Ketone Synthesis from Benzyldiboronates and Esters: Leveraging α-Boryl Carbanions for Carbon-Carbon Bond Formation

Article abstract of DOI:10.1021/jacs.9b11944

An alkoxide-promoted method for the synthesis of ketones from readily available esters and benzyldiboronates is described. The synthetic method is compatible with a host of sterically differentiated alkyl groups, alkenes, acidic protons α to carbonyl groups, tertiary amides, and aryl rings having common organic functional groups. With esters bearing α-stereocenters, high enantiomeric excess was maintained during ketone formation, establishing minimal competing racemization by deprotonation. Monitoring the reaction between benzyldiboronate and LiO^tBu in THF at 23 °C allowed for the identification of products arising from deborylation to form an α-boryl carbanion, deprotonation, and alkoxide addition to form an "-ate" complex. Addition of 4-trifluoromethylbenzoate to this mixture established the α-boryl carbanion as the intermediate responsible for C-C bond formation and ultimately ketone synthesis. Elucidation of the role of this intermediate leveraged additional bond-forming chemistry and enabled the one-pot synthesis of ketones with α-halogen atoms and quaternary centers with four-different carbon substituents.

Full text of DOI:10.1021/jacs.9b11944

Subscriber access provided by Imperial College London | Library
Article
Ketone Synthesis from Benzyldiboronates and Esters: Leveraging
#-Borylcarbanions for Carbon-Carbon Bond Formation
Boran Lee, and Paul J. Chirik
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b11944 • Publication Date (Web): 14 Jan 2020
Downloaded from pubs.acs.org on January 15, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 11
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Ketone Synthesis from Benzyldiboronates and Esters: Lever-
aging α-Boryl Carbanions for Carbon-Carbon Bond Formation
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Boran Lee and Paul J. Chirik*
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States
ABSTRACT: An alkoxide-promoted method for the synthesis of ketones from readily available esters and benzyldiboronates is described.
The synthetic method is compatible with a host of sterically differentiated alkyl groups, alkenes, acidic protons α to carbonyl groups, tertiary
amides and aryl rings having common organic functional groups. With esters bearing α-stereocenters, high enantiomeric excess was main-
tained during ketone formation, establishing minimal competing racemization by deprotonation. Monitoring the reaction between benzyldi-
boronate and LiOtBu in THF at 23 ºC allowed for the identification of products arising from deborylation to form an α-boryl carbanion,
deprotonation, and alkoxide addition to form an “-ate” complex. Addition of 4-trifluoromethylbenzoate to this mixture established the α-
boryl carbanion as the intermediate responsible for C–C bond formation and ultimately ketone synthesis. Elucidation of the role of this in-
termediate leveraged additional bond-forming chemistry and enabled the one-pot synthesis of ketones with α-halogen atoms and quaternary
centers with four-different carbon substituents.
Introduction. Methods for the construction of carbon–carbon
bonds that rely on common functional groups and readily available
reagents are attractive. Organoboronates have been classified as
synthetic lynchpins owing to their versatile and broad reactivity
coupled with their straightforward preparation and relative ease of
handling.1 Geminal polyboronates, compounds bearing two or
three borons on the same carbon atom, are emerging as a particu-
larly interesting and distinct class of organoboron compounds due
to their ability to promote unique C–C or C–heteroatom bond
formations,2 motivating additional studies to their applications in
synthesis. Introduction of additional boron substituents on a car-
bon atom enhances the reactivity of the existing C–B bond through
distinct activation modes.3 The empty p-orbital on boron stabilizes
adjacent carbanions, facilitating deprotonation of the α-C–H bond
under mild conditions, opening pathways to C–C bond formation
(Scheme 1, Path I).4 Alternatively, the inherent electrophilicity of
boron also promotes formation of borate complexes3a,4a and subse-
quent deborylation provides access to synthetically versatile α-boryl
carbanions (Scheme 1, Path II).5
Because of their potential value in synthesis, there has been in-
creased emphasis on the development of reliable and straightfor-
ward methods for the preparation of gem-polyboronates including:
the hydroboration of alkynes6 and borylalkenes,3b,7 diboration of
carbonyls,8 carbamates,9 N-tosylhydrazones,10 and diazo com-
pounds,5a,11 diborylation of dihalides,12 and diborylation by transi-
tion-metal-catalyzed C(sp3)–H functionalization.13 For the C–H
functionalization route, our group reported that α-diimine sup-
ported cobalt13d and nickel13e complexes promote the C(sp3)–H di-
and triborylation of alkyl arenes. Borylation of the benzylic C(sp3)–
H bond was predominant in most cases but chain running to re-
mote positions along the alkyl chain was also observed broadening
the scope of the method to functionalization of less activated posi-
tions.
Ketones are a particularly valuable class of compounds and
methods for their preparation have been of interest to chemists for
over a century. Classical methods rely on 1) addition of strong
nucleophiles such as Grignard or alkyl lithium reagents to Weinreb
amides14 and 2) reaction of lithiated dithianes with electrophiles.15
However, these approaches often require additional steps to pre-
pare reagents and can be limited by scope of the reaction owing to
the reliance on reactive organometallics.16 The discovery of meth-
ods that rely on milder conditions or reagents to expand the scope
of the reaction continues to be an area of ongoing effort.17 Early
examples with transition metals include hydroacylation of alkenes18
and carbonylative coupling between aryl halides and carbon nucle-
ophiles.19 Most recently, photoredox20 and electrochemical meth-
ods21 have been reported that exploit generation of radical interme-
diates under mild conditions.
Scheme 1. Activation of gem-Diboronates.
