Template Catalysis by Metal-Ligand Cooperation. C-C Bond Formation via Conjugate Addition of Non-activated Nitriles under Mild, Base-free Conditions Catalyzed by a Manganese Pincer Complex

Article abstract of DOI:10.1021/jacs.5b13208

The first example of a catalytic Michael addition reaction of non-activated aliphatic nitriles to α,β-unsaturated carbonyl compounds under mild, neutral conditions is reported. A new de-aromatized pyridine-based PNP pincer complex of the Earth-abundant, first-row transition metal manganese serves as the catalyst. The reaction tolerates a variety of nitriles and Michael acceptors with different steric features and acceptor strengths. Mechanistic investigations including temperature-dependent NMR spectroscopy and DFT calculations reveal that the cooperative activation of alkyl nitriles, which leads to the generation of metalated nitrile nucleophile species (α-cyano carbanion analogues), is a key step of the mechanism. The metal center is not directly involved in the catalytic bond formation but rather serves, cooperatively with the ligand, as a template for the substrate activation. This approach of "template catalysis" expands the scope of potential donors for conjugate addition reactions.

Full text of DOI:10.1021/jacs.5b13208

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Article
Template Catalysis by Metal-Ligand Cooperation. C–C Bond
Formation via Conjugate Addition of Non-activated Nitriles Under
Mild, Base-free Conditions Catalyzed by a Manganese Pincer Complex
Alexander Nerush, Matthias Vogt, Urs Gellrich, Gregory Leitus, Yehoshoa Ben-David, and David Milstein
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b13208 • Publication Date (Web): 10 May 2016
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Template Catalysis by Metal-Ligand Cooperation. C–C Bond
Formation via Conjugate Addition of Non-activated Nitriles
Under Mild, Base-free Conditions Catalyzed by a Manganese
Pincer Complex.
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†,§
Alexander Nerush,
†,#,§
†,§
‡
Matthias Vogt,
†
Urs Gellrich,
,†
Gregory Leitus,
Yehoshoa Ben-David, and David Milstein*
†
‡
Department of Organic Chemistry, and Department of Chemical Research Support, The
Weizmann Institute of Science, Rehovot 76100, Israel.
# Institut für Anorganische Chemie und Kristallographie, Leobener Str., Universität Bremen,
28359 Bremen, Germany.
§
These authors contributed equally to this work.
ABSTRACT The first example of a catalytic Michael addition reaction of non-
activated aliphatic nitriles, to α,β-unsaturated carbonyl compounds under mild,
neutral conditions is reported. A new de-aromatized pyridine-based PNP
pincer complex of the Earth-abundant, first row transition metal manganese
serves as the catalyst. The reaction tolerates a variety of nitriles and Michael
acceptors with different steric features and acceptor strengths. Mechanistic
investigations including temperature dependent NMR spectroscopy and DFT
calculations reveal that the cooperative activation of alkyl nitriles, which leads
to the generation of metallated nitrile nucleophile species (ꢀ–cyano carbanion
analogs), is a key step of the mechanism. The metal center is not directly
involved in the catalytic bond formation but rather serves, cooperatively with
the ligand, as a template for the substrate activation. This approach of
“template catalysis” expands the scope of potential donors for conjugate
addition reactions.
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INTRODUCTION
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Conjugate addition reactions are fundamental C–C bond formation reactions
in organic chemistry.1 For instance, the Michael addition of 1,3-dicarbonyl
compounds to activated olefins is regarded as one of the most important C–C
coupling reaction in organic synthesis.2 However, such Michael reactions
require the application of strong bases, which may not be compatible with
various functional groups and can lead to undesired side reactions. Transition
metal catalyzed Michael-type reactions, that can operate under mild and
neutral conditions and exhibit superior chemoselectivity, have been
reported.2,3
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Nitriles are important functional groups in organic synthesis due to their facile
transformation into various functional groups. Furthermore, nitriles themselves
are important constituents of modern pharmaceuticals. In 2010 more than 30
nitrile-containing drugs have been on the market and more than 20 leads-
containing nitrile functionalities have been in clinical development.4 Common
protocols for conjugate addition reactions involving nitriles make use of
activated nitriles with acidic ꢀ-protons (e.g. malononitriles, benzyl cyanide,
ethyl cyanoacetates, cyanoacetamides and the like). The same applies for
previously reported transition metal catalyzed Michael addition reactions,
therefore significantly limiting the substrate scope. The reaction usually
involves C–H activation at the ꢀ–carbon at the metal center to generate the
Michael donor moieties (i.e. metal stabilized carbanions).5-10 Fleming and co-
workers discussed the stereochemical aspects of ꢀ-lithiation and ꢀ-
magnesation of nitriles with strong bases.6,11 In an early report Rappoport and
co-workers described the utilization of a large excess of tetraethylammonium
fluoride to generate cyanmethide carbanions from acetonitrile and use them in
Michael addition reactions.12 An example making use of the bifunctional
reactivity of Ru and Ir-based amido complexes to activate ꢀ-substituted ꢀ-
cyano acetates was reported by Ikariya and co-workers.13
Non activated aliphatic nitriles have also been used in transition metal
catalyzed C–C bond forming reactions. However, due to the low acidity of the
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ꢀ-protons of aliphatic nitriles, no conjugate addition of nitriles to ꢀ,β-
unsaturated carbonyl compounds has been achieved so far. The
accomplishments in C–C bond forming reactions of alkyl nitriles are
summarized in a very recent review.14
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Recently, we reported a complementary approach for transition metal
catalyzed addition of nitriles to ꢀ,β-unsaturated carbonyl compounds. A
dearomatized PNP rhenium pincer complex was used as catalyst (Scheme 1).
Stoichiometric reactions of this dearomatized rhenium-pincer complex with
benzylic nitriles showed that an initial [1,3]-addition of the nitrile with C–C and
Re–N bond formation occurs. A subsequent tautomerization of the formed
ketimido complex leads to an enamido complex. This enamido complex is
assumed to be the actual nucleophile for the Michael addition. With regard to
the substrates, the rhenium pincer complex catalyzed conjugate addition was
limited to benzylic nitriles.15 Later, Pidko and co-workers described a pyridine-
based Ru-CNC carbene pincer complex, which, upon application of
phosphazene base, cooperatively binds acetonitrile and benzonitrile via a
similar [1,3]-addition reaction under C–C and N–Ru bond formation.16 Otten,
de Vries and co-workers reported an oxa-Michael addition reaction of alcohols
to unsaturated nitriles17 utilizing a pyridine based de-aromatized ruthenium
PNN pincer complex.
There is a strong current interest in replacing noble metal catalysts by
abundant and inexpensive base-metal catalysts. Manganese is one of the
most abundant transition metals on Earth's crust, third only to iron and
titanium. We report here the synthesis of a PNP pincer-type manganese
complex
([Mn(PNPtBu)(CO)3]Br,
2,
(PNPtBu
=
2,6-bis(di-tert-
butylphosphinomethyl)pyridine). This complex undergoes facile deprotonation
at the exo-cyclic methylene carbon moiety to yield a dearomatized complex
[Mn(PNPtBu*)(CO)2] (4) (the asterisks denotes dearomatized PNP ligand),
capable of the catalytic activation of nitriles, including non-activated aliphatic
nitriles, toward Michael acceptors under neutral conditions (Scheme 1).
