Amino-P Ligands from Iminosugars: New Readily Available and Modular Ligands for Enantioselective Pd-Catalyzed Allylic Substitutions

Article abstract of DOI:10.1021/acs.organomet.8b00140

The construction of a novel class of amino-phosphite/phosphinite/phosphine ligands containing a protected pyrrolidine-3,4-diol moiety is presented. These ligands are obtained from readily available sugars. They thus contain the advantages of carbohydrates in terms of selection of the stereogenic carbons, polyfunctional groups able to modulate the electronic and steric properties, and the general good stability of carbohydrate derivatives. They constitute a novel class of P,N-ligands that have been used in the enantioselective allylic substitutions of acyclic and cyclic substrates with varied electronic and steric requirements, using different C- and N-nucleophiles, with high enantioselectivities. Among the three groups of P,N-ligands (amino-P; P = phosphite, phosphinite, and phosphine groups) the new amino-phosphite ligands give the widest substrate and nucleophile scope, including the more challenging hindered linear and cyclic substrates. In particular, for carbohydrate-derived amino-phosphite ligands and linear substrates, high enantioselectivity in the reactions requires an R configuration of the binaphthyl moiety. However, for cyclic substrates both product enantiomers can be reached by setting out the chirality of the binaphthyl phosphite moiety. A detailed investigation of the appropriate Pd intermediates is also presented.

Full text of DOI:10.1021/acs.organomet.8b00140

Article
Cite This: Organometallics XXXX, XXX, XXX−XXX
Amino‑P Ligands from Iminosugars: New Readily Available and
Modular Ligands for Enantioselective Pd-Catalyzed Allylic
Substitutions
Carlota Borras,† Pilar Elías-Rodríguez,‡ Ana T. Carmona,‡ Inmaculada Robina,*,‡ Oscar Pamies,*,†
̀
̀
and Montserrat Dieguez*,†
́
†Departament de Química Física i Inorgan
Tarragona, Spain
‡Department of Organic Chemistry, University of Seville, C/ Prof. García Gonzal
́
ez 1, 41012 Seville, Spain
̀
ica, Universitat Rovira i Virgili, Campus Sescelades, C/Marcel·lí Domingo, 1, 43007
S
* Supporting Information
ABSTRACT: The construction of a novel class of amino-
phosphite/phosphinite/phosphine ligands containing a protected
pyrrolidine-3,4-diol moiety is presented. These ligands are
obtained from readily available sugars. They thus contain the
advantages of carbohydrates in terms of selection of the
stereogenic carbons, polyfunctional groups able to modulate the
electronic and steric properties, and the general good stability of
carbohydrate derivatives. They constitute a novel class of P,N-
ligands that have been used in the enantioselective allylic
substitutions of acyclic and cyclic substrates with varied electronic
and steric requirements, using different C- and N-nucleophiles, with high enantioselectivities. Among the three groups of P,N-
ligands (amino-P; P = phosphite, phosphinite, and phosphine groups) the new amino-phosphite ligands give the widest substrate
and nucleophile scope, including the more challenging hindered linear and cyclic substrates. In particular, for carbohydrate-
derived amino-phosphite ligands and linear substrates, high enantioselectivity in the reactions requires an R configuration of the
binaphthyl moiety. However, for cyclic substrates both product enantiomers can be reached by setting out the chirality of the
binaphthyl phosphite moiety. A detailed investigation of the appropriate Pd intermediates is also presented.
thioether,3 pyridine,4 imine,5 and amine6) have also been
INTRODUCTION
■
studied. Despite this, a few of them have provided excellent
results in a large number of substrates and nucleophiles.7 We
have contributed with improvements in catalyst performance
with heterodonor compounds that have biaryl phosphite
functionalities.2i,8 We found that biaryl phosphite moieties
improve substrate versatility because the flexibility of these
groups adapts the chiral pocket of the catalysts to the steric
bulkiness of the substrate.8e
Regardless of all the notable progress in catalyst design, still
few ligands have been effectively used in the allylic substitution
of substrates using different electronic and steric proprieties
with a large number of nucleophiles. “Privileged” ligands9 that
have wide substrate scope and are suitable for a large number of
nucleophiles would allow us to reduce the time invested in their
design/preparation, which is crucial for the sustainable
construction of all types of C−X bonds necessary for the
synthesis of complex molecules.
Catalysis has formed chemical production because catalysts are
used in the preparation of the majority of chemicals, resulting in
a multibillion dollar business. The development and improve-
ment of catalysts are therefore keys for attaining a sustainable
construction of all kinds of chemicals. Chirality is a fundamental
property for a large number of industrial and biological
compounds.1 Among the catalytic reactions leading to chiral
products, asymmetric Pd-catalyzed allylic substitution builds a
new stereogenic C−C or C−X bond, creating chiral molecules
that can be further transformed by taking advantage of the
alkene functionality.2 Other advantages of the Pd-catalyzed
allylic substitution are its tolerance to several functional groups
and the soft reaction conditions. Currently heterodonor
compounds are among the ligands that have provided the
best results in allylic alkylation reactions.2 Their success derives
mainly from the different trans influences of both types of
functional groups that create an electronic differentiation
between the two allylic terminal carbons and therefore favor
nucleophilic attack mostly trans to the donor group with
stronger trans influence. Among the heterodonor compounds,
phosphine/phosphinite-oxazoline ligands have been the most
studied.2 Other heterodonor phosphine/phosphinite ligands
containing a group more stable than oxazolines (such as
The search for such ligands that are solids and stable in air
(easy to manipulate), that are easy to prepare from simple
starting materials, and that are good for several substrates and
Received: March 7, 2018
© XXXX American Chemical Society
A
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Figure 1. Amino-phosphite/phosphinite/phosphine ligands L1a−d through L7a−d and their starting products, cyclic amino-alcohols 1−6.
Scheme 1. Synthesis of Ligands L1−L3
nucleophiles is a relevant topic in this reaction. Carbohydrates
are particularly useful for preparing ligands because they are
relatively abundant in an enantiomerically pure form, present a
wide stereochemical diversity, and are cheap and readily
available. Their polyfunctional structure facilitates its modular
reactivity in terms of electronic and sterical effects.10 Series of
ligands can be prepared and tested in the quest for the optimal
ligand for each type of substrate. Since the pioneering work of
Pregosin,11 among others,12 on the use of carbohydrates as
efficient ligands in allylic alkylations, many carbohydrates,
mostly heterodonors, have been prepared. However, still few of
them have shown a broad substrate scope.13
In our quest for efficient and stable catalysts, we herein
present the synthesis and screening of a new sugar-based
amino-phosphite/phosphinite/phosphine ligand library (L1a−
d through L7a−d; Figure 1) in the allylic substitution of a
range of substrates with different steric requirements with
several nucleophiles. These ligands have been prepared from
amino-alcohols 1−6, which are obtained from commercially
available, cheap carbohydrates. We believe that the modular
nature of the iminosugar backbone together with the
appropriate choice of the P functionality would be crucial in
fixing the configuration of the nitrogen upon the ligand
coordination to palladium,7 which in turn will aid in the
development of efficient ligands for this transformation. To
achieve such a control, several ligand parameters have been
easily tuned. We have studied the result of systematically
changing the substituent in the nitrogen moiety (L1−L3), the
configuration of carbons bearing the isopropylidene group
(ligands L1 vs L4), the rigidity of the ligand skeleton (ligands
L7), and the substituent/configuration of the biaryl phosphite
functionality (a−d). The effect of changing the phosphite by a
phosphinite (L5) or a phosphine (L6) group was also
investigated. We have also performed the synthesis and
elucidation of the appropriate Pd−allyl intermediates to
elucidate the enantioselectivities obtained.
RESULTS AND DISCUSSION
■
Preparation of Ligands. The preparation of ligands L1−
L3 started from pyrrolidine alcohol 7, easily obtained from D-
mannose following the procedure recently reported by us
(Scheme 1).14 Reduction of 7 with LiAlH4 gave N-
methylpyrrolidine alcohol 1. On its side, acidic deprotection
of the Boc group of 7 followed by reductive amination with
benzaldehyde and acetone afforded N-benzyl- and N-
isopropylhydroxypyrrolidine derivatives 2 and 3, respectively.
B
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Scheme 2. Synthesis of Ligands L4−L7
With these steps the appropriate variety in the steric and
electronic proprieties of the amine part was reached. Finally,
reaction of amino-alcohols 1−3 with the desired phosphoro-
chloridite (ClP(OR)2; OR = a−d) formed in situ gave access to
amino-phosphite ligands L1−L3 with the desired substituent/
configurations of the biaryl phosphite group.
The preparation of ligands L4−L6, with a different
configuration of the carbons bearing the isopropylidene group
in comparison to L1−L3, is outlined in Scheme 2. Alcohol 9
was prepared from D-ribose as previously reported.15 Protecting
group manipulation afforded N-Boc derivative 10 that after
reduction with LiAlH4 gave N-methylpyrrolidine alcohol 4. Its
reaction with ClP(OR)2 or ClPR2 furnished the corresponding
phosphite/phosphinite ligands L4 and L5. Standard tosylation
of 10 did not afford the corresponding tosylate derivative;
instead, cyclic carbamate 11 was obtained as previously
described for ent-10.14 Nucleophilic ring opening of 11 by
treatment with KPPh2 in THF at reflux gave phosphine 12.
Reaction with methoxycarbonyl chloride gave the correspond-
ing carbamate which, after reduction with LiAlH4, gave amino-
phosphine ligand L6 in 82% yield (two steps). On the other
hand, starting from D-arabinose, pyrrolizidine-alcohol 6 was
obtained (Scheme 2).16 Subsequent reaction with ClP(OR)2
afforded the corresponding amino-phosphites L7.
(Table 1). While the best enantioselectivities for S1 were
achieved with ligands L1a,d, for cyclic substrate S2 the best
enantioselectivities in both product enantiomers were achieved
using L1a,b and L7a,b.
Concerning the effect of the P functionality, we found that
enantioselectivity decreased considerably by changing the
Table 1. Results for the Pd-Catalyzed Allylic Substitution of
Substrates S1 and S2 using Dimethyl Malonate with P,N-
a
Ligands L1−L7
Advantageously, the amino-phosphite compounds are stable
in air and are stable to hydrolysis; therefore, they were further
manipulated and stored in air. The phosphinite and phosphine
analogues (L5 and L6), however, were less stable in air and
were stored under argon. The formation of the ligands was
confirmed by NMR spectra and mass spectrometry. For
spectral assignments bidimensional 1H−1H and 1H−13C spectra
were performed. It should be noted that for all compounds only
one isomer was observed.
Pd-Allylic Alkylation of Disubstituted Substrates S1
and S2 with Dimethyl Malonate. We initially tested the
capacity of ligands L1a−d throught L7a−d by applying them in
the allylic alkylation of substrates S1 and S2, which differ in
their steric properties, with dimethyl malonate as nucleophile
(eq 1). For substrate S2 it is harder to control enantiose-
lectivity, because of the lack of sterically hindered anti
substituents, which are known to play a key role in
enantiodiscrimination. Enantioselectivities were found to
depend on the ligand architecture and the substrate type
a
Reaction conditions: 0.5 mol % [PdCl(η3-C3H5)]2, ligand (0.011
mmol), substrate (1 mmol), CH2Cl2 (2 mL), BSA (3 equiv), dimethyl
b
malonate (3 equiv), KOAc (pinch). Conversion percentage
c
determined by 1H NMR. Enantiomeric excesses measured by
HPLC for 13 and by GC for 14. Absolute configurations are shown
in parentheses. Reaction carried out at 0 °C.
d
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Figure 2. Pd-catalyzed allylic substitution of linear disubstituted symmetric substrates with C and N nucleophiles using the Pd-L1a catalytic system.
