Deoxygenative α-alkylation and α-arylation of 1,2-dicarbonyls

Article abstract of DOI:10.1039/d0sc03118f

Construction of C-C bonds at the α-carbon is a challenging but synthetically indispensable approach to α-branched carbonyl motifs that are widely represented among drugs, natural products, and synthetic intermediates. Here, we describe a simple approach to generation of boron enolates in the absence of strong bases that allows for introduction of both α-alkyl and α-aryl groups in a reaction of readily accessible 1,2-dicarbonyls and organoboranes. Obviation of unselective, strongly basic and nucleophilic reagents permits carrying out the reaction in the presence of electrophiles that intercept the intermediate boron enolates, resulting in two new α-C-C bonds in a tricomponent process. This journal is

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Deoxygenative α-Alkylation and α-Arylation of 1,2-Dicarbonyls
Shengfei Jin, Hang T. Dang, Graham C. Haug, Viet D. Nguyen, Hadi D. Arman, and Oleg V.
Larionov*
Received 00th January 20xx,
Accepted 00th January 20xx
Construction of C‒C bonds at the α-carbon is a challenging but synthetically indispensable approach to α-branched
carbonyl motifs that are widely represented among drugs, natural products, and synthetic intermediates. Here, we
describe a simple approach to generation of boron enolates in the absence of strong bases that allows for introduction of
both α-alkyl and α-aryl groups in a reaction of readily accessible 1,2-dicarbonyls and organoboranes. Obviation of
unselective, strongly basic and nucleophilic reagents permits carrying out the reaction in the presence of electrophiles that
intercept the intermediate boron enolates, resulting in two new α-C‒C bonds in a tricomponent process.
DOI: 10.1039/x0xx00000x
1,1-Diboron-based generation of boron enolates
Introduction
[B]
H
Base
O
[B]
Chemists have long relied on reactions that allow for
generation of unstable and reactive intermediates but forcing
conditions, as well as strong and unselective reagents are
often required to achieve the desired transformations. Much
of the recent progress in synthetic methodology has been
fueled by the necessity to access transient reactive
intermediates in a rapid and modular manner and in the
absence of unselective reagents.1
or
[B]
[B]
[B]
O
O
OR
(Mattison, Pattison),
LiTMP
MeLi
LiOtBu
(Mukaiyama, Liu), (Chirik)
Base:
Recent applications of organoboranes in C-C bond-forming
reactions
Alkene synthesis
R
Ag
H
B
+
R
Enolates are among the most common and synthetically
versatile intermediates used for α-functionalization of
carbonyls. Despite their broad utility, the most common
method of generation of enolates remains deprotonation with
strong bases, e.g., organolithiums, lithium amides and
alkoxides that are incompatible with many base-sensitive
functional groups.2 Moreover, the deprotonation approach is
inherently synthetically inefficient, since it requires prior
assembly of the entire carbon skeleton of the carbonyl
precursor. Given the central role of enolates in organic
synthesis, reactions that allow for modular generation of
enolates, e.g., by carbon‒carbon bond-forming reactions
under neutral conditions and in the absence of strong bases
are highly sought after but have remained elusive.
Carboborative ring contraction
R
X
X
h
BR2
B
+
R
This work: Base-free synthesis of boron enolates for deoxygenative
-alkylation/arylation
MeO
OMe
OMe
+
(MeO)3P
P
O
O
O
P(OMe)3
O
O
O-
1
2
R
R
P(OMe)3
B
B
R
R
R
Since their introduction by Mukaiyama in 1973,3 boron
enolates have become the preferred class of carbon-centered
nucleophiles for many chemo- and stereoselective
carbon‒carbon bond-forming reactions, due to the presence
of the inherently Lewis acidic boryl group that enables more
B
BR2
+
(MeO)3P
O
R
O
BR
O
2
O
O=P(OMe)3
5
3
4
Modular construction of boron enolates in the absence
of strong bases.
E
-Arylation and -alkylation can both be performed


E
with the same reaction.
Synthesis of -branched carboxylic acids and ketones.

One or two -carbon-carbon bonds formed in one step.
Boron enolate serves as an additional point of
structural diversification.

O
Department of Chemistry, The University of Texas at San Antonio, One UTSA Circle,
San Antonio, TX 78249, USA. Email: oleg.larionov@utsa.edu
Scheme 1. Boron enolates and the deoxygenative α-alkylation/arylation of 1,2-
dicarbonyls.
