1, n-Bisborylalkanes via Radical Boron Migration

Article abstract of DOI:10.1021/jacs.0c03058

A systematic study of radical boron migration in diboronate complexes to form synthetically valuable 1,n-bisborylalkanes is reported. The boronate complexes are readily generated by reaction of commercial bis(pinacolato)diboron with alkyl Grignard compounds. C-radical generation at a defined position with respect to the diboron moiety is achieved either via intermolecular H-abstraction with a CF3-radical or via alkene perfluoroalkyl radical addition. It is shown that radical 1,2- and 1,4-boron migrations to provide geminal and 1,3-bisborylalkanes are efficient transformations. The 1,5-boron migration in the homologous series leading to 1,4-bisborylalkanes is also occurring, albeit with lower efficiency. Experimental results are supported by DFT calculations which also reveal the corresponding 1,3-boron migration in such diboronate complexes to be feasible.

Full text of DOI:10.1021/jacs.0c03058

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Communication
1,n-Bisborylalkanes via Radical Boron Migration
Dinghai Wang, Christian Mück-Lichtenfeld, and Armido Studer
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 03 May 2020
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1,n-Bisborylalkanes via Radical Boron Migration
Dinghai Wang, Christian Mück-Lichtenfeld, Armido Studer*
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Organisch-Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstraße 40, 48149 Münster, Germany
Supporting Information Placeholder
access multifunctionalized compounds.6,7 The current methods to
ABSTRACT: A systematic study of radical boron migration in
diboronate complexes to form synthetically valuable 1,n-
prepare these compounds use gem-dihalides,8 diazo compounds,9
alkynes,10 alkenes etc.,11 as substrates and mostly require a
bisborylalkanes is reported. The boronate complexes are readily
transition metal to catalyze or mediate the transformation.12 It is of
generated by reaction of commercial bis(pinacolato)diboron with
interest to develop
a convenient method to access 1,1-
alkyl Grignard compounds. C-radical generation at defined
position with respect to the diboron moiety is either achieved via
intermolecular H-abstraction with a CF3-radical or via alkene
perfluoroalkyl radical addition. It is shown that radical 1,2- and 1,4-
boron migration to provide geminal and 1,3-bisborylalkanes are
efficient transformations. The 1,5-boron migration in the
homologous series leading to 1,4-bisborylalkanes is also occurring,
albeit with lower efficiency. Experimental results are supported by
DFT calculations which also reveal the corresponding 1,3-boron
migration in such diboronate complexes to be feasible.
bisborylalkanes from simple starting materials under transition
metal free conditions.
Scheme 1. Synthesis of 1,n-bisborylalkanes via radical boron
migration
A) 1,2-alkyl/aryl migration via radical/polar cross over (ref 4)
O
B
O
B
O
B
1,2-R'-migration
R' = alkyl, aryl
SET
R
R
R
O
O
O
M+
R'
R'
R'
II
I
III
Bisborylalkanes are functionalized and versatile building blocks in
organic synthesis. Such B-compounds can act as coupling partners
in transition metal catalyzed cross-coupling reactions or as radical
precursors and both boryl moieties can in principle be selectively
converted to different functionalities.1 Boronate complexes are
reactive intermediates that are readily generated by the reaction of
organoboronic esters with organometallic reagents. These B-ate
complexes are reducing species that also undergo facile
hydrolysis.2 Recently, radical chemistry on boronate complexes has
emerged.3 It was found that C-radicals of type I derived from
boronate complexes are readily oxidized by single electron transfer
(SET) to give zwitter ions of type II in a radical/polar cross over
step (Scheme 1, A). Intermediates II in turn undergo a Matteson-
type 1,2-alkyl/aryl shift to afford -functionalized boronic esters
III.4 Although such transformations on boronate complexes
generated from alkyl and aryl boronic esters are meanwhile well
investigated, the corresponding radical reactions on diboronate
complexes derived from diborons (see IV) are underdeveloped.
Along these lines, Shi recently reported the construction of 1,1-
bisborylalkanes enabled by radical addition/1,2-boron migration.
