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PhBpin followed by addition of Cu–PhPyBox, propargyl
evaluated and generally worked well, with L1 and L2 being
optimal (Table 1, entries 2 and 4). Achiral ligand L3 was not
beneficial compared to others. Despite the fact that the
reaction was poorly enantioselective, chiral ligand L2 was
chosen for ease of reaction setup (L2–CuI is most soluble in
toluene). Interestingly, CuI is a competent catalyst in the
absence of PyBox ligand (Table 1, entry 7). Since CuI alone is
a competent catalyst, this may be, in part, the source of the
uniformly low levels of enantioselectivity observed. Other
bases such as NaOtBu and Cs CO were not compatible in the
acetate 2 and Et N led to generation of 3 in ꢀ 15% yield and
3
>
20:1 dr (55:45 er) [Eq. (1)].
2
3
reaction conditions. However, presence of base is crucial for
product formation (Table 1, entry 11). Finally, other reaction
parameters were tested, and it was found that the combina-
tion of CuI and Et N was ideal (Table 1, entry 4).
3
With an optimized set of conditions in hand, the scope of
the process was evaluated. With respect to the aryl lithium
component, both electron-withdrawing (products 8, 11, 13)
and electron-donating groups (products 9, 10, 15) were
tolerated. While sterically demanding substituents such as o-
Br did not react, o-F did allow for product formation (product
8). In general, halogen substituents (product 13) were well
tolerated in the reaction. It should also be noted that a furan
ring did not compete for the electrophilic Cu–allenylidene
species and product 14 was formed in high yield and dr.
Simple naphthyl (product 12) and highly electron-rich
piperonyl (product 15) groups migrated efficiently to deliver
the products in high yield. Reaction with nBuLi also allowed
for formation of 16, albeit in moderate yield due to instability
of the product upon purification. Surprisingly, alkenyl migrat-
ing groups remained unproductive under the reaction con-
ditions (see the Supporting Information). The group on indole
is not limited to only methyl, as simple benzyl protected
indole furnished the product 18 in high yield. Finally,
substitution of the indole unit at C6 with a Me-group (product
Based on the early results, optimization of the reaction
was carried out. Initially the reaction setup was altered such
that 2-Bpin-indole (4) in combination with PhLi was used (as
opposed to lithiation of N-Me-indole (1) and treatment with
PhBpin), which was operationally simpler. In addition,
preliminary studies revealed that use of the OBoc (6) vs.
OAc (2) propargyl electrophile was superior (Table 1,
entry 1). Under the adjusted reaction setup, evaluation of
solvents let to the finding that toluene was better than THF
and led to formation of the product in quantitative NMR yield
and > 20:1 dr (Table 1, entry 2). Other chiral ligands were
Table 1: Optimization.
1
7) was tolerated. In the case of the propargyl electrophile,
both electron-withdrawing (product 20) and electron-donat-
ing (product 19) groups worked well, although the latter was
superior. Sterically demanding o-Me (product 21) was also
tolerated to generate the product in good yield, but aliphatic
substituents on the propargyl Boc-carbonate did not allow for
product formation (see the Supporting Information). In all
cases products were obtained as a single observable diaste-
reomer (> 20:1 dr). The relative stereochemistry of the chiral
indoline 3 was determined by single crystal X-ray analysis.
While the reaction to generate the indoline demonstrated
in Scheme 2 is significant, preparation of highly substituted
indoles is also of high value. As such, after reaction workup,
oxidation of the Bpin resulted in formation of disubstituted
indoles (Scheme 3A). The scope of this reaction was demon-
strated with select substituted indoles (products 25–27). This
process is noteworthy as 2,3-disubstituted indoles are easily
prepared from simple components in two steps. Finally,
treatment of 19 with TBAF also induced a deborylation and
double bond isomerization to furnish allene 28 as a single
diastereomer (Scheme 3B). Our attempts to prevent the
alkyne isomerization by changing temperature or using
[
a]
Entry
Change of Conditions
Yield [%]
1
2
3
4
5
6
7
8
9
THF as solvent
Toluene as solvent
30
99
78
PhCF as solvent
3
[
b]
L2 as ligand
L3 as ligand
L4 as ligand
99 (78)
70
97
78
<5
25
<5
<10
No ligand, only CuI
NaOtBu as base
Cs CO as base
2
3
1
1
0
1
No CuI
No Base
1
[a] Yield and dr determined by H NMR analysis of the crude reaction
mixture using an internal standard. [b] Isolated yield.
TBAF·3H O were unsucessful. Base-mediated isomerization
2
[12]
of alkynes to allenes is well precedented in literature. The
2
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Angew. Chem. Int. Ed. 2021, 60, 1 – 6
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