Copper-catalyzed double borylation of silylacetylenes: Highly regio- and stereoselective synthesis of syn -vicinal diboronates

Article abstract of DOI:10.1021/ol300909k

Phosphite-copper(I) complexes efficiently catalyzed the double borylation of internal silylated alkynes to provide vicinal diboronates with excellent regio- and stereoselectivity. The copper-catalyzed reaction between bis(pinacolato)diboron (B₂

Full text of DOI:10.1021/ol300909k

ORGANIC
LETTERS
2012
Vol. 14, No. 10
2606–2609
Copper-Catalyzed Double Borylation of
Silylacetylenes: Highly Regio- and
Stereoselective Synthesis of Syn-Vicinal
Diboronates
Ho-Young Jung and Jaesook Yun*
Department of Chemistry and Institute of Basic Science, Sungkyunkwan University,
Suwon 440-746, Korea
jaesook@skku.edu
Received April 9, 2012
ABSTRACT
Phosphiteꢀcopper(I) complexes efficiently catalyzed the double borylation of internal silylated alkynes to provide vicinal diboronates with
excellent regio- and stereoselectivity. The copper-catalyzed reaction between bis(pinacolato)diboron (B2pin2) and aryl-substituted silylacetylenes
in the presence of MeOH resulted in double syn addition of the pinacolboronate moiety (Bpin) and H across the triple bond with complete
selectivity. While the double borylation was highly efficient for aryl-substituted alkynylsilanes and silylacetylene, only monoborylation took place
with alkyl-substituted alkynylsilanes to yield (Z)-(β-borylvinyl)silanes under the developed catalytic conditions.
Organoboron compounds are useful inorganic synthesis
because of their versatility as synthetic intermediates.
Increasing attention has been paid to copper-catalyzed
boron addition reactions to carbonꢀcarbon multiple
bonds as a straightforward procedure for preparing orga-
noboron compounds with high stereocontrol.1 In copper-
catalyzed boron additions, catalytically active ligand-co-
ordinated copper(I)ꢀboryl complexes,2 generated from
copper and diboron reagents, continue to show remark-
able efficiency and stereoselectivity.
Recently, we described a Cu-catalyzed regioselective
boron addition to carbonꢀcarbon triple bonds, such as
alkynoates3 and terminal3 and internal alkynes,4 using
bis(pinacolato)diboron (B2pin2, 1) and MeOH based on
phosphineꢀcopper catalysts. These catalytic reactions
worked well for internal alkynes resulting in monohydro-
borated, alkenylboronate products with excellent regio-
and stereoselectivity, which would be challenging to obtain
by conventional hydroboration processes.5 As part of our
ongoing project to synthesize functionalized organoboron
compounds, we became interested in the reactivity and
selectivity of silylated alkynes as substrates for copper-
catalyzed borylations. Silylated alkynes are intriguing
(1) (a) Takahashi, K.; Ishiyama, T.; Miyaura, N. Chem. Lett. 2000,
982–983. (b) Ito, H.; Yamanaka, H.; Tateiwa, J.-i.; Hosomi, A. Tetra-
hedron Lett. 2000, 41, 6821–6825. (c) Mun, S.; Lee, J.-E.; Yun, J. Org.
Lett. 2006, 8, 4887–4889. (d) Lee, J.-E.; Yun, J. Angew. Chem., Int. Ed.
2008, 47, 145–147. (e) Ito, H.; Sasaki, Y.; Sawamura, M. J. Am. Chem.
Soc. 2008, 130, 15774–15775. (f) Feng, X.; Yun, J. Chem. Commun. 2009,
6577–6579. (g) Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131,
3160–3161. (h) Chen, I.-H.; Yin, L.; Itano, W.; Kanai, M.; Shibasaki, M.
J. Am. Chem. Soc. 2009, 131, 11664–11665. (i) Gao, M.; Thorpe, S. B.;
Santos, W. L. Org. Lett. 2009, 11, 3478–3481. (j) Hirsch-Weil, D.;
Abboud, K. A.; Hong, S. Chem. Commun. 2010, 46, 7525–7527. (k)
Sasaki, Y.; Horita, Y.; Zhong, C.; Sawamura, M.; Ito, H. Angew. Chem.,
Int. Ed. 2011, 50, 2778–2782. (l) Yoshida, H.; Kawashima, S.; Takemoto,
Y.; Okada, K.; Ohshita, J.; Takaki, K. Angew. Chem., Int. Ed. 2012, 51,
235–238.
(3) Lee, J.-E.; Kwon, J.; Yun, J. Chem. Commun. 2008, 733–734.
(4) (a) Kim, H. R.; Jung., I. G.; Yoo, K.; Jang, K.; Lee, E. S.; Yun, J.;
Son, S. U. Chem. Commun. 2010, 758–760. (b) Kim, H. R.; Yun, J. Chem.
Commun. 2011, 47, 2943–2945.
(5) (a) Brown, H. C.; Gupta, S. K. J. Am. Chem. Soc. 1972, 94, 4370–
4371. (b) Tucker, C. E.; Davidson, J.; Knochel, P. J. Org. Chem. 1992,
57, 3482–3485. (c) Konno, T.; Chae, J.; Tanaka, T.; Ishihara, T.;
Yamanaka, H. Chem. Commun. 2004, 690–691. (d) Iwadate, N.; Suginome,
M. Org. Lett. 2009, 11, 1899–1902.
(2) (a) Laitar, D. S.; Tsui, E. Y.; Sadighi, J. P. J. Am. Chem. Soc. 2006,
128, 11036–11037. (b) Dang, L.; Lin, Z.; Marder, T. B. Organometallics
2008, 27, 4443–4454.
r
10.1021/ol300909k
Published on Web 05/01/2012
2012 American Chemical Society

molecules because the silyl group is known to display an
electronic boron directing effect to the R-carbon from the
silyl group6 and less of an activating effect on the triple
bond than an alkyl substituent in the conventional hydro-
boration of alkynes with dialkylborane serving as the
electrophilic reagent.7 Since a copperꢀboryl complex
serves as a nucleophilic entity in the borylation reaction,2b
reactivity and/or selectivity complementary to hydrobora-
tion might be achievable. Herein, we report an efficient
borylation of silylalkynes with a phosphiteꢀcopper cata-
lyst to produce vicinal alkyldiboronates through the highly
regio- and stereoselective double addition of a boronate
moiety and H to silylalkynes.
Table 1. Borylation Reaction of 1-Phenyl-2-trimethylsilylethyne
Under Various Conditions
B2pin2
(equiv)
MeOH conv product yield of 4b
entry ligand
(equiv) (%)a
3b: 4b
(%)b
1
2
3
P(p-tol)3
P(p-tol)3
P(OEt)3
1.1
2.2
2.2
2.2
2.2
1.1
1.5
2.2
2
2.2
2.2
3
52
1<: >99
44
86
100 1<: > 99
100
100
13
1<: >99
1<: >99
ꢀ
89
4c P(OEt)3
89
5
6
7
P(OEt)3
xantphos
xantphos
0
4
1
78
>99: <1
>99: <1
80: 20
49 (3b)
83 (3b)
40 (3b)
Scheme 1. Borylation of 1-TMS-1-hexyne
2
100
100
8d xantphos
2.2
a Determined by GC analysis based on consumption of 2b. b Isolated
yield of purified diboronate 4b. c Reaction time was 17 h. d Reaction was
carried out at 70 °C.
Increasing the amount of B2pin2 (1) to 2.2 equiv relative
to acetylene substrate led to complete conversion to pro-
duct 4b in high yield (entry 2). Using P(OEt)3 as the ligand
instead of P(p-tol)3 efficiently afforded the same product10
(entries 3 and 4), and MeOH was necessary for high con-
version (entry 5). On the other hand, the bidentate ligand
xantphos (= 9,90-dimethyl-4,5-bis(diphenyl-phosphino)-
xanthene) selectively gave monoaddition product (3b) as a
single product (entries 6 and 7). Increasing reaction tem-
perature with excess B2pin2 resulted in a mixutre of 3b and
4b, but the alkenylboron compound was still the major
product with the xantphos ligand (entry 8).
While catalytic diborations of alkenes with diboron
compounds offer a straightforward route to diboronate
compounds,11 alkene diboration has been most success-
ful thus far with terminal alkenes,12 cyclic alkenes with
internal strain,12b,d and disubstituted alkenes12d,e by em-
ploying bis(catecholato)diboron, which is less stable
and more reactive than bis(pinacolato)diboron. The
present approach provides a complementary synthetic route
to diboronates.13 Furthermore, sterically encumbered
In initial experiments, we carried out the borylation of
1-trimethylsilyl-1-hexyne (see Supporting Information)
using our previously reported conditions (CuCl, NaOt-
Bu, P(p-tol)3, and 1.1 equiv B2pin2, 2 equiv MeOH in
THF)4b at 50 °C for 24 h. The reaction proceeded to 67%
conversion, which was higher than the t-butyl analogue,8
and a single product was isolated in 51% yield (Scheme 1).
The product was characterized as (Z)-(β-borylvinyl)silane,
whose formation could be explained by β-carbon attach-
ment of the boronate group from the TMS group and syn
addition of boron and H. A similar borylation was con-
ducted employing a more hindered but activated 1-phenyl-
2-trimethylsilylacetylene (2b) (Table 1, entry 1). The reac-
tion led to partial conversion and the formation of a single
isomeric product. Surprisingly, the isolated product was
determined to be a vicinal diboronate with the two boronyl
groups in a syn relationship, and no monoborylated
vinylsilane intermediate was detected. The stereochemistry
of the resulting 1,2-bis(boronate) was determined by sub-
sequent oxidation to the corresponding syn-1,2-diol.9
(11) For recent reviews, see: (a) Beletskaya, I.; Moberg, C. Chem.
Rev. 2006, 106, 2320–2354. (b) Burks, H. E.; Morken, J. P. Chem.
Commun. 2007, 4717–4725.
(12) For selected reports on diboration: (a) Baker, R. T.; Nguyen, P.;
Marder, T. B.; Westcott, S. A. Angew. Chem., Int. Ed. Engl. 1995, 34,
1336–1338. (b) Ishiyama, T.; Yamamoto, M.; Miyaura, N. Chem.
Commun. 1997, 689–690. (c) Kliman, L. T.; Mlynarski, S. N.; Morken,
(6) (a) Uchida, K.; Utimoto, K.; Nozaki, H. J. Org. Chem. 1976, 41,
2941–2942. (b) Hassner, A.; Soderquist, J. A. J. Organomet. Chem. 1977,
131, C1–C4. (c) Zweifel, G.; Backlund, S. J. J. Am. Chem. Soc. 1977, 99,
3184–3185. (d) Hoshi, M.; Masuda, Y.; Arase, A. J. Chem. Soc. Perkin
Trans. 1 1990, 3237–3241.
(7) Soderquist, J. A.; Colberg, J. C.; Valle, L. D. J. Am. Chem. Soc.
1989, 111, 4873–4878.
(8) For comparison, 48% conversion of 1-t-butyl-1-octyne was ob-
tained under the same conditions.
(9) Page, P. C. B.; Rosenthal, S. Tetrahedron Lett. 1990, 46, 2573–
2586.
(10) When the same reactions were conducted at room temperature
for 12 h with P(p-tol)3 and P(OEt)3, respectively, both reactions gave
similar conversions, 79% and 80%. However, ∼3% of the monoaddi-
tion product (3b) was detected by GC in the latter reaction along with the
major product 4b. The results indicate that the phosphite system might
be less efficient than the phosphine in the double borylation. However,
the reactivity difference is so small that the phosphite can be used in the
double borylation at higher reaction temperature with the same effi-
ciency as the phosphine.
J. P. J. Am. Chem. Soc. 2009, 131, 13210–13211. (d) Ramırez, J.; Sanau,
´
ꢀ
ꢀ
M.; Fernandez, E. Angew. Chem., Int. Ed. 2008, 47, 5194–5197. (e)
Trudeau, S.; Morgan, J. B.; Shrestha, M.; Morken, J. P. J. Org. Chem.
2005, 70, 9538–9544.
(13) For a NHCꢀCu catalyzed borylation of terminal alkynes to
vicinal diboronates, see: Lee, Y.; Jang, H.; Hoveyda, A. H. J. Am. Chem.
Soc. 2009, 131, 18234–18235.
(14) For copper-catalyzed borylation reactions of β,β-disubstituted
or R,β-disubstituted R,β-unsaturated carbonyl compounds, see: (a)
´ ´
Lillo, V.; Prieto, A.; Bonet, A.; Dıaz-Requejo, M. M.; Ramırez, J.;
ꢀ
ꢀ
Perez, P. J.; Fernandez, E. Organometallics 2009, 28, 659–662. (b)
O’Brien, J. M.; Lee, K.-s.; Hoveyda, A. H. J. Am. Chem. Soc. 2010,
132, 10630–10663. (c) Feng, X.; Yun, J. Chem.;Eur. J. 2010, 16, 13609–
13612.
Org. Lett., Vol. 14, No. 10, 2012
2607

