Diborylation of alkynyl MIDA boronates and sequential chemoselective suzuki-miyaura couplings: A formal carboborylation of alkynes

Article abstract of DOI:10.1021/ol403326z

Platinum-catalyzed diborylation of phenylethynyl MIDA boronate with Bpin-Bpin proceeds to yield 1,1,2-triboryl-2-phenylethene with two different classes of the boron functionalities. Sequentially, the obtained 1,1,2-triboryl-2-phenylethene are subjected to Suzuki-Miyaura coupling to introduce a series of aryl groups chemoselectively to afford 1,1-boryl-2,2-diarylethenes.

Full text of DOI:10.1021/ol403326z

Letter
pubs.acs.org/OrgLett
Diborylation of Alkynyl MIDA Boronates and Sequential
Chemoselective Suzuki−Miyaura Couplings: A Formal
Carboborylation of Alkynes
Keita Hyodo,† Masato Suetsugu,† and Yasushi Nishihara*,†,§
†Division of Earth, Life, and Molecular Sciences, Graduate School of Nature Science and Technology, Okayama University, 3-1-1
Tsushimanaka, Kita-ku, Okayama 700-8530, Japan
§Japan Science and Technology Agency, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
S
* Supporting Information
ABSTRACT: Platinum-catalyzed diborylation of phenyl-
ethynyl MIDA boronate with Bpin−Bpin proceeds to yield
1,1,2-triboryl-2-phenylethene with two different classes of the
boron functionalities. Sequentially, the obtained 1,1,2-triboryl-
2-phenylethene are subjected to Suzuki−Miyaura coupling to
introduce a series of aryl groups chemoselectively to afford 1,1-boryl-2,2-diarylethenes.
ransition-metal-mediated1 and -catalyzed2 diborylation of
Scheme 1. Synthesis of Phenylethynyl MIDA Boronate 1
T
unsaturated organic molecules has received much
attention in the past decades after an emergence of compounds
bearing the B−B bond because of low toxic, economical and
maturely synthetic studies on these compounds.3 To synthesize
vic-bis(boryl)alkenes that are valuable starting materials for the
preparation of, for instance, bioactive chemicals or functional
materials through iterative transfomations, particularly, Suzuki−
Miyaura coupling,4 the transition-metal-catalyzed diborylation
of alkynes has been exploited extensively.5−8 The kinetic and
mechanistic studies on the platinum-catalyzed diborylation of
internal alkynes has been extensively exploited; platinum
diboryl complexes derived from oxidative addition of the B−
B bond have been isolated.9 The synthesized diborylated
alkenes can be transformed to the various organic compounds
with an aid of Suzuki−Miyaura coupling and other methods.10
But, when unsymmetrical vic-diborylalkenes are employed, an
accomplishment of chemoselective monofuctinalization was
found to be troublesome.11 We thus chose the masked
alkynylboron compounds alternative to the internal alkynes
because the diborylated product have different reactivity among
three C−B bonds. Among the reported several protective
groups,12,13 we chose the MIDA (N-methyliminodiacetic acid)
boronates.14,15 Herein, we report the platinum-catalyzed
diborylation of phenylethynyl MIDA boronates with bis-
(pinacolato)diboron ((Bpin)2), yielding 1,1,2-triboryalkenes
with a perfect stereoselectivity, followed by chemoselective
Suzuki−Miyaura coupling to give rise to an exclusive formation
of (Z)-1,1-diboryl-2-diarylethenes.16
Next, we investigated the platinum-catalyzed diborylation5b
of 1 with bis(pinacolato)diboron in toluene at 100 °C to afford
triborylated ethene 2 in 86% yield, as shown in Scheme 2. The
11B{1H} NMR spectrum of 2 in DMSO-d6 showed three
independent signals at δ 6.94, 11.1, 31.4.
Scheme 2. Platinum-Catalyzed Diborylation of 1
With the synthesized triborylated compound 2 in hand, we
screened the reaction conditions of the palladium-catalyzed
arylation reaction with 4-anisyl iodide. The results are listed in
Table 1. Among the palladium catalysts tested without any
ligands, Pd(dba)2 was found to be the best catalyst to give the
arylated product 3a in 67% yield (entries 1−4). In the 1H NMR
spectrum of the formed product 3a only one set of the Bpin
moiety was observed, indicating that one of two Bpin was
We first prepared phenylethynyl MIDA boronate 1 according
to the synthetic procedure for ethynyl MIDA boronate, utilizing
ethynylmagnesium bromide.15f Treatment of phenylethyne
with an equimolar of EtMgBr, followed by reaction with
B(OMe)3 at −78 °C for 1 h and an excess of MIDA at 130 °C,
gave rise to the desired 1-phenyethynyl MIDA boronate 1 in
83% yield as a white powder (Scheme 1).
Received: November 17, 2013
© XXXX American Chemical Society
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Table 1. Screening the Palladium Catalyst and the Ligand for
Suzuki−Miyaura Coupling of 2 with 4-Anisyl Iodide
Table 2. Chemoselective Suzuki−Miyaura Coupling of 2
a
a
with Aryl Iodides
b
entry
aryl
time (h)
product
yield (%)
b
entry
Pd cat.
ligand (mol %)
yield (%)
1
4-Me2NC6H4
4-MeCOC6H4
4-EtCO2C6H4
4-NCC6H4
4-CF3C6H4
3-MeOC6H4
3-MeC6H4
2-MeC6H4
1-naphthyl
4-FC6H4
9
12
9
3c
3d
3e
3f
74
77
88
84
87
75
80
83
60
85
83
46
1
2
3
4
5
Pd(PPh3)4
Pd(dba)2
39
67
53
50
57
72
61
72
62
49
91
2
3
PdCl2(NCPh)2
PdCl(dppf)
Pd(dba)2
4
9
5
6
3g
3h
3i
PEt3
6
16
12
9
c
6
Pd(dba)2
PtBu3
7
7
Pd(dba)2
PPh3
8
3j
8
Pd(dba)2
P(mesityl)3
XPhos
9
24
9
3k
3l
9
Pd(dba)2
10
11
12
10
Pd(dba)2
SPhos
HPtBu3BF4
3-FC6H4
12
16
3m
3n
d
11
Pd(dba)2
2-FC6H4
a
a
Reaction conditions: 2 (0.1 mmol), 4-anisyl iodide (0.1 mmol), Pd
Reaction conditions: 2 (0.1 mmol), aryl iodide (0.12 mmol),
Pd(dba)2 (5 mol %), HPtBu3BF4 (5 mol %), K3PO4 (0.3 mmol) in
DMSO (2 mL) at 80 °C. Isolated yields after column
chromatography.
catalyst (5 mol %), ligand (10 mol %), K2CO3 (0.3 mmol) in DMSO
b
b
(2 mL) at 80 °C for 16 h, unless otherwise stated. NMR yields.
c
d
Ligand (5 mol %). Pd catalyst (5 mol %), ligand (5 mol %), K3PO4
(0.3 mmol), 4-anisyl iodide (0.12 mmol), reaction time 9 h.
iodides bearing electron-donating (entry 1) and electron-
withdrawing (entries 2−5) groups in the 4-position with 2
proceeded in high yields. The substituted aryl iodides in the 3-
position also afforded the corresponding cross-coupling
products 3h and 3i in 75% and 80% yields, respectively
(entries 6 and 7). However, a sterically hindered 1-naphthyl
iodide required a longer reaction time and gave the desired
product 3k in 60% yield (entry 9).
replaced with a 4-anisyl group in preference to the Bmida moiety.
Next, we elucidated the effect of the ligand. With a comparison
of the phosphine ligands, the bulkier ligands gave the higher
yield of the desired product (entry 5 vs 6 and entry 7 vs 8).
Buchwald’s biphenyl-based ligands such as Xphos (2-
dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl)17 and
Sphos (2-dicyclohexylphosphine-2′,6′-dimethoxybiphenyl)18
gave inferior results (entries 9 and 10). Finally, we found that
the optimized condition; Pd(dba)2 (5 mol %), HPtBu3BF4 (5
mol %) in the presence of K3PO4 as the base, gave 91% of 3a
(entry 11). Although a variety of aryl iodides reacted smoothly,
under the optimized reaction conditions, the corresponding
aryl bromide (28%) and aryl chloride (0%) are found to be
unsuitable for the present reaction.
In order to compare an effect of the substituents in the
present cross-coupling reaction, the reactions of 2 with various
aryl fluorides were subjected. Under the optimized conditions,
chemoselective cross-coupling of p- and m-fluoroiodobenzenes
occurred to generate the corresponding arylated products 3l
and 3m as a sole product in 85% and 83% yields, respectively
(entries 10 and 11). In a sharp contrast, o-fluoroiodobenzene
gave the formation of 3n in only 46% yield, indicating that
reductive elimination of the cross-coupled product 3n was
certainly suppressed owing to the fluorine atom (entry 12).21
This is the first example to obtain gem-diborylated olefins
with two different boryl groups via a chemoselective arylation,
which is synthetically equivalent to carboborylation of the
alkynyl MIDA boronate. Although the conformational energies
(A values)22 of the Bmida groups has not been reported, the
chemoselectivity can be explained simply by a steric effect
because even an addition of 2 molar amounts of aryl iodides did
not form the diarylated products.23 Although other electro-
philes such as allyl chloride, ethyl iodide, (E)-octenyl iodide
were subjected to Suzuki−Miyaura coupling reactions of 2, no
desired coupled products were formed. When 2 reacted with
benzyl chloride (Scheme 4), only one isomer 5 was obtained in
38% yield as observed in the case of reactions with aryl
iodides.24
In order to determine the configuration of the arylated
product 3, Suzuki−Miyaura coupling of 2 with iodobenzene
affording 3b and sequential transformation of the Bmida group
into the Bpin group was carried out (Scheme 3). With a
Scheme 3. Determination of Stereochemistry of the Arylated
Product 3
procedure reported by Burke,15i the intermediate 3b was
treated with pinacol in the presence of NaHCO3 to generate 4
whose spectroscopic data were identical to those of an
authentic sample.19 The gem-diborylated olefins have been
known as useful building blocks for functional materials, natural
products, as well as bioactive pharmaceuticals.20
Furthermore, the present reaction of aromatic 1-alkynyl
MIDA boronate was extended to the reaction of an aliphatic 1-
alkynyl MIDA boronate. Accordingly, an 1-octynyl MIDA
boronate 6 was successfully synthesized from octynylmagne-
sium bromide in 53% yield. Compound 6 was subjected to the
Next, a series of aryl iodides were subjected to survey the
reaction scope. As shown in Table 2, the reactions of aryl
B
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Letter
Scheme 4. Suzuki−Miyaura Coupling of 2 with Benzyl
Chloride
REFERENCES
■
(1) Urry, G.; Kerrigan, J.; Parsons, T. D.; Schlesinger, H. I. J. Am.
Chem. Soc. 1954, 76, 5299.
(2) For reviews on diborylation of unsaturated C−C bonds, see:
(a) Marder, T. B.; Norman, N. C. Top. Catal. 1998, 5, 63.
(b) Ishiyama, T.; Miyaura, N. J. Organomet. Chem. 2000, 611, 392.
(c) Ishiyama, T.; Miyaura, N. Chem. Rec. 2004, 3, 271.
(3) (a) Buynak, J. D.; Geng, B. Organometallics 1995, 14, 3112.
(b) Suginome, M.; Matsuda, T.; Ito, Y. Organometallics 2000, 19, 4647.
(c) Suginome, M.; Noguchi, H.; Hasui, T.; Murakami, M. Bull. Chem.
Soc. Jpn. 2005, 78, 323. (d) Ohmura, T.; Masuda, K.; Furukawa, H.;
Suginome, M. Organometallics 2007, 26, 1291.
(4) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Miyaura, N. In Advances in Metal-Organic Chemistry; Liebeskind, L.
S., Eds.; JAI: Stanford, 1998; Vol. 6, p 187. (c) Suzuki, A. In Metal-
Catalysed Cross-Coupling Reactions; Stang, P. J., Ed.; VCH: Weinheim,
1998; p 49.
Pt-catalyzed diborylation with bis(pinacolato)diboron, afford-
ing 7 in 62% yield. Finally, the obtained hexylated triborylated
ethene 7 reacted with iodobenzene to produce the desired
products 8 (Scheme 5).
Scheme 5. Application to an Aliphatic 1-Alkynyl MIDA
Boronate
(5) Pt(PPh3)4: (a) Ishiyama, T.; Matsuda, N.; Miyaura, N.; Suzuki, A.
J. Am. Chem. Soc. 1993, 115, 11018. (b) Ishiyama, T.; Matsuda, N.;
Murata, M.; Ozawa, F.; Suzuki, A.; Miyaura, N. Organometallics 1996,
15, 713. (c) Prokopcova, H.; Ramirez, J.; Fernandez, E.; Kappe, C. O.
Tetrahedron Lett. 2008, 49, 4831.
(6) Other Pt catalysts: (a) Thomas, R. L.; Souza, F. E. S.; Marder, T.
B. J. Chem. Soc., Dalton Trans. 2001, 1650. (b) Lillo, V.; Mata, J.;
Ramirez, J.; Peris, E.; Fernandez, E. Organometallics 2006, 25, 5829.
(c) Braunschweig, H.; Kupfer, T.; Lutz, M.; Radacki, K.; Seeler, F.;
Sigritz, R. Angew. Chem., Int. Ed. 2006, 45, 8048.