Reactions were run at 0 °C with [PdCl(η3-C3H5)]2 (0.5 mol %), CH2Cl2 as solvent, ligand (1.1 mol %), BSA (3 equiv), and KOAc. Full conversions
were achieved after 12 h.
phosphite (L4) for phosphinite or phosphine groups (ligands
L5 and L6) (Table 1; entry 9 vs entries 11 and 12). It was also
found that the sense of enantioselectivity is controlled by the
configuration of the biaryl phosphite functionality. Accordingly,
ligands with R configuration at the biaryl phosphite moiety gave
(R)-alkylated products, while ligands with an S configuration at
the biaryl phosphite group gave (S)-alkylated products (e.g.,
entry 1 vs entry 2). In addition, for the linear substrate S1 the
enantioselectivity depends on the correct combination of the
configuration of the biaryl phosphite moiety and the ligand
backbone. The matched combination was therefore obtained
with ligand L1a, containing an (R)-biaryl phosphite group
(entry 1 vs entry 2). However, for the cyclic substrate the
combination of both ligand parameters on enantioselectivity is
less relevant. Therefore, by simply changing the configuration
of the phosphite functionality both product enantiomers can be
obtained (entries 1 and 2). For the cyclic substrate S2
enantioselectivity is also influenced by the substituents of the
biaryl phosphite functionality. Enantioselectivities are therefore
the highest when SiMe3 groups are present at the ortho
positions of the biaryl phosphite moiety (entries 1 and 2 vs
entries 3 and 4).
We also studied the application of ligands L7 with a more
rigid ligand backbone, since the nitrogen is constrained in a
bicyclic structure. However, while the use of ligands L7 has a
negative effect on enantioselectivity for substrate S1 (Table 1;
entries 1 and 2 vs entries 13 and 14) it has little effect for
substrate S2 (entries 1 and 2 vs entries 13 and 14).
Finally, enantioselectivity can also be enhanced by changing
the reaction parameters. Enantioselectivity was therefore
further improved by decreasing the temperature to 0 °C (ee
values up to 87% for S1 and 81% for S2; Table 1, entry 15). We
also tested the reaction using other base additives, since the
literature indicated that in some cases the source of base can
have a positive effect on the reaction,17 but the activities and
enantioselectivities did not improve further (the results of these
experiments can be found in the Supporting Information).
Pd-Allylic Substitution of Other Substrates and with
Other Nucleophiles: Scope and Limitations. The scope of
Pd/L1a−d through L7a−d catalysts was then extended to
other substrates and nucleophiles. As an example, Figures 2 and
3 show the results with ligand L1a, which had delivered
together with ligands L1d (for S1), and L1b and L7a,b (for
S2), one of the best results.
We first performed the substitution of substrate S1 with
several nucleophiles. Advantageously, enantioselectivity was
independent of the steric nature of the ester groups of the
malonate nucleophiles (products 13, 15, and 16) and also of
the replacement of the malonate by acetylacetone (product 22)
and benzylamine derivatives (products 23−25). In addition, a
broad range of substituted malonates, including those with
unsaturated groups, reacted smoothly with S1 to achieve the
On comparison of the results with ligands L1−L3, it can be
seen that the nature of the amine substituent has an effect on
enantioselectivity, which increases with the presence of less
sterically hindered substituents (Table 1; entries 1, 5, and 6).
The effect of configuration of carbons bearing the
isopropylidene group on enantioselectiviy was investigated,
observing that is larger for substrate S1 than S2 (entries 1−2 vs
9−10).
D
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explain the enantioselectivities achieved. We then prepared the
Pd-π-allyl complexes 36−39 [Pd(η3-allyl)(P−N)]BF4 (P−N =
L1a, L1b and L4a), which contain cyclohexenyl- and 1,3-
diphenylallyl groups, following a previously published method19
from the [PdCl(η3-allyl)]2 and the corresponding ligand with
silver tetrafluoroborate (Scheme 3). The formation of the
Scheme 3. Synthesis of [Pd(η3-allyl)(P−N)]BF4 Complexes
36−39
Figure 3. Pd-catalyzed allylic substitution of cyclic substrates with C
nucleophiles using the Pd-L1a catalytic system. Reactions were run at
0 °C with [PdCl(η3-C3H5)]2 (0.5 mol %), CH2Cl2 as solvent, ligand
(1.1 mol %), BSA (3 equiv), and KOAc. Full conversions were
achieved after 24 h.
complexes were confirmed by mass spectrometry and by NMR.
For spectral assignments bidimensional 1H−1H, 1H−13C,
1
31P−1H and H−1H NOESY spectra were performed.
To understand the reversal in the sign of the enantiose-
lectivity in the alkylation of cyclic substrates when varying the
configuration of the phosphite functionality (moving from a to
b), we studied the Pd-1,3-cyclohexenyl-allyl complex 36, which
has ligand L1a, and compare it with the related Pd/L1b
complex 37. The VT-NMR study (+30 to −80 °C) indicated a
mixture of two isomers, in equilibrium, in ratios of 1:8 and 20:1,
respectively (Scheme 4). The major isomer of compound 36
was attributed by NOE to the Pd-η3-exo form, while the NOE
indicated an endo disposition for the major isomer of 37
(Figure 4). Thus, varying the configuration of the phosphite
functionality led to a different ratio of the isomers that provide
both product enantiomers. For the major isomer of complex
36, the NOE indicates an interaction between the hydrogen of
the CH-N moiety and the central allyl proton, whereas for the
major isomer of 37, this NOE contact appears with one of the
methylene groups of the cyclohexenyl moiety (Figure 4). These
interactions are in agreement with exo and endo dispositions of
the major isomers of 36 and 37, respectively. Moreover, the
NOE also shows that for both isomers 36 the nitrogen adopts
an R configuration upon coordination, while for the the major
isomer of 37 it adopts an S configuration. Thus, for isomers 36,
we found a NOE contact between the hydrogens of the methyl
amine moiety with the terminal allylic proton trans to the
phosphite moiety, whereas for the major isomer of 37 this
NOE contact is found with the hydrogen of one of the CH−O
groups of the sugar backbone (Figure 4). For all of these
species, 13C NMR shows that the most electrophilic terminal
allylic carbon is trans to the P functionality (Scheme 4). If we
assume that the nucleophilic attack is at the most electrophilic
C, and since for complex 36 the enantioselectivity obtained
experimentally (75% ee R) is similar to the diastereoisomeric
excess of the Pd isomers (de = 78% R), we can conclude that
both isomers react at a similar rate. Therefore, for complex 36,
the enantioselectivity is mostly controlled by the ratio of the exo
and endo compounds. However, for complex 37 the
enantioselectivity obtained experimentally (72% S) is different
from the diastereomeric excess (90% S) of the Pd isomers. This
indicates that the minor isomer should react slightly more
quickly than the major isomer and that enantioselectivity is also
controlled by the different reactivities of the isomers of complex
37 toward the nucleophile.
corresponding alkylated products 17−21 in enantioselectivities
similar to those attained with dimethyl malonate (ee values up
to 91%). These results are important because products 18−21
can been used as intermediates for preparing more complex
chiral compounds.18 Interestingly, enantioselectivities compa-
rable to those achieved with S1 were also achieved in the
alkylation of other substrates (compounds 26−29), including
those more sterically demanding (compounds 28 and 29, ee
values up to 93% ee) than S1. These results show that the biaryl
phosphite functionality in the Pd/L1a catalyst is able to adjust
the chiral cavity to the steric and electronic demands of the
substrate and therefore alkylate them with comparably high
enantioselectivities in comparison with the case for S1.
Encouraged by the high enantioselectivity reached for the
challenging cyclic substrate S2 (see Table 1), we then moved to
the alkylation of cyclic substrates. For S2, several C
nucleophiles were used. In all cases, enantioselectivities (ee
values up to 83%, compounds 14 and 30−33) were similar to
those obtained when dimethyl malonate was used, even when
acetylacetone was used as nucleophile. High yields and
enantioselectivities were also reached when a seven-membered
cyclic substrate was used with dimethyl and propargyl
malonates as nucleophiles (products 34 and 35). Again,
compounds 31, 32, and 35 are relevant intermediates for the
synthesis of chiral polycyclic compounds.18a,d These results are
among the best reported for these substrates, even using
synthetically valuable nucleophiles other than dimethyl
malonate, for which few catalysts have afforded high catalytic
performance.
To sum up, the new sugar-based amino-phosphite ligands
L1a,d and L7a,b have provided good results in different
substrate types using several nucleophiles. The high catalytic
performance (ee values up to 86%) reached with cyclic
substrates are particularly encouraging. This fact, along with the
promising results obtained for a number of linear substrates (ee
values up to 93%, including the challenging sterically
demanding compounds 28 and 29), opens up the Pd−allylic
alkylation reactions to novel types of readily available, solid, air-
stable, and modular ligands.
Mechanistic Insights: Investigation of the Key Pd−π-
Allyl Intermediates. In this process it has been proved that
the enantioselectivity is controlled in the irreversible
nucleophilic attack.2 Therefore, studying the reactivity of the
nucleophile with the Pd-π-allyl intermediates is crucial to
Finally, to evaluate the effect of the configuration of carbons
bearing the isopropylidene group on the enantioselectivity
E
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a
Scheme 4. Pd−η3-Allyl Intermediates for Cyclic S2 Containing Ligands L1a (Isomers 36) and L1b (Isomers 37)
a
The ratio of each isomer is shown in parentheses. The chemical shifts (in ppm) of the allylic terminal carbons are also shown.
allyl group (Figure 5a). In addition, the NOE also indicates that
for both isomers the nitrogen adopts an R configuration upon
Figure 4. Selected NOE interactions from the NOESY spectra of Pd-
η3-allyl intermediates 36 and 37.
obtained in the allylic alkylation of S1, we studied the Pd allylic
complexes with ligands L1a and L4a (38 and 39, respectively).
Whereas ligand L1a provided high enantioselectivity (80% R),
ligand L4a, which differs in the configuration of the carbons
bearing the isopropylidene group, gave less enantioselectivity
(15% R).
The VT-NMR (+30 to −85 °C) investigation of Pd-allyl
intermediate 38, with ligand L1a, showed two isomers in
equilibrium in a ratio of 2.2:1. They were attributed by NMR to
the two syn/syn exo and endo compounds (Scheme 5). For both
the NOE experiment confirms a syn/syn disposition. Therefore,
we found NOE contacts between the terminal protons of the
Figure 5. (a) Selected NOE interactions from the NOESY spectrum
of Pd−η3-allyl intermediates 38 (exo and endo). (b) Reactivity of
intermediates 38 toward sodium dimethyl malonate at −80 °C:
31P{1H} NMR spectra before and after the addition of sodium
dimethyl malonate in CD2Cl2.
coordination. For the major isomer a NOE contact was also
found between the hydrogen of the CH-N group and the
central allyl proton, whereas for the minor isomer there is a
NOE contact of the methyl amine group with the hydrogen
placed at the ortho position of one of the phenyl groups of the
substrate. These interactions confirm an exo disposition for the
major isomer of 38 and an endo disposition for the minor
isomer (Figure 5a). The 13C NMR shows that the most
electrophilic terminal allylic C is again trans to the P
functionality. If we assume that the nucleophilic attack is at
the most electrophilic terminal C and since the enantiomeric
excess of the alkylation product (ee values up to 80% R) is
higher than the diastereoisomeric excesses of the Pd isomers
(de = 37% S), the minor endo isomer should react more quickly
than the exo isomer. To confirm this, we performed an in situ
NMR study of the reactivity of both Pd isomers with dimethyl
malonate at low temperature (Figure 5b). This experiment
shows that the minor isomer (endo) reacts around 15 times
faster with the nucleophile in comparison to the major isomer
(exo). If we consider the ratio of each reacting isomer and their
reactivity with dimethyl malonate, the theoretical ee should be
74% R, which is in agreement with the experimental
enantioselectivity (80% R). This is consistent with a
Scheme 5. Pd−η3-Allyl Intermediates for Linear S1
a
Containing Ligand L1a (Isomers 38)
a
The ratio of each isomer is shown in parentheses. The chemical shifts
(in ppm) of the allylic terminal carbons are also shown.
F
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nucleophilic attack mainly at the terminal C trans to the
phosphite functionality of the minor endo isomer. Conse-
quently, for substrate S1 and ligand L1a the enantioselectivity
seems to be controlled by the different reactivities of the Pd
isomers toward the nucleophile, rather than by the ratio of
isomers, as was the case for substrate S2 when the same ligand
L1a was used.
In contrast to the previous study with ligand L1a, the VT-
NMR (+30 to −85 °C) of Pd−allyl complexes 39 with L4a
showed three compounds in equilibrium at a ratio of 3.2:1.7:1.
The two major species were attributed to the syn/syn endo and
exo isomers of 39 (see relevant NOE contacts in Figure 6),
has been shown to provide higher conversion with lower
enantioselectivity in comparison to their bidentate analogues
because they have more degrees of freedom.20
The elucidation of the Pd−1,3-diphenylallyl intermediates
allows us to conclude that, for enantioselectivity to be high, a
proper combination of the ligand components is required to
avoid the formation of species with ligands coordinated in a
monodentate fashion.