substitutions smoothly occurred to give the corresponding
diboronates in a highly regio- and stereoselective fashion.
Substrates with electron-withdrawing or electron-donat-
ing substituents at either the para or meta positions under-
went clean reaction (entries 1ꢀ7). However, a substrate
bearing ortho substitution gave only partial conversion
generating the desired diborylated product along with a
monoborylated (β-borylvinyl)silane product (entry 8). The
reaction of trimethylsilylacetylene gave the 1,2-diboronate
in good yield as the major product (entry 9). To assess the
effect of the silyl group size on the reactivity and stereoselec-
tivity, bulky tert-butyldimethylsilyl (TBDMS) and tri-isopro-
pylsilyl (TIPS)-substituted phenyl acetylenes were prepared.
Under the present catalytic conditions, a TBDMS group was
accommodated in the reaction, but the TIPS-substituted
substrate resulted in low reactivity (entries 10 and 11).
The formation of syn-vicinal diboronate products can be
rationalized by the following mechanism. Insertion of the
alkyne into the phosphite-ligated Cuꢀboryl complex
places the pinacolboronate moiety at the β-carbon and
theCuattheR-carbon from thesilyl group, andsubsequent
protonolysis of the CuꢀC bond by MeOH gives (Z)-3b.
A fast second insertion of intermediate 3b into the CuꢀB
complex occurs regio- and stereoseletively with R-boron place-
ment to yield the diborylated product 4b.
Table 2. Synthesis of syn-Vicinal Diboronates Through Cu-
Catalyzed Double Borylation
Scheme 2
The β-selectivity (from TMS) for the first insertion is
different from the conventional hydroboration of sub-
stituted-(trimethylsilyl)acetylenes with alkyl boranes.6,7 Pre-
sumably, the first CuꢀB insertion is directed by a steric
effect of the silyl group that overrides electronic effects from
the aryl and TMS groups.15 Under conditions using a
monodentate ligand, the second insertion of the intermedi-
ate (Z)-(β-borylvinyl)silane into the CuꢀB complex occurs
faster than the starting alkyne, because it is electronically
activated by both the aryl and Bpin groups despite its steric
congestion. In contrast, the intermediate alkenyl boron is
less reactive than the alkyne16 with xantphos as the ligand
leading to the selective monoborylation.
a Determined by GC analysis. b Isolated yield of purified products.
c Reaction was performed at 70 °C. d A 34:66 ratio for 3j and 4j was
measured by GC. Monoborylated product (3j) was also isolated in 14%
yield. e Reaction was performed at 40 °C. f ∼5% of germinal diboronate
was detected by GC of the crude mixture.
A brief investigation of an enantioselective version of
this reaction was carried out with the silylacetylene 2b.
Among the screened chiral ligands including binaphthol-
based phosphites and phosphine ligands, Me-duphos
trisubstituted alkenes have not been the subject of copper-
catalyzed borylation14 using diboron reagents. Thus,
further examples of the double borylation were examined
with the catalytic combination of CuCl, NaOt-Bu and
P(OEt)3 in THF in the presence of 1 and MeOH, and the
results are summarized in Table 2.
(15) The ability of the carbon-silicon bond to stabilize an adjacent
electron-deficient center through hyperconjugation was proposed as an
explanation of the R-boron-directing effect. See: Wang, K. K.; Gu,
Y. G.; Liu, C. J. Am. Chem. Soc. 1990, 112, 4424–4431.
(16) See entries 7 and 8 in Table 1 and Scheme 3 for results with
bidentate ligands, such as xantphos and Me-duphos. The steric effect of
bidentate ligand-coordinated copper complexes possibly accounts for
the slow addition to the trisubstituted alkenyl intermediate.
As shown in Table 2, the Cu-catalyzed double boryla-
tion of aryl-substituted silylated alkynes with different
2608
Org. Lett., Vol. 14, No. 10, 2012

In summary, we have described a highly regio- and stereo-
selective double borylation of silylalkynes catalyzed by a
phosphiteꢀcopper complex that produces syn-vicinal di-
boronates in good yield. Asymmetric synthesis of chiral
vicinal diboronates and the stereoselective synthesis of
(β-borylvinyl)silanes, which are versatile intermediates that
include both vinylborane and vinylsilane moieties as well as
synthetic applications of these multifunctional compounds
are currently underway in our laboratory.
Scheme 3. Enantioselective Diborylation
Acknowledgment. This research was supported by the
Basic Science Research Program through the National Re-
search Foundation of Korea (NRF) funded by the Ministry
of Education, Science and Technology (NRF-20110009533).
Supporting Information Available. Experimental pro-
cedures and chracterization of the products. This material
is available for free of charge via the Internet at http://
pubs.acs.org.
and tangphos ligands with small bite angles have been
the most effective thus far in achieving appreciable
conversion of the starting material and produced the
chiral diboronate 4b in 68% and 27% ee, respectively
(Scheme 3).
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 10, 2012
2609