As mechanism of the boron migration, it was proposed that
B) 1,n-boron radical migration strategy
M+
1,(m+2)-radical
O
O
O
R
R
R
B-migration
SET
B
O
B
B
O
m
BPin
m
O
m
M+
BPin
BPin
VI
IV
V
C) 1,1-bisborylalkanes via 1,2-boron migration
O
B
O
B
O
B
1,2-B-migration
and SET
HAT
R
R
R
O
O
O
M+
M+
BPin
BPin
BPin
H
VII
VIII
IX
D) 1,n-bisborylalkanes via remote boron migration
remote
B-migration
O
B
O
O
B
R
R
B
m
R
m
O
m
and SET
O
O
BPin
M+
M+
BPin
BPin
X
XI
XII
In 2019, our group achieved transition metal free cross coupling of
organometallic reagents and organoboronic esters by
intermolecular α-HAT on the corresponding boronate complexes
with the trifluoromethyl radical followed by SET-oxidation and
ionic 1,2-alkyl/aryl migration.4d Encouraged by this study, we
decided to apply this strategy to prepare 1,1-bisborylalkanes via
diboronate complexes (see Scheme 1, C). The reaction of
bis(pinacolato)diboron (B2Pin2) with cyclopentylmagnesium
bromide (1.2 equiv) targeting gem-bisborylalkane 2a was selected
for optimization (Table 1).
diboronate complexes IV (m
= 0) are SET-oxidized to
intermediates of type II (R’ = BPin) which rearrange to geminal
bisborylalkanes via an ionic process.5 Herein, we disclose our
results on the systematic study of radical boron migration in radical
anions of type IV (m = 0-4) to give intermediates V where the two
B-atoms can interact. SET-oxidation finally leads to 1,n-
bisborylalkanes VI (Scheme 1, B). Considering, the 1,2-boron
shift, the radicals VIII are generated from ate complexes VII via
intermolecular hydrogen atom transfer (HAT)4d (Scheme 1, C).
Further, we will provide mechanistic insights into the reported5 1,2-
boron migration. In all other cases, site selective C-radical
generation (see XI) is achieved via radical addition to B-ate
complexes of type X (Scheme 1, D).
The diboronate complex 1a was generated in 1,2-dimethoxyethane
(DME) at 0 °C. The solvent was exchanged by acetonitrile and CF3I
was chosen as the terminal oxidant with the CF3-radical engaging
in selective HAT-abstraction at the -position to the B-atom in B-
ate complexes.4a Pleasingly, with tris[2-phenylpyridinato-
C2,N]iridium(III) (Ir(ppy)3, 1mol%) as a smart initiator13 at room
temperature, 2a was formed in 59% yield (Table 1, entry 1).
Besides 2a, we detected 8% cyclopentylboronic acid pinacol ester
The 1,2-boron shift to access geminal bisborylalkanes was studied
first. Notably, 1,1-bisborylalkanes are important building blocks to
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(Cp-BPin) and 14% B2Pin2. Other metal based and organic
isopropyl system provided the highest yield (80%, 2e). Due to the
higher steric demand of an ethyl over a methyl group, the yield of
2o was lower than the yields obtained for 1,1-bisborylalkanes 2e-
n. Of note, as Grignard reagents can be easily accessed from
commercial alkylbromides, the introduced method offers a cheap
and convenient approach to 1,1-bisborylalkanes.
1
2
3
4
5
6
7
8
initiators gave similar results (entry 2-6). The complex derived
from cyclopentylmagnesium chloride provided a slightly lower
yield (52%, entry 7, compare with entry 3), but the yield
significantly dropped to 18% with bis(neopentyl glycolato)diboron
(B2(neop)2) in place of B2Pin2 (entry 8). Without redox initiator, the
reaction also proceeded, albeit with lower efficiency (entry 9).
Upon lowering the temperature, formation of cyclopentylboronic
acid pinacol ester was suppressed and the yield of 2a improved to
68% (entry 10). Initiation by simple UV (365 nm) irradiation at -
Table 2. Geminal diborylation of alkylmagnesium bromides
- scope a
MgBr
o
MgBr+
20 C led to a further improvement, providing 2a in 76% yield
9
CF3I (1.5 equiv)
CH3CN, 365 nm
R1
O
O
BPin
H
(1.2 equiv)
R2
(entry 11). The boronate complex derived from cyclopentyllithium
gave a poor yield under the optimized conditions (16%, entry 12).