Notably, this transformation is difficult even under basic conditions.18
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To the best of our knowledge this is the first example of a first-row transition
metal catalyzed Michael addition of non-activated aliphatic nitriles.
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This nitrile activation is triggered by metal-ligand cooperation (MLC), in which
the manganese center, as well as the coordinated PNP-pincer ligand,
participate synergistically in a stepwise chemical bond activation process.
MLC has been developed into a versatile tool for chemical bond activation.19-
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Transition metal complexes with pyridine- and acridine-based LNL’-type (L
= N or P) pincer ligands exhibit MLC based on aromatization-
dearomatization26 of the pincer ligand, resulting in facile activation of various
X–H single bonds, including N–H,27,28 O–H,29 H–H,30-32 C–H,32-36 and S–H37,38
bonds. In contrast to the X–H (X = C, H, N, O, S) heterolytic single bond
activation via MLC, multiple bonds can be activated but not entirely cleaved.
Instead, a reduction in bond order is observed. For instance, the activation of
C=O bonds results in a C–O single bond, with concomitant formation of a C–C
bond between the carbonyl carbon and the exo-cyclic methine carbon of the
pincer ‘arm’ as well as formation of a M–O bond. We39-41and others42-44 have
previously reported on the activation of C=O double bonds, including also a
novel binding mode of CO2 to a metal complex.
In general, well-defined pincer complexes of Mn are scarce in the literature.
Reports comprise Mn(I) PNP compounds published by Nocera and Ozerov,45
a Mn(II) center with pyridine-based NNN-pincer motif bearing two pyrazole
‘arms’46 and Mn-PDI (PDI = 2,6-bisimino pyridine) species were described by
Chirik and co-workers.47
Scheme 1. Previously reported rhenium pincer complex-catalyzed addition of benzylic nitriles
to Michael acceptors, and the conjugate addition of non-activated aliphatic and benzylic
nitriles catalyzed by pincer complex 4 of Earth-abundant manganese.
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RESULTS AND DISCUSSION
Complex 2 is readily obtained upon stirring a solution of 2,6-bis(di-tert-
butylphosphinomethyl)pyridine (PNPtBu, 1) and [Mn(CO)5Br] for 30 hours at
ambient temperature (Scheme 2). Subsequent precipitation from benzene by
addition of pentane gives complex 2 as a yellow powder in 83% yield. In
contrast to our previously reported isoelectronic rhenium complex cis–
[Re(PNPtBu)(CO)2Cl], complex 2 forms a cationic tris-carbonyl complex with a
bromide counter anion. The IR spectrum exhibits absorption bands
characteristic of an octahedral tris-carbonyl complex in a meridional
arrangement (absorption maxima at 1919, 1932 cm–1 (partly overlapping) for
ꢀasym ꢀasym’ and at 2021 cm–1 for ꢀsym, respectively). The 31P{1H} NMR
+
spectrum of 2 exhibits a singlet at 109.4 ppm, indicating two chemically
equivalent phosphorus nuclei. The C{1H} NMR spectrum shows two triplet
13
2
resonances at 220.5 ppm (t, JCP = 15.9 Hz) for two chemically equivalent
carbon nuclei in mutual trans-positions (apical) and at 223.9 ppm (t,
2JCP = 12.8 Hz) for one carbon nucleus in the trans-position with respect to the
pyridine unit, respectively. Upon addition of one equivalent of the base KOtBu
to a suspension of 2 in THF, a color-change from yellow to brown is observed
and a solution comprising a mixture of the dearomatized tris– and bis-
carbonyl compounds mer-[Mn(PNPtBu*)(CO)3] (3) and cis–[Mn(PNPtBu*)(CO)2]
(4) is obtained in 2:1 ratio. However, complex 4 can be obtained as the sole
product upon heating the reaction mixture of 2 and KOtBu in THF under
vigorous reflux. Extraction with n-pentane and subsequent recrystallization at
–38 °C gives the complex cis–[Mn(PNPtBu*)(CO)2] (4) as a deep blue solid in
60% yield. The IR spectrum of 4 (KBr pellet) shows two strong absorptions at
1833 (ꢀasym) and 1904 cm–1 (ꢀsym) signifying the formation of a dicarbonyl
species. The 31P{1H} NMR spectrum indicates a reduced symmetry with
respect to complex 2. The spectrum exhibits an AB-spin system suggesting
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that the two phosphorus nuclei are chemically inequivalent with doublets at
2
87.2 and 101.3 ppm and a JPP coupling constant of 68 Hz. Consistently, the
5
6
1H NMR spectrum exhibits three distinct resonances in the aromatic regime,
signifying the reduction in symmetry, particularly the loss of the mirror plane
perpendicular to the pyridine ring. The three resonances are shifted to lower
frequencies (5.45, 6.36, and 6.40 ppm). As a result of the deprotonation of
one exo-cyclic methylene group, the 1H NMR spectrum shows two
resonances for the pincer ‘arm’ protons: a doublet at 2.77 ppm (2JHP = 9.2 Hz)
for the two equivalent CH2 protons and a broad singlet at 3.82 ppm for the
methine CH proton. Two sharp doublet resonances (1.00 and 1.28 ppm) are
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2
observed for the methyl groups of the four P(tBu)2 moieties, with JHP = 12.7
and 13.0 Hz, respectively. Consistently, only one resonance is observed in
the carbonyl regime in the 13C{1H} NMR spectrum for both CO ligands
2
(239.3 ppm, JCP = 17 Hz) indicating two chemically equivalent carbon nuclei.
These findings suggest the existence of a mirror plane through the PNP
pyridine ring and corroborate a trigonal bipyramidal coordination sphere
around the manganese center or a fast dynamic interconversion of two
equivalent square pyramidal structures with respect to the NMR time scale.
Single crystals suitable for an X-ray diffraction study were obtained from a
concentrated solution of 4 in n-pentane. The molecular structure of 4 is shown
in Figure 1. The tridentate pincer ligand PNPtBu binds the Mn(I) center in a
meridional fashion. The two carbonyl ligands are located in mutual cis-
positions (C–Mn–C = 86.5°), completing a distorted square pyramidal
coordination sphere around the Mn center. Carbon monoxide binds reversibly
to complex 4. Thus, the tris-carbonyl starting material mer-[Mn(PNPtBu*)(CO)3]
(3) is readily obtained, when a solution of 4 in C6D6 is subjected to one
atmosphere of CO gas; the unsaturated 4 is regenerated upon refluxing in
THF (Scheme 2).
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PtBu2
PtBu2
N
[P]= PtBu2
1
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[Mn(CO)5Br]
benzene
30h, 20°C
–2CO
THF
Ar purge cycles
reflux
–
+ Br
CO
KOtBu
THF
0.5h, 20°C
CO
P
P
P
N
Mn CO
+
N
Mn CO
N
Mn CO
CO
P
CO
P
P
CO
2
3
4
1 atm CO
benzene
Scheme 2. Synthesis of Mn PNP pincer complexes 2–4 (P = tBu2P).
