Relative Reactivity of Stable Ligated Boranes and a Borohydride Salt in Rhodium(II)-Catalyzed Boron-Hydrogen Insertion Reactions

Article abstract of DOI:10.1021/acs.joc.6b00091

Relative reactivities of a series of neutral ligated boranes L-BH₃ (where L is NHC, amine, pyridine, or phosphine) and the cyanoborohydride anion have been assessed in Rh(II)-catalyzed B-H insertion reactions with methyl 2-phenyl-2-diazoacetate

Full text of DOI:10.1021/acs.joc.6b00091

Article
pubs.acs.org/joc
Relative Reactivity of Stable Ligated Boranes and a Borohydride Salt
in Rhodium(II)-Catalyzed Boron−Hydrogen Insertion Reactions
Thomas H. Allen and Dennis P. Curran*
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States
*
S Supporting Information
ABSTRACT: Relative reactivities of a series of neutral ligated
boranes L-BH3 (where L is NHC, amine, pyridine, or
phosphine) and the cyanoborohydride anion have been
assessed in Rh(II)-catalyzed B−H insertion reactions with
methyl 2-phenyl-2-diazoacetate. Stable α-boryl ester products
were isolated by flash chromatography in all cases except for
the salt product from cyanoborohydride. All of the substrates
were either comparable to or more reactive than 1,4-
cyclohexadiene, which is one of the most reactive substrates in C−H insertion reactions. The range of reactivity between the
most reactive pyridine-borane and the least reactive phosphine-borane is a factor of approximately 40.
INTRODUCTION
Trivalent enol-boranes 1 have long been pivotal intermediates
in organic synthesis (Figure 1). However, it is increasingly
■
1
Figure 1. Enol-borane and α-boryl carbonyl isomers.
recognized that some classes of tetravalent boron compounds
with strong ligands to boron prefer to form as isomeric α-boryl
2
carbonyl compounds 2 rather than enol isomers. Such
compounds have value in synthesis as summarized in a timely
Figure 2. Rhodium(II)-catalyzed insertion reactions of NHC-boranes
and diazocarbonyl compounds give stable α-NHC-boryl carbonyl
compounds.
2
perspective by Yudin and co-workers. Yudin’s work has
focused on α-MIDA boryl carbonyl compounds such as
3
aldehyde 3, where MIDA is the trivalent N-methyliminodia-
raphy of the residue. α-Boryl ester 9a was isolated in 62% yield
as a stable white solid.
cetate ligand.
We recently showed that rhodium(II)-catalyzed insertion
reactions of α-diazocarbonyl compounds 4 into boron−
hydrogen bonds of N-heterocyclic carbene boranes 5 (here-
Shortly thereafter, Zhu and Zhou reported diazocarbonyl
insertion reactions of various amine- and phosphine-boranes
6
with both achiral and chiral copper catalysts. More recently,
after, NHC-boranes) occur rapidly at ambient temperature
4
Xu and co-workers reported asymmetric rhodium(II)-catalyzed
(
Figure 2a). The resulting α-NHC-boryl carbonyl compounds
7
insertions with both amine- and NHC-boranes. These groups
6
are stable in air, water, and chromatography, making them
also provided examples of the synthetic utility of the α-boryl
carbonyl products.
In a series of competitive insertion reactions, we learned that
the B−H bonds of NHC-boranes are considerably more
convenient to handle. Such compounds show no tendency to
isomerize to enol-NHC-boranes.
In a typical example (Figure 2b), a brief reaction of methyl 2-
diazo-2-phenylacetate 7 with 1,3-dimethylimidazol-2-ylidene
borane 8a and 1 mol % Rh (esp) (esp = 3,3′-(1,3-
2
2
5
phenylene)-bis(2,2-dimethylpropanoate) ) in CH Cl was
Received: January 14, 2016
2
2
followed by solvent evaporation and direct flash chromatog-
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b00091
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
reactive than most activated C−H bonds toward reaction with
Table 1. Boron−Hydrogen Insertion Reactions of Ligated
Boranes and a Borohydride
4
,8
rhodium carbenes. For example, THF is usually considered
9
to have an activated C−H bond toward carbene insertion;
however, it can actually be used as a solvent in B−H insertion
reactions of NHC-boranes (although dichloromethane provides
better yields).
