Breaking the regioselectivity rule for acrylate insertion in the Mizoroki-Heck reaction

Article abstract of DOI:10.1073/pnas.1101497108

In modern methods for the preparation of small molecules and polymers, the insertion of substrate carbon-carbon double bonds into metal-carbon bonds is a fundamental step of paramount importance. This issue is illustrated by Mizoroki-Heck coupling as the

Full text of DOI:10.1073/pnas.1101497108

Breaking the regioselectivity rule for acrylate
insertion in the Mizoroki–Heck reaction
Philipp Wuchera, Lucia Caporasob,1, Philipp Roeslea, Francesco Ragoneb, Luigi Cavallob,
Stefan Meckinga,1, and Inigo Göttker-Schnetmanna,1
aDepartment of Chemistry, University of Konstanz, 78464 Konstanz, Germany; and bDepartment of Chemistry, University of Salerno, Via Ponte Don
Melillo, 84084 Fisciano, Salerno, Italy
Edited* by Maurice Brookhart, University of North Carolina at Chapel Hill, Chapel Hill, NC, and approved April 7, 2011 (received for review January 28, 2011)
In modern methods for the preparation of small molecules and
polymers, the insertion of substrate carbon–carbon double bonds
into metal–carbon bonds is a fundamental step of paramount
importance. This issue is illustrated by Mizoroki–Heck coupling
as the most prominent example in organic synthesis and also by
catalytic insertion polymerization. For unsymmetric substrates
H2C ¼ CHX the regioselectivity of insertion is decisive for the
nature of the product formed. Electron-deficient olefins insert
Fig. 1. Insertion modes of olefins into metal–carbon bonds and release of
organic products by β-hydride elimination.
selectively in a 2,1-fashion for electronic reasons. A means for
controlling this regioselectivity is lacking to date. In a combined
experimental and theoretical study, we now report that, by desta-
bilizing the transition state of 2,1-insertion via steric interactions,
the regioselectivity of methyl acrylate insertion into palladium–
methyl and phenyl bonds can be inverted entirely to yield the
opposite “regioirregular” products in stoichiometric reactions.
Insights from these experiments will aid the rational design of
complexes which enable a catalytic and regioirregular Mizoroki–
Heck reaction of electron-deficient olefins.
larly for electron-deficient olefins. Although the reliability of this
concept to predict the regiochemistry of olefin insertions into
metal–carbon bonds is impressive, for electron-deficient olefins
it suggests a substantial limitation concerning product formation
from opposite regiochemistry of insertion.
Recent studies of the catalytic properties of the [di(2-anisyl)
phosphin-2-yl]benzenesulfonato Pd(II) methyl fragment (1) re-
vealed that a weakly coordinated ligand such as DMSO in the
single component catalyst precursor 1-DMSO enables the cata-
lytic homooligomerization of MA by a selective 2,1-insertion
mechanism (23). A similar high reactivity and selectivity toward
MA was also observed after silver-mediated chloride abstraction
from the sodium chloride coordinated complex 1-[Cl-Na(acet-
one)] to form the catalytically active fragment 1 (24) (Figs. 2, Left
and 3, Upper). The latter system is beneficial for quantitative
studies of insertion rates because, by comparison to 1-DMSO,
the actual insertion step of interest is not overlayed by the DMSO
dissociation preequilibrium.