B
10
11
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BPin
R1
R2
B2Pin2
BPin
-20 oC, over night
DME, 0 oC, 1 h
R1
H
R2
Table 1. Reaction optimization for the 1,1-diborylation of
1
2
a
cyclopentylmagnesium bromide with B2Pin2
BPin
BPin
BPin
BPin
74%
BPin
BPin
47%
BPin
BPin
Ph
MgBr
MgBr+
2a
2b
PC (1 mol%)
BPin
44%
2c
2d
57%
O
O
(1.2 equiv)
CF3I (1.5 equiv)
B
BPin
BPin
B2Pin2
Entry
2e
2f
2g
2h
2i
DME, 0 oC, 1 h
H
80% (R = Me)
52% (R = n-Pr)
45% (R = n-Bu)
60% (R = n-pentyl)
59% (R = n-hexyl)
465 nm (3 W)
CH3CN, rt, 12 h
BPin
BPin
F3C
BPin
2a
1a
R
BPin
PC
2a
Cp-BPin
Conv
2j
2k
60% (R = n-C7H15
50% (R = n-C10H21
)
CF3
2l
33%
)
1
2
3
4
5
6
Ir(ppy)3
59%
62%
63%
56%
35%
49%
8%
7%
9%
8%
20%
5%
86%
85%
82%
83%
82%
74%
BPin
BPin
Ir(ppy)2(dtbbpy)PF6
Ru(bpy)3(PF6)2
Eosin Y
BPin
BPin
BPin
Ph
nBuO
2m
Et
Et
BPin
51%
2n
45%
2o
28%
Rose Bengal
a Conducted at 0.2 mmol scale. Isolated yields provided in all cases.
Rhodamine B base
7b
Ru(bpy)3(PF6)2
52%
18%
30%
68%
7%
82%
100%
65%
82%
91%
61%
Table 3. Reaction optimization for 1,3,4-trifunctionalization
of homoallylmagnesium bromide – 1,4-boron migrationa
8c
Ru(bpy)3(PF6)2
28%
20%
<1%
9
-
MgBr+
PinB
PinB
10d
11e
12g
Ru(bpy)3(PF6)2
O
MgBr
BPin
PC (1 mol%)
C4F9I (1.5 equiv)
B
-
-
76% (74%f)
<1%
(1.2 equiv)
O
B2Pin2
+
BPin
C4F9
I
solvent
465 nm (3W)
rt, 12 h
DME
0 oC, 1 h
16%
17%
C4F9
a
Reactions conducted on a 0.2 mmol scale in CH3CN (2 mL),
conversion determined based on the recovered bisboryl reagent,
yields were determined by GC analysis with n-tetradecane as
4a
4a-I
3a
4a
4a-I
4%
Conv
87%
85%
91%
93%
77%
80%
80%
94%
90%
95%
57%
Entry PC
solvent
CH3CN
DMSO
DMF
b
internal standard on the crude reaction mixture.
1
Ir(ppy)3
79%
<1%
5%
Cyclopentylmagnesium
cyclopentylmagnesium
glycolato)diboron
chloride
bromide.
(B2(neop)2)
used
instead
Bis(neopentyl
instead of
of
c
2
Ir(ppy)3
33%
11%
2%
used
bis(pinacolato)diboron (B2Pin2). d Reaction conducted at -20 oC. e
365 nm (3 W) at -20 oC. f Isolated yield. g Cyclopentyllithium used
instead of cyclopentylmagnesium bromide.
3
Ir(ppy)3
4
Ir(ppy)3
DMA
2%
5
Eosin Y
Rose Bengal
CH3CN
CH3CN
76%
75%
79%
44%
3%
6
4%
With optimized conditions in hand, we prepared a series of 1,1-
bisborylalkanes from different alkyl Grignard reagents (Table 2).
Both primary (2c-d) and secondary (2a-b, 2e-o) alkylmagnesium
bromides engaged in the transformation to afford 1,1-
bisborylalkanes in moderate to good yields (28-80%). Some
functionalities such as phenyl, trifluoromethyl and alkoxy moieties
were tolerated. The reaction was found to be sensitive to sterics.