Figure 1. ORTEP diagram of [Mn(PNPtBu*(CO)2] (4) with thermal ellipsoids at 30% probability.
The P(tBu)2 groups are drawn as wire frames, and hydrogen atoms are partially omitted for
clarity. Selected
bond
lengths: C1–C2 = 1.369(3) Å, C2–C3 = 1.449(3) Å, C3–
C4 = 1.348(3) Å, C4–C5 = 1.407(3) Å, C5–C6 = 1.373(3) Å, C6–C7 = 1.498(3) Å, Mn1–
N1 = 2.0333(16) Å, Mn1–P1 = 2.2950(7) Å, Mn1–P2 = 2.3117(7) Å, Mn1–C24 = 1.744(2) Å,
Mn1–C25 = 1.768(2) Å, C24–O1 = 1.168(2) Å, C25–O2 = 1.171(2) Å.
Reaction of complex 4 with nitriles bearing α-CH2 groups
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The penta-coordinated dearomatized complex 4 reacts with benzyl cyanide
with formation of C–C and Mn–N bonds owing to a [1,3]-addition reaction
mediated by a dearomatization / aromatization pathway (Scheme 3). Upon
addition of two equivalents of benzyl cyanide to a deep blue solution of 4 in
THF a drastic color change to red is observed. Recrystallization from THF / n-
pentane at –38 °C gives the enamido complex [Mn(PNPtBu–
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HNCH=CHPh)(CO)2] 5 as large red crystals in 85% yield. The P{1H} NMR
31
spectrum of 5 shows the expected two doublets of the AB-spin system for two
phosphorus nuclei in different chemical environment at higher frequencies
(126.6 and 140.1 ppm) and with a significantly larger coupling constant with
respect to the dearomatized complex 4 (2JPP = 100 Hz in 5 vs. 68 Hz in 4).
1
The H NMR resonances centered at 4.39 ppm (s, amido 1H, Mn–NH) and
5.41 (s, olefinic 1H, C=CHPh) indicate the formation of an enamido motif in 5.
The carbonyl stretches in the IR spectrum (KBr pellet) appear at 1832 and
1905 cm–1 in a 1:1 ratio signifying a mutual cis-arrangement of both carbonyls.
An X-ray diffraction study of crystals of the enamido complex 5 (Figure 2)
exhibits a distorted octahedral coordination sphere, formed by the meridional
PNPtBu pincer ligand and two CO ligands in mutual cis-positions, and the
amido moiety in an axial position. A short C26–C27 inter-atomic distance
(1.383 Å) typical of a C=C double bond is observed, accompanied by a long
C26–N2 (1.345 Å) bond indicating a C–N single bond adjacent to an sp2
hybridized carbon. The [1,3]-addition of benzyl cyanide to 4 to form 5 is
characterized by the newly formed C—C single bond between the exo-cyclic
carbon of the pincer (C7–C26 = 1.540 Å), and a Mn–N bond (Mn1–
N2 = 2.058 Å).
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Scheme 3. Reversible binding of benzyl cyanide to complex 4 (P = tBu2P).
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The [1,3]-addition of benzyl cyanide to 4 with C–C and Mn–N bond formation
is reversible. This is clearly demonstrated when a solution of complex 5 in
benzene is treated with one atmosphere of CO gas at ambient temperature.
The dearomatized tris-carbonyl complex 3 is readily formed with concomitant
displacement of benzyl cyanide. The reaction can be conveniently followed by
31P{1H} NMR spectroscopy. Representative spectra of the transformation of 5
into 3 are shown in Figure 3.
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Figure 2. ORTEP diagram of [Mn(PNPtBu-HNCH=CHPh)(CO)2] x THF (5) with thermal
ellipsoids at 30% probability. The co-crystallized THF solvent molecule is omitted. The P(tert-
butyl)2 groups are drawn as wire frames, and hydrogen atoms are partially omitted for clarity.
Selected bond lengths: C1–C2 = 1.502(3) Å, C2–C3 = 1.385(3) Å, C3–C4 = 1.387(3) Å, C4–
C5 = 1.375(3) Å, C5–C6 = 1.390(3) Å, C6–C7 = 1.499(3) Å, C7–C26 = 1.540(3) Å, C26–
C27 = 1.383(3)Å, C27–C28 = 1.446(3) Å, C26–N2 =1.345(2) Å,
Mn1–N1 = 2.0519(16) Å,
Mn1–
Mn1–N2 = 2.058(2) Å, Mn1–P1 = 2.3241(7) Å, Mn1–P2 = 2.3254(8) Å,
C24 = 1.766(2) Å, Mn1–C25 = 1.780(2) Å, C24–O1 = 1.173(3) Å, C25–O2 =1.167(2) Å.
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Figure 3. 31P{1H} NMR spectra of the reaction of complex 5 with 1 atm of CO in C6D6 at
ambient temperature. Red: compound 5, green: after addition of CO, 10 min; blue: after
addition of CO, 1 h.
Catalytic Michael Reactions
As shown above, [Mn(PNPtBu*)(CO)2] (4) readily reacts with benzyl cyanide to
form the enamido complex 5. Both compounds 4 and 5 are potent catalysts
for the Michael addition of benzyl cyanide to ethyl acrylate. At ambient
temperature in benzene ethyl 4-cyano-4-phenylbutanoate is obtained within
12 h in 90% and 93% yield, respectively (1 mmol scale, 1:1 substrate ratio,
Scheme 4).
Scheme 4. Example of Michael addition catalyzed by complexes 4 or 5.
Screening of different solvents showed that non-polar solvents such as
pentane and benzene are most suitable for the catalytic reaction (for details of
solvent screening see the Supporting Information p. S10).
Importantly, a variety of aliphatic nitriles (R–CN with R = Me, Et, n-Pr, n-Bu,
Table 1; entries 1-5) undergo facile Michael addition to ethyl acrylate
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catalyzed by complex 4 (0.5 mol%). The catalytic reactions were performed
on a 2.5 mmol scale with a nitrile : ethyl acrylate ratio of 1:1, using benzene
as solvent. The ɣ-cyanoesters were obtained in moderate to excellent yields.
A common observed side product was the double addition product of two
nitrile donors to ethyl acrylate, resulting in moderate yields for the addition
reactions of acetonitrile (entry 1) to ethyl acrylate. When acetonitrile was also
used as solvent (entry 2) the mono addition product was formed exclusively.
Remarkably, the addition reaction of propionitrile to ethyl acrylate occurs very
selectively in high yield and short reaction time (entry 3).
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Table 1. Michael addition of aliphatic nitriles to ethyl acrylate catalyzed by 4.
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Time
(h)
Conversion
(%)
Entry
Nitrile
Yield (%)
26(21)
Product
1
20
69
CN
20(17)
89(83)
93(82)
2a
40
6
90
CN
3
>99
4
40
40
57
72
48(29)
67(48)
5
6
12
>99
94(84)
Reaction conditions: A solution containing 2.5 mmol of the substrates in a 1:1 ratio and
0.5 mol% complex 4 in 2 mL benzene was stirred under nitrogen at ambient temperature. a)
acetonitrile used as a solvent. Conversion with respect to the ethyl acrylate was determined
by 1H NMR spectroscopic analysis with suitable internal reference. The yields are determined
by H NMR spectroscopy analysis using reference substance (isolated yields are given in
parenthesis). For details see experimental section.