In fragment 1, the anisyl groups of the ð2-anisylÞ P phosphine
moiety are oriented away from the metal center,2 enforced by
the tetrahedral environment of the phosphorus atom. In order
to influence the insertion event of an olefin by increased steric
interactions, substituents at the phosphorus atom must be forced
into closer proximity to the metal. This aim was realized by
incorporation of the phosphorus-donor into a rigid 1,3-diaza-
2-phospholidine heterocycle substituted with bulky mesityl- or
2,6-di(isopropyl)phenyl groups. In [N,N′-di(aryl)-1,3-diaza-2-
phospholidin-2-yl]benzenesulfonato palladium methyl complexes
density functional theory calculation ∣ homogeneous catalysis ∣
organometallic ∣ regiochemistry
hereas the palladium-catalyzed Mizoroki–Heck coupling
W
is an established powerful strategy for the formation of
carbon–carbon bonds from electron-deficient and electron-rich
olefins (1–5), insertion (co)polymerization (6–8) of acceptor or
donor substituted olefins has only been demonstrated since the
mid-1990s, and only a few catalyst motifs are known to promote
such polymerizations (9, 10), which are based on palladium. The
regioselectivity of insertion follows the same pattern for both
reactions. Electron-deficient olefins [e.g., methyl acrylate (MA)]
selectively insert in a 2,1-fashion (6, 9–11), whereas electron-rich
olefins (e.g., vinyl ethers) insert in a 1,2-fashion (3, 6, 12–14, †)
(Fig. 1). Finally, apolar olefins (e.g., α-olefins) commonly afford
mixtures of both insertion modes in palladium-catalyzed Mizor-
oki–Heck (15) and polymerization reactions (16), whereas closely
related nickel-catalyzed polymerizations of α-olefins can proceed
with high selectivity by 1,2-insertion (17)—e.g., under kinetically
controlled low-temperature conditions when sterically demand-
ing ligands coordinate to nickel (16, 18).
The accepted rationale for these reactivity patterns is that
electronic effects govern the regiochemistry of insertion for
polarized carbon–carbon double bond substrates: In the Cossée-
Arlman-type insertion step, the metal-bound, nucleophilic carbon
atom migrates to the lower electron-density carbon atom of the
double bond, while the electrophilic palladium atom migrates to
the higher electron-density carbon atom of the double bond. In
contrast, the insertion regiochemistry of apolar carbon–carbon
double bonds is rather determined by steric effects (given that
there is little electronic discrimination of the two olefinic carbon
atoms), and under strict kinetic control the 1,2-insertion mode
may prevail. This intuitive rationale is supported by theoretical
studies both of Mizoroki–Heck (19, 20) and polymerization
catalysis (21, 22), which clearly indicate the predominance of
electronic factors for the insertion of polarized olefins, particu-
Author contributions: L. Caporaso, S.M., and I.G.-S. designed research; P.W., L. Caporaso,
P.R., F.R., and I.G.-S. performed research; P.W., L. Caporaso, P.R., F.R., L. Cavallo, S.M., and
I.G.-S. analyzed data; and L. Caporaso, L. Cavallo, S.M., and I.G.-S. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
Data deposition: X-Ray diffraction analyses of compounds 2a-DMSO, 2a-LiCl(MeOH),
2b-LiCl(2 THF), 3a, 3b, 4-(MeOH)(MeOH), and 6b-LiCl(acetone/DMSO) have been deposited
in the Cambridge Structural Database (CSD), Cambridge Crystallographic Data Centre,
Cambridge CB2 1EZ, United Kingdom (CSD reference nos. CCDC-792913 to CCDC-
792918, and CCDC-793498). These data are provided in the Supporting Information,
and can also be obtained free of charge at http://www.ccdc.cam.ac.uk/products/csd/
request/ by quoting the respective CCDC no.
1To whom correspondence may be addressed. E-mail: stefan.mecking@uni-konstanz.de,
inigo.goettker@uni-konstanz.de, or lcaporaso@unisa.it.
This article contains supporting information online at www.pnas.org/lookup/suppl/
doi:10.1073/pnas.1101497108/-/DCSupplemental.
www.pnas.org/cgi/doi/10.1073/pnas.1101497108
PNAS ∣ May 31, 2011 ∣ vol. 108 ∣ no. 22 ∣ 8955–8959

Fig. 2. Phosphine sulfonato and diazaphospholidine sulfonato palladium(II)
methyl complexes.
(2a,b-L) the ortho-substituents of the N,N′-arene rings are in
close proximity to the palladium center (Fig. 2, Right; synthetic
procedures and X-ray diffraction data can be found in the
SI Appendix and Dataset S1). A more quantitative evaluation
of the steric situation at the palladium center in fragments 2a
and 2b (and for comparison, fragment 1) was obtained by
theoretically calculated steric maps (see below).
Fig. 4. Ortep plots of the 1,2-MA-insertion product 3a (Left) and 3b. Ellip-
soids are shown with 50% probability. Hydrogen atoms are omitted for
clarity.