Electronic
Supplementary
Information
(ESI)
available:
See
DOI: 10.1039/x0xx00000x
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ARTICLE
Journal Name
selective reactions with a broader range of electrophiles.2,4
Consequently, there has been an upsurge of interest in new
approaches to their generation, exemplified by geminal
diboronate-based methods recently developed by Pattison, Liu
and Chirik rooted in the earlier studies by Mukaiyama and
Mattison.5
Organoboranes have long served as broadly useful synthetic
linchpins,6 and the recent examples of carbon‒carbon bond-
forming reactions, for instance, Lalic’s Z-alkene synthesis7 and
the carboborative ring contraction,8 showcase the untapped
reactivity of organoboranes. The versatility of organoboranes
coupled with the ease of their preparation by well-established
routes, e.g., hydroboration, ensures their continued presence
at the forefront of organic synthesis.9
Results and discussion
View Article Online
DOI: 10.1039/D0SC03118F
We chose triethylborane as a simple and readily available
boron reagent for our initial synthetic scope studies, based on
our prior experience8 and cognizant that successful
development of the reaction with BEt3 would enable utilization
of other organoboron sources, including the widely used
organo-9-borabicyclo[3.3.1]nonanes (BBN). We found that the
reaction of ester 6 with triethylborane and trimethyl phosphite
proceeded cleanly at 50 °C in THF, affording α-branched
carboxylate 7 in good yield (Scheme 2). Importantly, the more
readily available and inexpensive P(OMe)3 can be used,
although P(NMe2)3 is also a suitable PIII reagent.
O
BEt
3, P(OMe)3
THF, 50 o
85%
OEt
OEt
In a parallel development, there has been an increased
realization of the expanding synthetic potential of 1,2-
dicarbonyl compounds, stemming from the proximity of the
two reactive carbonyl groups and ready synthetic accessibility
of structurally diverse 1,2-dicarbonyls.10
C
O
O
6
7
Scheme 2. Deoxygenative α-alkylation/arylation of ester 6. Reaction conditions:
ester 6 (0.2 mmol), BEt3 (0.3 mmol), P(OMe)3 (0.24 mmol), THF (2 mL), 50 °C.
Merging these two classes of versatile synthetic intermediates,
we hypothesized that an addition of an organoborane to 1,2-
dicarbonyl–phosphite adducts 1 and 211 would be followed by
a 1,2-metallate shift that is accompanied by the departure of
phosphate 3 from the zwitterionic intermediate 4 by analogy
with the Matteson reaction that has recently been adopted to
a variety of valuable synthetic transformations.12 Subsequent
1,3-borotropic shift would result in the formation of boron
enolate 5. Notably, construction of the boron enolate would
be achieved in the absence of strong bases or strongly Lewis
acidic boron reagents (e.g., boryl triflates and halides) and in a
modular manner, i.e., with concomitant formation of a
carbon‒carbon bond in the α-position. Furthermore, the
modularity of the reaction combined with the neutral reaction
conditions and the weakly Lewis acidic character of the
boryloxy group were expected to enable a streamlined
synthesis of highly α-branched carboxylic acids and other
We then proceeded with the evaluation of the scope of the
deoxygenative alkylation reaction (Scheme 3). Halo, alkyl,
methoxy and thio-substituted aromatic keto esters were
suitable substrates (8-18). The electron-withdrawing cyano,
and the medicinally relevant trifluoromethyl and
trifluoromethoxy groups were also tolerated (19-21). Polycyclic
keto esters were readily converted to the corresponding α-
alkyl-branched esters in good yields (22-27). Similarly,
heterocyclic keto esters successfully participated in the
reaction, including substrates containing pyridine, thiophene,
dihydrobenzofuran, indole, carbazole, dibenzothiophene and
xanthene cores (28-37). Interestingly, vinylogous substitution
in the aromatic ring was also observed for the indole keto
ester (33). A reaction with N-methylisatin afforded 3-alkylated
indolone 38. Aliphatic keto esters reacted equally well and
produced the corresponding 2-alkyl branched esters 39-42 in
good yields. 1,2-Diketones were evaluated next with P(NMe2)3
as the optimal PIII reagent, likely due to the increased
nucleophilicity imparted by the more basic PIII reagent,18 and a
range of α-branched ketones 43-49 were prepared, further
highlighting the scope of the reaction. Esters 22, 23, and 35
were converted to corresponding acids, whose structures were
confirmed by X-ray crystallographic analysis.
carbonyls by engaging
a range of electrophiles in a
tricomponent cascade process.