1
We have also explored the scope of α,β-unsaturated carbonyl compounds as
suitable acceptors. Table 2 exhibits our results for reactions of propionitrile with
various acrylates, methyl crotonate and cyclohex-2-enone (entries 1-8). The
reactions were performed on a 1 mmol scale with respect to the Michael acceptor.
The reactions given in entries 4–8 were performed in neat propionitrile as solvent.
The reaction tolerates ketones (entry 2) as well as flourinated esters (entry 3),
however the reaction with phenyl acrylate proceeds at a slow rate (entry 4). The
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effect of terminal substitution of the double bond in the Michael acceptor is
significant. Reduction in the reaction rate and selectivity was observed in the addition
of propionitrile to trans-methyl crotonate (entry 8). After an extended reaction time of
24 h only 40% conversion of the crotonate was detected and the desired addition
product was formed in only 18% yield. In contrast, acceptors bearing a substituted
terminal double bond react well. Thus, under the same reaction conditions, methyl
methacrylate (entry 5) showed full conversion already after 12 h with the product
obtained in 92% yield. Similarly, trifluoroethyl methacrylate resulted in 93% yield after
5 hours (entry 6). The very reactive Michael acceptor cyclohex-2-enone (entry 7)
showed a tendency for homo-addition reactions to form [1,1’-bi(cyclohexan)]-6-ene-
2,3’-dione causing low yield of the desired product (for further details see Supporting
Information, S44).
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Reaction of aliphatic nitriles with complex 4.
5
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7
8
9
Table 2. Michael addition of propionitrile to α,β-unsaturated carbonyl compounds catalyzed by
complex 4.
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Time
(h)
Conversion
(%)
Entry
Acceptor
Yield (%)
93(71)a
Product
1
5
2
>99
>99
2
86(84)a
93(71)a
F
F
F
O
3
2
>99
O
OPh
4
26
12
58
52
O
5
>99
92(92)a
6
5
>99
93(90)a
7
5
>99
40
33
18
CN
O
8
24
OMe
Reaction conditions: 1 mmol of substrates, ratio 1:1. 0.5 mol% complex 4, ambient
temperature, 0.5 mL solvent: for entries 1-3 benzene; and for entries 4-8 neat propionitrile was
1
used. The conversion, with respect to the acceptor, is determined by H NMR spectroscopic
1
analysis. The yields were determined by H NMR spectroscopic analysis using reference
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Most significantly, non-activated, aliphatic nitriles are suitable substrates for Michael-
type C–C couplings catalyzed by complex 4. We therefore investigated the binding of
propionitrile to 4 by means of temperature dependent NMR spectroscopy. The
31P{1H} NMR spectrum of a solution containing complex 4 and twelve equivalents of
propionitrile in n-pentane at ambient temperature shows dynamic behavior with broad
resonances assigned to the dearomatized complex 4 (d at 83.9 and d at 98.9 ppm,
2JPP = 68 Hz). Upon cooling the sample stepwise to 235 K a new set of doublets at
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126.5 and 163.8 ppm appears (AB system with JPP = 107 Hz, Figure 4) indicating
reversible binding of propionitrile to complex 4. The following thermochemical
parameters for the binding of propionitrile to complex 4 were derived from a van’t Hoff
plot: ΔH = –13.6 ± 1.2 kcal/mol and ΔS = -69 ± 5.0 cal/molK.
Figure 4.31P{1H} NMR spectra at variable temperatures of complex 4 in n-pentane and 12 equivalents
of propionitrile.
In contrast to the reaction of 4 with benzyl cyanide, the 31P{1H} NMR spectrum of the
reaction with propionitrile in n-pentane shows resonances significantly shifted to
higher frequencies, when compared to the spectrum of 5 (d at 140.1 and 126.6 ppm),
signifying the formation of a ketimido complex rather than an enamido species. Note
that the 31P{1H} NMR spectrum of the ketimido complex [Mn(PNP-N=CPh)(CO)2],
prepared from the reaction of 4 and benzonitrile has similar chemical shifts of the two
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phosphorus resonances (i.e. doublet at 165.6 ppm and 126.5 ppm with
2JPP = 106 Hz); for NMR spectral details see supporting information (S9).
The P{1H} NMR spectrum of a sample of complex 4 dissolved in neat propionitrile
31
9
shows similar broad resonances at room temperature. Cooling the sample stepwise
to 225 K gives rise to the appearance of sharp resonances, consistent with the
formation of the ketimido species 6 as the major compound (d, 128.1 ppm and
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166.0 ppm, JPP = 106 Hz). However, these resonances are accompanied by the
formation of new signals, assigned to the enamido compound 7 as a minor species (d
2
at 127.7 and 134.1 ppm, JPP = 106 Hz). Representative 31P{1H} NMR spectra are
shown in Figure 5.
Figure 5. 31P{1H} NMR spectra at variable temperatures of complex 4 in neat propionitrile.
Assignment: (*) = complex 4; (+) = complex 6; (%) = complex 7.
Evidently, propionitrile does not readily give the enamido compound 7, unlike the
reaction of 4 with benzyl cyanide, which results in the enamido complex 5. However,
there is evidence for the formation of an enamido moiety upon the reaction of 4 with a
large excess of the nitrile at low temperature (Scheme 5). Temperature dependent
31P{1H} NMR spin saturation transfer (SST) experiments in neat propionitrile show
that the new species assigned to 7 is indeed in equilibrium with 6 but the transfer
from 6 to complex 4 remains predominant (for details see Supporting Information).
Undoubtedly, the enamido tautomer 5 is stabilized by conjugation with the aromatic
ring, which is lacking in case of 7. The finding that the spin saturation is at low
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temperatures exclusively transferred between 6 and 4 allowed us to determine the
activation parameters for the transformation of 4 to 6 were obtained from
31P{1H} NMR SST experiments of a solution of 4 in toluene-d8 in the presence of 12
equiv. propionitrile. The Eyring plot gives activation parameters of ΔH‡ = 11.7 ± 0.3
kcal / mol, ΔS‡ = - 7.0 ± 1.4 cal/mol, and ΔG‡ = 13.8 ± 0.7 kcal/mol, Note that in
contrast to a solution in n-pentane complex 7 can also be observed in a toluene-d8
solution of 4 in the presence of 12 equiv. of propionitrile. However, as
aforementioned, at low temperatures (247 K – 222 K) mutual SST occurs exclusively
between 4 and 6 (for details see Supporting Information).
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H
H
H
H
N
N
P
P
P
CH3CH2CN
N Mn
N Mn CO
CO
N
Mn CO
P
P
P
CO
CO
CO
7
6
4
ΔH = -13.6 kcal/mol, ΔS = - 69 cal/mol
ΔH = 11.7 kcal/mol, ΔS = - 7 cal/mol
equilbrium confirmed by SST
Scheme 5. Summary of the NMR investigations of the reaction of complex 4 with propionitrile.
P = tBu2P.