MA forms trace amounts (<5% NMR yield) of methyl crotonate
by 2,1-insertion of MA and concomitant β-hydride elimination
(see SI Appendix).
Density functional theory calculations at the BP86 generalized
gradient approximation level (26–28) illuminate the origin of the
unusual regioselectivity of MA insertion with fragments 2a and
2b. As for fragment 1 (24), MA insertion into fragments 2a
and 2b according to these calculations proceeds by η2-coordina-
tion of MA trans to the phosphorus donor atom, followed by
cis-trans isomerization to the less stable cis isomer from which
insertion occurs (Fig. 5). However, whereas the rate-determining
transition state for 2,1-insertion of MA into fragment 1 is favored
by 10 kJ mol−1 over the 1,2-insertion transition state (Fig. 5, first
line), 1,2-insertion of MA into fragment 2b is favored over
2,1-insertion by 9 kJ mol−1 (Fig. 5, second line). Consistent with
calculations on fragment 2b, a preference for 1,2-insertion of
MA is also calculated for fragment 2a (R ¼ mesityl), although
the difference is only 3 kJ mol−1 (see SI Appendix). Assuming
similar entropic contributions for the insertion of MA into frag-
ments 1, 2a, and 2b, the calculated energies are in qualitative
agreement with the experimentally observed regiochemistry of
insertion.
Inspection of the transition state geometries for MA insertion
into fragment 2b (Fig. 6) reveals that the 2,6-di(isopropyl)phenyl
groups of the [N,N′-di(aryl)-1,3-diaza-2-phospholidin-2-yl]benze-
nesulfonato ligands are in close proximity to the MA-methoxycar-
bonyl group in the transition state for the 2,1-insertion resulting
in repulsive energetic contributions. To alleviate this steric clash
in the transition state for 2,1-insertion into 2b, the MA rotates
away from the nearby 2,6-di(isopropyl)phenyl group, resulting
in a deviation from planarity of the four center Cossée-
Arlman-like transition state (the Me-Pd-C2-C1 dihedral angle
is −20°, see Fig. 6E; the respective dihedral angle is −27° for
the 2,1-insertion transition state of 2a, see SI Appendix). In
contrast, the [di(2-anisyl)phophin-2-yl]benzenesulfonato ligand
of fragment 1 does not sterically interfere as severely with the
coordinated MA in the 2,1-insertion transition state (Fig. 6B),
which results in an almost perfectly planar geometry (the Me-Pd-
C2-C1 dihedral angle is −4°, see Fig. 6B). In addition, inspection
of the corresponding transition states for 1,2-insertion (Fig. 6 A
and D) reveals that the coordinated MA does not sterically
interfere with any of the phosphine sulfonato ligands of the
precursor fragments 1 or 2b (and 2a, see SI Appendix). The
absence of steric pressure in the 1,2-transition state allows the
reacting atoms to assume an almost planar geometry both in 1
and 2b (the Me-Pd-C1-C2 dihedral angle is ∼0°, see Fig. 6 A
and D).
Results and Discussion
The reaction of mesityl-substituted complexes 2a-DMSO and
2a-[Cl-Li(acetone)] (in the presence of silver triflate) as well
as 2,6-(disopropyl)phenyl substituted complex 2b-½Cl-Li
ðtetrahydrofuranÞ2ꢀ (in the presence of silver triflate) with excess
MA (20 to 25 equivalents) in deuterated methylene chloride
was monitored by proton (1H) and phosphorus (31P) NMR spec-
troscopy. As with complexes 1-L (23, 24), insertion of MA into
the palladium-methyl bonds of fragments 2a and 2b takes place
at 298 K. However, whereas MA insertion into fragment 1
proceeds selectively by 2,1-insertion, MA insertion into fragments
2a and 2b proceeds selectively by 1,2-insertion, as judged by
formation of the insertion products 3a and 3b in ca. 95% NMR
yield and ca. 85% isolated yield (Fig. 3, Lower). Under pseudo-
first-order conditions (20 to 25 equivalents of MA), fragment 2a
generated by silver-mediated and instantaneous chloride abstrac-
tion from 2a-[Cl-Li(acetone)] reacts by MA insertion with a
rate constant kobs ¼ 6.0ðꢁ0.1Þ × 10−4 s1 at 298 K, whereas the
sterically more demanding species generated from 2b-½Cl-Li
ðtetrahydrofuranÞ2ꢀ decays with kobs ¼ 4.8ðꢁ0.1Þ × 10−4 s−1 at an
elevated temperature of 318 K. These rate constants compare to
kobs ¼ 12.4ðꢁ0.2Þ × 10−4 s−1 at 298 K for the disappearance of
fragment 1 (obtained by chloride abstraction from 1-[Cl-Na(acet-
one)]) in the presence of MA (25). From these data it seems
obvious that steric interactions have a pronounced influence
on the barrier of MA insertion.
