
8-(3-Methoxy-3-oxo-1-phenylpropyl)hexahydro-1,3,2-oxaza-
borolo[2,3-b]-1,3,2-oxazaborol-4-ium-8-uide (2c): white solid;
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NOTE
Table 1. Substrate Scope of the Two-Step Transesterification/Hydrolysis of Pinacolyl Boronate Estersa
a Each reaction was performed at least twice. Conditions: 1 (1 equiv), DEA (1.1 equiv), ether, rt, ∼30 min followed by 0.1 M HCl (20 min).
b Isolated yield. c Product was isolated as the pinacol ester.
88% yield; mp 188.7ꢀ189.9 °C; 1H NMR (500 MHz, CD3Cl)
δ 7.29ꢀ6.98 (m, 5H), 5.65 (s, 1H), 4.01ꢀ3.88 (m, 2H), 3.87ꢀ3.78
(m, 2H), 3.62 (s, 3H), 3.12ꢀ3.01 (m, 1H), 3.00ꢀ2.89 (m, 2H),
2.76ꢀ2.64 (m, 3H), 2.32 (dd, J = 5.5, 8.1 Hz, 1H); 13C NMR (125 MHz,
CD3Cl) δ 177.9, 147.34, 128.2, 127.8, 124.5, 63.4, 63.2, 51.7, 51.5, 51.4,
37.0; 11B NMR (160 MHz, CD3Cl) δ 11.25; HRMS (ESIþ) calcd for
C14H21BNO4 [M þ H]þ 278.1558, found 278.1543.
CD3Cl) δ 6.01 (s, 1H), 4.03ꢀ3.91 (m, 2H), 3.89ꢀ3.81 (m, 2H),
3.22ꢀ3.11 (m, 1H), 3.02ꢀ2.94 (m, 1H), 2.94ꢀ2.84 (m, 1H),
2.79ꢀ2.68 (m, 2H), 2.61 (dd, J = 4.8, 17.2 Hz, 1H), 2.27 (dd, J = 4.6,
8.9 Hz, 1H), 1.39 (s, 9H). 13C NMR (125 MHz, CD3Cl) δ 155.7, 131.8,
128.0, 127.8, 124.2, 80.3, 77.3, 77.0, 76.7, 63.4, 63.2, 51.3, 51.20, 38.5,
28.0. 11B NMR (160 MHz, CD3Cl) δ 10.38. HRMS (ESIþ) Calculated
for C17H27BNO4 [MþH]þ: 320.2028, found: 320.2006.
8-(3-tert-Butoxy-3-oxo-1-phenylpropyl)hexahydro-1,3,
2-oxazaborolo[2,3-b]-1,3,2-oxazaborol-4-ium-8-uide (2d):
8-(3-Oxo-3-phenoxy-1-phenylpropyl)hexahydro-1,3,2-oxaza-
borolo[2,3-b]-1,3,2-oxazaborol-4-ium-8-uide (2e): white solid;
84% yield; mp 173.9ꢀ174.8 °C; 1H NMR (400 MHz, CD3CN)
1
white solid; 75% yield; mp 186.5ꢀ187.7 °C; H NMR (500 MHz,
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NOTE
δ 7.41ꢀ6.99 (m, 9H), 4.96 (s, 3H), 3.82ꢀ3.70 (m, 2H), 3.67ꢀ3.49 (m,
2H), 3.01ꢀ2.85 (m, 1H), 2.82ꢀ2.60 (m, 6H), 2.34 (dd, J = 5.8,
9.8 Hz, 1H); 13C NMR (100 MHz, CD3CN) δ 174.7, 128.3, 128.0,
127.7, 127.6, 124.0, 117.3, 105.0, 65.2, 62.5, 62.4, 51.2, 51.0, 36.7; 11B NMR
(160 MHz, CD3Cl) δ 10.86; HRMS (ESIþ) calcd for C20H25BNO4
[M þ H]þ 354.1871, found 354.1878.