CONCLUSIONS
■
A series of new iminosugar-phosphite/phosphinite/phosphine
ligands have been screened in Pd allylic substitutions. These
ligands are obtained in enantiomerically pure form from readily
available sugars as starting materials. They thus contain the
advantages of carbohydrates in terms of selection of the
stereogenic carbons, polyfunctional groups able to modulate
the electronic and sterical properties, and the general good
stability of carbohydrate derivatives. Thus, several ligand
parameters can be systematically varied so that selectivities
can be maximized for each substrate. By choosing the ligand
components, we attained good results in a number of substrates
with several electronic and steric requirements and using C and
N nucleophiles (23 compounds in total with ee values up to
93%). For both substrate types (linear and cyclic), biaryl
phosphite groups in the ligand are needed for high
enantioselectivity. This is advantageous because the iminosu-
gar-phosphite ligands are air-stable solids, in contrast to their
amino-phosphinite/phosphine analogues. The influence of the
remaining ligand components (amine substituent, the config-
uration of carbons bearing the isopropylidene group, the
substituent/configuration of the phosphite functionality, and
the rigidity of the ligand) on the selectivity depends on each
type of substrate. Particularly, for linear substrates we found
that an R configuration of the binaphthyl moiety is needed for
high enantioselectivity. However, for cyclic substrates both
product enantiomers can be attained by setting the
configuration of the phosphite functionality. Additionally, for
cyclic substrates, in contrast to linear substrates, enantiose-
lectivity is also influenced by the substituent of the phosphite
functionality and there is a slight effect of the configuration of
carbons bearing the isopropylidene group and the rigidity of the
ligand. In comparison with previous air-unstable amino-P
ligands6 (P = phosphine, aminophosphine, and phosphinite
groups) found in the literature, the new amino-phosphite
ligands gave a better substrate and nucleophile scope (i.e.,
including more challenging hindered linear and cyclic
substrates, even with highly interesting nucleophiles such as
those α-substituted with unsaturated moieties). These results
pave the way for the further development of modular amino-
phosphite ligands, which are readily available and air stable, for
the asymmetric Pd-allylic substitution of different substrates,
including the more demanding cyclic substrates, with a broad
range of nucleophiles.
Figure 6. Selected NOE interactions from the NOESY spectrum of
Pd−η3-allyl intermediates 39 (exo and endo).
while the minor compound was assigned to a Pd−allyl complex
([Pd(η3-allyl)(L4a)2]BF4) with two P−N ligands coordinated
to the Pd in a monodentate fashion through the phosphite
functionality (Scheme 6). Monodentate coordination of L4a in
Scheme 6. Pd−η3-Allyl Intermediates for Linear S1
Containing Ligand L4a (Isomers 39 and [Pd(η3-
a
allyl)(L4a)2]BF4)
a
The ratio of each compound is shown in parentheses. The chemical
shifts (in ppm) of the allylic terminal carbons are also shown.
the minor species [Pd(η3-allyl)(L4a)2]BF4 is clearly disclosed
1
because the signals of the methyl amine in the H and 13C
NMR spectra are not shielded, as is the case when the amino
group coordinates to Pd. It should be pointed out that varying
the configuration of carbons bearing the isopropylidene group
also implied variations in the configuration of the nitrogen
upon coordination to palladium from R (in isomers 38) to S (in
isomers 39). Thus, for isomers 39, we found NOE contacts
between one of the methyl groups of the isopropylidene moiety
with the methyl of the amino group (Figure 6). The lower
enantioselectivity obtained with the Pd/L4a system in
comparison to that with the Pd/L1a system could be due to
the existence of [Pd(η3-allyl)(L4a)2]BF4. This type of complex
Finally, the elucidation of the Pd−π-allyl complexes allows us
to explain the enantioselectivities obtained. It shows that for
high enantioselectivities the ligand components need to be
appropriately mixed to either enhance the difference in the ratio
of the Pd−allyl isomers formed or to enhance the reactivity of
the nucleophile toward each Pd−allyl isomer, for cyclic
substrates. However, for linear substrates the combination of
ligand components has to suppress the formation of Pd−allyl
complexes with monodentate coordinated ligands. This study
also indicates that the sugar backbone is able to control the
G
DOI: 10.1021/acs.organomet.8b00140
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(75.4 MHz, CDCl3): δ 24.0 (−C(CH3)2), 26.3 (−C(CH3)2), 51.3 (C-
5), 59.5 (C-1′), 66.5 (C-2), 81.0 (C-4), 82.7 (C-3), 111.6
(−C(CH3)2). HRMS (ESI): m/z calcd for C8H16NO3, 174.1125 [M
+ H]+; found, 174.1121.
configuration of the amino group upon coordination, which in
turn can be efficiently shifted from R to S by varying the
configuration of the biaryl phosphite functionality.
(2S,3S,4R)-N-Benzyl-2-hydroxymethyl-3,4-O-isopropylidene-
pyrrolidine-3,4-diol (2). To a solution of 8 (125 mg, 0.72 mmol) in
anhydrous 1,2-dichloroethane (7.5 mL) were successively added
benzaldehyde (0.15 mL, 1.44 mmol) and NaBH(OAc)3 (320 mg, 1.51
mmol). The mixture was stirred at room temperature for 3 h, and then
a saturated aqueous solution of NaHCO3 (15 mL) was added. The
aqueous phase was extracted (×4) with EtOAc. The organic layers
were dried with Na2SO4, filtered, and evaporated. The residue was
purified by a chromatography column on silica gel (eluent: Et2O/
cyclohexane 3/1 → Et2O) to produce 2 (128 mg, 68%) as a pale
yellow oil. [α]2D8 +41.3 (c 0.94, CH2Cl2). 1H NMR (300 MHz,
CDCl3): δ 1.32 (s, 3H,−C(CH3)2), 1.54 (s, 3H, −C(CH3)2), 2.39 (br
s, 1H, OH), 2.61−2.66 (m, 1H, H-5a), 2.94−2.97 (m, 1H, H-2),
EXPERIMENTAL SECTION
■
General Considerations. All reactions were performed with
standard Schlenk techniques using an argon atmosphere, except for the
preparation of pyrrolidine alcohols and their precursors. Commercial
chemicals were used as received. Solvents were dried by means of
standard procedures and stored under argon. Phosphorochloridites
were synthesized in one step from the appropriate biphenols and
binols.21 Racemic substrates S1, S2, 1,3-di-p-tolylallyl acetate, 1,3-
bis(3-methoxyphenyl)allyl acetate, 1,3-di-o-tolylallyl acetate, 2,6-
dimethylhept-4-en-3-yl acetate, and cyclohept-2-en-1-yl acetate22 and
23
Pd−allyl complexes [Pd(η3-1,3-Ph2-C3H3)(μ-Cl)]2 and [Pd(η3-
24
cyclohexenyl)(μ-Cl)]2 were prepared as previously reported. TLC
3.17−3.23 (m, 1H, H-5b), 3.57 (dd, 1H, H-1′a, J1′a‑1′b = 11.1, J1′a‑2
3.6), 3.60 (d, 1H, CH2Ph, JH−H = 12.9), 3.65 (dd, 1H, H-1′b, J1′b‑2
=
=
was performed on silica gel HF254 (Merck), with detection by UV light
charring with H2SO4, p-anisaldehyde, vanillin, ninhydrin, KMnO4,
phosphomolybdic acid, or Pancaldi reagent ((NH4)6MoO4, Ce(SO4)2,
H2SO4, H2O). Silica gel 60 (Merck, 63−200 μm) was used for
preparative chromatography. Optical rotations were measured in a 1.0
cm or 1.0 dm tube with a Jasco P-2000 spectropolarimeter. Infrared
3.9), 3.98 (d, 1H, CH2Ph), 4.56−4.63 (m, 2H, H-3, H-4), 7.23−7.36
(m, 5H, Harom). 13C NMR (75.4 MHz, CDCl3): δ 25.0 (−C(CH3)2),
27.4 (−C(CH3)2), 58.3 (CH2Ph), 58.6 (C-5), 59.6 (C-1′), 70.1 (C-2),
78.6, 82.7 (C-3, C-4), 112.9 (−C(CH3)2), 127.5, 128.6, 128.9, 138.5
(Carom). HRMS (ESI): m/z calcd for C15H22NO3, 264.1594 [M + H]+;
found, 264.1594.
1
spectra were recorded with a Jasco FTIR-410 spectrophotometer. H,
13C{1H}, and 31P{1H} NMR spectra were performed in Bruker AV300
and AV500 and Varian Mercury-400 spectrometers for solutions in
CDCl3, C6D6, and DMSO-d6 at room temperature, except when
indicated. Chemical shifts are relative to that of SiMe4 (1H and
13C{1H}) as an internal standard or H3PO4 (31P) as an external
(2S,3S,4R)-N-Isopropyl-2-hydroxymethyl-3,4-O-isopropyli-
denepyrrolidine-3,4-diol (3). To a solution of compound 8 (121
mg, 0.70 mmol) in MeOH (1.5 mL) were added acetone (0.26 mL,
3.49 mmol) and Pd/C 10% (cat.). The reaction mixture was stirred
under H2 overnight. The catalyst was filtered through Celite and
washed with MeOH. The solvent was evaporated, and the residue was
purified by a chromatography column on silica gel (eluent: CH2Cl2/
MeOH − 30/1 → 20/1) to produce 3 (113 mg, 75%) as a pale yellow
oil. [α]2D7 +13.3 (c 0.79, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.00
(d, 3H, CH3, JH−H = 6.3), 1.09 (d, 3H, CH3), 1.31 (s, 3H,−C(CH3)2),
1.50 (s, 3H, C(CH3)2), 2.32 (br s, 1H, OH), 2.77 (dd, 1H, H-5a, J5a‑5b
= 10.2, J5a‑4 = 4.8), 2.97−3.06 (m, 2H, (CH3)2CH, H-2), 3.18 (dd, 1H,
H-5b, J5b‑4 = 6.0), 3.52 (dd, 1H, H-1′a, J1′a‑1′b = 10.8, J1′a‑2 = 2.7), 3.63
(dd, 1H, H-1′b, J1′b‑2 = 3.6), 4.52 (dd, 1H, H-3, J = 6.6, J = 3.0), 4.56−
4.62 (m, 1H, H-4). 13C NMR (75.4 MHz, CDCl3): δ 15.7 (CH3), 22.3
(CH3), 25.3 (−C(CH3)2), 27.6 (−C(CH3)2), 48.0 ((CH3)2CH), 51.6
(C-5), 59.6 (C-1′), 65.8 (C-2), 78.4 (C-4), 83.0 (C-3), 112.5
(−C(CH3)2). HRMS (ESI): m/z calcd for C11H22NO3, 216.1594 [M
+ H]+; found, 216.1589.
(2S,3R,4S)-N-tert-Butoxycarbonyl-2-hydroxymethyl-3,4-O-
isopropylidenepyrrolidine-3,4-diol (10). To a solution of
compound 915 (2.44 g, 9.28 mmol) in MeOH (70 mL) were added
Boc2O (2.02 g, 18.6 mmol) and Pd/C 10% (0.63 g). The reaction
mixture was stirred under H2 for 3 h. The catalyst was filtered through
Celite and washed with MeOH. The solvent was evaporated, and the
residue was purified by chromatography column on silica gel (eluent:
EtOAc/cyclohexane 1/2) to give 10 (2.18 g, 86%) as a colorless oil.
[α]2D4 +41.8 (c 1.00, CH2Cl2). NMR and IR data are in accordance
with those of its enantiomer.14 HRMS (ESI): m/z calcd for
C13H23NO5Na, 296.1468 [M + Na]+; found, 296.1465.
standard. Coupling constants are reported in Hz. 1H and 13C
assignments were confirmed by 1H−1H gCOSY, 1H−13C gHSQC,
and NOESY spectra. Mass spectra (CI and ESI) were recorded on
Micromass AutoSpeQ and QTRAP (Applied Biosystems) and
Orbitrap Elite spectrometers. NMR and mass spectra were registered
in CITIUS (University of Seville) and in SRCiT (Universitat Rovira i
Virgili).