(7) Co: Adams, C. J; Baber, R. A.; Batsanov, A. S; Bramham, G.;
Charmant, J. P. H.; Haddow, M. F.; Howard, J. A. K.; Lam, W. H.; Lin,
Z.; Marder, T. B; Norman, N. C.; Orpen, A. G. Dalton Trans. 2006,
1370.
(8) Cu: Yoshida, H.; Kawashima, S.; Takemoto, Y.; Okada, K.;
Ohshita, J.; Takaki, K. Angew. Chem., Int. Ed. 2012, 51, 235.
(9) (a) Iverson, C. N.; Smith, M. R., III. J. Am. Chem. Soc. 1995, 117,
4403. (b) Iverson, C. N.; Smith, M. R., III. Organometallics 1996, 15,
5155. (c) Lesley, G.; Nguyen, P.; Taylor, N. J.; Marder, T. B.; Scott, A.
J.; Clegg, W.; Norman, N. C. Organometallics 1996, 15, 5137.
(10) For reviews, see: (a) Dembitsky, V. M.; Ali, H. A.; Srebnik, M.
Appl. Organomet. Chem. 2003, 17, 327. (b) Shimizu, M.; Hiyama, T.
Proc. Jpn. Acad., Ser. B 2008, 84, 75.
(11) In some cases high chemoselectivity was achieved, but the
reactions are accompanied by double-coupled products and/or a
mixture of regioisomers; see: (a) Ishiyama, T.; Yamamoto, M.;
Miyaura, N. Chem. Lett. 1996, 1117. (b) Brown, S. D.; Armstrong, R.
W. J. Am. Chem. Soc. 1996, 118, 6331. (c) Brown, S. D.; Armstrong, R.
W. J. Org. Chem. 1997, 62, 7076. (d) Wenckens, M.; Jakobsen, P.;
Vedso, P.; Huusfeldt, P. O.; Gissel, B.; Barfoed, M.; Brockdorff, B. L.;
Lykkesfeldt, A. E.; Begtrup, M. Bioorg. Med. Chem. 2003, 11, 1883.
(12) Oxygen-based protective groups for the boronyl group:
(a) Contreras, R.; Garcia, C.; Mancilla, T.; Wrackmeyer, B. J.
Organomet. Chem. 1983, 246, 213. (b) Luithle, J. E. A.; Pietruszka, J. J.
Org. Chem. 2000, 65, 9194. (c) Gravel, M.; Thompson, K. A.; Zak, M.;
Berube, C.; Hall, D. G. J. Org. Chem. 2002, 67, 3. (d) Vedso, P.;
Olesen, P. H.; Hoeg-Jensen, T. Synlett 2004, 892. (e) Yan, J.; Jin, S.;
Wang, B. Tetrahedron Lett. 2005, 46, 8503.
(13) Nitrogen-based protective groups for the boronyl group:
(a) Noguchi, H.; Hojo, K.; Suginome, M. J. Am. Chem. Soc. 2007, 129,
758. (b) Noguchi, H.; Shioda, T.; Chou, C.-M.; Suginome, M. Org.
Lett. 2008, 10, 377.
(14) Mancilla, T.; Contreras, R.; Wrackmeyer, B. J. Organomet. Chem.
1986, 307, 1.
(15) (a) Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2007, 129, 6716.
(b) Lee, S. J.; Gray, K. C.; Paek, J. S.; Burke, M. D. J. Am. Chem. Soc.
2008, 130, 466. (c) Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2008,
130, 14084. (d) Uno, B. E.; Gillis, E. P.; Burke, M. D. Tetrahedron
2009, 65, 3130. (e) Knapp, D. M.; Gillis, E. P.; Burke, M. D. J. Am.
Chem. Soc. 2009, 131, 6961. (f) Gillis, E. P.; Burke, M. D. Aldrichimica
Acta 2009, 42, 17. (g) Lee, S. J.; Anderson, T. M.; Burke, M. D. Angew.
Chem., Int. Ed. 2010, 49, 8860. (h) Dick, G. R.; Knapp, D. M.; Gillis, E.