Computational Investigations
To allow for a better understanding of the elementary steps involved in the catalytic
transformation, we performed DFT calculations at the TPSS-D3BJ/def2-TZVP//BP86-
D3/def2-SV(P) level of theory. Since zwitterionic intermediates might be involved,
both the geometry optimizations and the single point energy calculations were
performed using the SMD solvation model for benzene. Propionitrile and ethylacrylate
were chosen as representative substrates. The calculated binding of the substrate to
4 follows a mechanism similar to the one suggested for the analogous rhenium
complex;15 the nitrile first coordinates to 4 to give 8, which can undergo C–C bond
formation to give the aforementioned ketimido complex 6 (Figure 6).
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Figure 6. Pathway for the formation of 6. Free energies (kcal/mol) with respect to the catalyst and the
separated reactants calculated at the TPSS-D3BJ/def2-TZVP//BP86-D3/def2-SV(P) level of theory are
given in brackets.
The formation of 6 is predicted to be endergonic at 298 K but is computed to be
slightly exergonic at 235 K (Scheme 6).
N
P
P
CH3CH2CN
N
N
Mn CO
Mn CO
P
P
CO
CO
4
6
ΔG (298 K) = 3.20 kcal/mol
ΔG (235 K) = -0.04 kcal/mol
Scheme 6. Calculated free energies of the propionitrile binding to 4 at 298 K and at 235 K (P = tBu2P).
The calculated free energies agree with the observation made by NMR (Figure 4) that
in the presence of an excess of propionitrile only 4 can be observed at 298 K,
whereas 6 is detectable at 235 K. Furthermore, the computed ΔH value of -10.3
kcal/mol is in favorable agreement with the value derived from the van’t Hoff analysis
of the temperature dependent NMR investigation in n-pentane (ΔH = -
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13.6 ± 1.2 kcal/mol). Also the activation barrier derived from DFT calculations
(ΔG‡ = 11.7 kcal/mol) is in good agreement with the experimental data. Next, we
investigated the tautomerism pathway leading to the enamide 7 (Figure 7). The
ketimide nitrogen in complex 6 can be assumed to be basic; therefore we
commenced to elucidate whether it could deprotonate an acidic CH of a second
propionitrile molecule. Starting from the hydrogen bound complex 9, a relaxed
potential energy surface scan over the N..H distance did not yield a barrier. The
zwitterionic complex 10 could be localized as local minima. A second proton transfer
via TS2 yields the tautomerized enamido complex 11 to which the second
propionitrile is bound via a N–H..N hydrogen bond.
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Figure 7. Pathways for the tautomerization of 6. Free energies with respect to 4 and the separated
reactants calculated at the TPSS-D3BJ/def2-TZVP//BP86-D3/def2-SV(P) level of theory are given in
brackets.
The overall barrier for this tautomerization via protonation-deprotonation of complex 6
is 32.6 kcal/mol. Since previous DFT studies revealed that water as proton shuttle
can be essential for related transformations in transition metal complexes with pincer
ligands, we furthermore computed an alternative mechanism with water molecules as
proton shuttle.48 A transition state with two water molecules (TS3) was found to lower
the barrier for tautomerization to 21.0 kcal/mol. Interestingly, further NMR and DFT
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investigations indicate that water can reversibly add to complex 4 yielding a
rearomatized hydroxy complex. We therefore conclude that small amounts of water,
only catalytic with respect to the catalyst, are necessary to allow the tautomerization
of 6. On the other hand, larger amounts of water can deactivate the catalyst.49 In
agreement with the NMR investigations (see Figure 5), complex 7 is predicted to be
less stable than complex 6 by 1.2 kcal/mol. To gain a deeper understanding of the
metal template strategy, the nitrile-ketimine-tautomerization of propionitrile itself was
also calculated.
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.
N
HN
ΔE+zpV (298 K) = 22.1 kcal/mol
ΔG (298 K) = 22.0 kcal/mol
Scheme 7. Energy and free energy for the nitrile-ketimine-tautomerization of propionitrile calculated at
the TPSS-D3BJ/def2-TZVP//BP86-D3/def2-SV(P) level (SMD for benzene).
The calculations predict the nitrile form to be more stable by 22 kcal/mol (Scheme 7).
Therefore, these results indicate that a first effect of the template strategy is the
stabilization of the nucleophilic tautomer of the nitrile substrate. Having established a
possible pathway for the formation of complex 7, we turned our attention to the C–C
bond formation. We assumed that hydrogen bond interactions may stabilize the
zwitterionic intermediate, which results from the nucleophilic attack of 7 at the
Michael acceptor. Indeed, a transition state for the C–C bond formation with a
hydrogen bond between the NH group of 7 and the carboxylic oxygen of ethylacrylate
could be localized (TS4 in Figure 8). A proton transfer for which a relaxed potential
energy surface scan over the OH bond length did not show a barrier, led to the enol
intermediate 13, which is high in energy. We therefore searched for alternative
pathways avoiding the intermediate enol formation. After attack of 7 via TS5 a
zwitterionic intermediate 14 is formed. Its energy is lower than that of the enol
intermediate 13.
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Figure 8. Pathway for product formation starting from the enamido complex 7. For the intermediates
14 and 15 and the transition states TS6 and TS7 the newly formed C–C bond is shown in a Newman
projection. Free energies with respect to 4 and the separated reactants calculated at the TPSS-
D3BJ/def2-TZVP//BP86-D3/def2-SV(P) level of theory are given in brackets.
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Rotation of the enolate group around the new carbon-carbon bond via the
staggered transition state TS6 leads to intermediate 15. This intermediate can
undergo a direct proton transfer from the NH group to the α-carbon of the enolate
group via TS7 to directly yield the keto intermediate 16, thus avoiding the
formation of the high energy enol intermediate 13. A similar transition state as
located for the binding of the propionitrile to 4 results in the product complex 17. In
this complex, the product is still bound to the manganese center via the nitrogen.
Dissociation of the product finally regenerates the active catalyst 4. Notably, the
pathway involving a zwitterionic intermediate not stabilized by hydrogen bonding
is lower in energy than the one involving the enol intermediate. Regarding the
overall transformation, the transition state for the water-assisted tautomerization is
the one highest in energy with respect to the catalyst and the separated reactants.
Remarkably, investigations on the temperature dependence of the catalytic
reaction revealed that the reaction is faster at lower temperatures.49 This is in
agreement with the conclusion derived from the temperature dependent NMR
investigations and the DFT calculations that the binding of the propionitrile to the
catalyst 4 is exothermic but endergonic.
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On the basis of the NMR investigations and the DFT calculations we propose the
following mechanism to be operative (Scheme 8): nitrile binding to complex 4
gives the ketimido compound I and subsequently a water-assisted tautomerization
takes place to give the enamido complex II. The carbon–carbon bond formation
yields a zwitterionic intermediate III. A proton transfer from the NH group leads
directly to an intermediate in the keto form (IV). No enol intermediate is involved in
the cycle. Product release regenerates the active dearomatized catalyst 4.
