Copper-catalyzed oxidative homo- and cross-coupling of grignard reagents using diaziridinone

Article abstract of DOI:10.1021/ol5030103

Transition-metal-catalyzed cross-coupling reactions are among the most powerful synthetic transformations. This paper describes an efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant under mild conditions, giving the coupling products in good to excellent yields. The reaction process has a broad substrate scope and is also effective for the C(sp)-C(sp³) coupling.

Full text of DOI:10.1021/ol5030103

Letter
pubs.acs.org/OrgLett
Copper-Catalyzed Oxidative Homo- and Cross-Coupling of Grignard
Reagents Using Diaziridinone
Yingguang Zhu,† Tao Xiong,† Wenyong Han,† and Yian Shi*
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States
S
* Supporting Information
ABSTRACT: Transition-metal-catalyzed cross-coupling reactions are among
the most powerful synthetic transformations. This paper describes an efficient
copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-
butyldiaziridinone as oxidant under mild conditions, giving the coupling
products in good to excellent yields. The reaction process has a broad substrate
scope and is also effective for the C(sp)−C(sp3) coupling.
a
ransition-metal-catalyzed cross-coupling reactions between
organometallic reagents and organic electrophiles have
Table 1. Studies on Reaction Conditions
T
become indispensable tools in organic synthesis.1 Oxidative
coupling reactions of various organometallic reagents present
new strategies for C−C bond formations and have received
intense attention in recent years.2 Grignard reagents, a class of
readily available organometallic reagents, have also been actively
investigated for oxidative coupling. A number of metal-mediated3
and -catalyzed4,5 as well as metal-free6 oxidative homocouplings
of Grignard reagents have been developed. Fewer examples of
the oxidative cross-coupling of Grignard reagents have been re-
ported.7−9 There are still some unsolved problems. For example,
the oxidative cross-coupling between alkynyl and alkyl Grignard
reagents for C(sp)−C(sp3) bond formation has remained
challenging. The development of new, efficient, mild, and
operationally simple cross-coupling reactions of Grignard
reagents is highly desirable and valuable.
Previously, we have shown that di-tert-butyldiaziridinone
(1)10 is a highly effective nitrogen source for the Pd(0)-11 and
Cu(I)-catalyzed12 diamination of olefins. In our subsequent
studies, diaziridinone 1 has also been found to be a versatile
oxidant for the oxidation of alcohols to aldehydes and ketones,13
homocoupling of anilines to azo compounds and hydrazines,14
and homocoupling of terminal alkynes to symmetrical 1,3-
diynes.15 In our continuing efforts, we have discovered that
various Grignard reagents can be efficiently coupled to give the
corresponding coupling products using di-tert-butyldiaziridinone
(1) in the presence of a metal catalyst (Scheme 1). In particular,
this coupling process is also effective for C(sp)−C(sp3) bond
formations.16−21 Herein we wish to report our preliminary
studies on this subject.
b
entry
catalyst
FeCl2
x (mol %)
yield (%)
1
5
5
5
5
5
5
5
5
5
5
5
5
5
1
0.1
1
85
94
90
96
76
95
94
95
95
94
93
46
97
97
83
11
8
2
CoCl2
3
NiBr2
4
Pd(OAc)2
Pd(PPh3)4
CuCl
5
6
7
CuBr
8
CuBr·SMe2
CuI
9
10
11
12
13
14
CuCl2
CuBr2
CuSO4
Li2CuCl4
Li2CuCl4
Li2CuCl4
Li2CuCl4
none
c
15
d
16
17
a
All reactions were carried out with phenylmagnesium bromide (2a)
(0.60 mmol), di-tert-butyldiaziridinone (1) (0.45 mmol), and catalyst
(0.1−5 mol %) in THF (0.60 mL) at rt under Ar for 3 h unless
otherwise stated. Isolated yield. Reaction time, 24 h. The reaction
b
c
d
was carried out in the absence of di-tert-butyldiaziridinone (1).
Our studies began with the homocoupling of Grignard
reagents. Phenylmagnesium bromide (2a) was used as test
substrate and was treated with di-tert-butyldiaziridinone (1) and
various transition-metal catalysts in THF at room temperature.
Scheme 1. Metal-Catalyzed Coupling of Grignard Reagents
Using Diaziridinone
Received: October 13, 2014
© XXXX American Chemical Society
A
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Letter
(Table 1, entries 1−11 and entry 13). The reaction yield did not
decreaseasthe amountofLi2CuCl4 was reduced from 5 to1 mol %
(Table 1, entries 13 and 14). A good yield (83%) was still
obtained when the reaction was carried out with 0.1 mol %
of Li2CuCl4 over 24 h (Table 1, entry 15). Only small amounts
of biphenyl (3a) were isolated when the reaction was
carried out in the absence of di-tert-butyldiaziridinone (1)
(Table 1, entry 16) or metal catalyst (Table 1, entry 17),
suggesting that both di-tert-butyldiaziridinone (1) and metal
catalyst are important for the coupling under the reaction
conditions.
Table 2. Copper-Catalyzed Oxidative Homocoupling
of Grignard Reagents
a
The generality of the oxidative homocoupling was subse-
quently investigated. As shown in Table 2, various aryl Grignard
reagents were smoothly coupled to give the corresponding
biaryls in 73−98% yield (Table 2, entries 1−7). Alkyl Grignard
reagents were also effective substrates for this reaction, giving the
corresponding coupling products in 93−98% yield (Table 2,
entries 8−10). In the case of phenethylmagnesium chloride, no
β-hydride elimination product styrene was observed (Table 2,