The increased availability of polyboronates has accelerated in-
terest in their synthetic application, including in the synthesis of
ACS Paragon Plus Environment

Journal of the American Chemical Society
ketones. Matteson pioneered the application of gem-diboronates to
Page 2 of 11
1
2
3
4
5
6
7
8
the synthesis of carbonyl compounds by generation of α,α-diboryl
carbanions from treatment with a base such as LiTMP (lithium
tetramethylpiperidide) and addition to alkyl halides and esters.4c
Pattison expanded this chemistry by trapping boron enolate inter-
mediates with electrophiles, substituting the two C–B bonds with
two new C–C or C–X (X = halogen) bonds (Scheme 2A, Path I).22
Mukaiyama has demonstrated that MeLi promotes the reaction
between gem-diborylalkanes and esters by forming the reactive α-
boryl carbanions through deborylation.23 Subsequently, Liu and
coworkers extended this activation mode to the transformation of
carboxylic acids to ketones but harsh conditions (8 hours at 100 ºC)
were required (Scheme 2A, Path II).24 gem-Diboronates have also
been effective substrates for the synthesis of aldehydes through
palladium cross coupling with aryl halides using DMF as the car-
bonyl source.25
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In our initial report of conjugate addition with benzyldiboro-
nates,13e an α,β-unsaturated ketone was identified as a minor prod-
uct following the LiTMP-promoted addition of methyl tiglate
(Scheme 2B). Identification of this product suggested that poly-
boron compounds may serve as versatile and straightforward pro-
nucleophiles for the synthesis of ketones from readily available
esters. The utility of the benzyltriboronates in a highly diastereose-
lective deborylative conjugate addition was demonstrated with the
stereoselectivity likely derived from formation of a six-membered
cyclic borate intermediate (Scheme 1B).13e These initial results
demonstrated that new C–C bond-forming chemistry was available
from polyboronates and inspired additional studies to expand their
role in organic synthesis. Here we describe realization of a versatile
and general method for the synthesis of ketones from esters, ter-
tiary amides, and carbonates using benzyldiboronates prepared
from C(sp3)–H borylation. NMR spectroscopic studies support
formation of an α-boryl carbanion, formed from the release of RO–
BPin, as the reactive intermediate that is responsible for C–C bond
formation with the carbonyl partner. With this mechanistic infor-
mation in hand, three methods for the preparation of functional-
ized ketones were explored where the substitution pattern of the
carbonyl product was controlled by changing the electrophile, start-
ing material, and additional quenching reagent of an alkylation step.
Scheme 2. Conversion of 1,1-Diboronate Esters into
Functionalized Ketones.
Results and Discussion.
Reaction Scope. Our study commenced with examination of
the reactivity of benzyldiboronate 1 with methyl butyrate. In the
presence of 1.5 equivalents of LiOtBu (lithium tert-butoxide) in
THF at 23 ºC, ketone, 3a was obtained in 86% yield. Compared to
previous reports where an excess of alkyldiboronates were re-
quired,22,24 this procedure was effective with a single equivalent of 1.
These initial conditions were found to be optimal as changing the
amount or identity of the base or reaction medium was deleterious
for the overall yield (Table S1).
Attention was devoted to the scope of the ketone synthesis by
alkoxide-promoted deborylative addition of benzyldiboronates to
esters (Tables 1 and 2). The procedure proved tolerant to a range
of sterically differentiated substituents on the ester as the high yield
of 3a was maintained with methyl, ethyl, and even tert-butyl butyr-
ate. Esters with larger substituents on the α-carbon were also well
tolerated with no measurable erosion of yield or discernable change
in efficiency. (3b-3d). Methyl pivalate produced 3d in slightly
higher yield compared to smaller esters (3a–3c) despite the pres-
ence of a tert-butyl substituent, presumably due to the absence of α-
ACS Paragon Plus Environment

Page 3 of 11
Journal of the American Chemical Society
protons on the carbonyl. In spite of the basicity of presumed inter-
mediates, substrates bearing acidic protons were also well tolerated
as esters containing an allylic proton (3e), a benzylic proton (3f),
and α-protons adjacent to nitrogen (3n and 3o) produced the
corresponding ketone in high yield (80-90%).
1
2
3
4
5
6
7
8
To further explore the possibility of competing deprotonation,
the compatibility of the reaction with enantioenriched esters was
examined. Synthesis of 3g, 3n and 3o was achieved with little ero-
sion in enantiomeric excess. This observation provides support for
the intermediacy of boron enolates, which effectively mask the
ketone products under the basic reaction conditions and render the
α-protons less acidic, thereby minimizing racemization during the
reaction.26 Likewise, the silyl-protected alcohol, 3g was compatible
with the reaction conditions and deprotected to yield a free hy-
droxyl group (3h). Esters with electron-donating aryl rings (3j),
electron-withdrawing groups (3k and 3m), and boron (3l) sub-
stituents also generated the desired ketones in moderate to high
yields (74-96%). With N-Boc-Pro-OMe and a dipeptide, C–C
bond formation was observed selectively at the most electrophilic
site, generating 3n and 3o, respectively. Finally, the transformation
was also effective in the presence of heteroaromatic rings such as
furan (3p) and pyridine (3q). In the case of 3q, both ester groups
were converted to ketones in a single step in high isolated yield
(94%).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Examination of the scope of ester partners.
Isolated yields are given. Conditions: 1 (1 equiv.), ester (1 equiv.),
LiOtBu (1.5 equiv.), THF (0.05 M with respect to 1), 23 ºC, 3 h. aEthyl
b
butyrate was used instead of methyl butyrate. tert-Butyl butyrate was
c
used instead of methyl butyrate. Enantiopurity of the corresponding
esters was >99% ee. Due to the non-polarity of 3g, ee determination of
3g was not successful. dConditions: 3g (1 equiv.), TBAF (tetrabu-
tylammonium fluoride) solution (1 M in THF, 1 equiv.), 0 ºC, 1 h.
eConditions:
1 (2 equiv.), dimethyl 2,6-pyridinedicarboxylate (1
equiv.), LiOtBu (2 equiv.), THF (0.05 M with respect to 1), 23 ºC, 3 h.