(2S,3S,4R)-N-Methyl-2-hydroxymethyl-3,4-O-isopropylide-
nepyrrolidine-3,4-diol (1). To a suspension of LiAlH4 (420 mg,
10.9 mmol) in anhydrous THF (22 mL) at 0 °C was added a solution
of 714 (600 mg, 2.19 mmol) in anhydrous THF (22 mL). The mixture
was heated at reflux for 2.5 h and then cooled at 0 °C. Diethyl ether
and a saturated aqueous solution of Na2SO4 were successively added,
and the mixture was filtered through Celite and washed with CH2Cl2.
The solvent was evaporated, and the residue was purified by a
chromatography column on silica gel (eluent: EtOAc/cyclohexane 1/
3) to produce 1 (345 mg, 84%) as a pale yellow oil. [α]2D4 −19.9 (c
1.08, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.11 (s, 3H,
−C(CH3)2), 1.51 (s, 3H, −C(CH3)2), 2.36 (s, 3H, N−CH3), 2.51−
2.57 (m, 2H, H-2, H-5a), 2.61 (br s, 1H, OH), 3.33−3.39 (m, 1H, H-
5b), 3.63 (dd, 1H, H-1′a, J1′a‑1′b = 11.4, J1′a‑2 = 2.7), 3.72 (dd, 1H, H-
1′b, J1′b‑2 = 3.6), 4.56−4.63 (m, 2H, H-3, H-4). 13C NMR (75.4 MHz,
CDCl3): δ 25.0 (−C(CH3)2), 27.3 (−C(CH3)2), 40.0 (N−CH3), 59.3
(C-1′), 62.0 (C-5), 71.6 (C-2), 77.8, 82.2 (C-3, C-4), 113.1
(−C(CH3)2). HRMS (ESI): m/z calcd for C9H18NO3, 188.1281 [M
+ H]+; found, 188.1276.
(2S,3R,4S)-N-Methyl-2-hydroxymethyl-3,4-O-isopropylide-
nepyrrolidine-3,4-diol (4). To a suspension of LiAlH4 (206 mg,
5.43 mmol) in anhydrous THF (11 mL) at 0 °C was added a solution
of 10 (292.6 mg, 1.09 mmol) in anhydrous THF (11 mL). The
mixture was heated at reflux for 2.5 h and then cooled at 0 °C. Diethyl
ether and a saturated aqueous solution of Na2SO4 were successively
added, and the mixture was filtered through Celite and washed with
CH2Cl2. The solvent was evaporated, and the residue was purified by a
chromatography column on silica gel (eluent: EtOAc/MeOH 7/1 →
5:1) to produce 4 (184.2 mg, 91%) as a pale yellow solid. [α]2D7 +72.5
(c 0.8, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.30 (s, 3H,
−C(CH3)2), 1.51 (s, 3H, −C(CH3)2), 2.06−2.13 (m, 1H, H-2), 2.19
(dd, 1H, H-5a, J5a‑5b = 11.4, J5a‑4 = 4.5), 2.32 (s, 3H, N−CH3), 3.25 (d,
1H, H-5b), 3.42 (br s, 1H, OH), 3.84 (dd, 1H, H-1′a, J1′a‑1′b = 11.7,
(2S,3S,4R)-2-Hydroxymethyl-3,4-O-isopropylidenepyrroli-
dine-3,4-diol (8). To a solution of 714 (203 mg, 0.74 mmol) in
anhydrous CH2Cl2 (10 mL) with 4 Å MS at 0 °C was added
anhydrous trifluoroacetic acid (1.9 mL). The mixture was stirred at
room temperature for 1 h and then was filtered, and the solvent was
evaporated. The residue was dissolved in anhydrous CH2Cl2, and
Ambersep 900 was added. The resulting mixture was filtered, and the
solvent was evaporated. The residue was purified by a chromatography
column on silica gel (eluent: CH2Cl2/MeOH 10/1, 1% Et3N) to
produce 8 (101 mg, 78%) as a pale yellow oil. [α]2D7 −26.2 (c 1.0,
1
CH2Cl2). H NMR (300 MHz, CDCl3): δ 1.30 (s, 3H, −C(CH3)2),
1.47 (s, 3H, −C(CH3)2), 3.08 (dd, 1H, H-5a, J5a‑5b = 13.5, J5a‑4 = 4.2),
3.19 (d, 1H, H-5b), 3.39 (dd, 1H, H-1′a, J1′a‑1′b = 11.1, J1′a‑2 = 8.7),
3.49 (dd, 1H, H-2, J2−1′b = 4.2), 3.65 (dd, 1H, H-1′b), 4.50 (d, 1H, H-
3, J3−4 = 5.4), 4.63 (br s, 2H, OH, NH), 4.76 (t, 1H, H-4). 13C NMR
J1′a‑2 = 6.0), 3.91 (dd, 1H, H-1′b, J1′b‑2 = 3.6), 4.61 (dd, 1H, H-4, J4−3
=
H
DOI: 10.1021/acs.organomet.8b00140
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
6.3), 4.70 (dd, 1H, H-3, J3−2 = 5.1). 13C NMR (75.4 MHz, CDCl3): δ
24.3 (−C(CH3)2), 25.9 (−C(CH3)2), 40.3 (N-CH3), 59.7 (C-1′), 61.7
(C-5), 69.7 (C-2), 78.0 (C-4), 81.8 (C-3), 111.3 (−C(CH3)2). HRMS
(ESI): m/z calcd for C9H18NO3, 188.1281 [M + H]+; found, 188.1277.
(6S,7R,7aS)-6,7-O-Isopropylidenetetrahydropyrrolo[1,2-c]-
oxazol-3-one-6,7-diol (11). To a solution of 10 (1.06 g, 3.89 mmol)
in anhydrous pyridine (15 mL) at 0 °C was slowly added TsCl (1.89 g,
9.74 mmol). After the mixture was stirred at room temperature
overnight, the solvent was evaporated and the residue was purified by a
chromatography column on silica gel (eluent: EtOAc/cyclohexane 1/1
→ 2/1) to produce 11 (713 mg, 92%) as a white solid. [α]2D2 +25.6 (c
0.82, CH2Cl2). HRMS (ESI): m/z calcd for C9H13NO4Na, 222.0737
[M + Na]+; found, 222.0735. NMR and IR data are in accordance with
those of its enantiomer.14
3H, CH3), 1.47 (s, 3H, CH3), 2.02 (s, 3H, CH3, NMe) 2.42 (dd, 1H,
CH2−N, 2JH−H = 9.6 Hz, 3JH−H = 4.6 Hz), 2.61 (m, 1H, CH), 2.95 (m,
1H, CH2−N), 3.53 (m, 1H, CH2−OP), 4.09 (m, 1H, CH2−OP), 4.24
(m, 1H, CH−O), 4.32 (m, 1H, CH−O), 6.86 (m, 2H, CH), 7.02
(m, 1H, CH), 7.12 (m, 1H, CH), 7.24 (d, 1H, CH, 3JH−H = 8.5
Hz), 7.33 (d, 1H, CH, 3JH−H = 8.5 Hz), 7.69 (d, 2H, CH, 3JH−H
=
8.2 Hz), 8.10 (d, 2H, CH, 3JH−H = 8.2 Hz). 13C NMR (100.6 MHz,
C6D6): δ −0.2 (CH3, SiMe3), −0.2 (CH3, SiMe3), 1.1 (CH3, SiMe3),
24.9 (CH3), 27.2 (CH3), 39.5 (CH3, NMe), 61.9 (CH2−N), 64.1
(CH2−OP), 70.3 (CH), 77.9 (CH−O), 82.4 (CH−O), 112.6 (C),
122.3−152.9 (Carom). Anal. Calcd for C35H44NO5PSi2: C, 65.09; H,
6.87; N, 2.17. Found: C, 65.69; H, 6.89; N, 2.12. TOF-MS (ESI+): m/
z calcd for C35H44NO5PSi2, 668.2388 [M + Na]+; found, 668.2387.
L1c. Yield: 71.5 mg (44%, reaction carried out using 0.25 mmol of
1
(2S,3R,4S)-2-Diphenylphosphinomethyl-3,4-O-isopropylide-
nepyrrolidine-3,4-diol (12). To a solution of 11 (147 mg, 0.74
mmol) in anhydrous THF (6.0 mL) at 0 °C was slowly added KPPh2
(0.5 M in THF, 1.8 mL, 0.89 mmol). The mixture was heated at reflux
for 2 h and then cooled to room temperature. IRA-120H+ was added,
and the resulting mixture was filtered through Celite and washed with
CH2Cl2. The solvent was evaporated, and the residue was purified by a
chromatography column on silica gel (eluent: Et2O/acetone 10/1, 1%
Et3N) to produce 12 (26 mg, 89%) as a colorless oil. [α]2D21+63.2 (c
0.57, CH2Cl2). 31P NMR (121.5 MHz, CDCl3): δ −20.9. H NMR
(300 MHz, CDCl3): δ 1.31 (s, 3H, −C(CH3)2), 1.46 (s, 3H,
−C(CH3)2), 1.95 (br s, 1H, NH), 2.37 (dd, 1H, H-1′a, J1′a‑1′b = 13.2,
J1′a‑2 = 8.1), 2.43 (dd, 1H, H-1′b, J1′b‑2 = 6.3), 2.50−2.62 (m, 2H, H-2,
H-5a), 3.02 (d, 1H, H-5b, J5b‑5a = 13.5), 4.57 (dd, 1H, H-3, J3−4 = 5.7,
J3−2 = 3.9), 4.61−4.64 (m, 1H, H-4), 7.29−7.35 (m, 6H, Harom), 7.42−
7.53 (m, 4H, Harom). 13C NMR (75.4 MHz, CDCl3): δ 24.1
(−C(CH3)2), 26.0 (−C(CH3)2), 27.3 (d, JC−P = 13.2, C-1′), 53.2
(C-5), 61.5 (d, JC−P = 16.3, C-2), 81.8 (d, JC−P = 4.5, C-3), 82.2 (C-4),
110.6 (−C(CH3)2), 128.4 (Carom), 128.5 (d, JC−P = 8.4, Carom), 128.6
(d, JC−P = 6.7, Carom), 128.9 (Carom), 132.8 (d, JC−P = 19.1, Carom),
133.1 (d, JC−P = 19.3, Carom), 138.6 (d, JC−P = 13.0, Carom−P), 138.9
(d, JC−P = 13.0, Carom−P). HRMS (ESI): m/z calcd for C20H25NO2P,
342.1617 [M + H]+; found, 342.1609.
General Procedure for the Synthesis of the Amino-
Phosphite Ligands L1a−d, L2a, L3a, L4a,b, and L7a,b. The
desired in situ prepared phosphorochloridite (1.1 equiv) was first
dissolved in toluene (5 mL/mmol), and then pyridine (3.8 equiv) was
added. After the corresponding alcohols 1−4 and 6 were azeotropi-
cally dried with toluene (3 × 1 mL), toluene (5 mL/mmol) and
pyridine (3.8 equiv) were added. The solution was transferred slowly
at 0 °C to a solution of the phosphorochloridite. The resulting
reaction mixture was stirred overnight at 80 °C, and then the pyridine
salts were removed by filtration. Evaporation of the solvent gave a
white foam, which was purified by flash chromatography in alumina
(eluent: toluene/triethylamine 100/1) to produce the corresponding
ligand as a white solid.
1). 31P NMR (161.9 MHz, C6D6): δ 129.6. H NMR (400 MHz,
C6D6): δ 1.98 (s, 3H, CH3), 2.11 (m, 2H, CH2), 2.28 (s, 3H, CH3)
2.31 (m, 6H, CH2), 2.38 (s, 18H, CH3, tBu), 2.92 (s, 3H, CH3, NMe),
3.07 (m, 1H, CH2), 3.35 (m, 9H, CH2, CH, CH2−N), 3.77 (dd, 1H,
2
3
CH2−N, JH−H = 9.5 Hz, JH−H = 6.1 Hz), 4.31 (m, 1H, CH2−OP),
4.86 (m, 1H, CH2−OP), 5.18 (m, 1H, CH−O), 5.34 (m, 1H, CH−
O), 7.96 (m, 2H, CH). 13C NMR (100.6 MHz, C6D6): δ 23.6
(CH2), 23.8 (CH2), 23.9 (CH2), 25.7 (CH2), 28.0 (CH2), 28.1 (CH2),
t
28.3 (CH3), 30.3 (CH3), 30.4 (CH2), 31.7 (CH3, Bu), 31.9 (CH3,
tBu), 32.0 (CH3, tBu), 35.3 (C, tBu), 35.4 (C, tBu), 40.2 (CH3, NMe),
62.7 (CH2−N), 63.5 (CH2−OP), 71.0 (CH), 78.9 (CH−O), 83.3
(CH−O), 113.3 (C), 126.1−139.3 (Carom). Anal. Calcd for
C37H52NO5P: C, 71.47; H, 8.43; N, 2.25. Found: C, 71.69; H, 8.42;
N, 2.23. TOF-MS (ESI+): m/z calcd for C37H52NO5P, 644.3475 [M +
Na]+; found, 644.3479.