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6
N
R
O
7
8
R
R'
R''
N
P
9
N Mn
CO
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P
CO
product release
Substrate binding
4
R''
O
R
N
R'
PH
N
R
N Mn
CO
P
P
CO
N Mn
CO
I
P
CO
water assisted
tautomerization
IV
R''
O
proton transfer
to α-carbon
R'
H
H
P
R
N
N
R
P
N Mn
CO
N Mn
CO
P
CO
P
II
CO
III
CC bond
formation
O
R'
R''
Scheme 8. Simplified catalytic cycle for the conjugate addition of unactivated nitriles to Michael
acceptors catalyzed by 4.
Essentially, the proposed catalytic cycle outlines a cascade of a stepwise reduction
and oxidation of the CN bond. The formal bond order (b.o.) decreases in the course
of the activation of the nitrile (nitrile (b.o. = 3) à ketimid (b.o. = 2) à enamid (b.o.
= 1)). Upon addition of the reduced enamido moiety to the Michael acceptor, the CN
bond order increases stepwise (ketimid (b.o. = 2) à nitrile (b.o. = 3).
SUMMARY AND CONCLUSIONS
The pincer complex [Mn(PNPtBu)(CO)3]Br (2), based on the abundant base-metal
manganese, undergoes deprotonation upon treatment with a base to form the
dearomatized complex 4, which reacts with nitrile triple bonds forming reversibly C–C
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and Mn–N bonds. Based on this reactivity pattern, we have developed an unusually
efficient Michael reaction catalyzed by complex 4 for the addition of non-activated
nitriles to α,β-unsaturated carbonyl compounds. Remarkably, non-activated aliphatic
nitriles can be used directly, for the first time, as Michael donor moieties under base-
free and very mild conditions, which can react with a wide range of α,β-unsaturated
carbonyl substrates in an atom-economic reaction.
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EXPERIMENTAL SECTION
All experiments were carried out in a M-BRAUN Unilab 1200/780 glovebox under
inert atmosphere of purified nitrogen, or using standard Schlenk techniques.
Tetrahydrofuran, toluene, benzene, dioxane and n-pentane were refluxed over
sodium/benzophenone, distilled under argon atmosphere, and stored over 4 Å
molecular sieves. Methylene chloride and acetonitrile were purchased from J. T.
Baker as a Photrex® reagent and as HPLC ultra gradient (respectively) and dried
over 4 Å molecular sieves. Deuterated solvents were degassed with argon and kept
in the glovebox over 4 Å molecular sieves. [Mn(CO)5Br] and KOtBu were purchased
from Sigma Aldrich and used as received. The PNPtBu ligand was prepared according
to the literature procedure [Organometallics 2002, 21, 812−818.]. Propionitrile,
butyronitrile, benzylcyanide and valeronitrile were distilled and kept over 4 Å
molecular sieves. All [α,β]-unsaturated compounds were distilled or condensed before
°
use (purity was confirmed by NMR spectroscopy) and kept in –38 C freezer inside
1
the glovebox. NMR spectroscopy: H-, 13C{1H} - and 31P{1H} NMR spectra were
1
recorded on Bruker AMX-300, AMX-400, and AMX-500 NMR spectrometers. H-,
13C{1H}-, and 13C{1H}-DEPTQ NMR chemical shifts are reported in ppm referenced to
tetramethylsilane. 31P{1H} NMR chemical shifts are reported in ppm referenced to an
external 85% solution of phosphoric acid in D2O. IR spectra were recorded on a
Nicolet FT-IR spectrophotometer. Mass spectra were recorded on Micromass
Platform LCZ 4000, using Electro Spray Ionization (ESI) mode. GC–MS was carried
out on HP 6890 / 5973 (MS detector) instruments equipped with a 30 m column
(Restek 5MS, 0.32 mm internal diameter) with a 5% phenylmethylsilicone coating
(0.25 mm) and helium as carrier gas. Elemental Analyses were performed on a
ThermoFinnigan Italia S.p.A-FlashEA 1112 CHN Elemental Analyzer by the
Department of Chemical Research Support, Weizmann Institute of Science.
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Crystallographic details are as follows. For complex 4, crystal data:
C25H42N1O2P2Mn1, black, 0.19 x 0.12 x 0.10 mm3, Orthorhombic, Pbca (N61),
a = 11.723(2), b = 16.048(3), c = 28.560(6) Å, from 20 degrees of data, T = 120(2) K,
V = 5373.0(18) Å3, Z = 8, Fw = 505.48, Dc = 1.250 mg.m-3, μ = 0.631 mm-1. Data
collection and processing: Nonius Kappa CCD diffractometer, MoKα (λ = 0.71073 Å),
graphite monochromator, 9254 reflections collected, -14 ≤ h ≤ 14, -19 ≤ k ≤ 19, -34 ≤ l
≤34, frame scan width = 1°, scan speed 1.0° per 120 sec, typical peak mosaicity
0.66°, 4892 independent reflections (R-int = 0.0202). The data were processed with
Denzo-Scalepack. Solution and refinement: Structure solved by direct methods with
SHELXS-97. Full matrix least-squares refinement based on F2 with SHELXL-97. 296
parameters with 0 restraints, final R1 = 0.0365 (based on F2) for data with I > 2σ(I)
and, R1 = 0.0492 on 4892 reflections, goodness-of-fit on F2 = 1.051, largest electron
density peak = 0.650 Å-3, deepest hole -0.301 Å-3. For complex 5, crystal data:
C37H57N2O3P2Mn1 (C33H49N2O2P2Mn1+C4H8O1), red, 0.20 x 0.13 x 0.12 mm3, Triclinic,
P-1 (N2), a = 11.956(2), b = 12.902(3), c = 13.400(3) Å, α = 116.17(3)o,
β = 91.63(2)o, γ = 98.83(3)o from 20 degrees of data, T = 120(2) K, V = 1822.4(9) Å3,
Z = 2, Fw = 694.73, Dc = 1.266 mg.m-3, μ = 0.487 mm-1. Data collection and
processing: Nonius Kappa CCD diffractometer, MoKα (λ = 0.71073 Å), graphite
monochromator, 14352 reflections collected, -14 ≤ h ≤ 15, -16 ≤ k ≤ 16, -16 ≤ l ≤ 16,
frame scan width = 1°, scan speed 1.0° per 100 sec, typical peak mosaicity 0.65°,
7693 independent reflections (R-int = 0.0324). The data were processed with Denzo-
Scalepack. Solution and refinement: Structure solved by direct methods with
SHELXS-97. Full matrix least-squares refinement based on F2 with SHELXL-97. 426
parameters with 1 restraints, final R1 = 0.0430 (based on F2) for data with I > 2σ(I)
and, R1 = 0.0595 on 7693 reflections, goodness-of-fit on F2 = 1.054, largest electron
density peak = 0.566 Å-3 , deepest hole -0.498 Å-3.