The scope of the benzyldiboronate partner on ketone synthesis
was also evaluated (Table 2). Methyl butyrate and methyl 4-
(trifluoromethyl)benzoate were selected as representative alkyl-
and aryl-substituted esters, respectively. Independent of electron-
donating (3r, 3t, 3w, 3x, 3z, and 3ac) or electron-neutral (3s and
3y) substituents at para- or meta-position, all diboryl reagents un-
derwent coupling with esters to produce the desired ketones in
high yields. Trimethylsilyl (3u and 3aa) and pinacol boronate
groups (3v and 3ab) were also well tolerated. Also, excellent yield
was obtained with 3-thienyl substituted substrate (3ad), showing
the possibility that this transformation can be extended to het-
eroaryl-substituted gem-diboronates.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 11
Table 2. Scope of benzyldiboronates.
characterized by NMR spectroscopy and applied in a host of syn-
thetic chemistries.29 Related “-ate” complexes and deborylated
compounds have also been generated from alkyl gem-diboronates
and identified by NMR spectroscopy.3a,4a,5b By contrast, few studies
have been conducted on the interaction of benzyldiboronates with
the bases used in this study.
1
2
3
4
5
6
7
8
9
Initial experiments were conducted in the absence of ester to ex-
plore the nature of the nucleophile generated from interaction of
the benzyldiboronate with the base. Figure 1A illustrates three
possible reactive species (6-8) and two boron-containing side
products (9 and 10) from the reaction of 1 and alkoxide base.
Monitoring the reaction mixture after the addition of 1.5 equiva-
lents of LiOtBu to a THF-d8 solution of 1 by both 1H and 11B NMR
spectroscopies revealed formation of three boron-containing prod-
ucts (Figure 1B and 1C), one of which was transient, persisting on
the order of one hour at 23 ºC.30 Independent syntheses and addi-
tional spectroscopic measurements were conducted to identify
each of the components formed.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Generation of 8 as the sole product was first explored. Treat-
ment of benzylmonoboronate 5 with LiTMP generated the same
1H NMR resonances as the transient intermediate confirming the
identity of this species as the α-boryl carbanion product, 8 arising
from deborylation.31 Sharp resonances at 21 and 5 ppm in 11B NMR
Isolated yields are given. Conditions: diboronate (1 equiv.), ester (1
equiv.), LiOtBu (1.5 equiv.), THF (0.05 M with respect to diboro-
nate), 23 ºC, 3 h.
Carbonyl compounds less electrophilic than esters were also ex-
amined as substrates for ketones synthesis. As illustrated in Scheme
3, tertiary amides were effective coupling partners with benzyldi-
boronate 1 as ketone 3ae was obtained in excellent yield. With
diethyl carbonate, a mixture of two products, 3f and 3af was ob-
tained when one equivalent of 1 was added with respect to car-
bonate.27 Poor selectivity was observed when one equivalent of 1
was used but using two equivalents of the diboronate produced 3f
as a sole product. Conversions of carbamate (N-Boc-pyrrolidine)
and urea (N,N,N’,N’-tetramethylurea) were also attempted, but no
reaction was observed.
spectrum support the formation of
9 and 10, arising from
deborylation and subsequent tert-butoxide association (Figure
1C).4a The lithiated benzyldiboronate 6 was synthesized by addi-
1
tion of LiTMP to 1 (see Figure S28 and S30 for H and 11B NMR
spectra of 6) and was identified as the major (42%) component of
the mixture.32 1H–13C HMBC correlations on the other major
product, accounting for approximately 39% of the mixture, were
consistent with the lithium “-ate” complex, 7 arising from addition
1
of the alkoxide base (see Figure S19). A H resonance at 7.08 ppm,
which corresponds to the ortho-Ar–H of 7, displays an HMBC
correlation to a 13C resonance at 36 ppm from either -BPin or -
OtBu. This 13C resonance also has a HMBC correlation to a 1H
resonance at 1.11 ppm. The resonance at 8 ppm in 11B NMR spec-
trum reveals another tetracoordinate boron complex is formed,
assigned as 7. In order to determine the fate of the transient species
8, the experiment was repeated in the presence of N,N-dimethyl-
para-toluidine as an internal standard. Monitoring by NMR spec-
troscopy demonstrated that 8 was converted into 6 (43%) and 7
(50%) over the course of 1 hour, and the ratio was constant over
the course of 24 hours.
Scheme 3. Scope of Carbonyl Coupling Partners.
The α-boryl carbanion 8 proved stable over 24 hours following
preparation by deprotonation of 5 with LiTMP (i.e. under alkox-
ide-free condition). To probe the interconversion between three
t
intermediates 6, 7, and 8, one equivalent of BuO–BPin was added
to the solution of 8. Within 30 minutes, complete consumption of
8 and formation of 6 and 7 were observed in a 1:0.7 ratio (Figure
S33–S35). To demonstrate the equilibrium between 6-8, 1 was
treated with LiTMP to generate α,α-diboryl carbanion 6, followed
Isolated yields are reported. Conditions: 1 (1 equiv.), LiOtBu (1.5
equiv.), carbonyl derivatives (1 equiv.), THF (0.05M with respect to
1
b
by subsequent addition of one equivalent of tert-butanol. The H
1), 23 ºC, 3 h. Only protodeboronated product 5 was observed in the
and 11B NMR spectra were then recorded over the course of one
NMR spectrum of the unpurified product.
t
hour. Upon addition of BuOH, conversion of 6 to a mixture of 7
Mechanistic Studies. To detect potential intermediates and
to gain insight into the preferred reaction pathway, the C–C bond-
forming reaction was monitored by 1H, 11B, 1H–13C HSQC and
HMBC NMR spectroscopies. The interaction of alkyl-substituted
gem-diboronates with bulky amide bases has been studied by Cho
and coworkers and the corresponding lithiated products have been
and 8 was observed initially (5 min) with 8 disappearing over the
course of 30 minutes, leaving 1:0.6 mixture of 6 and 7 along with
small amount of unidentified impurities (Figure S36–S38). Based
on these observations, 6, 7, and 8 interconvert and in the presence
of alkoxides, the equilibrium shifted toward 6 and 7 with only trace
amount of 8.
