Copper-catalyzed cross-coupling reactions of epoxides with gem-diborylmethane: access to γ-hydroxyl boronic esters

Article abstract of DOI:10.1039/c5cc09817c

Herein, we describe a novel copper-catalyzed epoxide opening reaction with gem-diborylmethane. Aliphatic, aromatic epoxides as well as aziridines are converted to the corresponding γ-pinacolboronate alcohols or amines in moderate to excellent yields. This new reaction provides beneficial applications for classic epoxide substrates as well as interesting gem-diborylalkane reagents.

Full text of DOI:10.1039/c5cc09817c

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Copper-catalyzed cross-coupling reactions of
epoxides with gem-diborylmethane: access to
c-hydroxyl boronic esters†
Cite this:DOI: 10.1039/c5cc09817c
Received 27th November 2015,
Accepted 28th February 2016
Ahmed Ebrahim-Alkhalil, Zhen-Qi Zhang, Tian-Jun Gong, Wei Su, Xiao-Yu Lu,
Bin Xiao* and Yao Fu*
DOI: 10.1039/c5cc09817c
www.rsc.org/chemcomm
Herein, we describe a novel copper-catalyzed epoxide opening reaction
with gem-diborylmethane. Aliphatic, aromatic epoxides as well as
aziridines are converted to the corresponding c-pinacolboronate
alcohols or amines in moderate to excellent yields. This new reaction
provides beneficial applications for classic epoxide substrates as well
as interesting gem-diborylalkane reagents.
Transition metal catalyzed cross-coupling reactions towards the
formation of C(sp3)–C(sp3) bonds play a significant role in organic
synthesis,1 whereas, in these reactions, alkyl halides and pseudo-
halides were the common electrophiles.2 As a class of functional
electrophiles, epoxide compounds could undergo ring-opening
Scheme 1 Previous studies on transition metal catalyzed Suzuki Miyaura
cross-coupling reaction of epoxides.
cross-coupling and result in the corresponding b-substituted or tertiary g-hydroxyl boronic esters. In addition, N-sulfonyl
alcohols.3 Compared to traditional organometallic reagents4 (e.g. aziridines were also suitable for this transformation to afford
Grignard reagents, organozinc reagents or organolithium reagents), the corresponding g-amino boronic esters. Thus, this new
cross-coupling of epoxides with less reactive nucleophiles,5 in reaction provides valuable applications for classic epoxide
particular organoborons,6 has received increasing attention. For substrates as well as interesting gem-diborylalkane reagents.
instance, Doyle has presented nickel-catalyzed Suzuki-type cross-
To verify our initial copper catalyst hypothesis, we started the
coupling of epoxides with a variety of aryl boronic acids, generating reaction by choosing 2-(phenoxymethyl)oxirane and diboryl-
rearranged products via a multicatalytic process.6b Very recently, our methane as the model substrates at 60 1C in argon. On the basis
research group realized the copper-catalyzed terminal direct ring- of previous studies on Cu-catalyzed cross-coupling,2c,6c,7g,9 various
opening coupling of epoxides with aryl boronic esters (Scheme 1a).6c bases were subsequently screened in this reaction, such as
Regarding another research interest of our group, gem- NaOtBu, KOtBu, K3PO4, Cs2CO3, LiOMe and LiOtBu (Table 1,
diborylalkanes7 emerged as a kind of valuable compounds entries 1–8), among which LiOtBu was found to be the optimal
due to their ability to introduce a boron group (i.e., Bpin, one and afforded product 3a, albeit in low yield (entry 9). The
pinacol boronic esters),8 in C–C bond-forming reactions, which process occurred smoothly in 1,4-dioxane with CuI as catalyst,
have more derived possibilities in further organic reactions. loading the expected product 3a in moderate yield (entry 10).
Herein, we report our efforts to expand the epoxide ring- To our delight, in THF, CuI performed well with high effectivity
opening reaction of our previously reported method to include delivering the deborylative alkylation alcohol product in high yield
the gem-diborylmethane derivative (Scheme 1b).
(88% GC yield and 85% isolated yield, entry 11). The decrease of
This study includes a series of aliphatic and aromatic copper catalyst loading to 10 mol% led to a slightly lower yield of
epoxides which were converted to the corresponding secondary 75% (entry 12). Next, a trace product was detected in the absence
of CuI (entry 13). Furthermore, the use of CuCl in this transfor-
mation afforded lower yield (entry 14). Finally, considering our
Hefei National Laboratory for Physical Sciences at the Microscale, iChEM, CAS Key
previously studies on using potassium iodide to promote the
Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of
cross-coupling reaction,6c the iodide source (potassium iodide or
Biomass Clean Energy, University of Science and Technology of China,
Bu4NI) was also examined, the results indicated that the addition
Hefei 230026, China. E-mail: binxiao@ustc.edu.cn, fuyao@ustc.edu.cn