Here, we extended the study of relative reactivity in B−H
insertion reactions to other classes of stable ligated boranes,
including neutral amine-, pyridine-, and phosphine-boranes and
an anionic cyanoborohydride. We found that all of these species
are highly reactive in B−H insertion reactions, though the order
of relative reactivity does not faithfully follow either bond
dissociation energies or nucleophilicity values.
RESULTS AND DISCUSSION
■
Synthesis of Ligated Borane Insertion Products. We
selected methyl 2-phenyl diazoacetate 7 as the diazo partner for
these experiments because it has commonly been used in
10
competitive C−H insertion and cyclopropanation reactions,
and because it was the substrate used in the previous B−H
4
insertion competition experiments. The first step was synthesis
and isolation of samples of the authentic products.
The α-NHC-boryl ester 9a was prepared according to the
4
prior report as summarized in Figure 2b. The other products
9
b−e were prepared similarly as summarized in Table 1. The
synthesis of α-pyridine-boryl ester 9b is typical (entry 1).
Pyridine-borane 8b (pyr-BH , 1 mmol) and Rh (esp) (1 mol
3
2
2
%
) were dissolved in CH Cl , and then a solution of methyl 2-
2 2
diazo-2-phenylacetate 7 in CH Cl (1.2 equiv) was added by
2
2
syringe pump over 2 h at ambient temperature. Simple solvent
evaporation and flash chromatography gave 9b in 79% yield.
Likewise, α-trimethylamine-boryl ester 9c was isolated in
4
3% yield (entry 2) from trimethylamine-borane 8c (Me N-
3
BH ). Triphenylphosphine-borane 8d (Ph P-BH ) produced α-
3
3
3
boryl ester 9d in 50% yield (entry 3), while tributylphosphine-
borane 8e (Bu P-BH ) produced 9e in 30% yield with
3
3
11
approximately 97% purity (entry 4). Insertion products 9a−
c were isolated in pure form as indicated by both spectroscopic
analysis and visual inspection (white solid or clear oil). In
contrast, samples of phosphine-boranes 9d and 9e were faint
orange and had small impurities in their spectra even after a
second flash chromatography.
a
Estimated from the 11B NMR spectrum of the crude reaction mixture.
b
c
Yield after flash chromatography. 4 mol % Rh (esp) used to offset
2
2
d
phosphine impurity. An 84/16 ratio of single-insertion product 9f
and double-insertion product [MeO CCH(Ph)] BHCN. Product is a
salt and was not isolated after column chromatography.
e
2
2
During these experiments, we found that free pyridine and
phosphine inhibit the insertion reaction. Thus, when using
small amounts of catalyst (1 mol %), it is important that the
ligated borane substrates 8b, 8d, and 8e do not have detectable
traces of free ligand.
chromatography. In contrast, the conversions of trimethyl-
amine-borane 8c and the phosphine-boranes 8d and 8e are
higher than the yields of the corresponding products 9c−e
(entries 2−4). This suggests that some decomposition may
have occurred during flash chromatography for these products.
Still, all of the products 9a−e are stable once isolated and can
be stored and handled in ambient lab conditions.
More simply, the amount of catalyst can be increased to
compensate for traces of free ligand. For example, our sample
of triphenylphosphine-borane 8d contained approximately 3%
3
1
triphenylphosphine by P NMR analysis. The characteristic
green color of the catalyst dissipated quickly when this sample
was mixed with 1 mol % Rh (esp) No reaction occurred when
We also investigated two reactions with borohydride anions
in place of the ligated boranes. Tetrabutylammonium counter-
ions were used for solubility in DCM. When Rh (esp) was
2
2.
2
2
the diazo compound was added to the resulting yellow solution.
However, when the same sample was mixed with 4 mol %
Rh (esp) , the green color persisted, and the reaction
mixed with tetrabutylammonium borohydride (Bu NBH ) in
DCM, the characteristic green color of the catalyst quickly
4 4
changed to dark brown. The syringe pump addition of 7 was
2
2
1
1
proceeded normally when the diazo compound was added
conducted, and the crude product was assessed by B NMR
(
entry 3).
spectroscopy; however, the major boron-containing component
was unreacted Bu NBH . Given the color change, Bu NBH
4 4 4 4
12
Table 1 also shows the percent of conversion of starting
material to product after completion of the syringe pump
may have destroyed the catalyst.