entry 10). The coupling of phenylethynylmagnesium bromide
afforded 1,4-diphenylbutadiyne (3k) in 96% yield (Table 2,
entry 11).
Having established the feasibility of copper-catalyzed homo-
coupling reactions of Grignard reagents with diaziridinone 1, we
next turned our attention to more challenging cross-coupling. As
shown in Table 3, the oxidative cross-coupling reaction can be
applied to C(sp2)−C(sp2) (Table 3, entry 1), C(sp)−C(sp2)
(Table 3, entries 2−5), and C(sp)−C(sp3) (Table 3, entries
6−18) bond formations, affording the coupling products in 55−
83% yield with 2 mol % CuBr·SMe2 and 1.1 equiv of di-tert-
butyldiaziridinone (1) in THF at rt for 3 h.22 The reaction is
amenable to gram scale as illustrated in the preparation of
product 4m (Table 3, entry 13). For the C(sp)−C(sp3) coupling,
both primary (Table 3, entries 6−11) and secondary (Table 3,
entries 12−18) alkyl Grignard reagents were effective coupling
partners. The current catalytic system well tolerates β-hydrogen-
containing alkyl Grignard reagents. In most cases, the desired
cross-coupling product was formed with high selectivity.
Little C(sp)−C(sp) homocoupling product was detected
by GC−MS. As shown in Scheme 2, the present coupling
process also proceeded smoothly with functionalized and
complex substrates such as D-glucose- and cholesterol-
derived propargyl ethers 5 and 6, giving products 4s−u in
62−80% yield.
a
All reactions were carried out with RMgX (2) (0.60 mmol), di-tert-
butyldiaziridinone (1) (0.45 mmol), and Li2CuCl4 (0.0060 mmol) in
THF (0.60 mL) at rt under Ar for 3 h. Isolated yield.
b
While a precise understanding of the reaction mechanism
awaits further study, a plausible catalytic pathway is proposed in
Scheme 3. The coupling process may begin with the insertion
of CuX into the N−N bond of di-tert-butyldiaziridinone
Scheme 2. Copper-Catalyzed Oxidative Cross-Coupling
of Grignard Reagents
Scheme 3. Proposed Catalytic Cycle
As shown in Table 1, the homocoupling was readily achieved
with 5 mol % of metal catalyst such as FeCl2, CoCl2, NiBr2,
Pd(OAc)2, Pd(PPh3)4, CuCl, CuBr, CuBr·SMe2, CuI, CuCl2,
CuBr2, and Li2CuCl4, giving biphenyl (3a) in 76−97% yield
B
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Letter
a
Table 3. Copper-Catalyzed Oxidative Cross-Coupling of Grignard Reagents
a
All reactions were carried out with R1 MgX (0.30 mmol), R2 MgX (0.54 mmol), di-tert-butyldiaziridinone (1) (0.33 mmol), and CuBr·SMe2
(0.0060 mmol) in THF (0.60 mL) at rt under Ar for 3 h unless otherwise stated. The left part of the newly formed C−C bond is from R1 MgX, and
b
c
the corresponding right part is from R2 MgX. Isolated yield of product 4 based on R1 MgX. The selectivity was determined by GC−MS analysis of
d
e
the crude reaction mixture using hexadecane as internal standard. Compound 4b is not volatile enough to be detected by GC even at 300 °C. The
alkynylmagnesium halide (R1 MgX) was prepared in situ from the corresponding alkyne (0.30 mmol) and R2 MgX (0.30 mmol), and additional R2
f
MgX (0.36 mmol) was used for the subsequent cross-coupling reaction. The alkynylmagnesium halide (R1 MgX) was prepared in situ from the
corresponding alkyne (0.30 mmol) and R2 MgX (0.30 mmol), and additional R2 MgX (0.54 mmol) was used for the subsequent cross-coupling
g
reaction. The reaction was carried out on 10.0 mmol scale.
(1) to form four-membered Cu(III) species A and/or
Cu(II) nitrogen radical B,12b,c,15 which then undergoes
transmetalations to give Cu(III) intermediate D. Upon
reductive elimination, intermediate D is converted into
coupling product 4 with the regeneration of the CuX catalyst.
A radical mechanism for the coupling process cannot be ruled
out at this moment.
In summary, we have developed a novel oxidative coupling
reaction of Grignard reagents with copper catalysts using di-
tert-butyldiaziridinone (1) as oxidant. A variety of aryl, alkynyl,
and alkyl Grignard reagents can be efficiently coupled to
give the corresponding homo- and cross-coupling products in
good yields. The reaction proceeds at room temperature in
short reaction time with low-loading cheap catalysts and is
amenable to gram scale synthesis. In particular, this method is
also effective for C(sp)−C(sp3) bond formations. In addition,
the current work provides new perspectives and mechanistic
insights for the development of other reaction processes with
diaziridinones.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures, GC−MS data, characterization data,
and NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: yian@lamar.colostate.edu.
Author Contributions
†These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
C
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Letter
(12) For Cu(I)-catalyzed diamination of olefins using 1, see: (a) Yuan,
W.; Du, H.; Zhao, B.; Shi, Y. Org. Lett. 2007, 9, 2589. (b) Zhao, B.; Peng,
X.; Cui, S.; Shi, Y. J. Am. Chem. Soc. 2010, 132, 11009. (c) Zhao, B.; Peng,
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2011, 133, 20890.
ACKNOWLEDGMENTS
■
We are grateful for the generous financial support from the
General Medical Sciences of the National Institutes of Health
(GM083944-07).
(13) Zhu, Y.; Zhao, B.; Shi, Y. Org. Lett. 2013, 15, 992.
(14) Zhu, Y.; Shi, Y. Org. Lett. 2013, 15, 1942.
(15) Zhu, Y.; Shi, Y. Org. Biomol. Chem. 2013, 11, 7451.
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