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Computational methods
All geometries were optimized with the BP86 generalized-gradient approximation
(GGA) functional and the def2-SV(P) basis set together with corresponding core
potential for ruthenium.50-53 The D3 dispersion correction was used for the geometry
optimizations.54 Thermodynamic properties were obtained at the same level of theory
from a frequency calculation. All free energies are calculated under standard
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conditions unless otherwise noted. Minima and transition states were characterized
by the absence and presence of one imaginary frequency, respectively. Single point
calculations were obtained with the TPSS meta-GGA functional in combination with
the D3 dispersion correction and Becke-Johnson dumping and the larger triple-zeta
def2-TZVP basis set.52,54,55,56 TheTPSS functional was recently shown to yield results
very close to explicitly correlated coupled cluster benchmark calculations for reaction
energies and barriers involving transition metal complexes with pincer ligands.55 In
order to improve the computational efficient, the density fitting approximation with the
W06 fitting basis sets, designed for use with the def2 basis sets, was used.58,59 In
order to take solvent effects into account, the SMD solvation model for benzene was
used for both, the geometry optimizations and the single point calculations.60 The
“ultrafine” (i.e., a pruned (99,590)) grid was used for all calculations. All calculations
were performed using Gaussian 09 Revision D.01.61
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mer-[Mn(PNPtBu)(CO)3]Br (2)
2,6-bis(di-tButyl-phosphinomethyl)pyridine (PNPt-Bu ligand) (537 mg, 1.36 mmol) was
dissolved in 9 mL of benzene and added to a stirred suspension of [Mn(CO)5Br]
(380 mg, 1.36 mmol) in 9 mL benzene in a 20 mL vial. The mixture was stirred at
room temperature for 30 h. The obtained suspension was distributed equally between
three vials, which were subsequently layered with n-pentene and kept at –38 °C. The
yellow precipitate was decanted, washed with n-pentane, and dried under reduced
pressure (700 mg, 83% yield). 31P{1H} NMR (162.07 MHz, (CD3)2SO, 25 °C): δ
3
109.37 (s, 2P).1H NMR (400.36 MHz, (CD3)2SO, 25 °C): δ 1.35 (d, JPH = 12.7Hz,
2
36H, (CH3)3CP), 4.07 (d, JHP = 7.0 Hz, 4H, PCH2), 7.65 (d, JHH = 7.7 Hz, 2H,
3
3
CHpyri(3,5)), 7.94 (t, JHH = 7.7 Hz, 1H, CHpyri(4)). 13C{1H} QDEPT NMR (100.67 MHz,
(CD3)2SO, 25 °C): δ 29.74 (s, 12C, (CH3)3CP), 36.76 (t,1JPC = 6.7 Hz, 4C,
(CH3)3CP)), 38.34 (t,1JPC = 8 .0 Hz, 2C, (CH2P)), 122.76 (s, 2C,CHpyri(3,5)), 139.68
2
(s,1C,CHpyri(4)), 163.23 (s, 2C,CHpyri(2,6)), 220.46 (t, JPC = 15.9 Hz, 2C,Mn-CO),
2
223.91 (t, JPC = 12.8 Hz, 1C,Mn-CO). IR (KBr, pellet, cm−1): 1919, 1932
(overlapping) (ν3CO asymmetric+ν'3CO asymmetric), 2021 (ν3CO
) in 10:1 ratio.
symmetric
Elemental analysis (C26H43BrMnNO3P2) calculated (found): C 50.83 (50.80) H 7.05
(7.04) N 2.28 (2.26)%.
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mer-[Mn(PNPtBu*)(CO)3] (3)
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Method A: via dearomatization of mer-[Mn(PNPtBu)(CO)3]Br (2): mer-
[Mn(PNPtBu)(CO)3]Br (2) (50 mg, 0.08 mmol) was suspended in 4 mL THF. KOtBu
(33 mg, 0.30 mmol) was dissolved in 2 mL THF and added dropwise to the
suspension, which dissolved completely to give a brown homogeneous solution. The
solution was allowed to stir for 0.5 h at ambient temperature. Subsequently all
volatiles were evaporated in vacuo. The remaining brown residue was extracted with
n-pentane (~10 mL) and filtered through a Teflon syringe filter (0.2 µm porosity).
Brown crystals and amorphous precipitate were formed upon storing the solution at –
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38 C for 48 h. The solids were decanted and dried under reduced pressure to yield
38 mg of a 2:1 mixture of mer-[Mn(PNPtBu*)(CO)3] (3) and cis-[Mn(PNPtBu*)(CO)2] (4).
Method B: via CO addition to cis-[Mn(PNPtBu*)(CO)2] (4): cis-[Mn(PNPtBu*)(CO)2] (4)
(8 mg, 0.016 mmol) was dissolved in 0.5 mL C6D6 and transferred to a J. Young NMR
tube with Kontes valve. The tube was degassed and subsequently filled with 1 atm of
CO gas, which resulted in a color change from dark blue to orange. Analysis by
multinuclear NMR spectroscopy indicated the quantitative formation of
mer-[Mn(PNPtBu*)(CO)3] (3). P{1H} NMR (162.07 MHz, C6D6, 25 °C): δ 100.84 (br,
31
1
3
1P), 108.34 (br, 1P). H NMR (400.36 MHz, C6D6, 25°C): δ 1.11 (d, JPH = 12.4Hz,
3
18H, (CH3)3CP), 1.45 (d, JPH = 12.6Hz, 18H, (CH3)3CP), 2.73 (d, JHP = 8.1Hz, 2H,
2
3
PCH2), 3.78 (s, 1H, PCH), 5.54 (d, JHH = 6.4 Hz, 1H, CHpyri(3)), 6.25 (d,
3
3JHH = 8.7 Hz,1H, CHpyri(5)), 6.48 (t, JHH = 7.3 Hz, 1H, CHpyri(4)).13C{1H} QDEPT NMR
(100.67 MHz, C6D6, 25 °C): δ 30.49 (s, 12C, (CH3)3CP), 31.19 (s, 12C, (CH3)3CP),
1
1
37.29 (d, JPC = 14.1Hz, 1C, CH2P), 37.64 (d, JPC = 11.5Hz, 2C, (CH3)3CP), 39.94
1
(d, JPC = 17.2Hz, 2C, (CH3)3CP), 67.52 (d, JPC = 40.2Hz, 1C, CHP), 102.11 (d,
1
3
3JPC = 7.6Hz, 1C,CHpyri(3)), 113.08 (d, JPC = 15.0Hz, 1C,CHpyri(5)), 131.96 (s,
1C,CHpyri(4)),157.85 (s, 1C,Cpyri(6)), 171.75 (d,2JPC = 17.2 Hz, 21.0 Hz, 1C,Cpyri(2)),
224.66 (br, 2C, Mn-CO), 226.27 (br, 1C, Mn-CO). IR (KBr, pellet, cm−1): 1884, 1924,
2020 ((ν3CO antisymmetric + ν3CO antisymmetric) + ν3CO symmetric in 10:10:1 ratio). Elemental
analysis (C26H42MnNO3P2) calculated (found): C 58.53 (59.27) H 7.94 (8.25) N 2.63
(2.60)%.
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cis-[Mn(PNPtBu*)(CO)2] (4)
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mer-[Mn(PNPtBu)(CO)3]Br (2) (150 mg, 0.24 mmol) was suspended in 7 mL THF.
