.
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evidence for the distinctive properties of 1 as a catalyst in
Michael additions.
In conclusion, the PNN pincer ruthenium complex
1 serves as an efficient catalyst for the oxa-Michael addition
of alcohols to b-substituted unsaturated nitriles. The dearom-
atized pincer backbone in 1 is of central importance to the
measured reactivity, which acts by transferring Brønsted basic
ꢀ
character to the nitrile N atom upon addition of the C N
bond through metal–ligand cooperativity. The isolation of
a
catalytically competent Ru–dieneamido complex 1PN
together with DFT calculations support a new mechanistic
route for efficient hetero-Michael addition chemistry that
takes place under mild, additive-free conditions.
Scheme 4. Products of hetero-Michael additions to a,b-unsaturated
nitriles catalyzed by 1 with yields of isolated products given. [a] Yield
of isolated product when starting from 3-alkenenitrile. [b] Reaction with
0.07 mol% catalyst. [c] 5 days at 408C. [d] 3 days at 608C. Bn=benzyl.
Experimental Section
Synthesis of 3-isopropoxypentanenitrile (3a): A Schlenk flask was
charged with 2-pentenenitrile (537 mg; 6.6 mmol), a 1:1 mixture of
isopropanol/THF (13.2 mL), and pentadecane (83 mL) as the internal
standard. Catalyst 1 (15 mg, 0.033 mmol) was added and the reaction
was stirred at room temperature for 17 h. After quenching by
exposure to air, all volatile components were condensed under high
vacuum into a clean flask to separate them from the catalyst residue
and pentadecane. The solvent was then evaporated by rotary
evaporation (408C, ca. 200 mbar) to yield 3a as a colorless oil in
89% yield (825 mg, 5.85 mmol). 1H NMR (200 MHz, CDCl3): d =
3.68 (sept, 1H, J = 6.1, CH3CHCH3), 3.53 (quint, 1H, J = 6.0,
CH2CHCH2), 2.44 (d, 2H, J = 5.7, CHCH2CN), 1.59 (m, 2H,
CH3CH2CH), 1.17 (d, 3H, J = 6.2, CH3CHCH3), 1.13 (d, 3H, J =
6.1, CH3CHCH3), 0.92 ppm (t, 3H, J = 7.3, CH3CH2). 13C NMR
(75 MHz, CDCl3): d = 118.1 (CN), 74.0 (CH2CHCH2), 71.0
(CH3CHCH3), 28.0 (CH3CH2CH), 23.6 (CHCH2CN), 23.0 and 22.5
((CH3)2CH), 9.7 ppm (CH3CH2). HRMS (ESI) calcd. for C8H16ON
[M+H+] 142.12264, found 142.12255.
isomers crotonitrile and allyl cyanide both react with iPrOH
to form the expected product 4 which was isolated in more
than 90% yield. For the more reactive substrate acrylonitrile,
the iPrOH addition product 5 was isolated in 95% yield using
a catalyst loading as low as 0.07 mol%. Intramolecular
reactions also proceeded smoothly, as shown by the high-
yield cyclization of 6-hydroxy-2-hexenenitrile and 7-hydroxy-
2-heptenenitrile to the corresponding 2-(tetrahydrofuranyl)-
and 2-(tetrahydropyranyl)acetonitriles 6a/b, respectively.
b-Disubstituted conjugate acceptors (3-methylcrotonitrile)
or tertiary O-containing nucleophiles (R = t-amyl, Ad) do
not go to completion (7, 26% conversion) or give no
conversion at all. The poor reactivity of these encumbered
systems likely relates to unfavorable reaction energetics
(DGr ꢁ 0 based on DFT calculations). The phenols PhOH
and p-NO2-C6H4OH also fail to give conversion of 2-PN,
which is likely due to formation of stable, catalytically inactive
Ru–aryloxide species.[6,25] The importance of the nitrile in
these oxa-Michael reactions was confirmed by the lack of
reaction between ethanol and methyl crotonate. Other
heteroatom-containing nucleophiles were subsequently
tested. The addition of 1-octanethiol to crotonitrile is
complete within 1 h at room temperature (8, 99% yield),
whereas the addition of amines is less efficient, as shown for
ethyl- and benzyl amine (9a/9b). Conversion into the aza-
Michael addition products is slow (9a: 54% after 5 days at
408C; 9b: 39% after 3 days at 608C), and the products were
isolated in 40 and 32% yields, respectively. To investigate
possible substrate inhibition in the aza-Michael addition
reaction, crotonitrile was reacted with a 1:1 mixture of EtOH
and EtNH2. The catalyst is active and highly chemoselective
for the addition of alcohol over amine,[26] with 94% con-
version obtained after 1 h and less than 2% of amine addition
product 9a detected. This conclusively shows that no sub-
strate inhibition takes place. Finally, using our novel base-free
procedure we were able to obtain the acetyl-substituted oxa-
Michael addition product 10. The attempted KOtBu-
catalyzed synthesis of 10 resulted in rapid loss of the acetyl
group by transesterification. These data provide further
Received: December 17, 2014
Published online: && &&, &&&&
Keywords: homogeneous catalysis · Michael addition ·
.
non-innocent ligands · pincer ligands · ruthenium
[1] a) E. Poverenov, D. Milstein in Organometallic Pincer Chemis-
try, Vol. 40 (Eds.: G. van Koten, D. Milstein), Springer, Berlin,
[4] a) M. Vogt, A. Nerush, Y. Diskin-Posner, Y. Ben-David, D.
Gargir, M. A. Iron, Y. Diskin-Posner, Y. Ben-David, D. Milstein,
[5] a) M. Vogt, A. Nerush, M. A. Iron, G. Leitus, Y. Diskin-Posner,
Conley, C. Copꢁret, M. Lutz, E. J. M. Hensen, E. A. Pidko, ACS
[6] S. Perdriau, M.-C. Chang, E. Otten, H. J. Heeres, J. G. de Vries,
4
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!