Highly regio- and stereoselective synthesis of boron-substituted enynes via copper-catalyzed borylation of conjugated diynes

Article abstract of DOI:10.1021/ol503720w

A mild copper-catalyzed regio- and stereoselective monoborylation of conjugated diynes with bis(pinacolato)diboron that affords enynylboronates is reported. The reaction is efficient for different types of conjugated diynes including unsymmetrical diynes

Full text of DOI:10.1021/ol503720w

Letter
pubs.acs.org/OrgLett
Highly Regio- and Stereoselective Synthesis of Boron-Substituted
Enynes via Copper-Catalyzed Borylation of Conjugated Diynes
DingXi Li, Yeong Eun Kim, and Jaesook Yun*
Department of Chemistry and Institute of Basic Science, Sungkyunkwan University, Suwon 440-746, Korea
*
S Supporting Information
ABSTRACT: A mild copper-catalyzed regio- and stereo-
selective monoborylation of conjugated diynes with bis-
(
pinacolato)diboron that affords enynylboronates is reported.
The reaction is efficient for different types of conjugated
diynes including unsymmetrical diynes and produces enynyl-
boron compounds with high and complementary regioselec-
tivity compared with classical hydrometalation reactions. In particular, the reactions of internal conjugated diynes with a silyl
substitution produced highly functionalized enynes with high regio- and stereoselectivity, which can be used in further
transformations.
7
rganoboron compounds are versatile reagents, and
vinylboronates represent especially useful reagents in
hydrostannation offered similar regioselectivities with the
metallic moiety (E) in internal positions. Therefore, develop-
ment of synthetic methods displaying complementary
regioselectivity to existing methods is valuable.
O
synthetic organic chemistry, as evidenced by their use in
1
transition-metal catalyzed cross-coupling reactions. Hydro-
boration of alkynes is one of the most convenient and
straightforward methods of producing a variety of vinyl-
boronates. However, control of regio- and stereochemistry
We have previously shown that catalytic borylcupration
(Cu−B) to C−C multiple bonds and protonolysis by methanol
2
,3
8
can produce hydroborylated products. In contrast to copper-
9
is a frequent obstacle faced in hydroboration.
catalyzed borylation of monoynes, the selective reaction of
1
0
Organic molecules with extended π-conjugation have
garnered much attention due to their wide application as
important building blocks for designing nanostructures,
diynes has not yet been reported. Indeed, selective
monoborylation of diynes is quite challenging because the
borylenyne products still possess reactive π-conjugated C−C
multiple bonds in the presence of the nucleophilic Cu−B
4
polymer synthesis, and organic synthesis. In this context, the
10
catalyst, in contrast to other π-conjugated starting substrates.
development of efficient methods for the synthesis of
enynylboronates with high regio- and stereoselectivity is of
considerable importance. While the hydroboration of mono-
ynes has been widely studied, reports on the hydroboration of
Herein, we present our results on the monoborylation of
conjugated diynes to produce enynylboron compounds with
the boron at the end position of various diynes.
We initially investigated the reaction of 1,4-diphenyl-
butadiyne (1a) as a model substrate under various reaction
conditions (Table 1). The reaction was optimized by the
combination of a catalytic copper chloride, NaOt-Bu, and P(p-
5
conjugated diynes are scarce. Indeed, there has been only one
study by Polston et al. on the selective hydroboration of
conjugated diynes with dialkylboranes as a hydroborating
5
a
reagent. In the report, the monohydroboration of symmetri-
cally alkyl-substituted diynes with disiamylborane afforded
enynes with boron in the internal positions of the diyne system
which are less sterically hindered positions (Scheme 1). Other
tol) in THF at 11 °C. The reaction yielded a high conversion
3
in 3 h and afforded the monoborylated product 2a as the major
11
product (entry 1). The structure of 2a was confirmed by
12
6
derivatizing it to the known structure, and the regioselectivity
was found to be complementary to the conventional hydro-
related hydrometalation processes such as hydrosilylation and
5
boration reaction, with the boron in external positions of the
Scheme 1. Regioselectivity in Hydrometalations
diyne system. Reactions using the weaker electron-donating
P(OEt) or PPh ligands resulted in a decreased yield or longer
3
3
reaction time (entries 2 and 3). Use of a bidentate ligand or
other bases was not beneficial to the reaction (entries 4 and 5).
Controlling the amount or concentration of the diboron
reagent or the temperature was not effective in increasing the
efficiency of the reaction (entries 6−8).
Received: December 26, 2014
©
XXXX American Chemical Society
A
DOI: 10.1021/ol503720w
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Organic Letters
Letter
Table 1. Screening under Various Conditions
Table 2. Regioselective Monoborylation of Symmetrical
a
Conjugated Diynes
a
b
entry
condition change
time (h) conv (%)
NMR yield (%)
c
1
2
3
4
5
6
7
8
no change
P(OEt)3
PPh3
3
95
93
92
−
83 (70)
3.5
9
61
84
64
35
68
78
70
d
Xantphos
24
24
3
LiOt-Bu
−
1.0 equiv of B pin
86
95
93
2
2