KOtBu (27 mg, 0.24 mmol) was dissolved in 5 mL THF and added dropwise to the
suspension to give a brown solution. The solution was subsequently transferred to a
Schlenk tube. The closed vessel was heated (oil-bath temperature of 90°C) and
purged ten times in 5 min intervals with a stream of argon followed by carful
degassing under reduced pressure. Eventually the solvent was removed completely
under reduced pressure. The resulting dark blue powder was dissolved in 10 mL of n-
pentane and filtered through a Teflon syringe filter (0.2 µm). The solution was kept at
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–38 C in a freezer for 48 h to form dark blue crystals. The crystals were decanted
and dried under vacuum. (77 mg, 60% yield). 31P{1H} NMR (202.5 MHz, C6D6, 25 °C):
2
2
δ 87.15 (d, JPP = 68.2 Hz, 1P, PCH=C), 101.30 (d, JPP = 68.1 Hz, 1P, PCH2C). 1H
3
NMR (500.13 MHz, C6D6, 25°C): 1.00 (d, JPH = 12.7 Hz, 18H, ((CH3)3CP), 1.28 (d,
2
3JPH = 13.0 Hz, 18H, ((CH3)3CP), 2.77 (d, JHP = 9.2 Hz, 2H, PCH2), 3.82 (s, 1H,
3
PCH), 5.45 (d, JHH = 5.9 Hz, 1H, CHpyri(3)), 6.36 (m, 1H, CHpyri(4)), 6.40 (m, 1H,
13
2
CHpyri(5)). C{1H} QDEPT NMR (125.76 MHz, C6D6, 25 °C): 29.34 (d, JCP = 3.9 Hz,
6C, (CH3)3CP), 29.92 (d, 2JCP = 3.8 Hz, 6C, (CH3)3CP), 34.88 (d, 1JCP = 13.4 Hz, 1C,
1
PCH2), 36.11 (d, JCP = 13.7 Hz, 2C, (CH3)3CP), 37.65 (d, JCP = 21.6 Hz, 2C,
1
1
(CH3)3CP), 71.42 (d, JCP = 43.9 Hz, 1C, PCH=C), 99.50 (d, JPC = 10.1 Hz,
3
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1C,CHpyri(3)), 117.06 (d, JPC = 17.3 Hz, 1C,CHpyri(5)), 132.06 (s, 1C,CHpyri(4)), 160.93
2,3
2,3
(dd,
J
= 5.2 Hz, 8.4 Hz, 1C, Cpyri(6)), 174.22 (dd,
J
= 5.8 Hz, 21.0 Hz,
PC
PC
2
1C,Cpyri(2)), 239.25(t, JCP = 17.3 Hz, 2C,Mn-CO). IR (KBr, pellet, cm−1): 1833, 1904
(ν2CO symmetric + ν2CO antisymmetric, 1:1 ratio). Elemental analysis (C25H42MnNO2P2)
calculated (found): C 59.40 (59.72) H 8.37 (8.46) N 2.77 (2.70)%.
cis-[Mn(PNPtBu-NHC=CHPh)(CO)2] (5)
cis-Mn(PNPtBu*)(CO)2(4) (22 mg, 0.043 mmol) was dissolved in 1 mL THF in a 20 mL
vial. Subsequently benzyl cyanide (10 mg, 0.085 mmol) was added resulting in a
color change of the solution from dark blue to red. The solution was layered with 4
mL n-pentane and kept at –38 °C in the freezer for 48 h. The formed large red
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crystals were decanted, washed with n-pentane and dried under reduced pressure.
(23 mg, 85% yield). 31P{1H} NMR (162.07 MHz, C6D6, 25 °C): δ 126.64 (d,
2
1
2JPP = 98.6 Hz, 1P), 140.14 (d, JPP = 100.7 Hz, 1P). H NMR (400.36 MHz, C6D6,
3
25 °C): δ 0.69 (d(br), JPH = 10.7 Hz, 9H, (CH3)3CP), 1.00 (d, JPH = 10.5 Hz, 9H,
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(CH3)3CP), 1.39 (d, JPH = 12.1 Hz, 9H, (CH3)3CP), 1.58 (d, JPH = 11.7 Hz, 9H,
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(CH3)3CP), 2.76 (dd, JHH = 16.1 Hz JHP = 10.2 Hz, 1H, (CH2)P), 3.21 (dd,
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2JHH = 16.0 Hz JHP = 3.7 Hz, 1H, (CH2)P), 4.09 (d, JHP = 9.3 Hz 1H, PCH),4.39 (s,
1H, Mn-NH), 5.41 (s, 1H, Ph-CH=C), 6.35 (d, 3JHH = 7.6 Hz, 1H,CH(pyridine(3))), 6.73 (d,
3JHH = 7.6 Hz, 1H, CH(pyridine(5))), 6.82 (t, 3JHH = 7.6 Hz, 1H, CH(pyridine(4))), 6.90 (t, 3JHH =
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7.3 Hz, 1H, CH(aryl-para)), 7.29 (t, JHH = 7.7 Hz, 2H, CH(aryl-meta)), 7.49 (d, JHH = 7.7
Hz, 2H, CH(aryl-ortho)).13C{1H} NMR (100.67 MHz, C6D6, 25 °C): δ 30.02 (br, 3C,
(CH3)3CP), 30.76, 30.98, 31.17 (3 peaks overlapping, 9C, (CH3)3CP), 36.84 (br, 2C,
1
(CH3)3CP), 37.20 (d, JPC = 11.8 Hz, 1C, PCH2), 37.81 (m, 2C, (CH3)3CP), 63.25 (d,
2
1JPC = 9.9 Hz, 1C, PCH), 91.19 (s, 1C, Ph-CH=C), 118.34 (d, JPC = 6.6 Hz,
2
1CCH(pyridine(3))), 118.79 (d, JPC = 5.9 Hz, 1CCH(pyridine(5))), 119.79 (s, 1C, CH(aryl-para)),
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123.30 (s, 2C, CH(aryl-ortho)), 128.70 (s, 2C, CH(aryl-meta)), 136.10 (d, JPC = 5.9 Hz, 1C
2
CH(pyridine(4))), 144.03 (s, 1C, Cipso (aryl)), 154.31 (d, JPC = 9.2 Hz, 1C, Cipso (pyridine)),
161.00 (d, 2JPC = 4.9 Hz, 1C, Cipso (pyridine)), 165.18 (m, 1C, CH=C-NH), 232.83 (br, 1C,
Mn-CO), 234.92 (br, 1C, Mn–CO). IR (KBr, pellet, cm−1): 1832, 1905 (ν2CO symmetric
2CO antisymmetric, 1:1 ratio). Elemental analysis (C33H49MnN2O2P2) calculated (found): C
+
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Procedure for the catalytic reactions of aliphatic nitriles and benzyl cyanide
with α,β-unsaturated esters and ketones
Procedure A (with additional solvent):
A stock solution containing 5 mg / mL (0.01 mmol / mL) of cis-[Mn(PNPtBu*)(CO)2] (4)
in the particular reaction media (solvent: C6H6, THF, DCM, or n-pentane) was
prepared. To 0.5 mL of the stock solution (0.005 mmol catalyst) 1 mmol of nitrile was
added followed by the addition of 1 mmol of the specific α,β-unsaturated compound.
The mixture stirred at room temperature (~22 °C) for the indicated time and quenched
by introduction of non-dried n-pentane. The yield was determined by integration of 1H
NMR signals with respect to the suitable standard, either toluene for the reaction in
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