L1d. Yield: 118.4 mg (61%, reaction carried out using 0.35 mmol of
1
1). 31P NMR (161.9 MHz, C6D6): δ 127.5. H NMR (400 MHz,
C6D6): δ 1.14 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.54 (s, 18H, CH3,
tBu) 1.64 (s, 3H, CH3), 1.74 (s, 3H, CH3), 2.02 (s, 3H, CH3), 2.04 (s,
2
3H, CH3), 2.07 (s, 3H, CH3, NMe), 2.43 (dd, 1H, CH2−N, JH−H
=
=
3
2
3
9.6 Hz, JH−H = 4.7 Hz), 2.58 (dd, 1H, CH, JH−H = 8.6 Hz, JH−H
4.0 Hz), 2.93 (dd, 1H, CH2−N, 2JH−H = 9.6 Hz, 3JH−H = 6.1 Hz), 3.49
(m, 1H, CH2−OP), 4.10 (m, 1H, CH2−OP), 4.34 (m, 1H, CH−O),
4.53 (m, 1H, CH−O), 7.17 (m, 1H, CH), 7.18 (m, 1H, CH). 13C
NMR (100.6 MHz, C6D6): δ 16.2 (CH3), 16.4 (CH3), 20.0 (CH3),
t
20.1 (CH3), 24.9 (CH3), 27.2 (CH3), 29.8 (CH3), 31.2 (CH3, Bu),
31.3 (CH3, tBu), 34.6 (C, tBu), 34.7 (C, tBu), 39.3 (CH3, NMe), 61.9
(CH2−N), 62.4 (CH2−OP), 70.3 (CH), 77.9 (CH−O), 82.5 (CH−
O), 112.4 (C), 125.3−146.2 (Carom). Anal. Calcd for C33H48NO5P: C,
69.57; H, 8.49; N, 2.46. Found: C, 69.70; H, 8.50; N, 2.44. TOF-MS
(ESI+): m/z calcd for C33H48NO5P, 592.3162 [M + Na]+; found,
592.3165.
L2a. Yield: 167.2 mg (50%, reaction carried out using 0.46 mmol of
1
2). 31P NMR (161.9 MHz, C6D6): δ 133.6. H NMR (400 MHz,
C6D6): δ 0.47 (s, 9H, CH3, SiMe3), 0.48 (s, 9H, CH3, SiMe3), 1.16 (s,
3H, CH3), 1.47 (s, 3H, CH3), 2.51 (dd, 1H, CH2−N, 2JH−H = 10.3 Hz,
3JH−H = 3.6 Hz), 2.76 (dd, 1H, CH2−N, 2JH−H = 10.3 Hz, 3JH−H = 3.6
L1a. Yield: 72.5 mg (56%, reaction carried out using 0.20 mmol of
1
1). 31P NMR (161.9 MHz, C6D6): δ 132.9. H NMR (400 MHz,
2
Hz) 2.92 (m, 1H, CH), 3.22 (d, 1H, CH22Ph, JH−H = 13.3 Hz), 3.36
C6D6): δ 0.52 (s, 9H, CH3, SiMe3), 0.54 (s, 9H, CH3, SiMe3), 1.17 (s,
3H, CH3), 1.46 (s, 3H, CH3), 1.96 (s, 3H, CH3, NMe) 2.37 (dd, 1H,
(m, 1H, CH2−OP), 3.64 (d, 1H, CH2Ph, JH−H = 13.3 Hz), 4.07 (m,
1H, CH2−OP), 4.27 (m, 1H, CH−O), 4.59 (dd, 1H, CH−O, 2JH−H
=
2
3
3
CH2−N, JH−H = 9.6 Hz, JH−H = 4.8 Hz), 2.47 (m, 1H, CH), 2.89
6.6 Hz, JH−H = 2.6 Hz), 6.84 (m, 2H, CH), 7.03 (m, 7H, CH),
2
3
7.20 (d, 1H, CH, 3JH−H = 8.6 Hz), 7.32 (d, 1H, CH, 3JH−H = 8.6
(dd, 1H, CH2−N, JH−H = 9.6 Hz, JH−H = 6.1 Hz), 3.45 (m, 1H,
CH2−OP), 4.11 (m, 1H, CH2−OP), 4.33 (m, 1H, CH−O), 4.53 (m,
1H, CH−O), 6.85 (m, 2H, CH), 7.01 (m, 1H, CH), 7.04−7.13
Hz), 7.65 (d, 2H, CH, 3JH−H = 8.4 Hz), 8.07 (d, 2H, CH, 3JH−H
=
4.7 Hz). 13C NMR (100.6 MHz, C6D6): δ −0.4 (CH3, SiMe3), −0.1
(CH3, SiMe3), 0.0 (CH3, SiMe3), 24.9 (CH3), 27.2 (CH3), 56.9
(CH2Ph), 58.5 (CH2−N), 62.8 (CH2−OP), 67.9 (CH), 78.6 (CH−
O), 82.7 (CH−O), 112.1 (C), 122.4−153.0 (Carom). Anal. Calcd for
C41H48NO5PSi2: C, 68.21; H, 6.70; N, 1.94. Found: C, 68.60; H, 6.76;
N, 1.90. TOF-MS (ESI+): m/z calcd for C41H48NO5PSi2, 744.2701
[M + Na]+; found, 744.2703.
3
(m, 1H, CH), 7.24 (d, 1H, CH, JH−H = 8.5 Hz), 7.36 (d, 1H,
CH, 3JH−H = 8.5 Hz), 7.69 (d, 2H, CH, 3JH−H = 8.5 Hz), 8.12 (d,
2H, CH, JH−H = 8.5 Hz). 13C NMR (100.6 MHz, C6D6): δ −0.2
3
(CH3, SiMe3), −0.1 (CH3, SiMe3), 1.0 (CH3, SiMe3), 24.9 (CH3),
27.2 (CH3), 39.3 (CH3, NMe), 61.8 (CH2−N), 62.3 (CH2−OP), 70.1
(CH), 77.8 (CH−O), 82.3 (CH−O), 112.5 (C), 122.5−153.1 (Carom).
Anal. Calcd for C35H44NO5PSi2: C, 65.09; H, 6.87; N, 2.17. Found: C,
65.30; H, 6.87; N, 2.15. TOF-MS (ESI+): m/z calcd for
C35H44NO5PSi2, 668.2388 [M + Na]+; found, 668.2390.
L3a. Yield: 148.9 mg (70%, reaction carried out using 0.30 mmol of
1
3). 31P NMR (161.9 MHz, C6D6): δ 134.24. H NMR (400 MHz,
C6D6): δ 0.49 (s, 9H, CH3, SiMe3), 0.51 (s, 9H, CH3, SiMe3), 0.69 (d,
3H, CH3, iPr, 2JH−H = 6.3 Hz) 0.78 (d, 3H, CH3, iPr, 2JH−H = 6.3 Hz),
1.21 (s, 3H, CH3), 1.46 (s, 3H, CH3), 2.63 (m, 3H, CH2−N, CH, iPr),
3.11 (m, 1H, CH), 3.38 (m, 1H, CH2−OP), 3.97 (m, 1H, CH2−OP),
L1b. Yield: 100.0 mg (60%, reaction carried out using 0.25 mmol of
1
1). 31P NMR (161.9 MHz, C6D6): δ 136.5. H NMR (400 MHz,
C6D6): δ 0.50 (s, 9H, CH3, SiMe3), 0.51 (s, 9H, CH3, SiMe3), 1.10 (s,
I
DOI: 10.1021/acs.organomet.8b00140
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
4.35 (m, 1H, CH−O), 4.60 (dd, 1H, CH−O, 2JH−H = 6.5 Hz, 3JH−H
=
SiMe3), 25.2 (CH3), 26.8 (CH3), 37.8 (CH2−CHOP), 59.5 (CH2),
60.4 (CH2), 70.6 (CH), 78.4 (CH−OP), 81.2 (CH−O), 84.9 (CH−
O), 111.2 (C), 122.3−152.3 (Carom). Anal. Calcd for C36H44NO5PSi2:
C, 65.72; H, 6.74; N, 2.13. Found: C, 65.84; H, 6.76; N, 2.12. TOF-
MS (ESI+): m/z calcd for C36H44NO5PSi2, 680.2388 [M + Na]+;
found, 680.2391.
3
1.2 Hz), 6.82 (t, 2H, CH, JH−H = 11.3 Hz), 7.08 (m, 2H, CH),
7.19 (d, 1H, CH, 3JH−H = 8.6 Hz), 7.29 (d, 1H, CH, 3JH−H = 8.5
3
Hz), 7.65 (m, 2H, CH), 8.08 (d, 2H, CH, JH−H = 9.3 Hz). 13C
NMR (100.6 MHz, C6D6): δ −0.3 (CH3, SiMe3), −0.2 (CH3, SiMe3),
−0.1 (CH3, SiMe3), 17.0 (CH3, iPr), 21.8 (CH3, iPr), 25.2 (CH3), 27.3
i
Procedure for the Preparation of the Amino-Phosphinite
Ligand L5. Pyrrolidine-hydroxyl compound 4 (93.1 mg, 0.5 mmol)
and DMAP (6.7 mg, 0.055 mmol) were first dissolved in toluene (1
mL). Then triethylamine was added (0.09 mL, 0.65 mmol) at room
temperature, followed by addition of the appropriate chlorodiphe-
nylphosphine (0.55 mmol) via syringe. The reaction mixture was
stirred for 1 h at room temperature. The solvent was then removed
and the product was purified by flash chromatography on alumina
(toluene/NEt3 100/1) to produce the corresponding ligand as an oil.
Yield: 30 mg (15%). 31P NMR (161.9 MHz, C6D6): δ 116.1. 1H NMR
(400 MHz, C6D6): δ 1.00 (s, 3H, CH3), 1.33 (s, 3H, CH3), 1.97 (s,
3H, CH3−N), 2.34 (m, 1H, CH2−N), 2.60 (m, 1H, CH-N), 2.79 (m,
1H, CH2−N), 3.67 (m, 2H, CH2−O), 4.12 (m, 1H, CH−O), 4.32 (m,
1H, CH−O), 6.86 (m, 7H, CH), 7.41 (m, 2H, CH), 7.83 (m,
1H, CH). 13C NMR (100.6 MHz, C6D6): δ 24.0 (CH3), 26.4
(CH3), 38.6 (CH3−N), 58.3 (CH2−O), 61.1 (CH2−N), 70.9 (CH−
N), 77.0 (CH−O), 81.5 (CH−O), 111.8 (CMe2), 126.6−130.9
(Carom). TOF-MS (ESI+): m/z calcd for C21H26NO3P, 394.1543 [M +
Na]+; found, 394.1538.
(CH3), 47.9 (CH, Pr), 52.8 (CH2−N), 62.8 (CH2−OP), 64.6 (CH),
78.5 (CH−O), 82.7 (CH−O), 111.7 (C), 122.4−153.0 (Carom). Anal.
Calcd for C37H48NO5PSi2: C, 65.94; H, 7.18; N, 2.08. Found: C,
66.03; H, 7.23; N, 2.07. TOF-MS (ESI+): m/z calcd for
C37H48NO5PSi2, 696.2701 [M + Na]+; found, 696.2700.
L4a. Yield: 71 mg (54%, reaction carried out using 0.20 mmol of 4).
31P NMR (161.9 MHz, C6D6): δ 135.6. 1H NMR (400 MHz, C6D6): δ
0.55 (s, 9H, CH3, SiMe3), 0.57 (s, 9H, CH3, SiMe3), 1.14 (s, 3H,
2
CH3), 1.37 (s, 3H, CH3), 1.55 (dd, 1H, CH2−N, JH−H = 10.8 Hz,
3JH−H = 4.6 Hz), 1.87 (s, 3H, CH3, NMe), 2.01 (m, 1H, CH), 2.88 (d,
1H, CH2−N, 2JH−H = 10.8 Hz), 3.59 (m, 1H, CH2−OP), 4.07 (m, 1H,
CH−O), 4.28 (m, 1H, CH−O), 4.52 (m, 1H, CH2−OP), 6.84 (m,
2H, CH), 7.04 (m, 2H, CH), 7.29 (dd, 2H, CH, 3JH−H = 15.1
Hz, 3JH−H = 8.4 Hz), 7.68 (m, 2H, CH), 8.12 (d, 2H, CH, 3JH−H
= 5.2 Hz). 13C NMR (100.6 MHz, C6D6): δ −0.2 (CH3, SiMe3), −0.1
(CH3, SiMe3), 1.1 (CH3, SiMe3), 25.1 (CH3), 26.0 (CH3), 40.2 (CH3,
NMe), 62.5 (CH2−N), 62.7 (CH2−OP), 69.4 (CH), 77.9 (CH−O),
80.2 (CH−O), 110.8 (C), 122.3−153.3 (Carom). Anal. Calcd for
C35H44NO5PSi2: C, 65.09; H, 6.87; N, 2.17. Found: C, 65.24; H, 6.87;
N, 2.15. TOF-MS (ESI+): m/z calcd for C35H44NO5PSi2, 668.2388
[M + Na]+; found, 668.2390.
Preparation of the Amino-Phosphine Ligand (2S,3R,4S)-N-
Methyl-2-diphenylphosphinomethyl-3,4-O-isopropylidene-
pyrrolidine-3,4-diol (L6). To a solution of 12 (94 mg, 0.28 mmol)
in anhydrous CH2Cl2 (1.5 mL) at 0 °C were successively added Et3N
(43 μL, 0.30 mmol) and ClCO2CH3 (24 μL, 0.30 mmol). The mixture
was stirred at 0 °C for 3 h. HCl (0.1 M) (6 mL) was added, and the
aqueous phase was extracted (×3) with CH2Cl2. The organic layers
were washed with a saturated aqueous solution of NaHCO3, dried with
Na2SO4, filtered, and evaporated. The resulting crude product was
dissolved in anhydrous THF (2 mL) and added to a suspension of
LiAlH4 (32 mg, 0.83 mmol) in anhydrous THF (1.0 mL) at 0 °C. The
reaction mixture was heated at reflux for 2 h and then cooled at 0 °C.
Diethyl ether and a saturated aqueous solution of Na2SO4 were
successively added, and the mixture was filtered through Celite and
washed with CH2Cl2. The solvent was evaporated, and the residue was
purified by a chromatography column on silica gel (eluent: EtOAc/
cyclohexane 1/2) to produce L6 (81 mg, 82%) as a colorless oil. [α]D24
L4b. Yield: 112.9 mg (43%, reaction carried out using 0.40 mmol of
1
4). 31P NMR (161.9 MHz, C6D6): δ 137.7. H NMR (400 MHz,
C6D6): δ 0.54 (s, 9H, CH3, SiMe3), 0.55 (s, 9H, CH3, SiMe3), 1.14 (s,
3H, CH3), 1.35 (s, 3H, CH3), 1.50 (dd, 1H, CH2−N, 2JH−H = 10.8 Hz,
3JH−H = 4.6 Hz), 1.66 (s, 3H, CH3, NMe), 2.00 (m, 1H, CH), 2.80 (d,
2JH−H = 10.8 Hz, 1H, CH2−N), 4.03 (m, 3H, CH2−OP, CH−O), 4.36
(m, 1H, CH−O), 6.83 (m, 2H, CH), 7.08 (m, 2H, CH), 7.25 (m,
2H, CH), 7.65 (m, 2H, CH), 8.06 (s, 2H, CH). 13C NMR
(100.6 MHz, C6D6): δ −0.2 (CH3, SiMe3), −0.1 (CH3, SiMe3), 0.00
(CH3, SiMe3), 1.0 (CH3, SiMe3), 25.1 (CH3), 25.9 (CH3), 39.8 (CH3,
NMe), 62.2 (CH2−N), 62.6 (CH2−OP), 69.8 (CH), 77.9 (CH−O),
80.1 (CH−O), 110.8 (C), 122.2−153.0 (Carom). Anal. Calcd for
C35H44NO5PSi2: C, 65.09; H, 6.87; N, 2.17. Found: C, 65.27; H, 6.88;
N, 2.15. TOF-MS (ESI+): m/z calcd for C35H44NO5PSi2, 668.2388
[M + Na]+; found, 668.2386.
1
+167.5 (0.58, CH2Cl2). 31P NMR (202 MHz, C6D6): δ −21.1. H
L7a. Yield: 51.9 mg (40%, reaction carried out using 0.20 mmol of
NMR (500 MHz, C6D6): δ 1.27 (s, 3H, −C(CH3)2), 1.59 (s, 3H,−
C(CH3)2), 2.02 (s, 3H, N−CH3), 1.54 (dd, 1H, H-5a, J5a‑5b = 10.5, J5a‑4
= 5.0), 1.71−1.76 (m, 1H, H-2), 2.44 (dt, 1H, H-1′a, J1′a‑1′b = 13.5,
J1′a‑2 = J1′a‑P = 2.5), 2.72−2.77 (m, 1H, H-1′b), 3.03 (d, H-5b, 1H,),
4.18 (dd, 1H, H-4, J4−3 = 6.0), 4.51 (dd, 1H, H-3, J3−2 = 4.5), 7.01−
7.13 (m, 6H, Harom), 7.49−7.52 (m, 2H, Harom), 7.54−7.57 (m, 2H,
Harom). 13C NMR (125.7 MHz, C6D6): δ 25.7 (−C(CH3)2), 26.6
(−C(CH3)2), 26.7 (d, JC−P = 13.9, C-1′), 39.6 (N-CH3), 62.7 (C-5),
68.1 (d, JC−P = 20.6, C-2), 78.3 (C-4), 81.5 (d, JC−P = 3.6, C-3), 111.2
(-C(CH3)2), 128.4 (Carom), 128.6 (d, JC−P = 6.2, Carom), 128.8 (d, JC−P
= 6.8, Carom), 129.0 (Carom), 132.9 (d, JC−P = 18.1, Carom), 133.6 (d,
1
6). 31P NMR (161.9 MHz, C6D6): δ 142.2. H NMR (400 MHz,
C6D6): δ 0.43 (s, 3H, CH3, SiMe3), 0.46 (s, 15H, CH3, SiMe3), 1.09 (s,
3H, CH3), 1.46 (s, 3H, CH3), 1.57 (m, 2H, CH2−CHOP), 2.67 (dd,
1H, CH2, 2JH−H = 13.3 Hz, 3JH−H = 5.6 Hz), 2.78 (dd, 1H, CH2, 2JH−H
= 11.4 Hz, 3JH−H = 4.9 Hz) 2.90 (d, 1H, CH2, 2JH−H = 13.3 Hz), 3.15
(m, 2H, CH2, CH), 4.21 (m, 2H, CH−O), 4.37 (m, 1H, CH−OP),
6.81 (m, 2H, CH), 7.03 (m, 2H, CH), 7.18 (d, 1H, CH, 3JH−H
3
= 7.5 Hz), 7.30 (d, 1H, CH, JH−H = 10.3 Hz), 7.66 (m, 2H,
CH), 8.06 (s, 1H, CH), 8.08 (s, 1H, CH). 13C NMR (100.6
MHz, C6D6): δ −0.2 (CH3, SiMe3), 0.0 (CH3, SiMe3), 25.1 (CH3),
26.8 (CH3), 37.0 (CH2−CHOP), 59.5 (CH2), 61.3 (CH2), 70.5
(CH), 78.5 (CH−OP), 81.1 (CH−O), 84.9 (CH−O), 111.2 (C),
122.3−157.2 (Carom). Anal. Calcd for C36H44NO5PSi2: C, 65.72; H,
6.74; N, 2.13. Found: C, 65.88; H, 6.75; N, 2.11. TOF-MS (ESI+): m/
z calcd for C36H44NO5PSi2, 680.2388 [M + Na]+; found, 680.2389.
L7b. Yield: 53.2 mg (40%, reaction carried out using 0.20 mmol of
JC−P = 19.8, Carom), 139.7 (d, JC−P = 15.0, Carom−P), 140.4 (d, JC−P
=
13.4, Carom−P). HRMS (ESI): m/z calcd for C21H27NO2P, 356.1774
[M + H]+; found, 356.1768.
General Procedure for the Preparation of [Pd(η3-allyl)(P−
N)]BF4 (36−39). The ligand (0.05 mmol) and the complex [Pd(μ-
Cl)(η3-1,3-allyl)]2 (0.025 mmol) were dissolved in CD2Cl2 (1.5 mL)
at room temperature under argon. After 30 min, AgBF4 (9.8 mg, 0.05
mmol) was added, and the mixture was stirred for another 30 min. The
mixture was then filtered through Celite under argon, and the resulting
solutions were analyzed by NMR spectroscopy. The complexes were
precipitated as pale yellow solids by adding hexane.
1
6). 31P NMR (161.9 MHz, C6D6): δ 141.0. H NMR (400 MHz,
C6D6): δ 0.45 (s, 9H, CH3, SiMe3), 0.47 (s, 9H, CH3, SiMe3), 1.15 (s,
3H, CH3), 1.51 (m, 4H, CH3, CH2−CHOP), 1.68 (m, 1H, CH2−
2
3
CHOP), 2.65 (dd, 1H, CH2, JH−H = 13.1 Hz, JH−H = 5.8 Hz), 2.84
2
(m, 2H, CH2, CH2), 3.07 (t, 1H, CH, JH−H = 8.4 Hz), 3.18 (m, 1H,
CH2), 4.19 (d, 1H, CH−O, JH−H = 6.2 Hz), 4.30 (m, 1H, CH−O),
2
[Pd(η3-1,3-cyclohexenyl)(L1a)]BF4 (36). Yield: 37.7 mg (82%). MS
HR-ESI: m/z found 832.2227, calcd for C41H53NO5PPdSi2 (M −
BF4)+ 832.2229. Data for the major isomer (89%) are as follows. 31P
4.39 (m, 1H, CH−OP), 6.82 (m, 2H, CH), 7.03 (m, 2H, CH),
7.21 (d, 1H, CH, 3JH−H = 8.5 Hz), 7.33 (d, 1H, CH, 3JH−H = 8.5
Hz), 7.65 (m, 2H, CH), 8.07 (s, 1H, CH), 8.08 (s, 1H, CH).
13C NMR (100.6 MHz, C6D6): δ −0.2 (CH3, SiMe3), 0.0 (CH3,
1
NMR (161.9 MHz, CD2Cl2, 298 K): δ 140.7 (s, 1P). H NMR (400
MHz, CD2Cl2, 298 K): δ 0.51 (s, 9H, CH3, CH3−Si), 0.53 (s, 9H,
J
DOI: 10.1021/acs.organomet.8b00140
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
CH3, CH3−Si), 0.88−2.21 (m, 6H, CH2), 1.41 (s, 3H, CH3), 1.57 (s,
3H, CH3), 3.12 (s, 3H, CH3−N), 3.17 (m, 1H, CH), 3.37 (b, 1H, CH
allyl trans to N), 3.44 (bd, 1H, CH2−N, J = 12.4 Hz), 3.99 (dd, 1H,
(CH3−Si), 23.0 (CH3), 25.7 (CH3), 50.1 (CH3−N), 63.7 (CH2−N),
67.4 (d, CH2−O, JC−P = 4.0 Hz), 77.0 (CH), 78.4 (CH−O), 78.5
(CH−O), 79.8 (CH allyl trans to N), 98.0 (d, CH allyl trans to P, JC−P
= 35.7 Hz), 111.5 (d, CH allyl central, JC−P = 6.2 Hz), 113.2 (CMe2),
120.4−151.9 (Carom). Data for the minor isomer (30%) are as follows.