For example, ate complex 1b derived from 3-phenyl
cyclopentylmagnesium bromide delivered the 1,1-bisboron
compound 2b with a decreased yield (44%) as compared to its less
bulky congener 1a (74%). Considering diboronate complexes
derived from primary alkylmagnesium bromides, the less bulky
ethyl derivative (2c) gave a slightly better yield than the
corresponding butyl-ate complex (2d). For complexes generated
from secondary alkylmagnesium bromides, the least bulky
7
Rhodamine B base CH3CN
CH3CN
Rhodamine B base CH3CN
CH3CN
Rhodamine B base CH3CN
3%
8
-
16%
9b
10d
11e
87% (83%c) 3%
-
87%
5%
3%
-
a Reactions conducted on a 0.2 mmol scale in the specified solvent
(2 mL), conversion (Conv) determined based on recovered bisboryl
reagent, yields determined by crude GC analysis with n-tetradecane
as internal standard. Conducted at -20 oC. c Isolated yield. 365
b
d
e
nm (3 W) at -20 oC. But-3-enyllithium, in situ generated by
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lithium/iodine exchange reaction of t-BuLi and 4-iodo-1-butene,
chemoselectively at the I-bearing C-atom to give 4h (61%).
1
2
3
4
5
6
7
8
used instead of but-3-enylmagnesium bromide, THF instead of
DME as solvent.
Iodoacetonitrile and ethyl iodoacetate only gave trace amounts of
the
targeted
products
(not
shown).
Unfortunately,
diastereoselectivity for the 1,4-boron shift in open chain systems
was very low (see 4i, 4j). However, for the cyclic rigid diboronate
complex 3k, 1,4-syn-boron-migration selectivity was complete and
also the initial CF3-radical addition occurred with excellent
stereocontrol (trans-addition) to provide product 4k as a single
diastereoisomer (64%).
We noted that there is currently no general method available for the
synthesis of 1,n-bisborylalkanes (n > 1)8a,14 and assumed the
unprecedented remote radical B-migration to offer an new
approach to access such compounds. Along these lines, we first
addressed the 1,4-boron migration and selected 3a, generated by
reacting B2Pin2 with but-3-enylmagnesium bromide, as model
substrate. To our delight, visible light irradiation (465 nm) of 3a in
the presence of C4F9I (1.5 equiv) and Ir(ppy)3 (1 mol%) as an
initiator in CH3CN provided the 1,3-bisborylalkane 4a in 79% yield
besides the iodine atom transfer product 4a-I (4%) and recovered
B2Pin2 (13%) (Table 3, entry 1). Solvent screening revealed that in
CH3CN better yields were obtained than in other polar solvents like
DMSO, DMF and DMA (entry 1-4). Ir(ppy)3 could be replaced by
organic dyes such as Eosin Y, Rose Bengal, and Rhodamine B base
without diminishing the yield (76-79%, entry 5-7). Without redox
initiator, the reaction also worked, but with lower efficiency (44%,
entry 8) and with the cheap organic Rhodamine B base as smart
initiator, the yield further increased to 87% upon lowering the
With 4-pentenylmagnesium bromide as starting material, we next
addressed the 1,5-boron migration and noted that with
perfluoroalkyl iodides as C-radical precursors, the I-atom transfer
compounds 5-I (not shown) were formed as major products and
targets 5 were obtained in low yields. Therefore, we had to switch
to the less reactive bromides. A moderate 31% yield of 5a was
achieved with n-perfluorohexyl bromide under the conditions
optimized for the 1,4-boron shift. Yield could be slightly improved
to 44% (see 5b) by installing a 3,3-dimethyl substitution pattern,
benefitting from the Thorpe-Ingold effect.15
9
10
11
12
13
14
15
16
17
18
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We also attempted the 1,6-boron migration on the homologous
diboronate complex derived from 5-hexenylmagnesium bromide
with CF3I as the radical precursor. However, the targeted 1,5
bisborylalkane was not identified and the reaction provided the
corresponding I-atom transfer product as the major product.
Switching to n-perfluorohexyl bromide, the 1,6-boron migration
product 6 could not be identified, indicating that this migration
cannot compete with other processes.
o
temperature to -20 C (entry 9). Notably, simple UV irradiation
(365 nm) at -20 oC in the absence of any initiator provided a similar
yield (entry 10). The boronate complex derived from but-3-
enyllithium gave a poor yield under the optimized conditions (5%,
entry 11).
Finally, to complete the series we tackled the 1,3-boron migration.
The required diboronate complex was formed by the reaction of
allylmagnesium bromide with B2Pin2. However, neither with
perfluorobutyl iodide nor with its bromide any 1,2-bisborylalkane
was identified and B2Pin2 was formed in large amount (85%) as
major product. Hence, SET-oxidation of allyl-B2Pin2MgX under all
tested conditions generating the stabilized allyl radical was too fast
and therefore this alkene could not act as a radical acceptor under
the applied conditions. Since we did not find any suitable system to
experimentally investigate the 1,3-boron migration, we decided to
approach that problem by using computational chemistry. DFT
calculations16 were performed on a series of pent-(m+1)-yl
substituted radical anions 7a-d (m=0-3, Scheme 2) to get a full
picture on the boron migration aptitude in these diboronate radical
anions.
Table 4. 1,4- and 1,5-boron migration reactions a
Rodamine B base
MgBr
MgBr+
(1 mol%)
O
R
Rf-I (1.5 equiv)
R
BPin
O
B
B2Pin2
Rf
CH3CN, -20 o
465 nm, 12 h
C
DME
0 oC, 1 h
BPin
R
BPin
3
4
Me
BPin
BPin Me
51%, dr = 1.25:1
BPin
BPin
F3C
Rf
F3C
BPin
BPin
4a
4b
4c
4d
4e
4f
83% (Rf = n-C4F9)
87% (Rf = CF3)
93% (Rf = C2F5)
82% (Rf = n-C3F7)
84% (Rf = n-C8F17
62% (Rf = n-C6F13
64% (Rf = i-C3F7)
61% (Rf = CF2CF2Cl)
4i
68%, dr = 1.2:1
4j
BPin
H
4k
64%, dr > 30:1
)
)
Scheme 2. DFT model calculations of diboronate radical anion
rearrangements
b
H
BPin
F3C
4g
4h
n=(3-m)
O
B
O
n
m
n
B
m
O
BPin
O
BPin
C6F13
BPin
B
n-C6F13
BPin n-C6F13
3
O
TS7b
TS7c
TS7d
(11.8)
(7.1)
(8.1)
O
BPin
BPin
BPin
b,c
m=1: 7b (0.0)
b,c
b,c
6
5b
not identified
5a
44%
31%
O
7c
7d
m=2:
m=3:
(0.0)
(0.0)
8b
8c
8d
(-9.1) 1,3-boron migration
(-16.8) 1,4-boron migration
(-16.5) 1,5-boron migration
n
m
B
a Conducted on a 0.2 mmol scale. b n-C6F13Br was used. c Reaction
conducted at room temperature.
O
B
O
O
O
Bu
Bu
Scope study of the trifunctionalization of homoallyl Grignard
reagents was conducted by applying the visible light/Rhodamine B
base initiation protocol (Table 3, entry 9) that proved to be more
general than the UV-initiation protocol. The perfluoroalkyl radical
precursor was varied first keeping complex 3a as the acceptor
(Table 4). Linear n-perfluoroalkyl iodides provided the
trifunctionalized 1,3-diboranes 4b-e in excellent yields (82-93%).
The less reactive n-perfluoroalkyl bromide also worked as C-
radical precursor, but as compared to the iodides, yield slightly
dropped (62%, 4f). With perfluoroisopropyl iodide a 64% yield of
4g was obtained. 1-Chloro-2-iodotetrafluoroethane reacted
B
n
m
O
O
O
BPin
CF3I
O
B
B
O
CF3I
SET
B
B
O
O
9b
9c
9d
(-64.3)
(-66.2)
(-65.8)
O
O
I-
CF3
8a
9a
(-55.2)
(0.0)
PWPB95-D3//PBE0-D3/def2-TZVP + COSMO-RS(MeCN)
In the study of the reactions, we have found bisborane radical anion
intermediates 8 with the spin localized in a BB single electron
bond, similar to those found in the 1,2-carboboration of alkenes
with B2Cat2.17 In case of the 1,2-boron migration (m=0),18 the
initial radical 7a exhibits this structure already, which means that
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Catal. DOI: 10.1002/adsc.201901503; (c) Tappin, N. D. C.; Renaud, P.
Radical Reactions of Boron-Ate Complexes Promoting a 1,2-Metaallate
Rearrangement. Chimia 2020, 74, 33-38.
1,2-boron radical migration is a spontaneous and barrierless
process. In the case of the distonic (m>0) radical anions 7b-7d, a
cyclization occurs with low free energy barriers (7-12 kcal/mol) to
form the analogous intermediates 8b-8d exergonically. These will
readily transfer likely assisted by the MgBr counter cation17c one
electron to the iodo reagent and regenerate the trifluoromethyl
radical, forming the 1,(m+1)-bisborylalkanes 9a-d. Compared to
the 1,4-boron migration, the barrier for the radical 1,3-boron
migration increases (from 7.1 kcal/mol to 11.8 kcal/mol). The 1,5-
boron migration (8.1 kcal/mol) showed a slightly higher barrier
than the 1,4-shift. In case of radical anion 7b (1,3-boron migration),
in the computation we did not find any indication for facile -
fragmentation leading to the B2Pin2-radical anion along with 1-
pentene. This supports our suggestion that the observed formation
of B2Pin2 in the reaction with allyl-B2Pin2MgX is likely caused by
initial SET-oxidation of allyl-B2Pin2MgX rather than -
fragmentation of the corresponding distonic radical anion of type
7b.
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(4) (a) Kischkewitz, M.; Okamoto, K.; Mück-Lichtenfeld, C.; Studer, A.,
Radical-polar crossover reactions of vinylboron ate complexes. Science
2017, 355, 936-938; (b) Gerleve, C.; Kischkewitz, M.; Studer, A., Synthesis
of alpha-Chiral Ketones and Chiral Alkanes Using Radical Polar Crossover
Reactions of Vinyl Boron Ate Complexes. Angew. Chem. Int. Ed. 2018, 57,
2441-2444; (c) Kischkewitz, M.; Gerleve, C.; Studer, A., Radical-Polar
Crossover Reactions of Dienylboronate Complexes: Synthesis of
Functionalized Allylboronic Esters. Org. Lett. 2018, 20, 3666-3669; (d)
Wang, D.; Mück-Lichtenfeld, C.; Studer, A., Hydrogen Atom Transfer
Induced Boron Retaining Coupling of Organoboronic Esters and
Organolithium Reagents. J. Am. Chem. Soc. 2019, 141, 14126-14130; (e)
Silvi, M.; Sandford, C.; Aggarwal, V. K., Merging Photoredox with 1,2-
Metallate Rearrangements: The Photochemical Alkylation of Vinyl
Boronate Complexes. J. Am. Chem. Soc. 2017, 139, 5736-5739; (f)
Lovinger, G. J.; Morken, J. P., Ni-Catalyzed Enantioselective Conjunctive
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Coupling with C(sp3) Electrophiles:
A Radical-Ionic Mechanistic
Dichotomy. J. Am. Chem. Soc. 2017, 139, 17293-17296; (g) Tappin, N. D.
C.; Gnägi-Lux, M.; Renaud, P., Radical-Triggered Three-Component
Coupling Reaction of Alkenylboronates, α-Halocarbonyl Compounds, and
Organolithium Reagents: The Inverse Ylid Mechanism. Chem. Eur. J.
2018, 24, 11498-11502.
(5) Zhao, B.; Li, Z.; Wu, Y.; Wang, Y.; Qian, J.; Yuan, Y.; Shi, Z., An
Olefinic 1,2-Boryl-Migration Enabled by Radical Addition: Construction
of gem-Bis(boryl)alkanes. Angew. Chem. Int. Ed. 2019, 58, 9448-9452.
(6) (a) Wu, C.; Wang, J., Geminal bis(boron) compounds: Their preparation
and synthetic applications. Tetrahedron Lett. 2018, 59, 2128-2140; (b)
Nallagonda, R.; Padala, K.; Masarwa, A., gem-Diborylalkanes: recent
advances in their preparation, transformation and application. Org. Biomol.
Chem. 2018, 16, 1050-1064; (c) Miralles, N.; Maza, R. J.; Fernández, E.,
Synthesis and Reactivity of 1,1-Diborylalkanes towards C–C Bond
Formation and Related Mechanisms. Adv. Synth. Catal. 2018, 360, 1306-
1327.
In summary, radical 1,2- and 1,4-boron migration reactions in
diboronate complexes derived from B2Pin2 are preparative useful
processes to access synthetically valuable 1,1- and 1,3-
bisborylalkanes. Considering the 1,3-functionalized compounds,
high selectivity in the boron migration can be achieved in cyclic
systems. The 1,5-boron migration leading to 1,4-bisborylalkanes is
also occurring, albeit with lower efficiency. The experimental
findings on the B-shift were supported by DFT calculations which
further revealed that the currently experimentally inaccessible 1,3-
boron migration to be feasible. Since B2Pin2 is commercially
available and the Grignard reagents are readily prepared from the
corresponding alkyl bromides, the introduced methods offers a
straightforward approach to 1,n-bisborylalkanes.