ACS Paragon Plus Environment

Page 5 of 11
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Figure 1. In situ monitoring of the treatment of benzyldiboronate 1 with LiOtBu in THF-d8 by 1H and 11B NMR spectroscopies.
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Having identified each product from the interaction of 1 with
LiOtBu, two distinct mechanisms based on the observed reaction
intermediates are proposed in Scheme 4. By a deprotonative path-
way (top line), an α,α-diboryl ketone is generated, which is in equi-
librium with O-bound boron enolate, 11. In the bottom case, 12
arises from a deborylative pathway (from 7 or 8). Alternatively, 12
can be obtained from the protodeboronation of 11 in the presence
of alkoxide base or tert-butanol. As a vinyl C–H of 12 can be used
as the NMR handle to probe which intermediate is formed during
the C–C bond-forming reaction and to distinguish which path is
operative, additional NMR experiments were performed in the
presence of a representative ester to determine the relative reactivi-
ty of each intermediate towards C–C bond and ultimately ketone
formation.
Scheme 4. Possible Mechanisms for C–C Bond Formation.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 11
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 2. (A) Reactions between activated benzyldiboronates and an ester and (B) 1H NMR spectrum of each reaction.
Under standard reaction conditions (e.g. treatment of 1 with 1.5
equivalents of LiOtBu in the presence of methyl 4-
(trifluoromethyl)benzoate, , the H NMR spectrum recorded after
To evaluate the reactivity of 7, 1 was treated with LiOtBu for one
hour prior to the addition of the ester and the resulting reaction
1
1
was monitored by H NMR spectroscopy (Figure 2, iv). Because 8
three hours established complete consumption of the esters with
concomitant formation of new resonances (Figure 2, i). A diagnos-
tic signal was observed at ꢀ = 5.83 ppm assigned to a vinylic proton,
supporting the formation of 12 through either a deborylative
pathway or a deprotonative coupling followed by protodeborona-
tion of 11. When 8 was generated by addition of LiTMP to 5 and
subsequently treated with the ester, an identical 1H NMR spectrum
was obtained as shown in Figure 2B, ii. However, the 1H NMR
spectrum obtained from deprotonation of 1 with LiTMP followed
by addition of ester produced a different product, 11 (Figure 2, iii).
The observation of broad peaks at 22 and 31 ppm in the 11B NMR
spectrum revealed a tricoordinate boron attached to C and that
attached to O, supporting the presence of 11 (Figure S55). Treat-
ment of 1 equivalent of LiOtBu to this reaction mixture did not
was unstable and disappeared within 60 minutes at ambient tem-
perature, only 6 and 7 existed at the time of ester addition. After 3
hours, 6, 7 and the ester were consumed, and new peaks corre-
spond to 11 (<27%), tert-butyl 4-(trifluoromethyl)benzoate (50%)
and unidentified byproducts appeared. This observation indicates
that 7 is unreactive toward deborylative addition to esters and de-
composes to byproducts. Also, a series of experiments was con-
ducted whereby LiOtBu was added to 1 and the injection time of
the ester was varied between 5, 15 and 60 minutes. The resulting
reactions were monitored by 1H NMR spectroscopy three hours
later after the ester addition. At longer time interval between addi-
tions, where the unstable α-boryl carbanion 8 is converted to 6 and
7 and exist at low concentration, the intensity of the diagnostic
vinylic proton resonance diminished (Figure S57). This is con-
sistent with the hypothesis that 8 is responsible for C–C bond for-
mation resulting in the boron enolate 12.
1
induce a significant change in H NMR spectrum, eliminating the
possibility that 11 is converted to 12 by alkoxide-promoted proto-
deboronation (Figure S56). To examine the possibility of deproto-
native pathway followed by protodeboronation induced by tert-
butanol generated from the initial deprotonation step, a crossover
experiment was designed. Mixture of the isotopologue of 1 with
aryl and benzylic C–D bonds and p-methoxybenzyl diboronate was
subjected to the reaction conditions and the isotopic incorporation
at the benzylic position of each ketone product was determined.
Scrambling of the hydrogen isotopes was not observed ruling out
A control experiment was performed where α-boryl carbanion 8
was alternatively prepared by deprotonation of benzylmonoboro-
nate 5 and treated with an ester (Scheme 5). Although α-C–H
bonds of alkylmonoboronates are typically not acidic enough to be
deprotonated by amide bases, stabilizing effect of the additional
phenyl group enables deprotonation of 54c,33 and the subsequent
addition of methyl butyrate affords 3a in 74% yield. Attempts to
extend the methodology to alkyl gem-diboronates were unsuccess-
ful. Subsequent NMR studies established that addition of LiOtBu
to the solution of alkyldiboronate produced no detectable change,
in contrast to the benzyldiboronate case (see Figure S69). These
t
protodeboronation of 11 induced by BuOH (see Supporting In-
formation for details).
ACS Paragon Plus Environment

Page 7 of 11
Journal of the American Chemical Society
fingdings suggest that the presence of functional groups capable of A third transformation involving deborylative addition of inter-
1
2
3
4
5
6
7
8
stabilizing the carbanion arising from deborylation is crucial. To
test the hypothesis, an alkyltriboronate (having an additional boryl
group) and an allyldiboronate (having a C=C bond) were exam-
ined and the corresponding ketone products were formed, albeit in
lower yields (54% and 41% yield, respectively, see Supporting In-
formation for details).
nal diboronates to an ester followed by trapping with an electro-
phile was also demonstrated (Scheme 6, Method C). The internal
benzyldiboronate 16 was synthesized by selective Ni-catalyzed
diborylation of benzylic C(sp3)–H bonds of pentylbenzene.13e De-
spite the increased steric hindrance at α-carbon, 16 still proved to
be a suitable reagent for deborylative addition to esters followed by
electrophile trapping, yielding 17a–17c with good efficiency (62-
73%). The results in Scheme 6 highlight the versatility of this trans-
formation in that new bonds were selectively formed in a predicta-
ble manner without waste of any C–B bond and in the case of
Method B, three different functional groups were introduced from
two identical C–B bonds.
