A frustrated-Lewis-pair approach to catalytic reduction of alkynes to cis -alkenes

TLDR: This work describes a general approach to the hydrogenation of alkynes to cis-alkenes under mild conditions using the unique ansa-aminohydroborane as a catalyst and proves the mechanism is verified by experimental and computational studies.

Abstract: Frustrated Lewis pairs are compounds containing both Lewis acidic and Lewis basic moieties, where the formation of an adduct is prevented by steric hindrance. They are therefore highly reactive, and have been shown to be capable of heterolysis of molecular hydrogen, a property that has led to their use in hydrogenation reactions of polarized multiple bonds. Here, we describe a general approach to the hydrogenation of alkynes to cis-alkenes under mild conditions using the unique ansa-aminohydroborane as a catalyst. Our approach combines several reactions as the elementary steps of the catalytic cycle: hydroboration (substrate binding), heterolytic hydrogen splitting (typical frustrated-Lewis-pair reactivity) and facile intramolecular protodeborylation (product release). The mechanism is verified by experimental and computational studies.

Figures

Figure 1. FLP-catalyzed hydrogenation of multiple C -C bonds. a, Traditional approach. b, Approach via hydroboration-hydrogen activation-protonation.

Figure 3. Solution-phase Gibbs free energy diagram computed for the hydrogenation of but-2-yne (10a). Optimized structures of transition states identified for hydroboration (TShydr ), heterolytic hydrogen splitting (TSsplit ) and protonation (TSprot ) steps are shown in the upper part of the figure. A detailed description of the structure and energetics of species involved in the catalytic cycle is given in the Supplementary Information.

Figure 5. Reaction of aminoborane 6 with hex-1-yne and H2.

Figure 2. Catalytic hydrogenation of alkynes into cis-alkenes. a, Formation of the active catalyst species 8 via hydrogenolysis of precatalyst 6. b, The catalytic cycle of alkynes hydrogenation. Intramolecular protonation of vinyl carbon in 28 causes cycle propagation, while C6F5 group cleavage leads to active catalyst degradation. c, Reaction of hydroboration intermediates 27 with D2 results in selective formation of monodeuterated cis-alkenes 21c, 26d-e and catalyst 8-d. Deuteration occurs selectively to the B–C carbon.

Figure 4. Reaction of 6 and 8 with alkenes. a , Alkenes hydroboration outcome depends on steric crowdness of the double bond: rapid and irreversible for terminal alkenes (12b); slow and reversible for cisdi(n-alkyl)ethenes (10b, 11b), no reaction for 15b, 18b, 21b. b, Alkylboranes 30 are produced from alkenes or alkynes and 6 under hydrogenation conditions.

Full text

1
Highly selective metal-free catalytic hydrogenation of unactivated
alkynes to cis-alkenes
Konstantin Chernichenko
1
, Ádám Madarász
2
, Imre Pápai
2
, Martin Nieger
1
, Markku Leskelä
1
, and
Timo Repo
1
*
1
Department of Chemistry, Laboratory of Inorganic Chemistry, University of Helsinki
P.O. Box 55, FIN-00014, Finland. Fax: +358 (9)19150198; E-mail:timo.repo@helsinki.fi
2
Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences
P.O. Box 17, H-1525 Budapest, Hungary
Recently, a new approach to dihydrogen activation known as frustrated Lewis pairs (FLPs) concept has
been introduced
1, 2, 3
. A combination of highly Lewis acidic boranes and sterically hindered bases can split
hydrogen heterolytically generating onium (phosphonium, ammonium, etc.) borohydrides. These compounds
show reduction activity resembling that of inorganic borohydrides like NaBH
4
, i. e. they are suitable mostly for
reduction of polarized multiple bonds. Imines, enamines, silyl ethers
4, 5, 6
, α,β-enones
7
, ynones
8
, N-
alkylanilines
9
were hydrogenated using stoichiometric or catalytic amounts of FLPs. Due to heterolytic nature
of FLP-H
2
adducts, hydrogenation of unactivated multiple C–C bonds using FLPs has some natural
limitations, since during the respective step of the catalytic cycle a proton transfer from catalyst to substrate
should take place (Fig. 1a). Although Greb et al. have implemented this approach to hydrogenation of
alkenes under ambient conditions, this method is predictably restricted to the alkenes with high proton
affinity
10
.