2.90ꢀ2.78 (m, 1H); 13C NMR (100 MHz, CD3CN) δ 132.5, 126.9,
126.7, 63.1, 51.1; 11B NMR (160 MHz, CD3CN) δ 10.55; HRMS
(ESIþ) calcd for C10H15BNO2 [M þ H]þ 192.1196, found 192.1204.
General Procedure for the Deprotection of DEA-boronate
Compound 2. To a solution of DEA-boronate 2 (1.1 mmol) in ether
was added 0.1 M HCl. After about 20 min as judged by TLC, the reaction
was extracted with ether (3ꢁ), washed with brine (1ꢁ), and dried with
sodium sulfate, and the organic solvent was removed under reduced
pressure. Evaporation of residual solvent provided the analytically pure
product as white solid. Because of their facile dehydration, boronic acids
tend to provide inconsistent melting points.50 Therefore, the melting
points for boronic acids were not taken.
8-(4-(Benzylamino)-4-oxobutan-2-yl)hexahydro-1,3,2-oxaza-
borolo[2,3-b]-1,3,2-oxazaborol-4-ium-8-uide (2f): white solid;
65% yield; mp 127.5ꢀ128.6 °C; 1H NMR (500 MHz, CD3Cl) δ 7.77
(s, 1H), 7.41ꢀ7.10 (m, 5H), 6.00 (s, 1H), 4.39 (d, J = 5.7 Hz, 2H),
4.04ꢀ3.77 (m, 4H), 3.35ꢀ3.01 (m, 2H), 2.82ꢀ2.68 (m, 2H),
2.49ꢀ2.10 (m, 2H), 0.99 (d, J = 6.1 Hz, 3H), 0.94 (dd, J = 9.1, 17.7
Hz, 1H); 13C NMR (125 MHz, CD3Cl) δ 177.3, 138.0, 128.8, 127.6,
127.6, 63.5, 63.4, 51.5, 51.3, 43.7, 40.8, 17.3; 11B NMR (160 MHz,
CD3Cl) δ 11.37; HRMS (ESIþ) calcd for C15H24BN2O3 [M þ H]þ
291.1874, found 291.1890.
(3-(Benzyloxy)-3-oxopropyl)boronic acid (3a): white solid;
1
95% yield; H NMR (500 MHz, CD3Cl) δ 7.45ꢀ7.22 (m, 5H), 5.13
(s, 2H), 2.53 (t, J = 7.2 Hz, 2H), 1.12 (t, J = 7.0 Hz, 2H); 13C NMR
(125 MHz, CD3Cl) δ 175.15, 136.02, 128.68, 128.35, 66.58, 28.69,
24.84; 11B NMR (160 MHz, CD3Cl) δ 31.59; HRMS (ESIþ) calcd for
C10H13BO4Cl [M þ Cl]þ 243.0601, found 243.0619.
8-(3-(Benzylamino)-3-oxo-1-phenylpropyl)hexahydro-1,3,
2-oxazaborolo[2,3-b]-1,3,2-oxazaborol-4-ium-8-uide (2g):
1
(3-Methoxy-3-oxopropyl)boronic acid (3b): white solid; 90%
yield; 1H NMR (500 MHz, CD3Cl) δ 3.66 (s, 3H), 2.48 (t, J = 7.2 Hz,
2H), 1.11 (t, J = 7.2 Hz, 2H); 13C NMR (125 MHz, CD3Cl) δ 175.9,
51.9, 28.4, 10.4; 11B NMR (160 MHz, CD3Cl) δ 31.49; HRMS (ESIþ)
calcd for C4H10BO4 [M þ H]þ 133.0672, found 133.0665.
