(CAAC)CuX-catalyzed hydroboration of terminal alkynes with pinacolborane directed by the X-ligand

Article abstract of DOI:10.1016/j.jorganchem.2016.09.025

When X is a basic ligand (CAAC)CuX complexes [CAAC?=?cyclic (alkyl) (amino)carbene] selectively promote the (E)-β-hydroboration of terminal alkynes with pinacolborane instead of the dehydrogenative borylation observed with weakly nucleophilic X ligand. This methodology is applicable to a variety of terminal alkynes. Deuterium labeling experiments coupled with stoichiometric reactions give evidence towards a plausible mechanism involving a σ-mono (copper)acetylide complex.

Full text of DOI:10.1016/j.jorganchem.2016.09.025

Journal of Organometallic Chemistry xxx (2016) 1e3
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
(CAAC)CuX-catalyzed hydroboration of terminal alkynes with
pinacolborane directed by the X-ligand
Erik A. Romero, Rodolphe Jazzar, Guy Bertrand*
a r t i c l e i n f o
a b s t r a c t
Article history:
When X is a basic ligand (CAAC)CuX complexes [CAAC ¼ cyclic (alkyl) (amino)carbene] selectively
Received 28 July 2016
Received in revised form
24 September 2016
Accepted 26 September 2016
Available online xxx
promote the (E)-b-hydroboration of terminal alkynes with pinacolborane instead of the dehydrogenative
borylation observed with weakly nucleophilic X ligand. This methodology is applicable to a variety of
terminal alkynes. Deuterium labeling experiments coupled with stoichiometric reactions give evidence
towards a plausible mechanism involving a
s
-mono (copper)acetylide complex.
© 2016 Elsevier B.V. All rights reserved.
Keywords:
Hydroboration
Homogenous catalysis
Copper
Carbene
Terminal alkynes
1. Introduction
(amino)carbene [6,7]] azide-alkyne cycloaddition (Click reaction)
[8]. We showed that basic X ligands favor the metallation
Due to the importance of the Suzuki-Miyaura cross-coupling
reaction, organoboronic esters have found wide applicability as
synthons in organic chemistry [1]. Alkenyl derivatives have been
prepared via transition metal-catalyzed hydroboration of the cor-
responding alkynes [2], with only seldom reports involving the use
of inexpensive metals such as copper [3e5]]. With this metal,
Yun et al. [5] recently described an elegant atom efficient
step leading to the
[9], but disfavor the formation of the catalytically active
-bis(copper)acetylide B (Fig. 1). Conversely, non-nucleophilic
s-mono (copper) acetylide complexes A [8b]
s,p
ligands favor the latter but slowly promote the former; this
problem could be circumvented, however, in the presence of an
external base. Using this knowledge, we recently demonstrated
[10] that (CAAC)CuX complexes, featuring a weakly nucleophilic X
ligand such as trifluoromethanesulfonate can selectively promote
the dehydrogenative borylation of terminal alkynes with pinacol
borane [11]. This result is due to the formation of B [8] in which
the triple bond is protected, and thus cannot participate in clas-
sical hydroboration. We hypothesized, that in contrast to B, A
features an unprotected and polarized CeC triple bond and should
readily undergo hydroboration. Here we report that indeed
a simple modification of the X ligand of (CAAC)CuX complexes
allows for switching the selectivity of the reaction of pinacolbor-
ane with terminal alkynes from dehydrogenative borylation to
methodology affording selectively the (E)-b-hydroboration or the
(Z)- -hydroboration products of terminal alkynes, using 1,8-
b
naphthalenediaminatoborane as the borane partner. There are no
extensive investigations detailing the hydroboration of terminal
alkynes to afford (E)-
copper catalyst. However, Hoveyda et al. [3a] demonstrated that
both (E)- - and -hydroboration of terminal alkynes can be ob-
b-hydroboration using pinacolborane and a
b
a
tained using bis(pinacolato)diboron (PinBBPin) as the boron part-
ner. Note that this synthetic method requires the presence of an
alkoxide, which generates a stoichiometric amount of ROBPin as
waste.
(E)-b-hydroboration.
Previously, we reported on the role of the X ligand in the
mechanism of the (CAAC)CuX-catalyzed [CAAC ¼ cyclic (alkyl)
2. Results and discussion
We started our investigation using a stoichiometric mixture of
phenylacetylene 1a and pinacolborane in C6D6 at room tempera-
ture for 2 h. We first checked that there was no reaction at room
temperature in the absence of catalyst (Table 1, Entry 1). As
*Correspondingauthor. UCSD-CNRSJoint ResearchChemistry Laboratory (UMI3555),
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla,
CA 92093-0358, USA
E-mail address: guybertrand@ucsd.edu (G. Bertrand).
http://dx.doi.org/10.1016/j.jorganchem.2016.09.025
0022-328X/© 2016 Elsevier B.V. All rights reserved.
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j.jorganchem.2016.09.025

