Transition-metal-free synthesis of vicinal triborated compounds and selective functionalisation of the internal C-B bond

Article abstract of DOI:10.1039/C8CC06153J

1,2,3-Triborated compounds can be prepared by simple nucleophilic borylation of 1,3-dienes, without the assistance of metal catalysts. Selective functionalisation of the internal C-B bond of the 1,2,3-triborated compounds, through cross-coupling with aryl

Full text of DOI:10.1039/C8CC06153J

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: E. Fernandez and
E. Davenport, Chem. Commun., 2018, DOI: 10.1039/C8CC06153J.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 4
View Article Online
DOI: 10.1039/C8CC06153J
Journal Name
COMMUNICATION
Transition-metal-free synthesis of vicinal triborated compounds
and selective functionalisation of the internal C-B bond
Elliot Davenport,a,b Elena Fernandez *a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
1,2,3-triborated compounds can be prepared by simple possibility to conduct
a 1,2,3-triboration reaction in a
nucleophilic borylation of 1,3-dienes, without assistance of metal transition-metal-free scenario, using allylic alcohols as
catalysts. Selective functionalisation of the internal C-B bond of substrates
and
conducting
a
one-pot
allylic
the 1,2,3-triborated compounds, through cross coupling with aryl borylation/diboration sequence (Scheme 1c).11 The activation
iodides, highlights the powerful methodology toward of the B2pin2 reagent was accomplished by the alkoxide
polyfunctionalisation.
formed from MeOH and base, that generates the Lewis acid–
base adduct, [Hbase]+[MeO-B2pin2]- characteristic of
a
nucleophilic sp2 boryl unit12 to promote the tandem
performance (Scheme 1c). Since transition-metal-free
borylations are gaining a representative space in the field of C-
B bond formation,13 we explored here a new synthetic
approach towards 1,2,3-triborated products by the simple
addition of B2pin2 and MeOH/base to 1,3-dienes (Scheme 1d)
Triboration reactions have been much less studied than the
corresponding hydroboration or diboration reactions, where
the addition of H-B or B-B reagents to unsaturated substrates
principally provides mono- and diborated products.1 However,
access to triborated compounds significantly enhances the
possibilities towards polyfunctionalisation, especially when
stereoselectivity is being achieved. That is the case of 1,1,2-
triborated alkenes,2-4 that further undergo stereoselective
polyfunctionalization to tetrasubstituted alkenes by
consecutive cross-coupling reactions. Similarly, 1,1,1-
triborylalkanes,5-8 have been efficiently prepared towards
selective functionalisation.
Introducing three vicinal boryl moieties in a one-pot protocol,
represents a challenging reaction. The triboration of alkyne
towards 1,2,3-triborated compounds has been accomplished
by Yoshida and co-workers9 via Cu-PCy3 catalysed
borylcupration of phenyl 2-alkynyl methyl ether followed by
σ-
bond metathesis of the -allyl copper intermediates (Scheme
π
1a). Alternatively, Ma and co-workers10 proved a highly
selective 1,2,3-triboration of propargylic carbonates to
generate (E)-propen-1,2,3-triboronates, by using two catalytic
systems Pd(PPh3)4 and CuCl, and suggesting the formation of
1,2-allenyl boronate intermediates (Scheme 1b). All the efforts
devoted to introduce three C-B bonds in a one-pot sequential
reaction required transition metal complexes to activate the
borane reagent and facilitate the addition to the saturated or
unsaturated substrates. Our group was the first to observe the
Scheme 1. Synthetic approaches towards 1,2,3-triborated compounds: a) Cu(II)
catalyzed triboration of phenyl 2-alkynyl methyl ether, b) Pd(0)/Cu(I) co-
catalyzed triboration of propargyl carbonates, c) transition metal-free
triboration of allylic alcohols and d) alternative transition-metal-free triboration
in this work
Initial substrate evaluation was conducted with trans-1-
phenyl-1,3-butadiene (1) and 1.1 equiv of B2pin2 in the
presence of 15 mol% of Na2CO3 and MeOH as solvent (1 mL).