2
3
CH2−N, JH−H = 12.4 Hz, JH−H = 3.6 Hz), 4.42−4.49 (b, 2H, CH2−
O), 5.02 (m, 2H, CH−O), 5.41 (m, 1H, CH allyl central), 6.05 (m,
1H, CH allyl trans to P), 6.92 (d, 1H, CH, 3JH−H = 8.0 Hz), 7.12 (d,
1
31P NMR (161.9 MHz, CD2Cl2, 298 K): δ 140.2 (s, 1P). H NMR
3
1H, CH, JH−H = 8.4 Hz), 7.24 (m, 1H, CH), 7.31 (m, 1H,
(400 MHz, CD2Cl2, 298 K): δ 0.52 (s, 9H, CH3, CH3−Si), 0.76 (s,
9H, CH3, CH3−Si), 1.27 (s, 3H, CH3), 1.49 (s, 3H, CH3), 2.83 (m,
1H, CH), 2.84 (bd, 1H, CH2−N, J = 13.2 Hz), 2.57 (s, 3H, CH3−N),
4.08 (bd, 1H, CH2−N, J = 13.2 Hz), 4.56 (m, 1H, CH allyl trans to
N), 4.75 (m, 1H, CH2−O), 4.81 (m, 1H, CH2−O), 5.30 (m, 1H,
CH−O), 5.35 (m, 1H, CH−O), 5.59 (m, 1H, CH allyl trans to P),
6.82 (m, 1H, CH allyl central), 6.2−8.3 (m, 20H, CH). 13C NMR
(100.6 MHz, CD2Cl2, 298 K): δ 0.6 (CH3−Si), 0.7 (CH3−Si), 23.90
(CH3), 26.0 (CH3), 49.8 (CH3−N), 61.0 (CH2−N), 64.4 (b, CH2−
O), 75.4 (CH), 78.4 (CH−O), 78.5 (CH−O), 79.4 (CH allyl trans to
N), 103.9 (d, CH allyl trans to P, JC−P = 32.7 Hz), 114.4 (d, CH allyl
central, JC−P = 12.2 Hz), 114.5 (CMe2), 120.4−151.9 (Carom).
CH), 7.47 (m, 1H, CH), 7.55 (m, 1H, CH), 7.98 (d, 1H,
CH, 3JH−H = 8.0 Hz), 8.04 (d, 1H, CH, 3JH−H = 8.0 Hz), 8.19 (s,
1H, CH), 8.22 (s, 1H, CH). 13C NMR (100.6 MHz, CD2Cl2, 298
K): δ −0.1 (CH3−Si), 0.5 (CH3−Si), 19.9 (CH2), 24.4 (CH3), 26.0
(CH3), 27.0 (CH2), 28.2 (b, CH2), 51.4 (CH3−N), 65.5 (d, CH2−O,
JC−P = 6.1 Hz), 67.4 (d, CH allyl trans to N, JC−P = 8.4 Hz), 68.7
(CH2−N,), 75.2 (d, CH, JC−P = 2.3 Hz), 77.9 (CH−O), 79.8 (CH−
O), 106.1 (d, CH allyl trans to P, JC−P = 39.4 Hz), 113.6 (d, CH allyl
central, JC−P = 6 Hz), 114.7 (CMe2), 120.6−151.5 (Carom). Data for
the minor isomer (11%) are as follows. 31P NMR (161.9 MHz,
1
CD2Cl2, 298 K): δ 142.7 (s, 1P). H NMR (400 MHz, CD2Cl2, 298
[Pd(η3-1,3-diphenylallyl)(L4a)]BF4 (39). Yield: 44 mg (83%). MS
HR-ESI: m/z found 944.2537, calcd for C50H57NO5PPdSi2 (M −
BF4)+ 944.2542. Data for the major isomer (67%) are as follows. 31P
K): δ 0.46 (s, 9H, CH3, CH3−Si), 0.59 (s, 9H, CH3, CH3−Si), 0.88−
2.21 (m, 6H, CH2), 1.36 (s, 3H, CH3), 1.56 (s, 3H, CH3), 3.17 (m,
1H, CH), 3.22 (s, 3H, CH3−N), 3.37 (b, 1H, CH allyl trans to N),
2
3.44 (bd, 1H, CH2−N, J = 12.4 Hz), 3.92 (dd, 1H, CH2−N, JH−H
=
1
NMR (161.9 MHz, CD2Cl2, 298 K): δ 135.0 (s, 1P). H NMR (400
3
12.6 Hz, JH−H = 4.0 Hz), 4.42−4.51 (b, 2H, CH2−O), 5.02 (m, 2H,
MHz, CD2Cl2, 298 K): δ 0.45 (s, 9H, CH3, CH3−Si), 0.75 (s, 9H,
CH3, CH3−Si), 1.21 (s, 3H, CH3), 1.36 (s, 3H, CH3), 2.70 (s, 3H,
CH3−N), 3.22 (m, 1H, CH), 3.36 (dd, 1H, CH2−N, J = 14.0 Hz, J =
5.6 Hz), 3.72 (m, 1H, CH2−N), 4.50−4.64 (m, 2H, CH−O), 4.70 (m,
1H, CH2−O), 4.82 (m, 1H, CH allyl trans to N), 4.86 (m, 1H, CH2−
O), 5.32 (m, 1H, CH allyl trans to P), 6.57−6.67 (m, 1H, CH allyl
central), 5.8−8.3 (m, 20H, CH). 13C NMR (100.6 MHz, CD2Cl2,
298 K): δ 0.3 (CH3−Si), 0.7 (CH3−Si), 22.9 (CH3), 25.5 (CH3), 53.1
(CH3−N), 63.7 (CH2−O), 64.1 (CH2−N), 64.7 (CH allyl trans to
N), 76.0 (CH), 80.5 (CH−O), 80.8 (CH−O), 95.6 (d, CH allyl trans
to P, JC−P = 35.7 Hz), 111.5 (d, CH allyl central, JC−P = 11.4 Hz),
112.8 (CMe2), 120.3−151.7 (Carom). Data for the minor isomer (35%)
are as follows. 31P NMR (161.9 MHz, CD2Cl2, 298 K): δ 137.7 (s, 1P).
1H NMR (400 MHz, CD2Cl2, 298 K): δ 0.51 (s, 9H, CH3, CH3−Si),
0.66 (s, 9H, CH3, CH3−Si), 1.22 (s, 3H, CH3), 1.44 (s, 3H, CH3),
3.22 (m, 1H, CH3−N), 3.71 (m, 1H, CH2−N), 3.80 (m, 1H, CH2−
N), 4.01 (m, 1H, CH), 4.50−4.64 (m, 2H, CH−O), 4.69 (m, 1H,
CH2−O), 4.82 (m, 1H, CH2−O), 5.09 (m, 1H, CH allyl trans to N),
5.54 (m, 1H, CH allyl trans to P), 6.57−6.67 (m, 1H, CH allyl
central), 5.8−8.3 (m, 20H, CH). 13C NMR (100.6 MHz, CD2Cl2,
298 K): δ −0.2 (CH3−Si), 0.5 (CH3−Si), 22.4 (CH3), 24.0 (CH3),
48.6 (CH3−N), 61.7 (CH2−N), 63.7 (CH2−O), 62.9 (CH allyl trans
to N), 77.8 (CH), 80.5 (CH−O), 80.2 (CH−O), 94.8 (d, CH allyl
trans to P, JC−P = 36.5 Hz), 111.9 (d, CH allyl central, JC−P = 11.4 Hz),
113.0 (CMe2), 120.3−151.7 (Carom). Data for [Pd(η3-1,3-
diphenylallyl)(L4a)2]BF4 (8%) are as follows. MS HR-ESI: m/z
found 1589.5046, calcd for C85H101N2O10P2PdSi4 (M − BF4)+
1589.5038. 31P NMR (161.9 MHz, CD2Cl2, 298 K): δ 137.7 (s, 1P).
1H NMR (400 MHz, CD2Cl2, 298 K): δ 0.55 (s, 9H, CH3, CH3−Si),
CH−O), 5.83 (m, 1H, CH allyl central), 6.28 (m, 1H, CH allyl trans to
P), 6.98 (d, 1H, CH, 3JH−H = 8.0 Hz), 7.10 (d, 1H, CH, 3JH−H
=
8.0 Hz), 7.24 (m, 1H, CH), 7.28 (m, 1H, CH), 7.48 (m, 1H,
CH), 7.51 (m, 1H, CH), 7.98 (m, 1H, CH), 8.03 (d, 1H,
CH, 3JH−H = 8.0 Hz), 8.16 (s, 1H, CH), 8.20 (s, 1H, CH). 13
C
NMR (100.6 MHz, CD2Cl2, 298 K): δ 0.0 (CH3−Si), 0.5 (CH3−Si),
19.3 (CH2), 24.3 (CH3), 25.9 (CH3), 26.9 (CH2), 29.6 (CH2), 50.9
(CH3−N), 65.3 (d, CH2−O, JC−P = 10.2 Hz), 66.5 (b, CH allyl trans
to N), 69.6 (CH2−N,), 75.02 (b, CH), 79.3 (CH−O), 80.8 (CH−O),
104.6 (d, CH allyl trans to P, JC−P = 42.6 Hz), 113.9 (d, CH allyl
central, JC−P = 8 Hz), 116.1 (CMe2), 120.6−151.5 (Carom).
[Pd(η3-1,3-cyclohexenyl)(L1b)]BF4 (37). Yield: 35 mg (76%). MS
HR-ESI: m/z found 832.2233, calcd for C41H53NO5PPdSi2 (M −
BF4)+ 832.2229. Data for the major isomer (96%) are as follows. 31P
1
NMR (161.9 MHz, CD2Cl2, 298 K): δ 142.5 (s, 1P). H NMR(400
MHz, CD2Cl2, 298 K): δ 0.47 (s, 9H, CH3, CH3−Si), 0.55 (s, 9H,
CH3, CH3−Si), 0.88−1.17 (m, 3H, CH2), 1.35 (s, 3H, CH3), 1.58 (s,
3H, CH3), 1.59 (m, 1H, CH2), 1.82 (m, 1H, CH2), 2.12 (m, 1H,
CH2), 3.34 (s, 3H, CH3−N), 3.48 (m, 1H, CH), 3.59 (bd, 1H, CH2−
N, J = 13.6 Hz), 3.67 (m, 1H, CH allyl trans to N), 3.75 (dd, 1H,
2
3
CH2−N, JH−H = 13.6 Hz, JH−H = 5.6 Hz), 4.15 (m, 1H, CH2−O),
4.45 (m, 1H, CH2−O), 4.71 (m, 1H, CH−O), 4.96 (m, 1H, CH−O),
5.49 (m, 1H, CH allyl central), 6.14 (m, 1H, CH allyl trans to P), 6.94
(d, 1H, CH, 3JH−H = 8.8 Hz), 7.13 (d, 1H, CH, 3JH−H = 8.4 Hz),
7.22 (m, 1H, CH), 7.32 (m, 1H, CH), 7.47 (m, 1H, CH), 7.56
3
(m, 1H, CH), 7.99 (d, 1H, CH, JH−H = 8.4 Hz), 8.04 (d, 1H,
CH, 3JH−H = 8.0 Hz), 8.20 (s, 1H, CH), 8.23 (s, 1H, CH). 13
C
NMR (100.6 MHz, CD2Cl2, 298 K): δ 0.8 (CH3−Si), 20.7 (CH2),
23.8 (CH3), 26.4 (CH3), 27.4 (CH2), 28.5 (CH2), 53.4 (CH3−N),
66.4 (d, CH2−O, JC−P = 6.8 Hz), 67.2 (d, CH2−N, JC−P = 8.3 Hz),
67.8 (b, CH allyl trans to N), 75.9 (CH), 80.0 (CH−O), 81.2 (CH−
O), 106.6 (d, CH allyl trans to P, JC−P = 38.7 Hz), 113.4 (d, CH allyl
central, JC−P = 10.7 Hz), 114.2 (CMe2), 121.3−151.9 (Carom). Data for
the minor isomer (4%) are as follows. 31P NMR (161.9 MHz, CD2Cl2,
298 K): δ 141.8 (s, 1P).
0.63 (s, 9H, CH3, CH3−Si), 1.18 (s, 3H, CH3), 1.27 (s, 3H, CH3),
1.81 (m, 1H, CH3−N), 2.52 (m, 1H, CH), 2.87 (b, 2H, CH2−N),
4.50−4.64 (m, 2H; CH−O), 4.57 (m, 1H, CH2−O), 4.90 (m, 1H,
CH2−O), 5.85 (m, 2H, CH allyl terminal), 6.57−6.67 (m, 1H, CH
allyl central), 5.8−8.3 (m, 20H, CH). 13C NMR (100.6 MHz,
CD2Cl2, 298 K): δ −0.1 (CH3−Si), 0.0 (CH3−Si), 23.1 (CH3), 24.5
(CH3), 42.5(CH3−N), 60.7 (b, CH2−N), 69 (b, CH2−O), 76.9−77.1
(CH−O), 77.6−77.8 (CH), 99.9 (m, CH allyl terminal), 112.0 (b, CH
allyl central), 112.3 (CMe2), 120.3−151.7 (Carom).