Scheme 5. Generation of α-Boryl Carbanion 8 and the
Subsequent Coupling Reaction.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 6. One-Pot Synthesis of Highly Substituted
Ketones from Benzyldiboronates.
Isolated yields are given. Conditions: 5 (1 equiv.), LiTMP (1
equiv.), THF (0.05 M with respect to 1), 0 ºC, 30 min, then methyl
butyrate (1 equiv.), rt, 3 h. See Table 1 for the reaction from 1.
Insights into the reaction mechanism and identification of a bo-
ron enolate inspired expansion of the method to leverage the utility
of this intermediate in ketone synthesis. As summarized in Scheme
6, three different approaches were explored. The first involved
coupling the C–C bond-forming event to an additional C–E bond-
forming reaction enabled by quenching the boron enolate interme-
diate with a reagent other than a proton source (Scheme 6, Method
A). As demonstrated previously,13e,22,24 alkyl electrophiles such as
iodomethane (13a), propargyl bromide (13b), and Eschen-
moser’s salt (13c) were successfully employed to yield ketones
14a, 14b, and 14c, respectively. Attempts to prepare the β-
aminoketone, expected from a Mannich-type reaction product
between boron enolate intermediate and 13c was unsuccessful but
intriguingly, the fully conjugated ketone, 14c was obtained as the
sole product following loss of dimethylamine. Incorporation of
fluorine and bromine was achieved using NBS (N-
bromosuccinimide, 13d) and NFSI (N-fluorobenzenesulfonimide,
13e) as the electrophile (14d–14g). In the case of the bromina-
tion reaction, introduction of the first halogen increases the acidity
of the α-proton such that tert-butoxide or methoxide (liberated
from the ester), promotes deprotonation and resulted in isolation
of the doubly brominated ketone (14f). Increasing the amount of
NBS in the reaction improved the yield of 14f. Thiophene-
substituted diboronate also afforded the corresponding α-
fluoroketone in good yield (14g, 83%).
The boron enolate intermediate was utilized for the synthesis of
quaternary centers with four different substituents. Given that the
deborylative activation mode does not require terminal C–H bonds
of the diboronate substrates, attempts were made to conduct these
transformations with internal diboronates. These substrates were
generated in situ by deprotonative alkylation of terminal benzyldi-
boronates and used directly in the subsequent coupling procedure
with esters followed by trapping with the electrophile (Scheme 6,
Method B). Fluorinated and allylated ketones 15a and 15b were
obtained in 83 and 75% yield, respectively using this approach from
a one-pot conversion from 1. The tetramethylpiperidine byproduct
formed from the LiTMP base had no discernable influence on the
outcome of the reaction.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 11
ed to tertiary amides and carbonates. NMR spectroscopic studies
1
2
3
4
5
6
support the formation of an α-boryl carbanion through an alkoxide-
mediated deborylative pathway that in turn serves as a reactive
intermediate for C–C bond formation and ultimately ketone syn-
thesis. Based on these findings, three methods to synthesize ke-
tones bearing tertiary and quaternary carbon centers were demon-
strated.
7
8
ASSOCIATED CONTENT
9
Supporting Information
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The Supporting Information is available free of charge via the internet
at http://pubs.acs.org.
Experimental details; characterization data including NMR spectra of
compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
* pchirik@princeton.edu
ORCID
Paul J. Chirik: 0000-0001-8473-2898
Boran Lee: 0000-0001-6664-8422
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank the National Institutes of Health (R01 GM121441) for
financial support. B. L. thanks Kwanjeong Educational Foundation. We
thank Dr. Simon Krautwald, Dr. Matthew, Dr. Cayetana Zarate, and
Dr. W. Neil Palmer for insightful discussions and helpful comments.
We acknowledge Kenith Conover and Dr. István Pelczer for helpful
discussions and assistance with NMR spectroscopy. The staff at Lotus
Separations are gratefully acknowledged for measuring the enantiopu-
rity of some products. We also thank Allychem for a generous gift of
B2Pin2.
ABBREVIATIONS
REFERENCES
(1) (a) Brown, H. C.; Singaram, B. The Development of a Simple
General Procedure for Synthesis of Pure Enantiomers via Chiral
Organoboranes. Acc. Chem. Res. 1988, 21, 287–293. (b) Miyaura, N.;
Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of
Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. (c) Neeve,
E. C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott, S. A.; Marder, T. B.
Diboron(4) Compounds: From Structural Curiosity to Synthetic
Workhorse. Chem. Rev. 2016, 116, 9091–9161. (d) Fyfe, J. W. B.;
Watson, A. J. B. Recent Developments in Organoboron Chemistry: Old
Dogs, New Tricks. Chem 2017, 3, 31–55. (e) Hartwig, J. F. Borylation and
a
Isolated yields are given. See SI for experimental details. LiOtBu (1
equiv.) b13a (1 equiv.) at 0 ºC, then 23 ºC, 10 h. c13b (2 equiv. 80 wt.%
in toluene) at 23 ºC then 45 ºC, 2 h. d13c (1.2 equiv.), 23 ºC, 18 h.
e13e (1.5 equiv.), 23 ºC, 1 h. 13d (1.2 equiv.), 23 ºC, 1 h. g13d (2.5
f
Silylation of C–H Bonds:
A Platform for Diverse C–H Bond
equiv.), 23 ºC, 1 h. h13e (1.2 equiv.), 23 ºC, 1 h. i13f (1.5 equiv.) at 23
ºC, then 45 ºC, 10 h.
Functionalizations. Acc. Chem. Res. 2012, 45, 864–873. (f) Hall, D. G.
Boronic Acids: Preparation, Applications in Organic Synthesis and
Medicine, 2nd ed.; Wiley-VCH: Weinheim, 2011.