The identity of 1,2-MA insertion products 3a and 3b is unam-
biguously established by one- and two-dimensional NMR techni-
ques of the crude reaction mixtures (for details, see SI Appendix)
by X-ray diffraction analyses of the isolated complexes after
recrystallization (Fig. 4), by elemental analyses, and by quantita-
tive formation of methyl methacrylate by β-hydride elimination
upon NMR-monitored thermolysis of 3b.
In addition to the highly selective formation of complexes 3a,
3b by 1,2-MA insertion into 2a, 2b, reaction of 2a and 2b with
Steric maps (29, 30) based on calculated ground state geome-
tries of 1-DMSO and 2b-DMSO show that all phosphine sulfo-
nato ligands exert some steric pressure in the two bottom
quadrants (Fig. 6 C and F) of the first coordination sphere around
the palladium atom. In the event of a 2,1-insertion, the methox-
ycarbonyl group of MA will occupy one of these bottom quad-
rants in the insertion transition state, whereas in the event of
Fig. 3. (Upper) Selective 2,1-insertion of MA into fragment 1 (23, 24); (Low-
er) 1,2-insertion of MA into fragment 2 to form complexes 3a and 3b.
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Fig. 5. Calculated 2,1- and 1,2-insertion of MA into the Pd-methyl (Pd-Me) bond of fragments 1 and 2b. Energies in kilojoule per mole. Transition state
energies biasing 1,2- vs. 2,1-insertion are in bold.
a 1,2-insertion, one of the top quadrants will be occupied by the
methoxycarbonyl group. Although the map of fragment 1
(Fig. 6C) displays some steric pressure in both bottom quadrants,
the bottom-left quadrant is much less encumbered than the
bottom-right quadrant, and the MA molecule inserts with the
methoxycarbonyl group occupying the bottom-left quadrant
which results in the electronically favored 2,1-insertion (Fig. 6 B
and C). However, in fragment 2b (Fig. 6F) both bottom quadrants
are highly encumbered, resulting in a destabilization of the
transition state for the 2,1-insertion relative to that for the 1,2-
insertion with the methoxycarbonyl group in the top-right quad-
rant (Fig. 6 C and F).
These experimental and theoretical data indicate that the
strong preference of fragments 2a and 2b for the regioirregular
1,2-insertion of MA results from a severe destabilization of the
(electronically favored) 2,1-insertion transition states by repulsive
steric interactions of the incoming MA with the N,N′-di(aryl)-1,3-
diaza-2-phospolidine moiety of the chelating ligand, which does
not affect the 1,2-transition states to this extent.
Mizoroki–Heck reaction, sp2 carbon atoms are coupled to olefins.
To this end, applicability of the concept of steric destabilization
of the 2,1-insertion transition state to the decisive elementary
step of the Mizoroki–Heck reaction of electron-deficient olefins
was probed.
In a control experiment, the reaction of [di(2-anisyl)phosphin-
2-yl]benzenesulfonato palladium phenyl (4-MeOH) with 25 equiv
1
of MA in methylene chloride-d2 solution was monitored by H
NMR spectroscopy. Insertion of MA into the palladium phenyl
bond is complete within 30 min at 318 K, and, as expected, gives
the regioregular Mizoroki–Heck product, methyl cinnamate
(compound 5), by selective 2,1-insertion in nearly quantitative
NMR yield (Fig. 7, first line).