(4-(Benzylamino)-4-oxobutan-2-yl)boronic acid (3f): white
solid; 98% yield; 1H NMR (500 MHz, CD3OD) δ 7.39ꢀ7.16 (m, 5H),
4.37 (q, J = 14.9 Hz, 2H), 2.32 (d, J = 8.3 Hz, 2H), 1.51ꢀ1.34 (m, 1H),
0.92 (d, J = 7.4 Hz, 3H); 13C NMR (125 MHz, CD3OD) δ 176.3, 138.4,
128.2, 127.3, 127.0, 43.2, 39.6, 14.3; 11B NMR (160 MHz, CD3OD) δ
26.96; HRMS (ESIþ) calcd for C11H20BN2O3 [M þ NH4] 239.1561,
found 239.1568.
white solid; 68% yield; mp 197.3ꢀ198.2 °C; H NMR (500 MHz,
CD3Cl) δ 7.34ꢀ7.19 (m, 10H), 7.08ꢀ7.01 (m, 1H), 6.04 (s, 1H), 4.39
(d, J = 5.7 Hz, 2H), 4.02ꢀ3.76 (m, 4H), 3.33ꢀ3.19 (m, 1H), 3.10ꢀ2.62
(m, 2H), 2.53ꢀ2.19 (m, 2H); 13C NMR (125 MHz, CD3Cl) δ 176.7,
148.1, 137.9, 128.8, 128.2, 127.9, 127.6, 124.4, 63.6, 63.5, 51.4, 43.8,
40.2; 11B NMR (160 MHz, CD3Cl) δ 11.03; HRMS (ESIþ) calcd for
C20H26BN2O3 [M þ H]þ 353.2031, found 353.2034.
8-(3-Oxocyclopentyl)hexahydro-1,3,2-oxazaborolo[2,3-b]-1,
3,2-oxazaborol-4-ium-8-uide (2h): white solid; 79% yield; mp
201.4ꢀ202.1 °C; 1H NMR (500 MHz, CD3CN) δ 5.13 (s, 1H),
3.88ꢀ3.77 (m, 3H), 3.73ꢀ3.63 (m, 3H), 3.16ꢀ3.03 (m, 3H), 2.82ꢀ
2.73 (m, 3H), 2.13ꢀ2.07 (m, 1H), 2.06ꢀ1.97 (m, 2H), 1.92ꢀ1.77
(m, 3H), 1.67ꢀ1.55 (m, 1H), 1.24ꢀ1.11 (m, 1H); 13C NMR
(125 MHz, CD3Cl) δ 171.2, 63.4, 63.3, 52.3, 42.2, 39.9, 31.1, 26.2;
11B NMR (160 MHz, CD3Cl) δ 11.56; HRMS (ESIþ) calcd for
C9H17BNO3 [M þ H]þ 198.1296, found 198.1308.
(3-(Benzylamino)-3-oxo-1-phenylpropyl)boronic acid (3g):
1
white solid; 69% yield; H NMR (500 MHz, CD3OD) δ 7.29ꢀ6.97
(m, 10H), 4.50ꢀ4.22 (m, 2H), 2.80ꢀ2.74 (m, 1H), 2.72ꢀ2.43 (m, 2H);
13C NMR (125 MHz, CD3OD) δ 176.7, 148.1, 137.9, 128.8, 128.2,
127.9, 127.7, 127.6, 124.4, 43.8, 40.2; 11B NMR (160 MHz, CD3OD)
δ 25.39; HRMS (ESIþ) calcd for C16H19BNO3 [M þ H]þ 284.1453,
found 284.1478.
8-(3-Oxo-1,3-diphenylpropyl)hexahydro-1,3,2-oxazaborolo-
[2,3-b]-1,3,2-oxazaborol-4-ium-8-uide (2i): white solid; 72%
1
yield; mp 170.0ꢀ171.4 °C; H NMR (400 MHz, CD3CN) δ 7.98ꢀ
1
(2-Cyanoethyl)boronic acid (3j): white solid; 31% yield; H
6.96 (m, 8H), 3.87ꢀ3.71 (m, 2H), 3.67ꢀ3.52 (m, 2H), 3.46ꢀ3.28
(m, 2H), 3.03ꢀ2.89 (m, 1H), 2.88ꢀ2.74 (m, 1H), 2.75ꢀ2.64 (m, 2H),
2.56ꢀ2.45 (m, 1H); 13C NMR (125 MHz, CD3Cl) δ 199.4, 148.0,
137.2, 133.3, 128.6, 128.3, 128.3, 128.1, 124.5, 63.5, 63.3, 51.5, 51.3, 43.3,
24.8; 11B NMR (160 MHz, CD3Cl) δ 11.32; HRMS (ESIþ) calcd for
C19H23BNO3 [M þ H]þ 324.1766, found 324.1777.