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5cc09817c of iodide salt did not accelerate this conversion.
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Table 1 Optimization of reaction conditionsa
Table 2 Scope of epoxidesa,b
Entry
[Cu]
Base
Additive
Solvent
Yielda (%)
1
2
3
4
5
6
7
8
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
—
NaOtBu
KOtBu
NaOtAm
K3PO4
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Bu4NI
KI
KI
THF
THF
THF
THF
THF
THF
CH3CN
Toluene
DMF
Dioxane
THF
THF
THF
THF
THF
THF
THF
Trace
n.r
Trace
n.r
Cs2CO3
LiOMe
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
n.r
Trace
Trace
Trace
21
9
10
11b,c
12e
13
14
15f
16g
17h
57
88(85d)
75
Trace
44
Trace
75
CuCl
CuCl
CuCl
CuCl
16
a
Reaction conditions: epoxide (0.2 mmol), diborylmethane (2 equiv.), CuI
(20 mol%), base (3 equiv.), in 0.5 mL of solvent at 60 1C for 24 h under an
Ar atmosphere. The yield was determined by GC using benzophenone as
internal standard (average of two GC runs). b At 80 1C, GC yield was 63%.
c
d
e
Reaction was performed for 18 h, yield = 69%. Isolated yield. CuI
f
g
(10 mol%) was used. Bu4NI (20 mol%) was added. KI (20 mol%) was
added. KI (1.5 equiv.) was used. DMF = N,N-dimethylformamide.
h
With the optimal reaction conditions in hand, various
epoxides were subjected to examination of the generality of this
new method (Table 2). First, as a series of analogues of 1a, we
continued our new reaction to other protected glycidyl substrates.
A variety of aryl (3a–i, k), benzyl (3j) and other alkyl (3m)
substrates effectively participated in the reaction and afforded
the products in good yields. The aromatic ring with the func-
tional groups substituted at the ortho-, meta-, para-position did
not affect the reaction results. Next, it is worth noting that the
substrates containing aryl chloride and bromide can be obtained
smoothly; wherein, these halides are susceptible for further
transformations by metal catalysis. Furthermore, this cross-
coupling reaction was not limited to glycidyl substrates, and
a
Reaction conditions: epoxides (0.2 mmol), diborylmethane (2 equiv.).
CuI (0.04 mmol), LiOtBu (0.6 mmol), in 0.5 mL of THF at 60 1C for 24 h
under an Ar atmosphere. Isolated yield.
b
non-glycidyl substrates (3l, 3o, 3n, 3p) were also suitable sub- identical terminal-selectivity to our previous studies.6c However,
strates. For instance, a heteroatom substituent on the side chain, 1,2-disubstituted epoxides did not afford the desired product.
such as sulfur (3o), and nitrogen (3n) were tolerable in this
The generation of alkylboronic ester derivatives, in particular
reaction. Finally, we found that the more active aromatic epoxide g-pinacolboronate amines, is important in organic synthesis, which
(3p) was the suitable substrate under our standard reaction have numerous transformations and pharmaceutical applica-
conditions, which was not tolerated in our previous work on tions.10 To our delight, under the standard reaction conditions,
Cu-catalyzed cross-coupling of epoxides with arylboronates.6c
2-butyl-1-tosylaziridine converted smoothly and provided the
Furthermore, 1,1-disubstituted epoxides were also used in corresponding amine (3ca) in good yield (Scheme 2, 79% yield).
this reaction and converted to tertiary alcohol products (Table 3). Due to the importance of chiral compounds in pharmaceu-
Aromatic compounds with para-substituted (e.g. electron rich tical chemistry, additional application of this reaction has been
aromatic PMP 3ba), naphthyl (3bb) and amide (3bc) groups were achieved for (S)-2-((benzyloxy)methyl)oxirane which reacted well
coupled well under standard conditions to give the desired products with diborylmethane, followed by oxidation step with basic H2O2
in moderate to good yields (59–74% yield). The ketal group survived at lower temperature,11 to give the 1,3-diol product in high yield
in this transformation and afforded the corresponding product (3bd) with fully maintained configuration as illustrated in Scheme 3.
in a yield of 60%, at a higher reaction temperature (i.e. 80 1C).
In conclusion, we have developed the first copper-catalyzed
The ring-opening cross-coupling of these compounds showed ring opening coupling of epoxides with gem-diborylmethane
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Table 3 Scope of 1,1-disubstituted epoxidesa,b
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Scheme 3 Copper-catalyzed cross-coupling of chiral epoxides.
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This work was financially supported by the 973 Program
(2012CB215306), NSFC(21325208, 21361140372, 21472181,
21572212), IPDFHCPST (2014FXCX006), CAS (KFJ-EW-STS-051,
YIPA-2015371), FANEDD (201424), FRFCU, PCSIRT and CAS-
TWAS President’s Fellowship for International PhD Students.
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