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 4
View Article Online
DOI: 10.1039/C8CC06153J
COMMUNICATION
Journal Name
The model reaction was carried out at 90ºC and the analysis of the sequential one-pot 1,4-hydroboration/diboration reaction,
the unpurified reaction mixture, by 1H NMR spectroscopy, with exclusive formation of the 1,2,3-triborated product. The
established 47% conversion towards the 1,4-hydroborated substrate (E)-1-(buta-1,3-dien-1-yl)-4-chlorobenzene (
7) was
product
2
and 22% of triborated product
3
(Scheme 2). The quantitatively transformed into the corresponding triborated
purification of the allylboronate product
2
allowed its isolation product
8
(Table 1, entry 2), whereas the electron rich
),
and (E)-1-
generated the
12 and 14 in 80-99% NMR yield (Table
underwent 1,4-hydroboration with HBpin in the presence of 1, entries 3-5). For the ortho-substituted-aryl-1,3-diene (E)-1-
iminopyridine Fe complexes, but forming principally the (buta-1,3-dien-1-yl)-2-methoxybenzene 15 the triboration
secondary (Z)-allylboronate. The synthesis of primary (Z)- reaction also proceed with high conversions (Table 1, entry 6).
allylboronates from the 1,4-hydroboration of has been Substrates with furyl and pyridyl groups such as (E)-2-(buta-
carried out with Ni catalysts and HBpin15 or Cu catalysts and 1,3-dien-1-yl)furan (17) and (E)-3-(buta-1,3-dien-1-yl)pyridine
B2pin2.16 Under our transition-metal-free initial conditions, we
19) could be moderately triborated (Table 1, entries 7, 8),
in 40% with a (E)/(Z) ratio of 2/1, respectively. Remarkably, this substrates (E)-4-(buta-1,3-dien-1-yl)-N,N-dimethylaniline
is the first attempt to borylate 1,3-dienes in a transition-metal- (E)-1-(buta-1,3-dien-1-yl)-4-methylbenzene 11
free context and the results seems to be complementary to (buta-1,3-dien-1-yl)-4-methoxybenzene 13
Huang and co-workers’ work,14 where the same substrate
triborated products 10
(9
(
)
(
)
1
,
(
)
1
(
explored the influence of the amount of B2pin2, as well as the although substrate 19 experimented some polymerization as a
base involved, and we found that by increasing the amount of secondary reaction. Interestingly, two distinctive type of
signals appeared in the 11B NMR spectra of triborated products
diboron reagent to 3 equivalents, the triborated product
3
could be formed exclusively, probably due to the in situ 18 (33.5 and 30.4 ppm) and 20 (34.4 and 22.2 ppm), that might
transition-metal-free diboration of 2 towards 3 (Scheme 2). suggest a plausible interaction between the closest Bpin unit
Despite the fact that other bases (Cs2CO3, NaOtBu) worked and O or n, respectively.
similarly, we selected Na2CO3 to extend the study to other 1-
Table 1. Transition-metal-free triboration of trans-1-aryl-1,3-butadienes, (E)-2-(buta-
1,3-dien-1-yl)furan and (E)-3-(buta-1,3-dien-1-yl)pyridine.a
substituted 1,3-dienes. When trans-1-methyl-1,3-butadiene (
reacted with 1.1 equiv of B2pin2 the 1,2-diboration of the
terminal alkene took place instead, to form product in 58%
4)
5
NMR yield, (33% isolated) (Scheme 2). However, the excess of
B2pin2 favored the quantitative formation of 1,2,3,4-
tetraborylated product 6, that could be isolated in 52% yield
Entry
1
Substrate
Product
%NMR Yieldb [%IY]c
94%[71%]
(Scheme 2). It seems that the competitive 1,2-diboration
versus 1,4-hydroboration is favored when there is no
conjugation with the alkyl group,17,18 in contrast to the Fe-Mg
catalyzed 1,4-hydroboration of 1-alkyl-substituted 1,3-dienes
or 2-alkyl-substituted 1,3-dienes, observed by the groups of
Huang and Ritter, respectively.14,19
Bpin
Bpin
2
3
4
5
6
7
8
99%[50%]
83%[60%]
85%[65%]
99%[60%]
99%[65%]
70%[64%]
33%[10%]
Bpin
Cl
8
OMe
Bpin
Bpin
Bpin
16
Scheme 2. Transition-metal-free borylation of trans-1-phenyl-1,3-butadiene and
trans-1-methyl-1,3-butadiene.
