Organic Letters
Letter
a
Table 1. Optimization of the Reaction Conditions
Moreover, the use of phenanthroline ligand L7 produced 3aa
in moderate yield (entry 17). Finally, phosphine ligands proved
to be ineffective. The use of PPh delivered 5aa as the sole
3
product in 97% yield (entry 18), and PCy led to the equal
3
amount of 3aa and 5aa (entry 19). It should be noted that the
alkenylboronate 3aa was obtained solely as the Z-isomer (Z/E
>
19:1).
1
a/2a/
3aa/4aa/5aa/6aa
Under the optimal reaction conditions, the scope of diazo
b
entry
cat.
B2pin
solvent
(%)
2
compounds was evaluated (Scheme 2). As observed, a range of
1
2
3
4
5
6
7
8
9
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuCl
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:1
1:1.5:2
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
DMF
70/0/5/<5
40/0/<5/<5
53/0/18/9
0/30/0/28
20/0/37/<5
51/0/9/<5
<5/−/−/16
0/0/27/<5
0/0/21/<5
0/55/0/20
88/0/<5/<5
76/0/<5/<5
73/0/10/<5
30/0/<5/<5
15/0/12/<5
0/0/84/12
42/0/7/<5
0/0/97/0
,
a b
DMSO
DMAC
CH Cl
Scheme 2. Scope of Three-Component Reaction
2
2
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
c
Cu(MeCN) BF
4
4
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
Cu(OTf)2
CuI/L1
CuI/L2
CuI/L3
CuI/L4
CuI/L5
CuI/L6
CuI/L7
CuI/PPh3
CuI/PCy3
23/0/23/<5
a
Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), B pin (0.6
2
2
mmol), copper salt (8 mol %), ligand (10 mol %, from entries 11 to
b
c
1
9) in solvent (4 mL) at 30 °C for 18 h. Isolated yields. Without
molecular sieves.
a
Reaction conditions: 1 (0.2 mmol), B pin (0.6 mmol), CuI (8 mol
2
2
%
), L1 (10 mol %), 4 Å MS (100 mg), and DMF (2 mL) were added
to a dry reaction tube, and then 2 (0.3 mmol) in DMF (2 mL) was
added and stirred at 30 °C for 18 h. Isolated yields for single isomer.
b
sulfoxide (DMSO) as the solvent gave 3a in 40% yield (entry
2
), whereas dimethylacetamide (DMAC) furnished a 53%
α-aryl and α-heteroaryl diazoacetates were found to work well,
delivering the corresponding alkenylboronates in moderate to
good yields. α-Aryldiazoacetates containing electron-donating
groups such as methyl, methoxy, phenyl, amide, benzodioxole,
and naphthyl reacted smoothly with 1a and B pin to deliver
the desired alkenylboronates (3ab−3ag) in 55% to 85% yields
with moderate to good Z/E ratios. α-Aryldiazoacetates bearing
electron-withdrawing groups such as fluoro, chloro, and bromo
at different positions of the phenyl ring were all tolerated,
providing the corresponding products (3ah−3al) in moderate
to good yields (56%−90%) with excellent Z-selectivity (Z/E >
19/1). Unfortunately, the α-aryldiazo substrate containing a
yield of 3aa together with an 18% yield of alkenylboronate 5aa
and a small amount of 6aa (entry 3). When dichloromethane
was used, the cyclopropene 4aa and alkene 6aa were isolated
as the major products (entry 4). Moreover, decreasing the
amount of B pin gave inferior results (entries 5 and 6).
2
2
2
2
Typically, the addition of 4 Å molecular sieves was crucial to
the reaction. Without molecular sieves, only a trace amount of
3
aa was detected (entry 7). Next, several copper salts were
screened. The use of CuCl and Cu(MeCN) BF furnished
4
4
byproduct 5aa in over 20% yield rather than the desired 3aa
entries 8 and 9), indicating the direct hydroboration of
(
alkynes was more easily to occur for such copper anions. In
contrast, cyclopropene 4aa was obtained as the major product
CF group failed to give the desired product (3am). This diazo
3
substrate was reduced to the corresponding hydrazone under
15
for Cu(OTf) , which indicated the cyclopropene reaction was
such conditions. The three-component-reaction of 1a, α-
thienyl diazoacetate, and B pin afforded 3an in 46% yield with
2
dominated for this anion (entry 10). By identifying CuI as the
best copper salt, various ligands were further evaluated. The
use of bipyridine ligand L1 provided an 88% yield of 3aa with
minimum byproducts (entry 11). The combination of CuI
with 4,4′-bipyridine ligands L2 and L3 also worked well to give
2
2
excellent Z-selectivity. The use of pyridine-derived diazoacetate
only led to an 18% yield of 3ao together with a large amount of
5aa. For phenyl diazoacetates bearing different esters, the
products (3ap−3aq) were obtained in moderate yields. Next,
the scope of terminal alkynes was investigated. It was found
that both electron-rich and electron-poor aromatic alkynes
were tolerated, affording the corresponding products (3ba−
3ja) in moderate to good yields with an excellent Z/E ratio.
The reaction can be performed in gram scale, and
3aa as the major product but in slightly lower yields (entries 12
and 13). As observed, sterically hindered 2,2′-bipyridine
ligands could not promote the reaction. For example, L4 and
L5 gave low yields of 3aa (entries 14 and 15). The direct
borylation of alkyne was dominated for L6 (entry 16).
3
707
Org. Lett. 2021, 23, 3706−3711