[Pd(η3-1,3-diphenylallyl)(L1a)]BF4 (38). Yield: 40 mg (78%). MS
HR-ESI: m/z found 944.2539, calcd for C50H57NO5PPdSi2 (M −
BF4)+ 944.2542. Data for the major isomer (70%) are as follows. 31P
1
NMR (161.9 MHz, CD2Cl2, 298 K): δ 145.0 (s, 1P). H NMR (400
Study of the Reactivity of [Pd(η3-allyl)(L)]BF4 with Sodium
Malonate by in Situ NMR Spectroscopy.25 A solution of in situ
prepared [Pd(η3-allyl)(L)]BF4 (L = amino-phosphite, 0.05 mmol) in
CD2Cl2 (1 mL) was cooled in the NMR spectrometer to −80 °C. At
this temperature, a solution of cooled sodium malonate (0.1 mmol)
was added. The reaction was then followed by 31P NMR spectroscopy.
The relative reaction rates were calculated using a capillary that
contained a solution of triphenylphosphine in CD2Cl2 as the external
standard.
MHz, CD2Cl2, 298 K): δ 0.64 (s, 9H, CH3, CH3−Si), 0.67 (s, 9H,
CH3, CH3−Si), 1.27 (s, 3H, CH3), 1.39 (s, 3H, CH3), 2.57 (s, 3H,
CH3−N), 3.01 (bd, 1H, CH2−N, J = 13.6 Hz), 3.18 (m, 1H, CH),
4.09 (bd, 1H, CH2−N, J = 13.6 Hz), 4.59 (m, 1H, CH2−O), 4.93 (m,
1H, CH2−O), 5.22 (m, 1H, CH allyl trans to N), 5.30 (m, 1H, CH−
O), 5.31 (m, 1H, CH−O), 5.78 (m, 1H, CH allyl trans to P), 5.8
(m,1H, CH), 6.62 (m, 1H, CH allyl central), 6.2−8.3 (m, 19H,
CH). 13C NMR (100.6 MHz, CD2Cl2, 298 K): δ 0.5 (CH3−Si), 0.8
K
DOI: 10.1021/acs.organomet.8b00140
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Typical Procedure for the Allylic Alkylation of Disubstituted
Linear and Cyclic Substrates. A solution of [PdCl(η3-C3H5)]2 (0.9
mg, 0.0025 mmol) and the desired ligand (0.0055 mmol) in CH2Cl2
(0.5 mL) was prepared. After 30 min, a solution of the appropriated
substrate (0.5 mmol) in CH2Cl2 (1.5 mL), nucleophile (1.5 mmol),
N,O-bis(trimethylsilyl)acetamide (370 μL, 1.5 mmol), and KOAc (3
mg, 0.03 mmol) was added. Then, the reaction mixture was stirred at
room temperature during the time indicated in the text. The reaction
mixture was subsequently quenched by adding Et2O (5 mL) and
saturated NH4Cl(aq) (25 mL). The mixture was then extracted with
Et2O (3 × 10 mL), and the collected organic phases were dried over
2017. (b) Homogeneous Catalysts: Activity-Stability-Deactivation; van
Leeuwen, P. W. N. M., Chadwick, J. C., Eds.; Wiley-VCH: Weinheim,
Germany, 2011. (c) Catalytic Asymmetric Synthesis; Ojima, J., Ed.;
Wiley: Hoboken, NJ, 2010.
(2) For reviews, see: (a) Tsuji, J. In Palladium Reagents and Catalysis:
Innovations in Organic Synthesis; Wiley: New York, 1995. (b) Trost, B.
M.; van Vranken, D. L. Chem. Rev. 1996, 96, 395−422. (c) Johannsen,
M.; Jorgensen, K. A. Chem. Rev. 1998, 98, 1689−1708. (d) Pfaltz, A.;
Lautens, M. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Berlin, 1999; Vol. 2,
Chapter 24. (e) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33,
1
MgSO4. Conversions were measured by H NMR, and enantiomeric
́
336−345. (f) Martin, E.; Dieguez, M. C. R. Chim. 2007, 10, 188−205.
excesses were determined by HPLC (compounds 13, 15−22, and 26−
(g) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921−2944.
(h) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258−297.
1
28), GC (compounds 14 and 30−35), or H NMR using [Eu(hfc)3]
(compound 29). For characterization and ee determination details see
the Supporting Information.
́ ̀
(i) Dieguez, M.; Pamies, O. Acc. Chem. Res. 2010, 43, 312−322.
(j) Trost, B. M.; Zhang, T.; Sieber, J. D. Chem. Sci. 2010, 1, 427−440.
(k) Trost, B. M. Org. Process Res. Dev. 2012, 16, 185−194. (l) Butt, N.;
Zhang, W. Chem. Soc. Rev. 2015, 44, 7929−7967. (m) Grange, R. L.;
Clizbe, E. A.; Evans, P. A. Synthesis 2016, 48, 2911−2968. (n) Butt, N.;
Yang, G.; Zhang, W. Chem. Rec. 2016, 16, 2687−2696.
Typical Procedure for the Allylic Amination of Disubstituted
Linear Substrate S1. A solution of [PdCl(η3-C3H5)]2 (0.9 mg,
0.0025 mmol) and the desired ligand (0.0055 mmol) in CH2Cl2 (0.5
mL) was prepared. After 30 min, a solution of rac-1,3-diphenyl-3-
acetoxyprop-1-ene (S1; 0.5 mmol) in CH2Cl2 (1.5 mL), the desired
amine (1.5 mmol), N,O-bis(trimethylsilyl)acetamide (370 μL, 1.5
mmol), and KOAc (3 mg, 0.03 mmol) were added. Then, the reaction
mixture was stirred at room temperature for the time indicated in the
text. The reaction mixture was subsequently quenched by adding Et2O
(5 mL) and saturated NH4Cl(aq) (25 mL). The mixture was then
extracted with Et2O (3 × 10 mL), and the collected organic phases
were dried over MgSO4. Conversions were measured by 1H NMR, and
enantiomeric excesses were determined by HPLC. For characterization
and ee determination details see the Supporting Information.
(3) See: (a) Evans, D. A.; Campos, K. R.; Tedrow, J. S.; Michael, F.
́
E.; Gagne, M. R. J. Am. Chem. Soc. 2000, 122, 7905−7920 (up to 98%,
90%, and 65% ee at −20 °C for S1, S2, and S4, respectively).
(b) Nakano, H.; Okuyama, Y.; Hongo, H. Tetrahedron Lett. 2000, 41,
4615−4618 (up to 94% ee at −30 °C for S1). (c) García Mancheno,
̃
́ ́
O.; Priego, J.; Cabrera, S.; Gomez Arrayas, R.; Llamas, T.; Carretero, J.
C. J. Org. Chem. 2003, 68, 3679−3686 (up to 97% ee at −20 °C for
S1). (d) Enders, D.; Peters, R.; Runsink, J.; Bats, J. W. Org. Lett. 1999,
1, 1863−1866 (up to 97% ee at −20 °C for S1). (e) Guimet, E.;
Dieg
959−963 (up to 93% ee at 0 °C for S1). (f) Caldentey, X.; Pericas
A. J. Org. Chem. 2010, 75, 2628−2644 (up to 96% ee at room
temperature for S1). (g) Margalef, J.; Coll, M.; Norrby, P.-O.; Pamies,
O.; Dieguez, M. Organometallics 2016, 35, 3323−3335 (up to >99%
and 98% ee at room temperature for S1 and S2, respectively).
́
uez, M.; Ruiz, A.; Claver, C. Tetrahedron: Asymmetry 2005, 16,
̀
, M.
ASSOCIATED CONTENT
* Supporting Information
■
S
̀
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00140.
́
(4) See for instance: (a) Bunlaksananusorn, T.; Luna, A. P.; Bonin,
M.; Micouin, L.; Knochel, P. Synlett 2003, 2240−2242. up to 96% ee
for S1 (b) Ito, K.; Kashiwagi, R.; Iwsaki, K.; Katsuki, T. Synlett 1999,
1999, 1563−1566 (up to 96% ee for S1). (c) Goldfuss, B.;
1
31P{1H} and H and 13C{1H} NMR spectra of new
ligands L1a−d through L7a−d, Pd intermediates 36−39,
and ligand intermediates 1−4, 8, 10, and 12 (PDF)
Loschmann, T.; Rominger, F. Chem. - Eur. J. 2004, 10, 5422−5431
̈
(up to 83% ee for S1). (d) Liu, Q.-B.; Zhou, Y.-G. Tetrahedron Lett.
2007, 48, 2101−2104 (up to 95% ee for S1). (e) Meng, X.; Gao, Y.;
Li, X.; Xu, D. Catal. Commun. 2009, 10, 950−954 (up to 97% ee for S1
AUTHOR INFORMATION
Corresponding Authors
*E-mail for I.R.: robina@us.es.
■
and 80% ee for S2). (f) Leca, F.; Fernan
Reau, R.; Gomez, M. Eur. J. Inorg. Chem. 2009, 2009, 5583−5591 (up
to 12% ee and 31% ee for S1 and S2, respectively). (g) Lega, M.;
Margalef, J.; Ruffo, F.; Pamies, O.; Dieguez, M. Tetrahedron:
́
dez, F.; Muller, G.; Lescop, C.;
́
́
*E-mail for O.P.: oscar.pamies@urv.cat.
*E-mail for M.D.: montserrat.dieguez@urv.cat.
ORCID
̀
́
Asymmetry 2013, 24, 995−1000 (up to 50% ee for S1 and 86% ee
Montserrat Dieguez: 0000-0002-8450-0656
́
at 0 °C for S2).
(5) See for example: (a) Jang, H.-Y.; Seo, H.; Han, J. W.; Chung, Y.
K. Tetrahedron Lett. 2000, 41, 5083−5087. up to 98% ee for S1
(b) Lee, J. H.; Son, S. U.; Chung, Y. K. Tetrahedron: Asymmetry 2003,
14, 2109−2113 (up to 98% ee for S1). (c) Hu, X.; Dai, H.; Hu, X.;
Chen, H.; Wang, J.; Bai, C.; Zheng, Z. Tetrahedron: Asymmetry 2002,
13, 1687−1693 (up to 96% ee at 0 °C for S1). (d) Hu, X.; Dai, H.;
Chen, H.; Wang, J.; Bai, C.; Zheng, Z. Tetrahedron: Asymmetry 2004,
15, 1065−1068 (up to 99% ee at 0 °C for S1 and 73% ee for S2).
(e) Thiesen, K. E.; Maitra, K.; Olmstead, M. M.; Attar, S.
Organometallics 2010, 29, 6334−6342 (up to 94% ee for S1).
(f) Tsarev, V. N.; Lyubimov, S. E.; Bondarev, O. G.; Korlyukov, A.;
Antipin, M. Y.; Pretovskii, P. V.; Davankov, V. A.; Shiryaev, A. A.;
Benetsky, E. B.; Vologzhanin, P. A.; Gavrilov, K. N. Eur. J. Org. Chem.
2005, 2005, 2097−2105 (up to 97% ee for S1).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the Spanish Ministry of Economy and
Competitiveness (CTQ2016-74878-P and CTQ2016-77270-
R), the European Regional Development Fund (AEI/FEDER,
UE), the Catalan Government (2014SGR670 and
2017SGR1472), and the ICREA Foundation (ICREA Academ-
ia award to M.D.) is gratefully acknowledged. We also
acknowledge the Spanish Ministry of Economy and Com-
petitiveness for an FPU fellowship (P.E.-R.) and the CITIUS-
NMR-MS service of the University of Seville for technical
assistance.
(6) See, for instance: (a) Koga, K.; Kubota, H. Heterocycles 1996, 42,
543−547 (up to >95% ee for S1). (b) Jin, M.-J.; Jung, J.-A.; Kim, S.-H.
Tetrahedron Lett. 1999, 40, 5197−5198 (up to 98% ee at 0 °C for S1).
(c) Okuyama, Y.; Nakano, H.; Hongo, H. Tetrahedron: Asymmetry
2000, 11, 1193−1198 (up to 96% ee for S1). (d) Widhalm, M.;
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DOI: 10.1021/acs.organomet.8b00140
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
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DOI: 10.1021/acs.organomet.8b00140
Organometallics XXXX, XXX, XXX−XXX