Based on the optimised reaction conditions for the triboration
aReaction conditions: Substrate (0.2 mmol), B2pin2 (3 eq), Na2CO3 (30 mol%), MeOH (1
mL), 90ºC, 16h. b% NMR yields calculated in 1H NMR spectra with naphthalene as
internal standard. c[% Isolated yields].
of trans-1-phenyl 1,3-dienes with the Lewis acid–base adduct,
[Hbase]+[MeO-B2pin2]-, we extended the study to
a
representative scope of trans-1-aryl-1,3-butadienes. Table 1
shows the range of aryl substituents that efficiently followed
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 3 of 4
View Article Online
DOI: 10.1039/C8CC06153J
Journal Name
COMMUNICATION
The more sterically hindered substrate buta-1,3-diene-1,1- (2-bromobuta-1,3-dien-1-yl)benzene (33) was borylated, we
diyldibenzene 21 was triborated under the previous observed as the unique product the triborated compound 3
(
)
optimized reaction conditions. The expected 1,2,3-triborated (Table 2, entry 7). Its formation might be explained by the
1
product was formed in 56% but the H NMR of the crude also bromide elimination after the initial C-B formation, generating
showed the presence of 1,4-hydroborated (14%) and 1,2- an allene intermediate
hydroborated (15%) as byproducts (Table 2, entry 1). The more protodeborylation to form the model 1,3-diene
sterically hindrance in 21 might difficult the diboration from triborated towards (Scheme 3). In order to confirm the
the 1,4-hydroborated intermediate. The internal 1,3-dienes implication of the allene intermediate 34 in the reaction,20 we
(penta-1,3-dien-1-yl)benzene (23), 1-chloro-4-(penta-1,3-dien- conducted the triboration of but-3-en-1-yn-1-ylbenzene (35
1-yl)benzene 25 and N,N-dimethyl-4-(penta-1,3-dien-1- under the same reaction conditions (Scheme 3). This
yl)aniline (27) are triborated with less extension (substrate is experiment allowed product as the unique triborated
(
34)
that could suffer
γ-
1
that is in situ
3
)
(
)
3
still remained in the 1H NMR of the crude) since the first product with similar percentage as the triboration of 33 (Table
nucleophilic borylation is sterically disfavored (Table 2, entries 2, entry 8). The low yield might be due to the consumption of
2-4). From the previous results we expected no triboration of the diboron reagent along the sequential hydroboration of the
substrate (E)-(4-methylpenta-1,3-dien-1-yl)benzene (29), and original substrate, followed by hydroboration/diboration of
1
in fact less than 10% was detected by H NMR (Table 2, entry the 1,3-diene intermediate
5).