α-Branched carbonyl compounds, in particular carboxylates,
are among the most synthetically valuable and medicinally
important structural motifs, whose applications range from
non-steroidal anti-inflammatory drugs (NSAIDs)13 to versatile
reagents for late stage functionalization enabled by resurgent
decarboxylative methodologies.14
A number of synthetic
The reaction can be further extended to other organoboranes
(Scheme 4). α-Arylation of carboxylic acids and other carbonyl
compounds remains a long-standing synthetic challenge.[15]
Significantly, facile arylation can be achieved, providing a
metal-free access to α-mono- and diarylated esters and
ketones (50-55). Other alkylboranes can be used as well (56-
62), including those derived from alkenes by hydroboration
(58-62). Importantly, 9-BBN-derived organoboranes that can
be easily prepared by hydroboration of alkenes and other
methods19 proved to be suitable reagents for the transfer of
approaches to α-branched carbonyls have recently emerged,
including transition metal-catalyzed α-arylation of enolates,15
carbonylation16 and electrophilic α-alkylation.17 However,
many challenges remain unsolved, including the lack a unified
synthetic platform that can enable both α-arylation and α-
alkylation under essentially neutral conditions and in the
absence of non-chemoselective or expensive reagents and
catalysts. Thus, further work is needed to develop such a
synthetic platform for production of structurally diverse α-
branched carbonyls by a conceptually distinct aryl‒Cα and
alkyl‒Cα bond forming process that encompasses both α-
arylation and α-alkylation.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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DOI: 10.1039/D0SC03118F
ARTICLE
O
BEt3
P(OMe)3
O
O
OEt
OEt
OEt
OEt
OEt
OEt
OEt
O
O
O
O
O
O
O
F
Cl
Br
7
8
, 70%
, 85%
9
10
11
12
13
, 90%
, 75%
, 70%
, 81%
, 72%
1.3 g, 60%
OEt
MeO
MeO
OEt
F
OEt
MeO
MeO
OEt
OEt
OEt
O
O
O
O
O
O
MeO
CF3
MeO
F
MeS
NC
14
15
16
17
18
19
, 58%
, 86%
, 71%
, 74%
, 63%
, 83%
OEt
F
OEt
OEt CF3O
OEt
O
O
O
O
in
in
22
23
23
-H
20
21
, 84%
22-H
, 70%
, 75%
, 78%
OEt
OEt
OEt
OEt
OEt
OEt
O
O
S
O
S
O
O
O
MeO
[a]
[a]
24
25
26
27
28
29
, 92%
, 62%
, 50%
, 68%
, 51%
, 45%
OEt
OEt
OEt
OEt
OEt
OEt
S
F
O
O
O
O
O
O
N
N
N
N
O
Boc
Boc
34
33
, 40%
30
31
, 43%. (6 : 1)
, 80%
, 50%
32
, 66%
OEt
OEt
OEt
O
in
O
O
O
N
N
S
O
38
35
35
37
, 75%
, 53%
, 68%
-H
36
, 83%
Cl
OEt
OEt
OEt
OEt
O
, 84%
O
O
O
O
O
F
[b]
39
40
41
42
43
, 66%
, 68%
, 70%
, 65%
F
OMe
S
O
MeO
OMe
O
O
O
S
48
O
O
O
O
MeO
F
[b]
[b]
[b]
[b]
[b]
[b]
44
45
47
49
, 60%
, 88%
, 50%
46
, 62%
, 58%
, 83%
[a]
[b]
Scheme 3. Scope of 1,2-dicarbonyl compounds. Reaction conditions: 1,2-dicarbonyl (0.1–0.2 mmol), BEt3 (1.5–2 equiv.), P(OMe)3 (1.2–2 equiv.) THF (1–4 mL), 50 °C. 80 °C.
P(NMe2)3 was used.
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DOI: 10.1039/D0SC03118F
ARTICLE
O
R
P(OMe)3
+
B
R
O
O
with BAr3 and BAlk3
OMe
OEt
OEt
CF3O
OEt
Cl
OEt
OEt
O
O
O
O
O
O
MeO
MeO
53
54, 60%
55
, 60%
50
51
52
, 50%
, 57%
, 65%
, 55%
OtBu
OMe
tBu
OEt
O
OEt
OEt
OEt
O
OEt
O
O
O
O
O
MeO
O
56
57
58, 69%
, 80%
, 50%
59
60
61
, 70%
, 79%
, 64%
1.5 g, 68%
with R-BBN
MeO
MeO
F
OH
O
OEt
OEt
OEt
F
OEt
O
O
O
N
O
MeO
O
MeO
62
, 65%
63
64
65
66
, 67%
, 50%
, 52%
, 50%
O
OCF3
S
F
MeO
F
OEt
OEt
OEt
OEt
O
OEt
O
O
O
O
MeO
MeO
O
67
68
69
70
71
, 60%
, 66%
, 55%
, 52%
, 64%
Scheme 4. Scope of organoboron reagents. Reaction conditions: see footnote for Scheme 2.
alkyl (63-65), aryl (66, 67), vinyl (68) and heteroaryl groups (69-
71).
ClC(O)CO2Et, AlCl3
COOH
ibuprofen
75
BMe3, P(OMe)3
then LiOH
Given the importance of α-arylpropionic acids as NSAIDs, we
evaluated trimethylborane in the synthesis of ibuprofen,
naproxen and flurbiprofen (72-74, Scheme 5). In all three
cases, NSAIDs 72-74 were readily accessed in two synthetic
operations from the corresponding precursors 75-77, pointing
to the potential of the deoxygenative alkylation reaction in
drug discovery applications.
72
, 82% from
75
Mg, then ClC(O)CO2Et
Br
COOH
naproxen
BMe3, P(OMe)3, then LiOH
MeO
MeO
73
76
, 57% from
76
A remarkable feature of the reaction is that it produces
reactive boron enolates under neutral conditions in the
absence of strong bases that are typically required for
generation of enolates. We, therefore, next explored the
F
F
Br
COOH
Mg, then ClC(O)CO2Et
flurbiprofen
77
BMe3, P(OMe)3, then LiOH
74
, 67% from
77
Scheme 5. Synthesis of NSAIDs 72-74 with trimethylborane.
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ARTICLE
O
E
smoothly in a tricomponent manner under the conditions of
the deoxygenative α-alkylation (86-91, Scheme 6), presumably
due to the Lewis acidic character of the boryl group of the
intermediate boron enolate, leading to concomitant
construction of two C–C bonds and an all-carbon quaternary α-
position in one step.
BEt3
E
,
View Article Online
DOI: 10.1039/D0SC03118F
OEt
OEt
P(OMe)3
O
O
HO
HO
HO
D
OEt
OEt
OEt
OEt
O
O
, 85%
2.2 g, 88%
acetone
O
O
The deoxygenative α-alkylation can be further leveraged for
construction of all-carbon quaternary α-positions in carboxylic
acids by the Ireland-Claisen rearrangement of the intermediate
boron enolates,23 e.g., 92 (Scheme 7). The Ireland-Claisen-
enhanced deoxygenative α-alkylation reaction enables
installation of allylic α-side chains (93), including the sterically
encumbered β,β-dimethylallyl group in the α-branched acid
94. Expansion of the scope to propargylic and allenylic
substrates provides straightforward access to carboxylic acids
bearing α-allenyl and α-dienyl groups (95 and 96). The
deoxygenative α-alkylation can also be combined with the Pd-
catalyzed allylation (Scheme 7, 97), indicating that the
intermediate boron enolates can serve as a platform for C‒C
bond-forming functionalization by means of transition metal
catalysis. Furthermore, the deoxygenative coupling reaction
can be readily carried out on gram scale (8, 56, 79).
79
78
, 72% (92% D)
80
81
, 71%
, 79%
D O
2
with cyclopentanone with cyclohexanone
with
with
Boc
N
HO
HO
O
HO
OEt
OEt
OEt
O
O
O
82
83
84
, 73%
3-oxetanone
, 63%
, 68%
N-Boc-4-piperidone
cyclobutanone
with
with
with
Boc
O
O
O
HO
N
OEt
OEt
O
OEt
OEt
O
O
O
85
88
, 68%
, 66% with
N-Boc-3-azetidinone
86
87
with
, 65%
, 65%
EtCN
MeCN
with
PhCH CN
with
2
CF3
F3C
BEt
THF, 70-80 o
O
3, P(OMe)3
O
C
O
OH
O
OEt
O
OEt
Cl
F
OEt
F
O
O
O
O
O
O
O
MeO
93
, 78%
MeO
MeO
with
BEt2
89
, 59%
90
with
, 56%
PhCN
91
, 66%
3,5-(F C) C H CN
o-ClC H CH CN
with
6
4
2
3
2 6 3
92
via
Scheme 6. Scope of the tricomponent reaction. Reaction conditions: see
footnote for Scheme 2, in the presence of electrophile.
•
OH
OH
OH
feasibility of carrying out the reaction directly in the presence
O
O
O
of electrophiles. This combination would enable
a
94
95
, 78%
96, 42%
, 60%
tricomponent coupling process that, due to the mildness of the
reaction conditions and the enhanced reactivity of boron
enolates, could engage a range of electrophiles, including both
very reactive (e.g., proton sources) and typically unreactive
ones (e.g., nitriles and ketones). Indeed, the reaction could be
successfully carried out in the presence of deuterium oxide,
and the corresponding α-deuterated ester 78 was isolated in
72% yield with 92% deuterium incorporation (Scheme 6). This
result suggests that the method may be useful in the context
of deuterated drug discovery as a means of improving
metabolic stability.20
O
O
O
•
O
3, P(OMe)3, THF, 50 o
then
Pd(MeCN)2Cl2 (5 mol%)
dppe (8 mol%), 80 o
C
BEt
OEt
OEt
O
O
C
97
, 60%
O
O
O
Ketones are typically challenging electrophiles for enolate
trapping, because of their facile enolization, lower reactivity
and reversibility of the addition reaction.21 Interestingly, a
variety of ketones were compatible with the deoxygenative α-
alkylation reaction, and the corresponding sterically congested
addition products 79-85 featuring two adjacent quaternary
carbons were readily formed in good yields.
+
(Me2N)3P
O
-
O
BEt3
98
Intermolecular C-acylation of enolates with nitriles is a
potentially synthetically attractive approach to β-dicarbonyl
compounds. However, examples of such reactions are rare.22
Significantly, both aliphatic and aromatic nitriles reacted
Scheme 7. Construction of quaternary all-carbon α-positions in carboxylic acids
and the structure of intermediate 98.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Journal Name
A.
B.
triethylborane, and first order in α-keto ester and trimethyl
phosphite (Figure 1.A-C). The intermediacy of boron enolates
View Article Online
DOI: 10.1039/D0SC03118F
was supported by kinetic 11B NMR spectroscopy studies that
confirmed formation of the dialkylboryloxy group (δ = 53.1
ppm)2 with concomitant consumption of triethylborane (Figure
1.D). Moreover, zwitterionic adduct 98 crystallized from a
P(NMe2)3-mediated reaction of the corresponding 1,2-
diketone with triethylborane and was characterized by X-ray
crystallography (Scheme 7), confirming participation of
adducts 2 in the process. However, an adduct analogous to 98
was not isolated or observed with ester 6 and triethyl
phosphite, indicating that it is less stable for these reactants.
A DFT computational study provided further insights into the
mechanism of the reaction that were consistent with the
experimental data (Figure 2). We found that the addition of
phosphite to the carbon of the keto group (99) that is followed
by a 1,2-phospha-Brook migration of the phosphite group to
the oxygen with subsequent ring closure en route to adduct
100 was kinetically accessible (TS-A and TS-B) with an overall
barrier of 22.9 kcal/mol, in excellent agreement with the
experimental value (22.7 kcal/mol). Alternative mechanisms of
formation of adduct 100 (e.g., a direct addition of phosphite to
the O atom of the carbonyl or a [4+1] cheletropic cycloaddition
of phosphite to ester 6) were also considered, but were found
to proceed over prohibitively high barriers (ΔG≠ > 40 kcal/mol,
see SI). The addition of the organoborane to cyclic ester–
phosphite adduct 100 further produced zwitterionic
C.
D.
Figure 1. Kinetic studies of the deoxygenative α-alkylation and boron enolate
formation. A. Order in α-keto ester. B. Order in trimethyl phosphite. C. Order in
triethylborane. D. Time course of triethylborane consumption and boron enolate
formation during the reaction of ester 6 with triethylborane and trimethyl
phosphite.
Kinetic and computational studies were further performed to
clarify the reaction mechanism. We found that TEMPO had no
detrimental effect on the reaction performance, indicating
that the reaction does not proceed by a radical pathway.
Furthermore, organoboranes are known to form adducts with
phosphites,24 and this process was expected to take place
under the conditions of the deoxygenative α-alkylation/α-
arylation. Indeed, formation of the 1:1 adduct was observed by
intermediate 101 that underwent
a
Matteson-type
displacement via TS-C en route to α-boryl ester 102.
Subsequent low-barrier (TS-D) exergonic 1,3-borotropic shift
produces E- and Z-isomers of boron enolate 103, with the E-
enolate being the more stable isomer.
NMR spectroscopy with Kassoc
=
1.62×103 M-1 for the
association of triethylborane with trimethyl phosphite.
Additionally, variable time normalization analysis25 revealed
that the deoxygenative α-alkylation was zero order in
PhCOCO2Et
BEt3
22.9
TS-B
22.4
TS-C
21.2
TS-A
19.8
99
6
19.0
TS-E
16.7
101
(MeO)3P+
-
O
5.2
100
OP(OMe)3
MeO
OMe
+P OMe
O
0.0
P(OMe)3
3
O
Ph
CO2Et
TS-D
MeO
OMe
OMe
Ph
Z
-24.9
-
P
O
O
Et3B
OEt
Ph
-26.4
OEt
E
-34.9
-47.0 (Z)
102
-48.1 (E)
Et2B Et
103
OEt
Et
Ph
O
OEt
BEt
Ph
O
2
Figure 2. Computed Gibbs free energy profile of the deoxygenative α-alkylation reaction, ΔG, kcal/mol.
6 | J. Name., 2012, 00, 1-3
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Although the computed difference between TS-B and the Center (TACC) at UT Austin for providing computational
second highest barrier (TS-C) is relatively small, we note that resources.
formation of adduct 101 as a rate-limiting step (i.e., higher TS-
B) is consistent with the experimentally observed zero order in
organoborane and first order in both ester 6 and phosphite.
Notes and references
The alternative pathway that proceeds via the acyclic adduct
of type 1 was also investigated but was found to proceed over
higher barriers and with the Matteson-type displacement as
the rate-limiting step (see SI), thus being inconsistent with the
experimental data. Taken together, our experimental and
computational studies support the proposed mechanism of
the modular boron enolate synthesis from organoboranes and
1,2-dicarbonyl–phosphite adducts.
1
2
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Conclusions
In conclusion, we have developed a modular construction of
boron enolates in the absence of strong bases that enables
installation of both α-alkyl and α-aryl groups in a reaction of
readily accessible 1,2-dicarbonyls with organoboranes (easily
derived by hydroboration from alkenes or from other
precursors). The reaction produces α-branched carboxylates
and ketones that are valuable synthetic intermediates and
medicinally important motifs. The intermediacy of boron
enolates enables a tricomponent coupling process with a
range of electrophiles, including the typically unreactive
nitriles and ketones, resulting in the construction of two α-C‒C
bonds. The utility and scope of the reaction are demonstrated
5
6
with profen-type NSAIDs and
a variety of substituted
7
8
carbocyclic and heterocyclic carbonyls that can be further
diversified by means of one-pot rearrangements and a
palladium-catalyzed allylation of the intermediate boron
enolates. The mechanism of the reaction was investigated
experimentally and computationally, revealing the central role
of 1,2-dicarbonyl–phosphite adducts and a 1,2-metallate shift
in enabling the deoxygenative C–C bond-forming process.
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Conflicts of interest
There are no conflicts to declare.
Acknowledgements
Financial support by the Welch Foundation (AX-1788), the NSF
(CHE-1455061), and NIGMS (GM134371) is gratefully
acknowledged. The NMR and X-ray crystallography facilities
were supported by the NSF (CHE-1625963 and CHE-1920057).
The authors acknowledge the Texas Advanced Computing
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O
E
[B]
E
B]
O[
O
O
Base- and metal-free access to boron enolates
Construction of two -C-C bonds in a tricomponent process

One reaction enables both -alkylation and -arylation


α-Branched carboxylic acids and other carbonyls are readily
accessed by a metal-free deoxygenative α-alkylation and α-
arylation of abundant 1,2-dicarbonyls: the reaction enables
generation of boron enolates under base-free conditions,
resulting in
a
tricomponent coupling process with
unconventional electrophiles.
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