(2) (a) Nallagonda, R.; Padala, K.; Masarwa, A. Gem-Diborylalkanes:
Recent Advances in Their Preparation, Transformation and Application.
Org. Biomol. Chem. 2018, 16, 1050–1064. (b) Abu Ali, H.; Dembitsky, V.
M.; Srebnik, M. Recent Developments in Bisdiborane Chemistry: B-C-B,
Concluding Remarks. In summary, an efficient and opera-
tionally simple method for conversion of esters to ketones using
benzyldiboronates has been developed. The method is tolerant of
most common organic functional groups, including substrates with
acidic α-protons adjacent to carbonyl groups, and has been extend-
ACS Paragon Plus Environment

Page 9 of 11
Journal of the American Chemical Society
(13) (a) Cho, S. H.; Hartwig, J. F. Iridium-Catalyzed Diborylation of
B-C-C-B, B-C=C-B, and B-C≡C-B Compounds and Their Biological
Benzylic C–H Bonds Directed by a Hydrosilyl Group: Synthesis of 1,1-
Benzyldiboronate Esters. Chem. Sci. 2014, 5, 694–698. (b) Jayasundara,
C. R. K.; Sabasovs, D.; Staples, R. J.; Oppenheimer, J.; Smith III, M. R.;
Maleczka Jr., R. E. Cobalt-Catalyzed C–H Borylation of Alkyl Arenes and
Heteroarenes Including the First Selective Borylations of Secondary
Benzylic C–H Bonds. Organometallics 2018, 37, 1567–1574. (c) Mita, T.;
Ikeda, Y.; Michigami, K.; Sato, Y. Iridium-Catalyzed Triple C(sp3)–H
Borylations: Construction of Triborylated sp3-Carbon Centers. Chem.
Commun. 2013, 49, 5601–5603. (d) Palmer, W. N.; Obligacion, J. V;
Pappas, I.; Chirik, P. J. Cobalt-Catalyzed Benzylic Borylation: Enabling
Polyborylation and Functionalization of Remote, Unactivated C(sp3)–H
Bonds. J. Am. Chem. Soc. 2016, 138, 766–769. (e) Palmer, W. N.; Zarate,
C.; Chirik, P. J. Benzyltriboronates: Building Blocks for Diastereoselective
Carbon–Carbon Bond Formation. J. Am. Chem. Soc. 2017, 139, 2589–
2592. (f) Shimada, S.; Batsanov, A. S.; Howard, J. A. K.; Marder, T. B.
Formation of Aryl- and Benzylboronate Esters by Rhodium-Catalyzed
C−H Bond Functionalization with Pinacolborane. Angew. Chem. Int. Ed.
2001, 40, 2168–2171.
1
2
3
4
5
6
7
8
Applications. Stud. Inorg. Chem. 2005, 22, 59–117.
(3) (a) Endo, K.; Ohkubo, T.; Hirokami, M.; Shibata, T.
Chemoselective and Regiospecific Suzuki Coupling on a Multisubstituted
sp3-Carbon in 1,1-Diborylalkanes at Room Temperature. J. Am. Chem.
Soc. 2010, 132, 11033–11035. (b) Lee, J. C. H.; McDonald, R.; Hall, D. G.
Enantioselective Preparation and Chemoselective Cross-Coupling of 1,1-
Diboron Compounds. Nat. Chem. 2011, 3, 894–899.
(4) (a) Joannou, M. V; Moyer, B. S.; Goldfogel, M. J.; Meek, S. J.
Silver(I)-Catalyzed
Diastereoselective
Synthesis
of
Anti-1,2-
Hydroxyboronates. Angew. Chem. Int. Ed. 2015, 54, 14141–14145. (b)
Matteson, D. S.; Moody, R. J. Carbanions from Deprotonation of gem-
Diboronic Esters. J. Am. Chem. Soc. 1977, 99, 3196–3197. (c) Matteson,
D. S.; Moody, R. J. Deprotonation of 1,1-Diboronic Esters and Reactions of
the Carbanions with Alkyl Halides and Carbonyl Compounds.
Organometallics 1982, 1, 20–28.
(5) (a) Wommack, A. J.; Kingsbury, J. S. On the Scope of the Pt-
Catalyzed Srebnik Diborylation of Diazoalkanes. An Efficient Approach to
Chiral Tertiary Boronic Esters and Alcohols via B-Stabilized Carbanions.
Tetrahedron Lett. 2014, 55, 3163–3166. (b) Hong, K.; Liu, X.; Morken, J.
P. Simple Access to Elusive α-Boryl Carbanions and Their Alkylation: An
Umpolung Construction for Organic Synthesis. J. Am. Chem. Soc. 2014,
136, 10581–10584.
(6) (a) Soundararajan, R.; Matteson, D. S. Hydroboration with
Haloborane/Trialkylsilane Mixtures. Organometallics 1995, 14, 4157–
4166. (b) Endo, K.; Hirokami, M.; Shibata, T. Synthesis of 1,1-
Organodiboronates via Rh(I)Cl-Catalyzed Sequential Regioselective
Hydroboration of 1-Alkynes. Synlett 2009, 2009, 1331–1335. (c) Zuo, Z.;
Huang, Z. Synthesis of 1,1-Diboronate Esters by Cobalt-Catalyzed
Sequential Hydroboration of Terminal Alkynes. Org. Chem. Front. 2016,
3, 434–438.
(7) (a) Feng, X.; Jeon, H.; Yun, J. Regio- and Enantioselective
Copper(I)-Catalyzed Hydroboration of Borylalkenes: Asymmetric
Synthesis of 1,1-Diborylalkanes. Angew. Chem. Int. Ed. 2013, 52, 3989–
3992. (b) Scheuermann, M. L.; Johnson, E. J.; Chirik, P. J. Alkene
Isomerization–Hydroboration Promoted by Phosphine-Ligated Cobalt
Catalysts. Org. Lett. 2015, 17, 2716–2719.