2
BH
R
1
R
2
B
R
1
R
2
R
6
H
R
4
R
3
R
5
BaseH
+
R
5
R
6
R
4
R
3
R
5
R
6
R
3
R
4
Hydroboration
(substrate binding)
Protonative
elimination
1
2
3
4
5
B
-
R
1
R
2
R
6
H
R
5
R
3
R
4
H
Base
H
2
Hydrogen
activation
(FLP reactivity)
R
4
R
3
R
5
R
6
R
4
R
3
R
5
R
6
Substrate
Protonation
B
a
s
e
H
2
Hydrogen
activation
(FLP reactivity)
B
R
1
R
2
R
3
B
-
R
1
R
2
BaseH
+
R
3
H
R
4
R
3
R
5
R
6
B
-
R
1
R
2
R
3
H
H
+
H
H
Recombination
(Hydride Transfer)
a
b
Figure 1. FLP-catalyzed hydrogenation of multiple C-C bonds. a, Traditional approach. b, Approach via
hydroboration-hydrogen activation-protonation.
Combining the FLP approach and previous knowledge about borane-catalyzed hydrogenation of
alkenes
11, 12, 13, 14
and polyarenes
15, 16, 17, 18
, we propose herein a new general catalytic pathway to the
hydrogenation of unsaturated hydrocarbons (Fig. 1b) and demonstrate its validity by the highly selective
hydrogenation of alkynes into cis-alkenes. Stereoselective hydrogenation of alkynes is an important protocol
in synthesis of natural and industrially relevant compounds.
19, 20, 21, 22, 23
. Heterogeneous as well as
homogeneous metal catalysts for this purpose are known
24, 25, 26, 27, 28
, however, metal-free catalytic
hydrogenation of unactivated alkynes into alkenes has not been reported previously.
In contrast to classical FLP-catalyzed reactions, the substrate is bound to the catalyst 1 by
hydroboration prior to hydrogen activation (Fig. 1b). The resulting borane 3, together with a Lewis base
cocatalyst can activate hydrogen, producing the adduct 4. In this onium borohydride 4 a proton transfer can
occur liberating the initial borane 1, the Lewis base and the hydrogenated substrate 5. To the best of our
knowledge, this approach has not been studied experimentally or theoretically.
Initially, we attempted to use Piers' borane, (C
6
F
5
)
2
BH
29
, as a catalyst. (C
6
F
5
)
2
BH smoothly hydroborates
different alkenes and alkynes
30, 31
. Moreover, it was shown that the resulting
bis(pentafluorophenyl)alkylboranes as well as (C
6
F
5
)
2
BH itself
32
together with the properly chosen Lewis
bases can split hydrogen heterolytically to give the respective onium borohydrides
33
. However, upon heating
of these compounds only hydrogen release was observed, demonstrating the reversibility of H
2
uptake by
these FLPs. Our numerous attempts to realize the approach depicted in Fig. 1b using (C
6
F
5
)
2
BH together
with different bases and additives were unsuccessful
34
.
Recently, we have reported 2-[bis(pentafluorophenyl)boryl]-N,N-dialkylanilines exemplifying a new class
of bridged frustrated B/N Lewis pairs
35
. Interestingly, compound 6 exists as an intramolecular Lewis adduct,

3
containing a strained four-membered C–N→B–C cycle. Due to strain the B-N bond in 6 is relatively weak,
since at room temperature 6 reversibly reacts with hydrogen to give ammonium borohydride 7 (Fig. 2a)
New ansa-aminohydroborane as a catalyst
In this work we report that upon heating of aminoborane 6 at 80 °C under 2 bar H
2
new signals different
from those of 6 or 7 in the
1
H,
19
F and
10
B NMR spectra appear along with formation of C
6
F
5
H. The new
species was isolated as a greenish oil and identified as the hydroborane 8 (Fig. 2a) containing in the
1
H NMR
spectrum a characteristic partially relaxed quadruplet (δ = 4.35 ppm, J = 105 Hz) attributed to BH signal. This
reactivity is unprecedented, since neither inter- no intramolecular FLPs have been reported to undergo B–
C
6
F
5
hydrogenolysis as a result of hydrogen activation
36, 37, 38
.
Since 8 is a potentially hydroborating BH-species and can be produced in situ from 6, we attempted to
use 8 as a catalyst in hydrogenation of unactivated alkenes and alkynes following the strategy depicted in
Fig. 1b. Hex-1-ene (12b), hex-1-yne (12a) and hex-3-yne (11a) were heated separately together with 10 mol.
% of precatalyst 6 in C
6
D
6
under 2 bar H
2
at 80 °C. After 15 h, no products of hex-1-ene and hex-1-yne
hydrogenation were detected by NMR. In case of 11a no evidence of starting alkyne were found but a
complex mixture of alkenes comprising mostly of cis-hex-3-ene 11b. Minor amounts of trans-hex-3-ene and
other hexenes were attributed to isomerization of initially produced cis-hex-3-ene via
hydroboration/retrohydroboration sequence, catalyzed either by 8 or other hydroborane species. When
hydrogenation of 11a was repeated for 3 h with 5 mol. % of 6, cis-hex-3-ene 11b was produced almost
exclusively according to NMR.