In contrast, a similar reaction with the milder reducing agent
tetrabutylammonium cyanoborohydride 8f (Bu NBH CN,
entry 5) behaved visually like the other reactions in Table 1:
1
1
addition, measured by B NMR spectroscopy. The conversion
and yield in the pyridine-boryl series are roughly the same,
showing that α-pyridine-boryl ester 9b is stable to flash
4
3
B
DOI: 10.1021/acs.joc.6b00091
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
the green color persisted until the end of the syringe pump
addition of the diazo partner, at which point the mixture
became yellow. Analysis of the mixture showed full conversion
to a mixture of two products in an approximately 84/16 ratio.
The major product was assigned as single-insertion product 9f,
while the minor product is believed to result from double
insertion (doublet at −27.2 ppm in the B NMR spectrum).
An attempt to purify insertion product 9f by flash
chromatography failed; the salt never eluted. However, 9f is
stable while standing in solution and was further characterized
9b/9a (unknown/standard) was determined by integration as
72/28 (Table 2, entry 1). These results show that pyridine-
borane 8b is even more reactive than NHC-borane 8a in these
B−H insertion reactions.
Two additional competition experiments were conducted
with 8a and 8b, increasing the amount of one or the other to a
significant excess (entries 2 and 3). The ratios of products 9b/
9a shifted accordingly. When excess 8b was used (8b/8a, 5.8/
1
1
1
), the ratio increased to 94/6, whereas when excess 8a was
used (8b/8a, 1/5.0), the ratio decreased to 36/64. The
calculated relative reactivities of 8b/8a in these experiments
range from 2.3 to 2.8. In other words, pyridine-borane 8b is
approximately 2.5 times more reactive than NHC-borane 8a in
these Rh(II)-catalyzed B−H insertion reactions.
We next conducted competition experiments with the other
NHC-boranes, and Table 2 shows the results with equal
amounts (2 equiv each) of standard and unknown ligated
boranes. Experiments with other ratios gave the same relative
reactivities within approximately 25%. Trimethylamine-borane
1
11
13
1
in situ by H, B, and C{ H} NMR and HRMS. For example,
11
a triplet (JBH = 94 Hz) was observed at −28.3 ppm in the
B
1
NMR spectrum. The α-proton was observed in the H NMR
spectrum as a broad triplet (small coupling to the vicinal
protons on boron) at 3.15 ppm, while the α-carbon resonance
1
1
was a broad, weak quartet (coupled to B) at 44.4 ppm in the
C{ H} NMR spectrum. These features map well onto the
1
3
1
13
spectra of the ligated boranes 9a−e, which shows that 9f is an
α-cyanoborohydride ester, not an enol cyanoborohydride
isomer. Substituted borohydrides such as 9f could be used in
situ or perhaps purified by nonchromatographic means.
8
8
c proved to be about 3 times less reactive than NHC-borane
a (entry 4).
Competition Experiments. Previous work has shown that
NHC-borane 8a is approximately 10 times more reactive than
cyclohexadiene and roughly 100 times more reactive than THF
in competitive B−H versus C−H insertion reactions with
The phosphine-boranes 8d and 8e and tetrabutylammonium
cyanoborohydride 8f were less reactive still; therefore, we used
trimethylamine-borane 8c as the standard. The results of the
equimolar competition experiments with these boranes are
shown in entries 4−7, with the standard trimethylamine-borane
4
diazoacetate 7 and Rh (esp) . Preliminary experiments showed
2
2
that samples 8b−d were also more reactive than cyclo-
hexadiene; therefore, NHC-borane 8a was initially used as
the competitive standard. The results of the representative
competition experiments are shown in Table 2.
8c performing best in all cases. When corrected for the different
standards, the two phosphine-boranes are approximately 20
times less reactive than NHC-borane 8a, and the cyanobor-
ohydride is approximately 6 times less reactive than NHC-
borane 8a.