In summary, we have successfully performed the synthesis of
gem-diborylated olefins having two types of boryl groups via a
formal carboborylation of an alkyne; diborylation and chemo-
selective arylation sequences. Utilizing a different reactivity
between the Bmida and Bpin moieties, our attempts to realize
selective transformations such as Suzuki−Miyaura coupling
reactions,15i palladium-catalyzed fluorination,25 and copper-
mediated fluorination26 have thus far been unsuccessful. Efforts
to clarify the factors for the selectivity and to explore the
chemoselective transformation toward the synthesis of multi-
substituted olefins are in progress in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and full characterizations are available
for all new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: ynishiha@okayama-u.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was partly supported by the program for promoting
the enhancement of research universities. We gratefully thank
Dr. Masayuki Iwasaki (Okayama University) for the HRMS
measurements, Ms. Megumi Kosaka and Mr. Motonari
Kobayashi (Department of Instrumental Analysis, Advanced
Science Research Center, Okayama University) for the
elemental analyses, and the SC-NMR Laboratory of Okayama
University for the NMR measurements.
C
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P.; Burke, M. D. Org. Lett. 2010, 12, 2314. (i) Fujii, S.; Chang, S. Y.;
Burke, M. D. Angew. Chem., Int. Ed. 2011, 50, 7862. (j) Woerly, E. M.;
Struble, J. R.; Palyam, N.; O’Hara, S. P.; Burke, M. D. Tetrahedron
2011, 67, 4333. (k) Dick, G. R.; Woerly, E. M.; Burke, M. D. Angew.
Chem., Int. Ed. 2012, 51, 2667. (l) Woerly, E. M.; Miller, J. E.; Burke,
M. D. Tetrahedron 2013, 69, 7732.
(16) Although diborylation of alkynylboron compounds are known,
no further reactions toward the formed C−B bond have been
explored. For example, see: (a) Maderna, A.; Pritzkow, H.; Siebert, W.
Angew. Chem., Int. Ed. Engl. 1996, 35, 1501. (b) Abu Ali, H.; Al
Quntar, A. A.; Goldberg, I.; Srebnik, M. Organometallics 2002, 21,
4533.
(17) Huang, X.; Anderson, K. W.; Zim, D.; Jiang, L.; Klapars, A.;
Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 6653.
(18) Strieter, E. R.; Buchwald, S. L. Angew. Chem., Int. Ed. 2006, 45,
925.
(19) (a) Kurahashi, T.; Hata, T.; Masai, H.; Kitagawa, H.; Shimizu,
M.; Hiyama, T. Tetrahedron 2002, 58, 6381. (b) Shimizu, M.; Nagao,
I.; Kiyomoto, S.-i.; Hiyama, T. Aust. J. Chem. 2012, 65, 1277.
(20) (a) Hata, T.; Kitagawa, H.; Masai, H.; Kurahashi, T.; Shimizu,
M.; Hiyama, T. Angew. Chem., Int. Ed. 2001, 40, 790. (b) Shimizu, M.;
Nakamaki, C.; Shimono, K.; Schelper, M.; Kurahashi, T.; Hiyama, T. J.
Am. Chem. Soc. 2005, 127, 12506. (c) Shimizu, M.; Schelper, M.;
Nagao, I.; Shimono, K.; Kurahashi, T.; Hiyama, T. Chem. Lett. 2006,
35, 1222. (d) Shimizu, M.; Shimono, K.; Schelper, M.; Hiyama, T.
Synlett 2007, 12, 1969.
(21) Nishihara, Y.; Onodera, H.; Osakada, K. Chem. Commun. 2004,
192.
(22) (a) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic
Compounds; John Wiley and Sons: New York, 1993; p 696.
(b) Kitching, W.; Olszowy, H. A.; Drew, G. M.; Adcock, W. J. Org.
Chem. 1982, 47, 5153.
(23) Examples of chemoselective Suzuki−Miyaura coupling reactions
of vic-diborylated alkenes: (a) Ishiyama, T.; Yamamoto, M.; Miyaura,
N. Chem. Lett. 1996, 1117. (b) Wenckens, M.; Jakobsen, P.; Vedso, P.;
Huusfeldt, P. O.; Gissel, B.; Barfoed, M.; Lundin Brockdorff, B.;
Lykkesfeldt, A. E.; Begtrup, M. Bioorg. Med. Chem. 2003, 11, 1883.
(24) When the reaction was conducted with the more reactive benzyl
bromide, the desired 5 was obtained in 2% NMR yield. We thus
assume that Kornblum oxidation took place under the reaction
conditions because of a detection of benzaldehyde after the reaction.
(25) Mazzotti, A. R.; Campbell, M. G.; Tang, P.; Murphy, J. M.;
Ritter, T. J. Am. Chem. Soc. 2013, 135, 14012.
(26) Ye, Y.; Schimler, S. D.; Hanley, P. S.; Sanford, M. S. J. Am.
Chem. Soc. 2013, 135, 16292.
D
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