Table 2. Transition-metal-free triboration of sterically hindered trans-1-aryl-1,3-
butadienesa
Entry
1
Substrate
Product
%NMRYield[%IY]b
56%[47%]
Scheme 3. Transition-metal-free triboration of substrate (Z)-(2-bromobuta-1,3-
dien-1-yl)benzene and but-3-en-1-yn-1-ylbenzene
In order to explore a plausible polifunctionalisation of the
1,2,3-triborated products, we conducted a straightforward
cross coupling reaction of the model triborated product
3 with
1-iodo-4-methylbenzene and, to our delight, we could observe
that the internal C-B2 bond from the 1,2,3-vicinal triborated
specie reacted selectively to form the new C-C bond providing
53%[30%]
40%[20%]
2
3
the compound 36 (Scheme 4). Similarly,
3 was transformed
into the arylated product 37 when reacted with 1-iodo-4-
methoxybenzene (Scheme 4). To the best of our knowledge,
this is the first time that this type of 1,3-diborated products
have been prepared, and only the unsaturated version 2,4-
Bpin
Bpin
28
52%[30%]
< 10%
4
Bpin
Me2N
diphenyl 1,3‐bis(4,4,5,5‐tetramethyl[1,3,2] dioxaborolan‐2‐yl)‐
buta 1Z,3E diene was prepared through zirconocene-mediated
‐
reductive cyclization of alkynylboronates followed by
‐
5c
6
treatment with acid.21
Pd(OAc)2
O
Ar
O
B
O
O
68%[48%]
30%[15%]
34%[31%]
O
B2
O
B
RuPhos
B3
O
1 O
B3
O
1 O
Ar-I
Ar
THF/H2O (10:1)
90ºC, 12h
Bpin
Ar
Bpin
7
Bpin
3
H2O2/NaOH
Bpin
OH
8
Bpin
36, 22%
OH
35
40, 20%
OMe
aReaction conditions: Substrate (0.2 mmol), B2pin2 (3 eq) Na2CO3 (30 mol%),
MeOH (1 mL), 90ºC, 16h; b%NMR yields, [%Isolated yields]; c110ºC
OMe
Bpin
Bpin
Bpin
Bpin
O
Bpin
41, 50%
Bpin
37, 40%
Bpin
39, 40%
Bpin
38, 30%
Interestingly,
substrate
(E)-(2-methylbuta-1,3-dien-1-
MeO
yl)benzene (31) could be efficiently converted to the desired
product 32, despite the methyl-substitution at the internal
double bond (Table 2, entry 6). When the similar substrate (Z)-
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 4
View Article Online
DOI: 10.1039/C8CC06153J
COMMUNICATION
Journal Name
Scheme 4. Cross-coupling of 1,2,3-triborated products with 1-iodo-4-
methylbenzene and 1-iodo-4-methoxybenzene in the presence of
B. Marder, J. M. Murphy, J. F. Hartwig, Chem. Rev., 2010,
110, 890; e) H. E. Burks, J. P. Morken, Chem. Commun., 2007,
4717.
Pd(OAc)2/RuPhos, and in situ oxidation of 36
.
2
a) G. Lesley, P. Nguyen, N. J. Taylor, T. B. Marder, A. J. Scott,
W. Clegg, N. C. Norman, Organometallics 1996, 15, 5137; b)
H. Abu Ali, A. E. A. Al Quntar, I. Goldberg, M. Srebnik,
Organometallics 2002, 21, 4533.
Unlike to the functionalisation of the terminal C-B bond in 1,2-
diborated vicinal products observed by Morken et al.,22 in our
hands the 1,2,3-triborated species allows a selective cross-
coupling at the internal B2, under the same reaction
conditions. The reaction has been extended to the cross-
coupling between 1-iodo-4-methylbenzene and the 1,2,3-
3
4
K. Hyodo, M. Suetsugu, Y. Nishihara, Org. Lett. 2014, 16, 440.
C.-I. Lee, W.-C. Shih, J. Zhou, J. H. Reibenspies, O. V. Ozerov,
Angew. Chem., Int. Ed. 2015, 54, 14003.
Y. Gu, H. Pritzkow, W. Siebert, Eur. J. Inorg. Chem. 2001, 373.
T. Mita, Y. Ikeda, K. Michigami, Y. Sato, Chem. Commun.,
2013, 49, 5601.
a) W. N. Palmer, J. V. Obligacion, I. Pappas, P. J. Chirik, J. Am.
Chem. Soc., 2016, 138, 766; b) W. N. Palmer, C. Zarate, P. J.
Chirik, J. Am. Chem. Soc., 2017, 139, 2589.
S. Krautwald, M. J. Bezdek, P. J. Chirik, J. Am. Chem. Soc.,
2017, 139, 3868.
5
6
triborated compounds 14
general for para- and ortho- substituted aryl systems as well as
the furyl group forming the desired products 38 39 and 41
, 16 and 18 making the protocol
7
,
respectively (Scheme 4). Product 38 could be full characterised
by X-Ray diffraction (Figure 1). Following with the attempt to
fully functionalise the triborated compounds, we proceeded
towards the in situ oxidation of the diborated product 36, in
the presence of H2O2/NaOH, forming the corresponding 1,3-
butanediol 2,4-diaryl system 40 (Scheme 4).