In contrast, chloride abstraction from {N,N′-di[2,6-di(isopro-
pyl)phenyl]-1,3-diaza-2-phospholidin-2-yl}benzenesulfonato pal-
ladium phenyl (6b-[Cl-Li•2(acetone/DMSO)]) by silver triflate
in the presence of 25 equiv MA yields only ca. 7% methyl cinna-
mate (compound 5) under otherwise identical conditions,
whereas the 1,2-insertion product 7b is formed in ca. 90%
NMR yield. The thermal stability of 7b allowed isolation (83%
yield) and full characterization by NMR techniques and elemen-
tal analysis. The identity of 7b was further corroborated by
thermally induced β-hydride elimination in tetrachloroethane-
d2 solution (11 h at 363 K), which gave the regioirregular Mizor-
oki–Heck product (2-phenyl)MA (compound 8) in quantitative
NMR yield (Fig. 7, second line). (For preparation procedures
and characterization, see SI Appendix.)
The above systems most specifically resemble the active
species of olefin insertion polymerization chemistry in that the
Pd-methyl species represent the growing polymeryl chain. In the
In summary, these findings present a concept which allows
reversal of the commonly valid regioselectivity rule for the inser-
tion of the electron-deficient olefin MA into palladium carbon
bonds. Appropriately arranged steric bulk of the ligands bound
to the palladium center results in a severe steric repulsion with
the incoming substrate in the electronically favored 2,1-insertion
transition states. This steric repulsion makes the less sterically en-
cumbered 1,2-insertion transition states competitive and strongly
favored, thus overriding the usual distinct electronic determina-
tion of the insertion reaction. Although the regioirregular Mizor-
oki–Heck reaction of MA to form (2-phenyl)MA is so far
stoichiometric in palladium, the concept of sterically destabilizing
the electronically favored transition state of insertion elaborated
in this work will certainly aid the rational design of catalysts that
provide selective access to a catalytic regioirregular Mizoroki–
Heck reaction.
Fig. 6. Transition state geometries for 1,2- (Left) and 2,1-insertion (Center)
of MA into the Pd-Me bond of fragment 1 (A and B) and of fragment 2b (D
and E). Relative energies (E) in kilojoule per mole. Steric maps (Right) of the
fragments 1 (C) and 2b (F). The colored scale indicates the isocontour levels, in
angstrom. Orientation of the ligands in the steric maps as in A and B and D
and E.
Materials and Methods
Full experimental details and spectral data are included in the SI Appendix.
Unless noted otherwise, all manipulations of phosphorous halides or
palladium complexes were carried out under an inert nitrogen or argon
atmosphere using standard glovebox or Schlenk techniques. Methylene
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Fig. 7. Regioregular 2,1-insertion of MA into complex 4-MeOH (first line) and selective regioirregular 1,2-insertion of MA into complex 6b-[Cl-Li•2(acetone/
DMSO)] (second line).
chloride, DMSO, and pentane were distilled from calcium hydride, toluene
and benzene from sodium, THF and diethyl ether from blue sodium/benzo-
phenone ketyl, and methanol from activated (iodine) magnesium under
argon prior to use. Acetone per analysis and MA were degassed by repetitive
freeze–thaw cycles and used without further purification. All other solvents
were commercial grade. Palladium(II)-chloride was obtained from Merck,
2,4,6-trimethylaniline (98%) and 2,6-di(isopropyl)aniline (90%, technical
grade) was purchased from Acros, and trichlorophosphine (99%) was pur-
chased from Riedel-de Haën. Cyclooctadiene palladium-methyl chloride
(31) and 2-chloro-1,3-di(aryl)-1,3,2-diazaphospholidines (32) were synthe-
sized according to literature procedures. All deuterated solvents were
supplied by Eurisotop. The identity of so-far unreported compounds was
established by 2D NMR experiments [1H-1H gCOSY, 1H-13C gradient hetero-
nuclear single quantum coherence (gHSQC), and 1H-13C gradient heteronuc-
lear multiple bond correlation (gHMBC)] in addition to 1D NMR experiments.
NMR temperature calibration was performed using pure methanol (low-
temperature) or ethylene glycol (high-temperature) samples. NMR spectra
were recorded on a Varian Unity Inova 400, a Bruker Avance III DRX 400,
or a Bruker Avance DRX 600 instrument. 1H NMR spectra were referenced
to residual protiated solvent signals. 13C NMR spectra were referenced to
the solvent signals, and 31P NMR spectra to external 85% H3PO4. The purity
of so-far unreported compounds was established by elemental analyses.
Single crystals of complexes 2a-DMSO, 2a-LiCl•(MeOH), 2b-LiCl•(2 THF), 3a,
3b, 4-MeOH•(MeOH), and 6b-LiCl•(acetone/DMSO) were analyzed by X-ray
diffraction analysis.
nate•(0.75 THF) (2180 mg, 9.60 mmol, 96%) which was used in the next
step without further purification.
To o-dilithiobenzenesulfonate•(0.75 THF) (448 mg, 2 mmol) and 2-chloro-
1,3-[di-(2,6-diisopropyl)phenyl]-1,3,2-diazaphospholidine (935 mg, 2.1 mmol)
in a 20-mL Schenk tube was added THF (10 mL) and the resulting suspension
was heated under stirring to 340 K for 1 h. The clear solution was cooled to
room temperature and the solvent removed in vacuo (10−3 mbar). Diethyl
ether (10 mL) was added to the remaining glassy solid and the mixture
was sonicated for 20 min while a fine white precipitate formed. The white
precipitate was cannula transferred into a Schlenk frit, washed with diethyl
ether (2 × 5 mL) and pentane (2 × 10 mL), dried under high vacuum, and
dissolved in hot benzene (50 mL). The resulting opaque mixture was filtrated
through a pad of celite, and the solvent removed in vacuo. The remaining
solid was triturated with pentane (10 mL) to yield ligand L1b containing
1 equiv of diethyl ether (1072 mg, 1.66 mmol, 82.8%) after drying under
vacuum.
[(DMSO)2Pd(Ph)Cl]. In a 100-mL Schlenk tube, palladium dichloride (887 mg,
5 mmol) was dissolved in DMSO (6 mL) at 383 K under stirring. After cooling
to 298 K, diethyl ether was added (70 mL) under stirring, the resulting orange
solid collected by filtration, washed with diethyl ether (4 × 10 mL), and dried
under vacuum to yield [ðDMSOÞ2PdCl2] (1.630 g, 4.89 mmol, 97.7%). To a
suspension of [ðDMSOÞ2PdCl2] (334 g, 1 mmol) in a mixture of DMSO
(3 mL) and THF (15 mL) in a 50 mL septum capped Schlenk tube was added
tetraphenyl tin (215 mg, 503.3 μmol). The solution was stirred for 8 h at 298 K
while the orange starting material dissolved and an orange-red solution
containing some palladium black formed. The mixture was concentrated
to ca. 5 mL, DMSO (5 mL) was added and the resulting mixture filtered
through a syringe filter into a 100-mL Schlenk flask. Removal of all volatiles
under high vacuum (298 K, 10−3 mbar) gave an orange solid, which was
dispersed in THF (15 mL) and cannula transferred into a Schlenk frit. The
solid was filtered off, washed with THF (4 × 10 mL), and dried under vacuum
to yield a white-gray powder of [ðDMSOÞ2PdðPhÞCl] which contained traces
of palladium black (361.1 mg, 0.965 mmol, 96.5%).
Computational Details. The Amsterdam Density Functional (ADF) program
(26, 33–35) was used. The electronic configuration of the molecular systems
was described by a triple-ζ Slater-type orbitals (STO) basis set on Pd (ADF basis
set TZV). Double-ζ STO basis sets, augmented by one polarization function,
were used for main group atoms (ADF basis sets DZVP). The inner shells on Pd
(including 3d), P and S (including 2p) C and O (1s), were treated within the
frozen core approximation. Energies and geometries were evaluated using
the local exchange-correlation potential by Vosko et al. (35), augmented in a
self-consistent manner with Becke’s (26) exchange gradient correction and
Perdew’s (27, 28) correlation gradient correction (BP86 functional). The tran-
sition states were approached through a linear transit procedure starting
from the coordination intermediates. The forming C–C bond was assumed
as reaction coordinate during the linear transit scans. Full transition state
searches were started from the maxima along the linear transit paths. Steric
maps were constructed as indicated in the SI Appendix.