Figure 3 shows the approximate reactivity scale that emerges,
again relative to NHC-borane 8a. Here, the 1,3-cyclohexadiene
is added as a reference substrate with reactive C−H bonds
Table 2. Results of Competitive B−H Insertion Experiments
with Two Ligated Boranes (One Standard and One
Unknown), Diazoacetate 7 (1 equiv), and Rh (esp) (1 mol
2
2
%)
krel
standard
(stn)
equiv
unk/stn
(ukn/
stn)
a
entry unknown (ukn)
prods
ratio
1
2
3
4
5
6
7
pyr-BH 8b
NHC-
1.1/1.0
5.8/1.0
1.0/5.0
1.1/1.0
1.0/1.0
1.0/1.0
1.0/1.0
9b/9a
72/28
2.3
3
BH 8a
3
pyr-BH 8b
NHC-
9b/9a
9b/9a
9c/9a
9d/9c
9e/9c
9f/9c
94/6
2.7
3
BH 8a
3
pyr-BH 8b
NHC-
36/64
27/73
16/84
17/83
35/65
2.8
3
BH 8a
3
Me N-BH 8c
NHC-
0.33
0.19
0.20
0.54
3
3
BH 8a
3
b
b
Ph P-BH 8d
Me N-
3
3
3
BH 8c
3
Bu P-BH 8c
Me N-
3
3
3
BH 8c
3
Bu NBH CN
Me N-
4
3
3
8c
BH 8c
3
a
Determined by integration of the 11B NMR spectrum of the reaction
b
mixture. 4 mol % Rh (esp) was used to offset the traces of free
2
2
phosphine in 8d.
In a typical competition experiment, a solution of methyl 2-
diazo-2-phenylacetate diazoacetate 7 (0.2 mmol) in DCM was
added by syringe pump to a solution of Rh (esp) (4 μmol, 1
2
2
mol % relative to 8a), NHC-borane 8a (0.4 mmol), and pyr-
Figure 3. Approximate relative reactivities in insertion reactions
compared to NHC-borane 8a. Available BDEs and N-values are
provided for comparison: (a) B−H BDEs taken from ref 14 and the
CHD value taken from ref 15; (b) N-values taken from ref 16; and (c)
for Me P-BH .
BH 8b (0.44 mmol). Relative to the limiting diazo ester 7, the
3
mixture contains 2 equiv of 8a, 2.2 equiv of 8b, and 2% catalyst.
After 2 h, the reaction mixture was concentrated, and an 11
B
NMR spectrum was recorded. The relative ratio of the products
3
3
C
DOI: 10.1021/acs.joc.6b00091
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1H), 3.62 (s, 3H), 3.26 (s, 1H), 2.51 (s, 9H); 13C NMR (100 MHz,
because it is highly reactive compared to most other substrates
with C−H bonds. The range from the least reactive phosphine-
boranes to the most reactive pyridine-borane is a factor of
approximately 40. The least reactive phosphine-boranes are still
comparable to cyclohexadiene.
CDCl ) δ 178.5, 143.4, 129.1, 127.8, 124.9, 52.4, 51.2, 46.5 (weak);
3
11
B NMR (160 MHz, CDCl ) δ −1.5 (t, J = 99 Hz); IR (film) 3022,
3
BH
−
1
2
946, 2367, 2309, 1715, 1480, 1451, 1353, 1171 cm ; mp 95−97 °C;
+
HRMS (ESI) m/z (M ) calcd for C H O NBNa 244.1479, found
12 20
2
2
44.1476.
(2-Methoxy-2-oxo-1-phenylethyl)(triphenyl-λ -phosphanyl)-
dihydroborate 9d. Reaction of triphenylphosphine-borane (285.0 mg,
.00 mmol), Rh (esp) (32 mg, 0.04 mmol), and methyl 2-diazo-2-
Also shown in Figure 3 under the relative reactivities are both
4
14
the calculated B−H bond dissociation energies (BDEs) and
17
16
Mayr nucleophilicity scale (N-scale) values, where available.
BDE was selected because the B−H bond breaks in the
reaction, and N was selected because the TS is thought to have
1
2
2
phenylacetate (211.0 mg, 1.20 mmol) was conducted according to the
11
general procedure. An B NMR spectrum of the crude product
4
hydride transfer character. However, a quick glance suffices to
showed 71% conversion to the single-insertion product. The residue
show that neither of these sets of values correlates well with the
was purified by flash chromatography (hexane/ethyl acetate, 3/2) to
relative reactivity. In BDE, for example, Me N-BH (102.6 kcal
1
3
3
yield 211.0 mg (50%) of 9d as an orange solid: H NMR (400 MHz,
−
1
mol ) has a stronger B−H bond than R P-BH (92.8 kcal
3
3
CDCl ) δ 7.49−7.47 (m, 9H), 7.43−7.39 (m, 6H), 7.35−7.32 (m,
3
−1
mol ), but the amine-borane is more reactive. Likewise, the
NHC-borane 8a (N = 11.88) is a better hydride donor than
pyridine-borane 8b (N = 10.01), but pyridine-borane is more
2
H), 7.17−7.13 (m, 2H), 7.06−7.02 (m, 1H), 3.33 (s, 1H), 3.17 (s,
13
3H); C NMR (125 MHz, CDCl ) δ 178.8, 178.7, 144.4, 133.5,
131.3, 128.9, 127.8, 127.7, 127.4, 124.8, 50.5, 41.7 (weak); B NMR
3
1
1
1
8
reactive. Steric and other factors may also play a role in these
reactions. Trends aside, the overarching conclusion is that all
these B−H bonds are highly reactive in Rh(II)-catalyzed
insertion reactions.
(160 MHz, CDCl ) δ −23.4 (br); IR (film) 3058, 3023, 2946, 2375,
3
−
1
1720, 1484, 1436, 1136 cm ; mp 110−115 °C; HRMS (ESI) m/z
+
(M ) calcd for C27
2-Methoxy-2-oxo-1-phenylethyl)(tributyl-λ -phosphanyl)-
dihydroborate 9e. Reaction of tributylphosphine-borane (216.0 mg,
.00 mmol), Rh (esp) (32 mg, 0.04 mmol), and methyl 2-diazo-2-
H O BNaP 447.1656, found 447.1646.
26 2
4
(
1
CONCLUSIONS
Representative ligated boranes L-BH , where L is either NHC,
2
2
■
phenylacetate (211.0 mg, 1.20 mmol) was conducted according to the
3
11
general procedure. An B NMR spectrum of the crude product
amine, or phosphine, have been made, and their reactivities
have been studied in Rh(II)-catalyzed B−H insertion reactions
with methyl 2-phenyl-2-diazoacetate 7. Stable α-boryl ester
products 9a−e were formed in all cases and could be isolated
showed 86% conversion to the desired single-insertion product. The
residue was purified by flash chromatography (hexane/acetone, 30/1)
1
to yield 110.0 mg (30%, 97% purity) of 9e as an orange oil: H NMR
(
500 MHz, CDCl ) δ 7.43−7.41 (m, 2H), 7.23−7.20 (m, 2H), 7.32−
3
by flash chromatography. Reaction with Bu NBH CN also gave
4
3
7.35 (m, 2H), 7.10−7.07 (m, 1H), 3.62 (s, 1H), 3.21−3.16 (m, 1H),
13
stable α-borohydride ester 9f, though the product is a salt that
did not emerge from flash chromatography. All of the substrates
were either comparable to or more reactive than 1,4-
cyclohexadiene, which is one of the most reactive substrates
in C−H insertion reactions. The range of reactivity between the
most reactive pyridine-borane and the least reactive phosphine-
borane was a factor of approximately 40.
1.43−1.29 (m, 20H), 0.88 (t, J = 7 Hz, 9H); C NMR (125 MHz,
CDCl ) δ 179.3, 179.2, 144.4, 144.4, 128.7, 127.6, 124.8, 51.0, 41.9,
3
11
24.6, 24.3, 24.2, 20.7, 20.5, 13.4; B NMR (160 MHz, CDCl ) δ
3
−25.8 (br); IR (film) 2957, 2932, 2871, 2356, 1719, 1494, 1276, 1014,
−1
+
700 cm ; HRMS (ESI) m/z (M ) calcd for C21H O BP 365.2775,
39 2
found 365.2779.
Tetrabutylammonium Cyano(2-methoxy-2-oxo-1-phenylethyl)-
dihydroborate 9f. Tetrabutylammonium cyanoborohydride (283.0
mg, 1.00 mmol) and Rh (esp) (7.9 mg, 0.01 mmol) were dissolved in
EXPERIMENTAL SECTION
2
2
■
dry CH Cl (2 mL) under argon. A solution of methyl 2-diazo-2-
2
2
General Procedure for the Synthesis of Reference Samples
4
phenylacetate (211.0 mg, 1.20 mmol) in CH Cl (2 mL) was added
2 2
of Products. (2-Methoxy-2-oxo-1-phenylethyl)(1λ -pyridin-1-yl)-
via syringe pump over 2 h. The reaction mixture color transitioned
from light blue to pink. An 11B NMR spectrum of the crude product
showed 86% conversion to the single-insertion product and 14%
conversion to the double-insertion product. Isolation of pure insertion
dihydroborate 9b. Pyridine-borane (93.0 mg, 1.00 mmol, 1.0 equiv)
and Rh (esp) (7.9 mg, 0.01 mmol, 1 mol %) were dissolved in dry
2
2
CH Cl2 (5 mL) under argon. A solution of methyl 2-diazo-2-
2
phenylacetate (211.0 mg, 1.20 mmol, 1.2 equiv) in dry CH Cl (5 mL)
2
2
was added via syringe pump over a period of 2 h. The solution color
transitioned from light green to orange. An 11B NMR spectrum of the
crude product showed 79% conversion to the single-insertion product.
The reaction mixture was concentrated under vacuum and purified by
product 9f by flash chromatography failed, presumably because the
1
product is a salt: H NMR (400 MHz, CDCl ) δ 7.43−7.45 (m, 2H),
3
7.13−7.17 (m, 2H), 6.98−7.03 (m, 1H), 3.57 (s, 3H), 3.16 (br, 1H),
3.00−3.04 (m, 8H), 1.46−1.54 (m, 8H), 1.33−1.38 (m, 8H), 0.97 (t, J
=
7 Hz, 12H); 13C NMR (100 MHz, CDCl ) δ 180.1, 146.4, 129.2,
flash chromatography (hexane/ethyl acetate, 1/1) to yield 189.4 mg
3
1
(
79%) of 9b as a colorless oil: H NMR (400 MHz, CDCl ) δ 8.21−
11
3
128.7, 123.7, 58.4, 50.4, 44.7 (weak), 23.8, 19.6, 13.6; B NMR (160
MHz, CDCl ) δ −27.2 (t, J = 94 Hz); HRMS (ESI) m/z (M ) calcd
for C H O NB 188.0877, found 188.0881.
8
1
1
(
(
.20 (m, 2H), 7.95−7.91 (m, 1H), 7.43−7.39 (m, 2H), 7.17−7.11 (m,
+
H), 3.60 (s, 3H), 3.40 (s, 1H); 13C NMR (100 MHz, CDCl ) δ
3
BH
3
10
11
2
78.1, 147.4, 142.5, 140.0, 127.8, 127.7, 124.8, 124.3, 50.8, 48.8
Typical Procedure for the Competitive Insertions between
weak); 11B NMR (128 MHz, CDCl ) δ −2.8 (t, J = 101 Hz); IR
1
2
3
BH
L -BH (Unknown) and L -BH (Standard) (Taken from Table 1,
3
3
neat) 3059, 3022, 2947, 2393, 2340, 1710, 1622, 1599, 1458, 1362
Entry 1). Pyridine-borane 8b (34.5 mg, 0.4 mmol, 2.0 equiv) and
NHC-borane 8a (41.2 mg, 0.4 mmol, 2.0 equiv) were dissolved in dry
−1
+
cm ; HRMS (ESI) m/z (M ) calcd for C H O NBNa 264.1166,
14
16
2
found 264.1164.
11
CH Cl (1 mL) under argon. An B NMR spectrum of the reaction
4
2
2
(
2-Methoxy-2-oxo-1-phenylethyl)(trimethyl-λ -azanyl)-
mixture was obtained prior to addition of the diazo substrate and
catalyst to determine the initial 11B NMR integration of both borane
species. After addition of Rh (esp) (2.8 mg, 0.02 mol %), a solution of
dihydroborate 9c. Reaction of trimethylamine-borane (75.0 mg, 1.00
mmol), Rh (esp)2 (7.9 mg, 0.01 mmol), and methyl 2-diazo-2-
2
phenylacetate (211.0 mg, 1.20 mmol) was conducted according to the
2
2
general procedure. An 11B NMR spectrum of the crude product
methyl 2-diazo-2-phenylacetate diazoacetate (38.5 mg, 0.2 mmol, 1.0
equiv) in CH Cl (1 mL) was added by syringe pump to the reaction
showed 72% conversion to the single-insertion product. The residue
2
2
was purified by flash chromatography (hexane/ethyl acetate, 1/1) to
solution. After 2 h, the reaction mixture was concentrated under
1
11
yield 95.0 mg (43%) of 9c as a white solid: H NMR (400 MHz,
vacuum, and an B NMR spectrum of the residue was recorded and
CDCl ) δ 7.45−7.43 (m, 2H), 7.26−7.22 (m, 2H), 7.12−7.09 (m,
integrated.
3
D
DOI: 10.1021/acs.joc.6b00091
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b00091.
■
*
S
General information and copies of spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
E-mail: curran@pitt.edu.
■
*
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the National Science Foundation for funding.
■
REFERENCES
■
(
2
1) (a) Cowden, C. J.; Paterson, I. Org. React. (N.Y.) 1997, 51, 1−
00. (b) Kim, B. M.; Williams, S. F.; Masamune, S. Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press:
Oxford, 1991; Vol. 2, p 239.
(
1
(
2) He, Z.; Zajdlik, A.; Yudin, A. K. Dalton Trans. 2014, 43, 11434−
1451.
3) Trinchera, P.; Corless, V. B.; Yudin, A. K. Angew. Chem., Int. Ed.
2
(
(
(
015, 54, 9038−9041.
4) Li, X.; Curran, D. P. J. Am. Chem. Soc. 2013, 135, 12076−12081.
5) Fiori, K. W.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562−568.
6) Cheng, Q. Q.; Zhu, S. F.; Zhang, Y. Z.; Xie, X. L.; Zhou, Q. L. J.
Am. Chem. Soc. 2013, 135, 14094−14097.
7) Chen, D.; Zhang, X.; Qi, W.-Y.; Xu, B.; Xu, M.-H. J. Am. Chem.
Soc. 2015, 137, 5268−5271.
8) Li, X. Ph.D. Thesis, University of Pittsburgh, Pittsburgh, PA,
014. http://d-scholarship.pitt.edu/20815/.
9) Davies, H. M. L.; Pelphrey, P. M. Org. React. (N.Y.) 2011, 75,
5−212.
10) Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. Am. Chem. Soc.
000, 122, 3063−3070.
11) The two phosphine-boranes have also been made by copper-
catalyzed insertion reactions (see reference 6).
12) There was a small triplet at −22.4 ppm in the 11B NMR
spectrum that might be from the target borohydride insertion product.
13) There should be an even weaker septet due to coupling with
(
(
2
(
7
(
2
(
(
(
1
0
B, but this was not visible.
(
(
14) Rablen, P. R. J. Am. Chem. Soc. 1997, 119, 8350−8360.
15) Agapito, F.; Nunes, P. M.; Costa Cabral, B. J.; Borges dos
Santos, R. M.; Martinho Simo
223.
16) (a) Funke, M.A.; Mayr, H. Chem. - Eur. J. 1997, 3, 1214−1222.
b) Horn, M.; Mayr, H.; Lacote, E.; Merling, E.; Deaner, J.; Wells, S.;
McFadden, T.; Curran, D. P. Org. Lett. 2012, 14, 82−85.
17) (a) Mayr, H.; Patz, M. Angew. Chem., Int. Ed. Engl. 1994, 33,
̃
es, J. A. J. Org. Chem. 2008, 73, 6213−
6
(
(
̂
(
9
5
38−957. (b) Mayr, H.; Ofial, A. R. J. Phys. Org. Chem. 2008, 21, 584−
95.
(
18) For example, a reaction of 7 with the hindered 1,3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidene borane under these conditions
did not provide the corresponding insertion product.
E
DOI: 10.1021/acs.joc.6b00091
J. Org. Chem. XXXX, XXX, XXX−XXX