NMR (500 MHz, (CD3)2CO) δ 2.42 (t, J = 5 Hz, 2H), 1.08 (t, J = 5 Hz,
2H); 13C NMR (125 MHz, CD3Cl) δ 120.8, 11.3; 11B NMR (160 MHz,
(CD3)2CO) δ 18.89; HRMS (ESIþ) calcd for C3H6BNO2Cl [M þ
Cl]þ 134.0186, found 134.0180.
8-(2-Cyanoethyl)hexahydro-1,3,2-oxazaborolo[2,3-b]-1,3,
2-oxazaborol-4-ium-8-uide (2j): White solid, 76% yield; mp
’ ASSOCIATED CONTENT
1
Supporting Information. 1H, 13C, and 11B NMR spectra
S
218.6ꢀ220.4 °C; H NMR (400 MHz, CD3CN) δ 3.81 (td, J = 9.3,
b
5.4 Hz, 1H), 3.74 ꢀ 3.63 (m, 1H), 3.23 ꢀ 3.04 (m, 1H), 2.84 ꢀ 2.69
(m, 1H), 2.20 (dd, J = 16.1, 7.8 Hz, 1H), 0.75 ꢀ 0.61 (m, 1H). 13C NMR
(100 MHz, CD3CN) δ 117.3, 62.5, 51.2, 12.5. 11B NMR (160 MHz,
CD3Cl) δ 11.28. HRMS (ESIþ) Calculated for C7H14BN2O2 [MþH]:
169.1148, found: 169.1165.
of new compounds and CIF file for 2b. This material is available
free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: santosw@vt.edu.
8-(2-Cyano-1-phenylethyl)hexahydro-1,3,2-oxazaborolo-
[2,3-b]-1,3,2-oxazaborol-4-ium-8-uide (2k): white solid; 97%
yield; mp 147.5ꢀ148.9 °C; 1H NMR (500 MHz, CD3CN)
δ 7.34ꢀ7.07 (m, 6H), 4.86 (s, 1H), 3.82ꢀ3.71 (m, 3H), 3.67ꢀ3.61
(m, 1H), 3.56 (dt, J = 4.8, 9.9 Hz, 1H), 3.04ꢀ2.94 (m, 1H), 2.74ꢀ2.61
(m, 7H), 2.18 (t, J = 8.3 Hz, 1H), 2.14 (s, 1H); 13C NMR (125 MHz,
CD3CN) δ 145.3, 128.1, 128.0, 124.9, 117.4, 62.6, 62.5, 51.3, 51.2, 19.6;
11B NMR (160 MHz, CD3CN) δ 10.47; HRMS (ESIþ) calcd for
C13H16BN2O2 [M þ H]þ 243.1310, found 243.1335.
’ ACKNOWLEDGMENT
We thank Dr. Carla Slebodnick for assistance with X-ray
crystallography and the Department of Chemistry at Virginia
Tech and the National Institutes of Health (RO1 GM093834)
for financial support.
8-Phenylhexahydro-1,3,2-oxazaborolo[2,3-b]-1,3,2-ox-
azaborol-4-ium-8-uide (2l): white solid; 88% yield; mp 215.1ꢀ
217.5 °C; 1H NMR (400 MHz, CD3CN) δ 7.55ꢀ7.15 (m, 2H), 3.97
(td, J = 9.3, 5.4 Hz, 1H), 3.93ꢀ3.81 (m, 1H), 3.28ꢀ3.14 (m, 1H),
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