{(κ2-P,O)-2-[1,3-di(2,6-diisopropyl)phenyl-1,3,2-diazaphospholidin-2-yl) benzene-
sulfonato]-palladium(II)-phenyl} lithium chloride adduct [6b-LiCl•(DMSO)]. To
L1b • ðEt2OÞ (65 mg, 100 μmol) and [ðDMSOÞ2PdðPhÞCl] (previous step;
39.8 mg, 106 μmol) in an NMR tube was added methylene chloride-d2
(400 μL). The tube was shaken for 5 min at 298 K and then centrifuged.
Monitoring of the solution by 1H and 31P NMR indicated consumption of
L1b • ðEt2OÞ and formation of one new 31P containing species in >90% NMR
yield. The solution was filtrated, concentrated to dryness, and the resulting
solid extracted with pentane (2 × 3 mL) to yield complex 6b-LiCl•(DMSO)
after drying under vacuum (66.7 mg, 72 μmol, 72%). Crystals of 6b-LiCl•
(1.8 acetone, 0.2 DMSO) suitable for X-ray diffraction analysis were grown
from 6b-LiCl•(DMSO) (12 mg) in acetone (60 μL) after layering with pentane.
Exemplified procedure for the preparation of {[(κ2-P,O)-2-(1,3-di(2,6-diisopropyl)
phenyl-1,3,2-diazaphospholidin-2-yl) benzenesulfonato] palladium(II)-[(κ2-C,O)-
3-methoxy-2-phenyl-3-oxopropyl]} (7b). Lithium 2-[1,3-di-(2,6-diisiopropyl)phe-
nyl]-1,3,2-diazaphospholidin-2-yl) benzenesulfonate (L1b). To a solution of
benzenesulfonic acid (1582 mg, 10 mmol) in THF (35 mL) in a septum capped
Schlenk tube was slowly added by syringe butyl lithium (14 mL 1.6 M pentane
solution, 22.4 mmol) at 298 K under stirring. The formed suspension was
stirred for 30 min at 298 K, then cannula transferred into a Schlenk frit,
and filtrated. After washing with pentane (4 × 15 mL) the off-white powder
was dried under high vacuum (10−3 mbar) to leave o-dilithiobenzenesulfo-
{[(κ2-P,O)-2-(1,3-di(2,6-diisopropyl)phenyl-1,3,2-diazaphospholidin-2-yl) benze-
nesulfonato] palladium(II)-[(κ2-C,O)-3-methoxy-2-phenyl-3-oxopropyl]} (7b).
To a solution complex 6b-LiCl•(DMSO) (38 mg, 41 μmol) in methylene chlor-
ide-d2 in an NMR tube was added MA (88 mg, 1.03 mmol, 25 equiv). The
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mixture was monitored by 1H and 31P NMR, then silver triflate (10.8 mg,
42 μmol, 1.02 equiv) was added and the tube was shaken for 2 min and
centrifuged whereby silver chloride deposited. The resulting solution was
monitored by 1H and 31P NMR at 318 K. Formation of complex 7b (ca. 90%
NMR yield by 1H and 31P NMR) together with methyl cinnamate (5) (ca. 7%
NMR yield) was complete after ca. 25 min at 318 K. Isolation of complex 7b
was accomplished by filtration, removing all volatiles under vacuum, washing
the residue with pentane (4 × 2 mL), and cold diethyl ether (1 mL, 243 K), and
crystallization from methylene chloride (100 μL) after layering with pentane
(1.5 mL) in an NMR tube (28.3 mg, 33.9 μmol, 82.6%).
cif-file, NMR spectra of key-compounds and in situ reactions, theoretical
procedures, and calculated geometries and energies) are given in the
SI Appendix.
ACKNOWLEDGMENTS. S.M. is indebted to the Fonds der Chemischen Industrie.
The authors thank the high performance computing team of the Agenzia
nazionale per le nuove tecnologie, l’energia e lo sviluppo economico soste-
nibile, for use of the facilities in the Centro computazionale di RicErca
sui Sistemi COmplessi in Portici, Italy. Financial support of part of this work
by the Deutsche Forschungsgemeinschaft (Me1388/10-1 to S.M.) and by the
Ausschuss für Forschungsfragen at the University of Konstanz (I.G.-S.) is
gratefully acknowledged.
Further procedures and data (synthetical procedures, analytical character-
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May 31, 2011
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no. 22
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