Organic Letters
Letter
the hydroamination product 12l,m observed, which can be
rationalized by the higher reactivity of the hydroamination
product and, consequently, a rapid hydrolysis by trace amounts
of water in the reaction mixture. The limitations of the present
methodology lie within the use of strong electron-withdrawing
groups (e.g., CN) or the use of N-heterocycles (Scheme 2,
11o,p). For both, no product of the hydroamination was
observed, which might be explained by poisoning of the
cationic Au(I) catalyst by the Lewis basic 3-pyridylacetylene or
by hydrolysis of the reaction product in the case of the cyano-
substituted phenylacetylene. Similarly, 1,2-disubstituted al-
kynes (11q,r), styrene (13), or phenylallene (14) did not
react in this hydroamination reaction. An interesting
observation was made with 1-trimethylsilyl-2-phenylacetylene
11n: in this case, the hydroamination reaction proceeded in
moderate yield with concomitant cleavage of the silyl group to
give product 12a.
product were observed when employing [H6]-carbazole (16),
indole (17), or phenothiazine (18) as the reaction partner,
which might be related to the ease of hydrolysis of the reaction
product or poisoning of the electrophilic Au(I) catalyst as
observed by 31P NMR of the Au(I) catalyst in the presence of
heterocycles 17 and 18.15
Based on the importance of carbazole heterocycles in
materials’ applications, we next studied this protocol in multi-
hydroamination reactions (Figure 1). For this purpose, we
Subsequently, we applied this hydroamination protocol
under slightly modified conditions (L1 instead of XPhos; for
tion) to aliphatic, terminal alkynes, which reacted in moderate
yield to the desired vinyl-substituted carbazole (12s−w). Even
cyclopropyl acetylene smoothly reacted in this hydroamination
reaction without ring opening of the cyclopropane ring.
Further studies focused on the influence of the substitution
pattern of the carbazole heterocycle (Scheme 3). While
Figure 1. Multi-hydroamination reactions (reaction conditions: 5 mol
% of (XPhos)AuCl, 10 mol % of NaBArF, carbazole (1.0 equiv for 19
and 20, 2.0 equiv for 21−23, 3.0 equiv for 24) and acetylene
derivative (for 19 and 20: 11a, 4.0 equiv; for 21−24: 1.0 equiv) were
dissolved in 2.0 mL of DCM and stirred for 12 h at room
temperature).
Scheme 3. Substrate Scope of N-Heterocycles
studied 5,7-dihydroindolo[2,3-b]carbazole in the reaction with
phenylacetylene under the previously optimized conditions,
which gave the double hydroamination product 19 in
moderate yields. The closely related isomer 20 did not react
in the hydroamination reaction. The missing reactivity of 20
might be related to the strong coordinating properties of the
two adjacent nitrogen atoms, which shuts down the catalytic
activity of the Au(I) complex. Next, we employed all isomers
of di(ethynyl)benzene to probe a double hydroamination
reaction onto one alkyne reaction partner. The double
hydroamination products 21 and 22 could indeed be obtained
under the same reaction conditions in good isolated yields for
1,4-di(ethynyl)benzene and 1,3-di(ethynyl)benzene, respec-
tively. On the contrary, no reaction was observed when
studying 1,2-di(ethynyl)benzene (23). Finally, we probed the
hydroamination reaction of 1,3,5-tri(ethynyl)benzene, which
gave the product of triple hydroamination 24 in 49% yield.
From a mechanism perspective, we hypothesize that the
present reaction proceeds via π-coordination of the alkyne to
the cationic Au(I) complex 26 as can be observed by a distinct
shift in 31P NMR upon addition of alkyne 11a to in situ formed
26. A competitive complexation of the Au(I) complex 26 with
carbazole 10a is not likely to occur as no change of chemical
shift in 31P NMR was observed. The Au(I)−alkyne complex 27
then undergoes addition of the carbazole heterocycle leading
to formation of a putative Au(I)−vinyl complex 29.17 Release
of the reaction product by protodeauration refurnishes the
catalytically active Au(I) complex 26 (Scheme 4). The distinct
role of NaBArF in this transformation still remains unclear, and
detailed studies via DFT calculations will be necessary to fully
understand the role of the counterion in this transformation.
substitution in the 2-, 3-, and 6-position of the carbazole
framework had only little influence on the hydroamination
reaction, a pronounced decrease in the reaction yield was
observed for 1-bromocarbazole. In this case, the hydro-
amination product was isolated in only 37% yield, which can
be attributed to steric hindrance of the bromo substituent. In
this context, we also studied bis-carbazole 13j and the
benzannellated carbazole 13i, both of which gave the desired
hydroamination product 14j and 14i in high yield, respectively.
In this context, we also studied the application of different
unprotected N-heterocycles. While the hydroamination prod-
uct 15 of [H4]-carbazole could be isolated in moderate yield,
only trace amounts of the corresponding hydroamination
C
Org. Lett. XXXX, XXX, XXX−XXX