2
E.A. Romero et al. / Journal of Organometallic Chemistry xxx (2016) 1e3
X = PhO
X = TfO
decreasing the concentration from 2.3 to 1.6 mol/L had little effect
X
L
on the selectivity (Entry 10), but further dilution to 1.3 mol/L
significantly affects the formation of 2a (Entry 11). Lastly,
decreasing the catalyst loading below 2.5 mol% also proved detri-
mental to the reaction (Entries 12e13).
X = PhO
X = TfO
H
R
Cu
L
Cu
R
+
L
Cu
R
LCuX
A
X = TfO
+ base
B
Using the optimized conditions, the scope of the hydroboration
reaction was then investigated at room temperature in acetonitrile
(2.3 0.1 M) using 3.65 mmol of alkyne and 3.74 mmol of borane in
the presence of 2.5 mol% (CAAC)CuOPh (Fig. 2). This reaction en-
compasses a wide range of electronically diverse terminal alkynes.
In most cases, the NMR spectra of the crude reaction mixture
showed excellent selectivity, and the alkenylboronic esters 2a-m
were isolated in good to excellent yields. Importantly, purification
of products 2a-m is readily achieved in air by filtration through a
short plug of silica with pentane as the eluent. This protocol also
allows for gram-scale syntheses, as shown with 2a.
We then turned our attention to the mechanism of the reaction.
We previously showed that (CAAC)CuOPh reacts with terminal al-
kynes to afford the copper acetylide complex B with elimination of
phenol [8b]. Note that complexes of type B can be isolated, and that
phenol readily reacts with pinacol borane to afford the catalytically
inert PinBOPh (See SI for characterization). In accordance with
recent work by Roesky et al., [12]] we postulate that a 1,2-addition
of PinB-H across the C (sp)-C (sp) bond of B gives rise to a copper
alkenyl boronic ester, which could not be isolated. Then, as already
observed in the copper-catalyzed azide-alkyne cycloaddition re-
action (CuAAC) [8], the alkyne should be acidic enough to induce a
protonolysis, which affords 2 and regenerates the copper acetylide
complex B (Fig. 3). In order to confirm this hypothesis, we per-
formed the catalytic reaction using deuterium labelled phenyl-
acetylene, and as expected, we observed the formation 2a-D (90%
D-incorporation). In addition, when a stoichiometric amount
of copper phenylacetylide Ba and PinB-H were reacted with a
X = -OTf
NEt3 (cat)
R
BPin
-H2
H
R
Dehydrogenative
Borylation
LCuX
(cat)
+
O
H
B
H
R
BPin
H
X = -OPh
O
Hydroboration
This work
Fig. 1. (CAAC)CuOTf has been shown to promote the dehydrogenative borylation of
terminal alkynes due to the formation of B. (CAAC)CuOPh should catalyze the
hydroboration of terminal alkynes via the copper acetylides A.
Table 1
Effect of the X ligand, solvent, and concentration on the b
-hydroboration reaction.a
Entry
LCuX (mol%) X
Solvent
Conc. (M)
2a (%)b
3a (%)b
1
2
3
4
5
6
7
8
e
C6D6
C6D6
C6D6
C6D6
C6D6
C6D6
CD2Cl2
THF-d8
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
2.3
2.3
2.3
2.3
2.3
2.3
2.3
2.3
2.3
1.6
1.3
2.3
2.3
0
1
1
0
6
90
20
10
0
0
0
0
0
OTf (2.5)
OTf (2.5)c
OBz (2.5)
OAc (2.5)
OPh (2.5)
OPh (2.5)
OPh (2.5)
OPh (2.5)
OPh (2.5)
OPh (2.5)
OPh (1)
30
40
61
85
79
94
91
77
81
53
R
H
LCuOPh (2.5 mol%)
BPin
2a-m
+
R
Acetonitrile (2.3 M), 2-4 h, RT
PinB-H
9
BPin
BPin
BPin
10
11
12
13
0
0
0
Bu
2a 92%a
2b 95%a
2c 98%a
OPh (0.5)
gram scale : 1.89 g (84%)
Bolded Entry 3 and Entry 9 correspond to the best reaction conditions for the se-
lective formation of 3a and 2a respectively.
BPin
BPin
MeO
BPin
BPin
a
Reactions were carried out for 2 h in a test tube at RT under an argon atmo-
sphere using 0.69 mmol of phenylacetylene and 0.71 mmol of pinacol borane.
b
OMe
2d 81%a
Measured by NMR using CH2Cl2 or toluene as an internal standard.
c
5 mol% Et3N.
2e 99%a
2f 99%a
BPin
BPin
previously reported [10], in the presence of 2.5 mol% of (CAAC)
CuOTf no significant reaction occurred which stems for the diffi-
culty of triflate (pKa ¼ ꢀ12) to deprotonate 1a (Entry 2). However,
in the presence of Et3N (5 mol%), as an additive, selective formation
of the dehydrogenative borylation product 3a was observed (Entry
3). In marked contrast, with the more basic phenoxide anion
(pKa ¼ 10), which favors the formation of A at the expense of the
Cl
F
N
2i 84%b
2g 86%b
2h 52%b
BPin
BPin
BPin
BPin
dinuclear complex B, the (E)-b-hydroboronic ester 2a was obtained
2j 97%a
2k 74%a
2l 95%a
with no trace of 3a (Entry 6). The influence of the basicity of the X
ligand was confirmed, using the benzoate (pKa ¼ 4.2) and the ac-
etate (pKa ¼ 4.8) (Entry 4e5).
O
Me3Si
2m 62%b
A survey of solvent polarities (Entries 6e9) revealed that the
reaction is in all cases very selective for the formation of 2a with
acetonitrile giving the best results (94% NMR yield). We found that
Fig. 2. Scope of the hydroboration of terminal alkynes. [a] reaction time 2 h [b] re-
action time 4 h.
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E.A. Romero et al. / Journal of Organometallic Chemistry xxx (2016) 1e3
3
dx.doi.org/10.1016/j.jorganchem.2016.09.025.
L
Cu
OPh
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Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
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