4
B
-
C
6
F
5
N
+
H
F
F
F
F
F
2 bar H
2
, 80 °C,
C
6
D
5
Br, 6 h, >90%,
or
2 bar H
2
, 80 °C,
toluene, 7 h, 80%
B
C
6
F
5
N
B
C
6
F
5
N
R
2
R
1
H
R
1
R
2
H
2
(H–H)
B
-
N
+
R
2
R
1
H
H
H
R
2
R
1
H
H
B
C
6
F
5
N
C
6
F
5
H
80 °C,
-C
6
F
5
H
6
8
27
28
B
C
6
F
5
H
N
R
2
R
1
H
H
+
F
F
F
F
F
k
1
k
2
H
2 bar H
2
, 12h, 100%
r.t. C
6
D
6
a
b
D
2
B
C
6
F
5
N
D
8-d
+
7
D
R
2
R
1
H
21c (R
1
, R
2
= Ph)
26d:26e=79:21
c
Ar, 10 mol. %/day
r.t. C
6
D
6
-H
2
27, 28:
a (R
1
, R
2
= Me)
b (R
1
, R
2
= Et)
c (R
1
, R
2
= Ph)
26, 27, 28:
d (R
1
= CD
3
, R
2
= 4-MePh)
e (R
1
= 4-MePh, R
2
= CD
3
)
27d:27e=79:21
29
Figure 2. Catalytic hydrogenation of alkynes into cis-alkenes. a, Formation of the active catalyst species
8 via hydrogenolysis of precatalyst 6. b, The catalytic cycle of alkynes hydrogenation. Intramolecular
protonation of vinyl carbon in 28 causes cycle propagation, while C
6
F
5
group cleavage leads to active
catalyst degradation. c, Reaction of hydroboration intermediates 27 with D
2
results in selective formation of
monodeuterated cis-alkenes 21c, 26d-e and catalyst 8-d. Deuteration occurs selectively to the B–C carbon.
Various dialkyl-, diaryl-, arylalkylacetylenes were successfully hydrogenated under standard conditions:
5 mol % of 6 in C
6
D
6
, 2 bar of H
2
, 80 °C, 3 h (Table 1), demonstrating the generalit y of the approach and
providing exceptional cis-stereoselectivity., Enynes, silyl-protected ynols diynes and silyl-protected esters
(Table 1, entries 10, 19, 12, 13,) were successfully hydrogenated as well. The products were isolated in
excellent yields in experiments scaled up to 10 mmol of substrate. Some of the substrates required
prolonged reaction time or/and higher temperature and the catalyst loading, while some were not
hydrogenated at all. There are essentially two substrate classes which are unreactive with the current
method: terminal alkynes and alkynes comprising a terminal double bond. Nevertheless, terminal alkynes
can be silylated using conventional methods and the obtained silylacetylenes were smoothly hydrogenated
(Table 1, entries 11, 16). Catalytic activity up to 31.6 h
-1
was estimated using 6 or 8 as the catalyst under
standard conditions and 11a or 15a as substrates. Remarkably, the catalytic hydrogenation proceeds at
room temperature, though 20 times slower than at 80 °C. Conversely, high pressure of H
2
(30 bar) causes
almost 10-fold acceleration of hydrogenation up to 296 h
-1
(Supp. § 7).

5
No over-reduction to alkanes was detected. Under standard conditions cis-alkenes were produced
exclusively, the traces of other products like trans-alkenes have been barely detected by
1
H NMR. The only
exception found is 1-trimethylsilyl-2-phenylacetylene 22a: the substantial amount of trans-alkene 22c was
produced (12 mol. %) independently on the conversion level (Table 1, entries 16, 17). 22c is likely to be
produced directly during hydrogenation. Accumulation of trans-alkenes as a result of isomerization was
observed when prolonged heating and/or high temperature (120 °C) was applied to force hydrogenation of
poorly reactive substrates (Table 1, entries 19, 21).
Table 1. Catalytic hydrogenation of alkynes using 6 as a precatalyst.
R
2
R
1
cat. - 6
2.2 bar H
2
C
6
D
6,
D
R
2
R
1
H
H
Entry
Substrate(s) Product(s) Catalyst
6,
mol. %
Time,
h
T,
°C
Conversion
a
(isolated yield)
1
10a
10b
7 3 80 100
2
11a
11b
5 3 80 100
3
12a
– 5 15 80 n.r.
b
4
: 12b
1:1
– 5 3 80 n.r.
5
:
1:1
– 5 3 80 n.r.
6
13a
13b
7 3 80 100
7
14a
14b
10 3 80 100
8
15a
15b
5 3 80 100 (80)
9
O
OSiMe
2
t-Bu
16a
O
t
-BuMe
2
SiO
16b
5 3 80 100 (98)
10
17a
17b
5 3 80 100
11
Cl
Si
18a
Cl
Si
18b
5 3 80 100 (95)
12
O
Si
19a
O Si
19b
5 3 80 100
13
20a
20b
5 3 80 100 (94)
14 5 3 80 52
15
21a
21b
9 80 100 (91)