0.125 M THF
8
0 °C
6
a
Determined by GC analysis with an internal standard based on
b
consumption of 1a. NMR yield was determined using DMF as an
internal standard. Isolated yield was obtained by column chromatog-
raphy at low temperature (0 °C). Xantphos = 9,9′-dimethyl-4,5-
bis(diphenylphosphino)xanthene.
c
d
13
We next investigated the reaction of symmetrical diynes
with various aryl or alkyl substituents (Table 2). Gratifyingly,
the reaction with the diynes afforded the desired monobory-
14
lated enyne products without the other regioisomer. The B-
substituted enyne products were isolated in good yields as the
Bpin derivatives (2) or the corresponding and more stable
trifluoroborate salts (3). Diyne substrates with electron-
withdrawing or -donating aryl substituents were suitable
substrates for the reaction (entries 2 and 3). The more
sterically hindered o-tolyl-substituted diyne (1d) also afforded
the product in good yield (entry 4). The reaction of electron-
rich diynes with alkyl or electron-donating aryl substituents
proceeded well with P(OEt)3 as the ligand at room
temperature. Primary (1e) and secondary (1f) alkyl-substituted
diynes reacted smoothly to give the desired products with the
boron in the external position, but the tertiary alkyl-substituted
diyne (1g) afforded the product 3g with the opposite
15
regioselectivity (entries 5−8). The results indicated that
severe steric bulkiness of the tert-butyl group of diynes could
alter the regioselectivity of the current catalytic reaction.
We further investigated the monoborylation of unsymmetri-
cally substituted conjugated diynes, the results of which are
shown in Table 3. Surprisingly, the reaction of 1-phenyl-1,3-
pentadiyne (4a) afforded 5a with excellent regioselectivity with
the boron at the external position close to the methyl group
a
The reaction was conducted with the combination of 5 mol % CuCl,
6
mol % P(p-tol) , 10 mol % NaOt-Bu, and 2 equiv of MeOH in THF
3
b
at 11 °C for 2−4 h. Isolated yield of 2 or 3. See Supporting
Information for details PPh was used. P(OEt) ligand was used at
room temperature. Reaction was performed at room temperature.
c
d
3
3
e
(
Table 3, entry 1). The reaction of primary alkyl-substituted
diyne 4b gave product 5b with the same type of regioselectivity
as that of 4a (entry 2). In contrast to the aryl-substituted
conjugated diynes (4a and 4b), silyl-substituted diynes (4c and
diborylated compound (entry 6). However, diyne 4f with
different aryl substituents resulted in poor regioselectivity and
produced both regioisomeric products in a 1:1 ratio (entry 7),
which indicated no strong directing bias between the two aryl
groups.
4
d) showed an alternative regioselectivity in which the boron
17
was attached at the external carbon positioned away from the
silyl group via regioselective borylcupration to the more
16
electrophilic triple bond (entries 3−5). These results indicate
that the silyl group acted as a strong directing group. In all of
these examples, the boron addition occurred at the external
positions with excellent regioselectivity with no observation of
the other regioisomers. Finally, other diyne substrates such as
terminal or electronically different aryl-substituted diynes were
investigated. The terminal diyne 4e gave the monoborylation
product in good yield without significant formation of the
Synthetic applications of boron-substituted enynes were
carried out to illustrate their usefulness in organic synthesis
(Scheme 2). Palladium-catalyzed cross-coupling of borylenynes
(2a and 5a) with iodobenzene gave the corresponding
1
2,18
enynes
in good yields. Protonolysis of 3a gave an 86%
yield of the corresponding cis-enyne 9. Selective desilylation of
6c was possible to yield 10 with a terminal alkynyl group, which
B
DOI: 10.1021/ol503720w
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Letter
Table 3. Monoborylation of Unsymmetrical Conjugated
Diynes
showed a complementary regioselectivity to that of 5e,
obtained from the monoborylation of the terminal diyne
a
(
Table 3, entry 6).
In summary, we have developed a copper-catalyzed regio-
and stereoselective monoborylation of conjugated diyne
compounds that affords boron-containing enynes. The reaction
is efficient for different types of conjugated diynes including
unsymmetrical diynes. The regioselectivity obtained was
complementary to that of classical hydrometalation reactions,
with the boron moiety at the external carbons of conjugated
diynes. In particular, the reactions of silyl-substituted
conjugated diynes produced highly functionalized enynes with
high regio- and stereoselectivity, which can be used in further
transformations.
ASSOCIATED CONTENT
■
*
S
Supporting Information
Experimental procedures and characterization of products and
1
13
copies of the H and C NMR spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*
E-mail: jaesook@skku.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by the Basic Science Research
Program through the National Research Foundation of Korea
(
NRF) funded by the Ministry of Education, Science, and
Technology (NRF-2013R1A1A2058160).
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(
(
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DOI: 10.1021/ol503720w
Org. Lett. XXXX, XXX, XXX−XXX