(8) Wang, L.; Zhang, T.; Sun, W.; He, Z.; Xia, C.; Lan, Y.; Liu, C. C–O
Functionalization of α-Oxyboronates: A Deoxygenative gem-Diborylation
and gem-Silylborylation of Aldehydes and Ketones. J. Am. Chem. Soc.
2017, 139, 5257–5264.
(9) Zhao, H.; Tong, M.; Wang, H.; Xu, S. Transition-Metal-Free
Synthesis of 1,1-Diboronate Esters with a Fully Substituted Benzylic
Center via Diborylation of Lithiated Carbamates. Org. Biomol. Chem.
2017, 15, 3418–3422.
(10) Li, H.; Shangguan, X.; Zhang, Z.; Huang, S.; Zhang, Y.; Wang, J.
Formal Carbon Insertion of N-Tosylhydrazone into B–B and B–Si Bonds:
gem-Diborylation and gem-Silylborylation of sp3 Carbon. Org. Lett. 2013,
16, 448–451.
(11) (a) Abu Ali, H.; Goldberg, I.; Kaufmann, D.; Burmeister, C.;
Srebnik, M. Novel C1-Bridged Bisboronate Derivatives by Insertion of
Diazoalkanes into Bis(Pinacolato)Diborane(4). Organometallics 2002,
21, 1870–1876. (b) Abu Ali, H.; Goldberg, I.; Srebnik, M. Addition
Reactions of Bis(Pinacolato)Diborane(4) to Carbonyl Enones and
Synthesis of (Pinacolato)2BCH2B and (Pinacolato)2BCH2CH2B by
Insertion and Coupling. Organometallics 2001, 20, 3962–3965.
(12) (a) Atack, T. C.; Cook, S. P. Manganese-Catalyzed Borylation of
Unactivated Alkyl Chlorides. J. Am. Chem. Soc. 2016, 138, 6139–6142.
(b) Ito, H.; Kubota, K. Copper(I)-Catalyzed Boryl Substitution of
Unactivated Alkyl Halides. Org. Lett. 2012, 14, 890–893. (c) Shimizu, M.;
Schelper, M.; Nagao, I.; Shimono, K.; Kurahashi, T.; Hiyama, T. Synthesis
and Applications of 1,1-Diborylated Cyclopropanes: Facile Route to 1,2-
Diboryl-3-Methylenecyclopentenes. Chem. Lett. 2006, 35, 1222–1223.
(d) Yang, C.-T.; Zhang, Z.-Q.; Tajuddin, H.; Wu, C.-C.; Liang, J.; Liu, J.-
H.; Fu, Y.; Czyzewska, M.; Steel, P. G.; Marder, T. B.; Liu, L. Alkylboronic
Esters from Copper-Catalyzed Borylation of Primary and Secondary Alkyl
Halides and Pseudohalides. Angew. Chem. Int. Ed. 2011, 51, 528–532.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(14) (a) Nahm, S.; Weinreb, S. M. N-Methoxy-N-Methylamides as
Effective Acylating Agents. Tetrahedron Lett. 1981, 22, 3815–3818. (b)
Singh, J.; Satyamurthi, N.; Aidhen, I. S. The Growing Synthetic Utility of
Weinreb′s Amide. J. Prakt. Chem. 2000, 342, 340–347.
(15) (a) Smith, A. B.; Boldi, A. M. Multicomponent Linchpin
Couplings of Silyl Dithianes via Solvent-Controlled Brook Rearrangement.
J. Am. Chem. Soc. 1997, 119, 6925–6926. (b) Smith, A. B.; Pitram, S. M.;
Boldi, A. M.; Gaunt, M. J.; Sfouggatakis, C.; Moser, W. H. Multicomponent
Linchpin Couplings. Reaction of Dithiane Anions with Terminal Epoxides,
Epichlorohydrin, and Vinyl Epoxides: Efficient, Rapid, and
Stereocontrolled Assembly of Advanced Fragments for Complex Molecule
Synthesis. J. Am. Chem. Soc. 2003, 125, 14435–14445. (c) Tietze, L. F.;
Geissler, H.; Gewert, J. A.; Jakobi, U. Tandem-Bisalkylation of 2-
Trialkylsilyl-1,3-Dithiane: A New Sequential Transformation for the
Synthesis of C2-Symmetrical Enantiopure 1,5-Diols and β,Β′-
Dihydroxyketones as Well as of Enantiopure 1,3,5-Triols. Synlett 1994,
1994, 511–512. (d) Yus, M.; Nájera, C.; Foubelo, F. The Role of 1,3-
Dithianes in Natural Product Synthesis. Tetrahedron 2003, 59, 6147–
6212.
(16) (a) Erdik, E.; Ay, M. Electrophilic Amination of Carbanions.
Chem. Rev. 1989, 89, 1947–1980. (b) Seyferth, D. The Grignard
Reagents. Organometallics 2009, 28, 1598–1605.
(17) (a) Murphy, J. A.; Commeureuc, A. G. J.; Snaddon, T. N.;
McGuire, T. M.; Khan, T. A.; Hisler, K.; Dewis, M. L.; Carling, R. Direct
Conversion of N-Methoxy-N-Methylamides (Weinreb Amides) to
Ketones via a Nonclassical Wittig Reaction. Org. Lett. 2005, 7, 1427–
1429. (b) Simmons, B. J.; Weires, N. A.; Dander, J. E.; Garg, N. K. Nickel-
Catalyzed Alkylation of Amide Derivatives. ACS Catal. 2016, 6, 3176–
3179.
(18) Willis, M. C. Transition Metal Catalyzed Alkene and Alkyne
Hydroacylation. Chem. Rev. 2010, 110, 725–748.
(19) Wu, X.-F.; Neumann, H.; Beller, M. Palladium-Catalyzed
Carbonylative Coupling Reactions between Ar–X and Carbon
Nucleophiles. Chem. Soc. Rev. 2011, 40, 4986–5009.