Frequently asked questions

Q1. What was the amount of stoichiometric or catalytic amount of FL?

enamines, silyl ethers4, 5, 6, α,β-enones7, ynones8, Nalkylanilines9 were hydrogenated using stoichiometric or catalytic amounts of FLPs. 

Q2. What is the role of mutual ansa-B/N geometry in the catalytic?

Mutual ansa-B/N geometry plays a key role in all elementary steps, especiallyduring protodeborylation, which proceeds in a single step, rather than including carbocation intermediates. 

Q3. What is the reason for the inability to hydrogenate terminal alkenes?

the inability to hydrogenate terminal alkynes is a result of the catalysts degradation into species inert to hydrogen due to complete elimination ofthe perfluorophenyl groups. 

Q4. What is the reaction reaction of diphenylacetylene 21a?

diphenylacetylene 21a remains intact with 8 at room temperature and requires heating at 80 °Cmaking the hydroboration, apparently, the rate-limiting step in the overall slow hydrogenation of thissubstrate. 

Q5. What is the reason for the phenyl group being removed from the Lewis acceptor?

heterolytic H2 splitting with B/N FLPs containing only one electron withdrawing C6F5 group on the Lewis acceptor site is unprecedented due to reduced acidity of the resulting borane. 

Q6. What is the effect of the ortho-phenylene linker on the zwitterio?

However,as pointed out previously, the ortho-phenylene linker between the B/N centers provides significant electrostatic stabilization in the zwitterionic species formed upon the H2 cleavage 40. 

Q7. How many new aminoborane species were formed after 3 h?

after 3 h three new aminoborane species were formed in the ratio 3:3:2, each containing the hex-1-ynyl group, as evident by 1H and 11B NMR. 

Q8. What is the limiting factor towards the hydrogenation of alkenes using the present approach?

this step represents the only limiting factor towards the hydrogenationof alkenes using the present approach, and it is associated with the lack of π-system in the zwitterionicintermediate formed in the H2 activation step. 

Q9. What is the ratio of reaction rates of these two pathways?

Assumingthe C6F5H elimination to be the only catalyst degradation pathway, the ratio of reaction rates of these two intramolecular protonation pathways corresponds to maximum turnover number, which was found to be 91for hydrogenation of hex-3-yne (Supp. § 9). 

Q10. Why is the B-N bond in 6 relatively weak?

Due to strain the B-N bond in 6 is relatively weak,since at room temperature 6 reversibly reacts with hydrogen to give ammonium borohydride 7 (Fig. 2a)New ansa-aminohydroborane as a catalyst 

Q11. How many mmol of C6D6 were placed into a Schlenk tube?

MethodsStandard protocol: 0.2–0.5 mmol of an alkyne were placed into a 25 ml Schlenk tube, followed by 5 mol %of 6 and 0.7 ml of C6D6. 

Q12. What was the reaction time for cis-hex-3-ene 11b?

Whenhydrogenation of 11a was repeated for 3 h with 5 mol. % of 6, cis-hex-3-ene 11b was produced almostexclusively according to NMR. 

Q13. What is the reversibility of hydroboration in the reaction with cis-?

Although atthe end of 11a hydrogenation the catalyst is present as alkylborane 30c, the latter can easily dissociate togive active catalyst species 8 pointing again to the reversibility of hydroboration in the reactions with cis-di(n-alkyl)ethenes (Supp. § 33). 

Q14. What is the dft method for the hydroboration of a catalyst?

DFT calculations (Supp. § 49) carried out for the reaction of catalyst 8 with but-2-yne (10a) predictrelatively small activation barrier (16.2 kcal/mol) for the hydroboration process, and point to high exergonicityof this step (see Fig. 3).