(7) (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) Sun, W.; Wang,
L.; Xia, C.; Liu, C., Dual Functionalization of α-Monoboryl Carbanions
through Deoxygenative Enolization with Carboxylic Acids. Angew. Chem.
2018, 130, 5599-5603; (c) Miura, T.; Nakahashi, J.; Zhou, W.; Shiratori,
Y.; Stewart, S. G.; Murakami, M., Enantioselective Synthesis of anti-1,2-
Oxaborinan-3-enes from Aldehydes and 1,1-Di(boryl)alk-3-enes Using
Ruthenium and Chiral Phosphoric Acid Catalysts. J. Am. Chem. Soc. 2017,
139, 10903-10908; (d) Miura, T.; Nakahashi, J.; Murakami, M.,
Enantioselective Synthesis of (E)-δ-Boryl-Substituted anti-Homoallylic
Alcohols Using Palladium and a Chiral Phosphoric Acid. Angew. Chem.
2017, 129, 7093-7097; (e) Liu, X.; Deaton, T. M.; Haeffner, F.; Morken, J.
P., A Boron Alkylidene–Alkene Cycloaddition Reaction: Application to the
Synthesis of Aphanamal. Angew. Chem. Int. Ed. 2017, 56, 11485-11489; (f)
Lee, Y.; Baek, S.-y.; Park, J.; Kim, S.-T.; Tussupbayev, S.; Kim, J.; Baik,
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website at DOI: xxx.
Experimental details and characterization data (PDF)
NMR spectrum of new compounds (PDF)
DFT calculations (PDF)
AUTHOR INFORMATION
Corresponding Author
studer@uni-muenster.de
M.-H.;
Cho,
S.
H.,
Chemoselective
Coupling
of
1,1-
Notes
Bis[(pinacolato)boryl]alkanes for the Transition-Metal-Free Borylation of
Aryl and Vinyl Halides: A Combined Experimental and Theoretical
Investigation. J. Am. Chem. Soc. 2017, 139, 976-984; (g) Murray, S. A.;
Green, J. C.; Tailor, S. B.; Meek, S. J., Enantio- and Diastereoselective 1,2-
Additions to α-Ketoesters with Diborylmethane and Substituted 1,1-
Diborylalkanes. Angew. Chem. Int. Ed. 2016, 55, 9065-9069; (h) Jo, W.;
Kim, J.; Choi, S.; Cho, S. H., Transition-Metal-Free Regioselective
Alkylation of Pyridine N-Oxides Using 1,1-Diborylalkanes as Alkylating
Reagents. Angew. Chem. 2016, 128, 9842-9846; (i) Joannou, M. V.; Moyer,
B. S.; Meek, S. J., Enantio- and Diastereoselective Synthesis of 1,2-
Hydroxyboronates through Cu-Catalyzed Additions of Alkylboronates to
Aldehydes. J. Am. Chem. Soc. 2015, 137, 6176-6179; (j) 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; (k) Sun, C.; Potter, B.; Morken, J. P., A
Catalytic Enantiotopic-Group-Selective Suzuki Reaction for the
Construction of Chiral Organoboronates. J. Am. Chem. Soc. 2014, 136,
6534-6537; (l) Potter, B.; Szymaniak, A. A.; Edelstein, E. K.; Morken, J.
P., Nonracemic Allylic Boronates through Enantiotopic-Group-Selective
Cross-Coupling of Geminal Bis(boronates) and Vinyl Halides. J. Am.
Chem. Soc. 2014, 136, 17918-17921; (m) 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,
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We thank the Alexander von Humboldt foundation (postdoctoral
fellowship to D.W.) and the European Research Council ERC
(advanced grant agreement No. 692640) for supporting this work.
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radical
B-migration
O
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R
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BPin
m
O
O
M+
SET
BPin
1,1-bisborylalkanes (m = 0)
1,3-bisborylalkanes (m = 2)
1,4-bisborylalkanes (m = 3)
generated by HAT
or radical addition
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