(20) (a) Amani, J.; Alam, R.; Badir, S.; Molander, G. A. Synergistic
Visible-Light Photoredox/Nickel-Catalyzed Synthesis of Aliphatic Ketones
via N–C Cleavage of Imides. Org. Lett. 2017, 19, 2426–2429. (b)
Capaldo, L.; Riccardi, R.; Ravelli, D.; Fagnoni, M. Acyl Radicals from
Acylsilanes: Photoredox-Catalyzed Synthesis of Unsymmetrical Ketones.
ACS Catal. 2017, 8, 304–309. (c) Chu, L.; Lipshultz, J. M.; MacMillan, D.
W. C. Merging Photoredox and Nickel Catalysis: The Direct Synthesis of
Ketones by the Decarboxylative Arylation of α-Oxo Acids. Angew. Chem.
Int. Ed. 2015, 54, 7929–7933.
(21) Ni, S.; Padial, N. M.; Kingston, C.; Vantourout, J. C.; Schmitt, D.
C.; Edwards, J. T.; Kruszyk, M. M.; Merchant, R. R.; Mykhailiuk, P. K.;
Sanchez, B. B.; Yang, S.; Perry, M. A.; Gallego, G. M.; Mousseau, J. J.;
Collins, M. R.; Cherney, R. J.; Lebed, P. S.; Chen, J. S.; Qin, T.; Baran, P. S.
A Radical Approach to Anionic Chemistry: Synthesis of Ketones, Alcohols,
and Amines. J. Am. Chem. Soc. 2019, 141, 6726–6739.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 11
(22) Iacono, C. E.; Stephens, T. C.; Rajan, T. S.; Pattison, G. A
(28) (a) He, Z.; Zajdlik, A.; Yudin, A. K. α-Borylcarbonyl Compounds:
Coupling Approach for the Generation of α,α-Bis(Enolate) Equivalents:
Regioselective Synthesis of gem-Difunctionalized Ketones. J. Am. Chem.
Soc. 2018, 140, 2036–2040.
(23) Mukaiyama, T.; Murakami, M.; Oriyama, T.; Yamaguchi, M. A
New Aldol Reaction: A Method for the Generation of Vinyloxyboranes by
the Acylation of Boron-Stabilized Carbanions. Chem. Lett. 1981, 10,
1193–1196.
(24) Sun, W.; Wang, L.; Xia, C.; Liu, C. Dual Functionalization of α-
Monoboryl Carbanions through Deoxygenative Enolization with
Carboxylic Acids. Angew. Chem. Int. Ed. 2018, 57, 5501–5505.
(25) (a) Zheng, P.; Zhai, Y.; Zhao, X.; XU, T. Difunctionalization of
Ketones via gem-Bis(Boronates) to Synthesize Quaternary Carbon with
High Selectivity. Chem. Commun. 2018, 54, 13375–13378. (b) Zheng, P.;
Zhai, Y.; Zhao, X.; XU, T. Palladium-Catalyzed Cross-Coupling of gem-
Bis(Boronates) with Aryl Halides: An Alternative to Access Quaternary α-
Aryl Aldehydes. Org. Lett. 2019, 21, 393–396.
(26) A related example where the reaction of α, α-diborylcarbanion and
a chiral aldehyde results in complete retention of stereochemistry:
Stephens, T. C.; Pattison, G. Transition-Metal-Free-Homologative Cross-
Coupling of Aldehydes and Ketones with Geminal Bis(boron)
Compounds. Org. Lett. 2017, 19, 3498–3501.
From Transient Intermediates to Robust Building Blocks. Dalton Trans.
2014, 43, 11434–11451. (b) Ng, E. W. H.; Low, K.-H.; Chiu, P. Synthesis
and Applications of Unquaternized C-Bound Boron Enolates. J. Am.
Chem. Soc. 2018, 140, 3537–3541.
(29) Lee, Y.; Park, J.; Cho, S. H. Generation and Application of
(Diborylmethyl)Zinc(II) Species: Access to Enantioenriched gem-
Diborylalkanes by an Asymmetric Allylic Substitution. Angew. Chem. Int.
Ed. 2018, 57, 12930–12934.
1
2
3
4
5
6
7
8
(30)The activation of 1 was also observed upon treatment of 1
n
equivalent of BuLi. For details, see Supporting Information (Figure S58–
9
S61).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(31) This assignment was further corroborated by comparison to the
NMR data obtained from the mixing of internal benzyldiboronate 16 and
LiOtBu where the deborylated product was formed exclusively (Figure
S41–S47).
(32) The formation of tert-butanol, which is generated by the
deprotonation event, was not observed presumably due to the interaction
between tert-butanol and boron-containing molecules.
(33) (a) Matteson, D. S.; Majumdar, D. α-Trimethylsilyl Boronic Esters.
Pinacol Lithio(Trimethylsilyl)Methaneboronate, Homologation of
Boronic Esters with [Chloro(Trimethylsilyl)Methyl]Lithium, and
Comparisons with Some Phosphorus and Sulfur Analogues.
Organometallics 1983, 2, 230–236. (b) Matteson, D. S.; Arne, K.
Carbanions from Deprotonation of α-(Phenylthio)Alkaneboronic Esters. J.
Am. Chem. Soc. 1978, 100, 1325–1326. (c) Matteson, D. S.; Arne, K. H.
Carbanions from α-Phenylthio Boronic Esters as Synthetic Intermediates.
Organometallics 1982, 1, 280–288.
(27) Observation of 3f is consistent with a second addition of the α-
boryl carbanion 8 after the first addition to diethylcarbonate. This is con-
sistent with formation of a reactive C-bound boron enolate 4a as a reaction
intermediate, species that are rare as compared to their O-bound tautomer,
4b.28 Byproduct 3af was likely generated by nucleophilic attack of the O-
bound boron enolate intermediate on diethylcarbonate.
ACS Paragon Plus Environment

Page 11 of 11
Journal of the American Chemical Society
For Table of Contents Use
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11
ACS Paragon Plus Environment