8
9
H. Yoshida, S. Kawashima, Y. Takemoto, K. Okada, J. Ohshita,
K. Takaki, Angew. Chem. Int. Ed., 2012, 51, 235.
10 Z. Yang, T. Cao, Y. Han, W. Lin, Q. Liu, Y. Tang, Y. Zhai, M. Jia,
W. Zhang, T. Zhu, S. Ma, Chin. J. Chem. 2017, 35, 1251.
11 N. Miralles, R. Alam, K. Szabó, E. Fernández, Angew. Chem.
Int. Ed., 2016, 55, 4303.
12 J. Cid, H. Gulyás, J. J. Carbó, E. Fernández, Chem. Soc. Rev.
2012, 41, 3558.
13 A. B. Cuenca, R. Shishido, H. Ito, E. Fernández, Chem. Soc.
Rev. 2017, 46, 415.
14 Y. Cao, Y. Zhang, L. Zhang, D. Zhang, X. Leng, Z. Huang, Org.
Chem. Front., 2014,
15 a) R. J. Ely, J. P. Morken, J. Am. Chem. Soc., 2010, 132, 2534;
1,1101.
38
Figure 1. X-Ray Diffraction Data for compound 38
b) R. J. Ely,, Z. Yu, J. P. Morken, Tetrahedron Lett., 2015, 56
3402.
,
.
16 K. Semba, M. Shinomiya, T. Fujihara, J. Terao, Y. Tsuji, Chem.
Eur. J. 2013, 19, 7125.
17 M. Zaidlewicz, J. Meller, Tetrahedron Lett., 1997, 38, 7279.
18 Competitive copper catalyzed 1,2- versus 1,4-arylborylation:
In conclusion, we have been able to perform a direct 1,2,3-
triboration reaction in a transition metal-free context, by 1,4-
hydroboration of 1,3-dienes followed by in situ diboration
reaction of the internal double bond. In order to confirm the
S. R. Sardini, M. K. Brown, J. Am. Chem. Soc., 2017, 139
9823.
19 J. Y. Wu, B. Moreau, T. Ritter, J. Am. Chem. Soc., 2009, 131
12915.
20 C. Zhu, B. Yang, Y. Qiu, J.-E. Bäckvall, Chem. Eur. J., 2016, 22
2939.
,
,
,
suggested mechanism, the 1,4-hydroborated intermediate
was isolated and a consequent diboration under the same
reaction conditions took place to form exclusively product
2
3.
The reactions are carried out with quantitative conversion for
terminal 1,2-dienes, and moderate yields for internal 1,3-
dienes, with tolerance to heterofunctional groups. When the
1,2,3-triborated compounds were exposed to cross coupling
conditions, only the internal C-B bond could be arylated in a
selective way, as a plausible double assistance of the two
vicinal boryl moieties. This is an unprecented access to 1,2,3-
triborated compounds but also the fact that they can be
exclusively functionalised makes this methodology of great
applicability in synthetic organic purposes.
21 a) G. Desurmont, R. Klein, S. Uhlenbrock, L. Laloe, L. Deloux
D. M. Giolando, J. M. Kim, S. Pereira, M. Srebnik M.
Organometallics 1996, 15, 3323; b) A. Shibli, H. Abu Ali, I.
Goldberg, M. Srebnik, Appl. Organomet. Chem., 2005, 19
171.
,
22 S. N. Mlynarski, C. H. Schuster, J. P. Morken, Nature, 2014,
505, 386.
The present research was supported by the Spanish Ministerio
de Economia y competitividad (MINECO) through project
FEDER-CTQ2016-80328-P. We thank AllyChem for the gift of
diboranes
Notes and references
1
a) E. C. Neeve, S. J. Geiger, I. A. I. Mkhalid, S. A. Westcott, T.
B. Marder, Chem. Rev., 2016, 116, 9091; b) J. Takaya, N.
Iwasawa, ACS Catal., 2012, 2, 1993; c) J. F. Hartwig, Chem.
Soc. Rev., 2011, 40, 1992; d) I. A. I. Mkhalid, J. H. Barnard, T.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins