Generating Active L-Pd(0) via Neutral or Cationic π-Allylpalladium Complexes Featuring Biaryl/Bipyrazolylphosphines: Synthetic, Mechanistic, and Structure-Activity Studies in Challenging Cross-Coupling Reactions

Article abstract of DOI:10.1021/acs.joc.5b01005

Two new classes of highly active yet air- and moisture-stable π-R-allylpalladium complexes containing bulky biaryl- and bipyrazolylphosphines with extremely broad ligand scope have been developed. Neutral π-allylpalladium complexes incorporated a range of biaryl/bipyrazolylphosphine ligands, while extremely bulky ligands were accommodated by a cationic scaffold. These complexes are easily activated under mild conditions and are efficient for a wide array of challenging C-C and C-X (X = heteroatom) cross-coupling reactions. Their high activity is correlated to their facile activation to a 12-electron-based L-Pd(0) catalyst under commonly employed conditions for cross-coupling reactions, noninhibitory byproduct release upon activation, and suppression of the off-cycle pathway to form dinuclear (μ-allyl)(μ-Cl)Pd₂(L)₂ species, supported by structural (single crystal X-ray) and kinetic studies. A broad scope of C-C and C-X coupling reactions with low catalyst loadings and short reaction times highlight the versatility and practicality of these catalysts in organic synthesis.

Full text of DOI:10.1021/acs.joc.5b01005

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Article
Generating Active “LPd(0)” via Neutral or Cationic pi-Allylpalladium
Complexes Featuring Biaryl/Bipyrazolylphosphines: Synthetic, Mechanistic
and Structure-Activity Studies in Challenging Cross-Coupling Reactions
Andrew J. DeAngelis, Peter G. Gildner, Ruishan Chow, and Thomas J. Colacot
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01005 • Publication Date (Web): 02 Jun 2015
Downloaded from http://pubs.acs.org on June 8, 2015
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Generating Active “LPd(0)” via Neutral or Cationic -
Allylpalladium Complexes Featuring Biaryl/Bipyrazolylphosphines:
Synthetic, Mechanistic and Structure-Activity Studies in Challenging
Cross-Coupling Reactions
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A. J. DeAngelis, Peter G. Gildner, Ruishan Chow, and Thomas J. Colacot*
Johnson Matthey Catalysis and Chiral Technologies, 2001 Nolte Dr., West Deptford, NJ 08066, United States.
ABSTRACT: Two new classes of highly-active, yet air- and moisture-stable -R-allylpalladium complexes containing bulky biaryl- and
bipyrazolylphosphines with extremely broad ligand scope have been developed. Neutral -allylpalladium complexes incorporated a range
of biaryl/bipyrazolylphosphine ligands, while extremely bulky ligands were accommodated by a cationic scaffold. These complexes are
easily activated under mild conditions and are efficient for a wide array of challenging CC and CX (X = heteroatom) cross-coupling
reactions. Their high activity is correlated to their facile activation to a 12 electron-based “L-Pd(0)” catalyst under commonly employed
conditions for cross-coupling reactions, non-inhibitory by-product release upon activation, and the suppression of the off-cycle pathway to
form dinuclear (-allyl)(-Cl)Pd (L) species, supported by structural (single crystal X-ray) and kinetic studies. A broad scope of CC and
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CX coupling reactions with low catalyst loadings and short reaction times highlight the versatility and practicality of these catalysts in
organic synthesis.
INTRODUCTION
Pd-catalyzed cross-coupling reactions have become arguably the most practiced reactions of the 21st century in modern synthetic organic
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chemistry. These reactions have been a benefactor to many areas of chemical research, as they are extensively utilized to prepare privi-
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leged structures for pharmaceutical, agrochemical, and electronics applications. Traditionally the presumed active catalyst in these trans-
formations, a ligated-Pd(0) complex, has been generated in situ by mixing a ligand with one of various Pd-precursors such as Pd (dba) or
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Pd(OAc) . The drawbacks and limitations of these methods are well documented in the literature. The original use and development of
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preformed L Pd(0) complexes for cross-coupling applications by Fu and our group, respectively, have helped to alleviate some of these
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issues, although these catalysts are air-sensitive and contain an extra ligand which is often not necessary for many catalytic processes (Fig-
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ure 1A). Hartwig has introduced the use of a monoligated Pd(I)-dimer {[P(t-Bu) ]PdBr} for relatively challenging cross-coupling reac-
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tions. However, this Pd(I) dimer complex is more air-sensitive in comparison to [P(t-Bu) ] Pd and has limitations with respect to ligand
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scope, which has hindered the development of a broad family of precatalysts.
Figure 1. Examples of preformed Pd-complexes used in cross-coupling.
To address the issues described above, the development and use of air-stable, preformed monoligated-Pd complexes (Figure 1B) has
become an emerging trend. These so-called “precatalysts” have been designed to generate the active monoligated 12-electron-based “L-
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Pd(0)” upon activation, ideally under the same conditions employed in cross-coupling reactions.
For example, Nolan has introduced
NHC-ligated -allylpalladium chloride (NHC = N-heterocyclic carbene) complexes for mild Suzuki-Miyaura and Buchwald-Hartwig ami-
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nation reactions, while Organ has utilized pyridine stabilization to synthesize precatalysts with similar ligand types (PEPPSI catalysts).
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Shaughnessy and Colacot together and independently described the preparation and use of phosphine-ligated -allylpalladium chlo-
ride complexes, which were shown to be highly efficient and superior in a variety of CC and CN cross-coupling reactions in comparison
to the in situ systems. Nolan has additionally described a phosphine-ligated -cinnamylpalladium complex for aryl amination reactions.
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Among the most versatile precatalysts available today are the ligated palladacycle precatalysts developed by Buchwald’s group and re-
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searchers at Merck. These complexes have been prepared with a large scope of ligand types across several generations, and are easily
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activated to generate “L-Pd(0)” quantitatively with excellent reactivity in a broad range of cross-coupling reactions.
Despite these
considerable advances, limitations still exist for certain applications/systems. For example, the synthesis and activation processes of
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aminobiphenyl-based palladacycles (2 and 3 generation) involve suspected carcinogens aminobiphenyl (starting material) and carbazole
(by-product), respectively; the presence of which can complicate reaction work-up from a product purification and safety point of view.
Furthermore, the reductively eliminated carbazole (Scheme 1A) can consume the aryl-electrophile starting material and also significantly
retard the rate of some cross-coupling reactions (vide infra). Recently, Buchwald et. al. have introduced N-substituted aminobiphenyl-
13e
based precatalysts to address some of these issues.
However, comparatively less toxicity data is available on N-substituted
aminobiphenyls and N-substituted carbazoles, and the scope of ligands that could be incorporated into these complexes is not as vast as
with their unsubstituted congeners. Herein, we report the synthesis and applications of two classes of highly active, yet air-stable -
allylpalladium precatalysts featuring either a neutral allylpalladium chloride or a cationic allylpalladium triflate platform, that together
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encompass an extremely broad ligand scope. Upon activation, -allylpalladium precatalysts release relatively benign substituted olefin
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by-products (Scheme 1B).
These systems address many of the above issues from a practical and technological perspective. Mechanis-
tic studies aimed at understanding the high efficiency of these precatalysts in accessing the active “L-Pd(0)” with respect to the effects of
the ligand, substitution on the allyl group, and the counterions are also discussed in detail.
Scheme 1. A) Activation of Palladacycle Precatalysts. B) Activation of -Allylpalladium Precatalysts.
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RESULTS AND DISCUSSION
Design and Synthesis of Pd(R-allyl)(L)Cl and [Pd(R-allyl)(L)]OTf complexes. Prior studies have demonstrated that upon treatment of
ligated allylpalladium chloride complexes with base, the resultant “L-Pd(0)” species can be consumed by the yet unreacted Pd(R-
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allyl)(L)Cl to form the (-allyl)(-Cl)-bridged dimer as shown in Scheme 2.
Recently, the groups of Balcells and Hazari have ele-
gantly studied the effects of allyl group substitution with respect to -allyl-bridged-dimer formation and catalytic activity with Nolan’s
Pd(R-allyl)(NHC)Cl complexes. They found that increased catalytic activity with substituted -allylpalladium complexes was correlated to
an increased barrier to dimer formation via comproportionation. Subsequent studies by Balcells and Hazari have revealed that the catalytic
activity of Pd(R-allyl)(NHC)Cl complexes is inversely related to the relative thermodynamic stability of the corresponding -allyl-bridged
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dimers. Although -allyl-bridged Pd(I)-dimers do function well as precatalysts in certain catalytic applications,
dimer formation is a
non-productive off-cycle pathway, and disproportionation back to L-Pd(0) (and the ligated allylpalladium(II) complex) is required for cata-
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lytic activity. We therefore rationalized that the incorporation of very sterically bulky ligands such as biarylphosphines or bipyrazol-
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ylphosphines into the -allylpalladium phosphine complex platform should help to avoid the formation of -allyl-bridged Pd(I)-dimers
upon activation through the intrinsic steric demand of these ligands, thereby providing highly-active precatalysts. Additionally, the excep-
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tionally high rate of oxidative addition of aryl halides to the catalysts generated using biarylphosphines should rapidly draw the active L-
Pd(0) into the catalytic cycle, thus disfavoring the non-productive comproportionation process.
Scheme 2. Mechanistic Rationale for the High Activity of R-Allylpalladium Complexes with Biaryl/Bipyrazolylphosphine
Ligands.
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Accordingly, we generated a library of allyl-, crotyl-, and cinnamyl -substituted palladium complexes with biaryl/bipyrazolyl-based
ligands (Table 1, left) in uniformly high yields (76 – 99%) as air- and moisture-stable complexes (1A – 6B) by reacting the appropriate
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ligand (L1 – L6) with [Pd(R-allyl)Cl] (R = H, Me, Ph) at room temperature.
Although these complexes were easily synthesized in
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high yield with the smaller ligands from the biaryl/bipyrazolylphosphine series (L1 – L6), attempts to incorporate the larger ligands of this
class (L7 – L12) were unsuccessful. It is known that Pd-centers bearing exceptionally sterically demanding ligands can, in some cases,
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force a counterion out of the metal coordination sphere. Given this, we hypothesized that a cationic -allyl-Pd precatalyst scaffold could
potentially accommodate extremely bulky biaryl/bipyrazolylphosphines. Although some examples of cationic [Pd(allyl)(L) ]X (n = 1, 2,
n
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bidentate) complexes have been reported, the synthetic procedures typically rely on either halide abstraction from the corresponding
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30l-m,31
Pd(allyl)(PR )Cl with an appropriate silver salt (e.g. AgOTf),
or by reacting a ligand with [Pd(MeCN) (allyl)]OTf.
The halide
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abstraction strategy was not feasible for our application as the required chloride complexes were challenging to prepare with extremely
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bulky ligands, while the instability of [Pd(MeCN) (allyl)]OTf (unstable above 20 °C) limited the practicality of the latter approach.
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Therefore, we turned our attention to pre-forming an allylpalladium complex functionalized with an easily dissociable counterion such as
triflate, followed by an in situ reaction with an appropriate ligand. This technique obviates the need for synthesizing Pd(allyl)(L)Cl starting
materials as well as avoids the isolation and handling of unstable “[Pd(R-allyl)]OTf” (14) intermediates. Indeed, stirring a mixture of
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[
Pd(allyl)Cl] with AgOTf for 30 min at room temperature, followed by the addition of a ligand (L4, L7 – L12) cleanly afforded R-
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allylpalladium triflate complexes 7A – 13A with high yields (84 – 99%) as air- and moisture-stable solids (Table 1, right). Using this
synthetic approach we incorporated both extremely bulky di-tert-butyl- (L7, L9 – L12) and di-1-adamantyl-substituted (L8) ligands, in-
cluding those with substitution on the phosphine-containing (top) aryl ring. Thus, utilizing either the chloride (neutral) or triflate (cationic)

-allylpalladium precatalyst scaffold, 27 new precatalyst compounds were synthesized and fully characterized, encompassing an extremely
broad scope of ligands.
Table 1. Synthesis of R-Allylpalladium Precatalysts with Ligands L1 – L12.
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In order to gain more insight into the structure of these complexes, single crystal X-Ray structures of allyl- and crotyl-substituted
RuPhos complexes 1A and 1B, as well as of [Pd(allyl)(tBuBrettPhos)]OTf 8A (Figure 2) were determined. In accord with previous studies,
the crotyl complex 1B features an elongated Pd-C3 bond relative to the analogous allyl complex 1A (2.26 Å vs. 2.19 Å), which has been
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previously correlated with more facile catalyst activation.
The X-ray structure of 8A confirms the cationic nature of the Pd, as the
triflate anion is dissociated from the metal center. (Pd – OTf distance = 4.31 Å) The Pd-center features a slightly distorted square planar
geometry; however, in contrast to complexes of type 1-6 where the chloride occupies the fourth coordination site of the Pd, in 8A the ipso-
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carbon of the triisopropylphenyl ring (Ci) from L7 occupies this site.
Figure 2. X-ray crystal structures of 1A, 1B, and 8A. Thermal ellipsoid plot at 50% probability (hydrogen atoms, co-crystals, and solvent
omitted for clarity).
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Application Studies. The Pd(R-allyl)(L)Cl complexes were studied in a variety of cross-coupling reactions by comparing their reactivity
with the corresponding palladacycles. We began our application studies by examining the amination of 4-chloroanisole with morpholine as
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a model reaction using RuPhos (L1)-based catalysts (Table 2) using reported reaction conditions. L1 has been previously shown by
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Buchwald to be an excellent ligand for aminations using secondary amines. Although the RuPhos G1 precatalyst showed good reactivity,
giving 66% conversion within 2 hours (Table 2, entry 1), the G2 and G3 precatalysts provided ≤ 5 % conversion (entries 2 and 3). Our -
allyl complexes 1A – 1C were highly active under the same conditions. In particular, crotyl (1B) and cinnamyl (1C) complexes gave the
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highest levels of conversion: 87% (100% at 2.5 hours with added L1 ) and 95%, respectively (entries 5-6). It has been previously shown
by Nolan as well as by our group that substituted -allyl complexes can be more easily activated in comparison to their unsubstituted ana-
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logues.
As G2 and G3 precatalysts release carbazole upon activation, we considered the possibility that this by-product was inhibiting
the reactions. To substantiate this hypothesis, 0.5 mol % of carbazole was added to the reactions employing RuPhos G1 or 1B as precata-
lysts, and low conversions (≤ 6%) were again observed (entries 7-8).
a
Table 2. Precatalyst Screen for the Amination of 4-Chloroanisole with Morpholine.
b
Entry
Catalyst
RuPhos G1
RuPhos G2
RuPhos G3
1A
Conversion (%)
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RuPhos G1
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Reaction conditions: 4-chloroanisole (1.0 mmol), morpholine (1.2 mmol), NaOt-Bu (1.2 mmol), catalyst (0.5 mol %), THF (2 mL). De-
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termined by GC using dodecane as an internal standard. With 0.5 mol % of carbazole added. With 0.5 mol % additional RuPhos added.
Reaction time was 2.5 h.
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We examined the versatility of catalyst 1B in a variety of amination reactions, and the results are summarized in Table 3. Fast reaction
rates with secondary amines were observed with 100% conversion reached within 1 – 2.5 hours (Table 3, top). For 15e, a milder base
(
K CO ) was required, demonstrating that strongly basic conditions are not necessary for catalyst activation. As BrettPhos (L4) has been
2 3
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demonstrated to be an excellent ligand for the monoarylation of primary amines, we also studied the primary amination reactions using
complex 7B (Table 3, bottom). For the reaction of 4-chloroanisole with n-butylamine at 0.3 mol % catalyst loading, complete and rapid
rd
conversion to product (15f) was observed within 10 min. In contrast, the reaction catalyzed by the L4-3 generation palladacycle precata-
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lyst was noticeably slower, requiring 2 hours for the reaction to reach completion. Similar to what we observed in secondary amination,
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carbazole was again identified as the cause of the rate retardation in primary amination, albeit to a lesser extent. Secondary aryl amines
5f – 15h were formed with fast reaction times (5 – 10 min) using primary aliphatic (entry 15f), aromatic (entry 15g), and optically active
-chiral (entry 15h) amines at 0.3 mol % catalyst loading. Notably, 15h was formed with high stereochemical fidelity (99% stereoreten-
1

4
1
tion), whereas erosion of enantiopurity of -chiral amines in Buchwald-Hartwig amination reactions can be problematic. Heterocyclic
substrates which contain more than one nitrogen atom were efficiently coupled in good to high yields using 1B or 7B (entries 15c, 15i –
1
5k) under slightly modified conditions. The similar yields of 15f observed using 7B and 7C (96%) demonstrate the interchangeability of
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crotyl- and cinnamyl-substituted complexes.
Table 3. Scope of Amination Reactions using 1B (2°-Amines) and 7B (1°-Amines).
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b
c
(0.5 mol %), THF (2 mL). 1 mol % 1B / 1 mol % RuPhos, K CO , 2-methyl-2-butanol, 110 °C, 18 h. General conditions for primary
2
3
amination: ArCl / HetArCl (1.0 mmol), amine (1.2 mmol), NaOt-Bu (1.2 mmol), 7B (0.3 mol %), L4 (0.3 mol %), THF (2 mL), 80 °C.
d
e
f
7
C (0.3 mol %) was used. Base was K CO (1.4 mmol), solvent was 2-methyl-2-butanol (2 mL), 110 °C. Base was LiHMDS (2.4
2 3
g
mmol), 7B (1.0 mol %), no added L4, 65 °C. 7B (1.2 mol %), L4 (1.2 mol %).
Previous work from our group demonstrated the effectiveness of -allylpalladium chloride complexes of AmPhos, Q-Phos, P(t-Bu) , and
3
1
1b
(t-Bu) NpP (Np = neopentyl) in Suzuki-Miyaura reactions. Our group was the first to show that these complexes could be activated in
2
1
1b
26
the presence of weak bases. Thus, we investigated the L3-based (XPhos) precatalyst 3B for Suzuki-Miyaura coupling reactions under
mild conditions. L3 has previously been shown to be an extremely useful ligand for Suzuki-Miyaura reactions, even with challenging un-
42
stable boronic acid/derivatives. Using precatalyst 3B, the coupling of 3-chloropyridine with p-tolylboronic acid gave 91% conversion in
1
3b
30 minutes, (Table 4, entry 1) while the XPhos G3 palladacycle was less active (65% conversion; entry 2) under reported conditions.
Interestingly, under these reaction conditions carbazole does not appear to have a negative effect on Suzuki-Miyaura reactions; the addition
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of 2 mol % of carbazole to the reaction catalyzed by 3B did not significantly affect the conversion (entry 3). Thus, the higher conversion
observed with 3B likely reflects the relative rates of catalyst activation.
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
a
Table 4. Precatalyst Evaluation for the Suzuki-Miyaura Coupling.
0
1
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9
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9
0
b
Entry
Catalyst
Pd(crotyl)(XPhos)Cl (3B)
XPhos G3
Conversion (%)
c
1
2
3
91 / 100
65
89
d
3B
a
Reaction conditions: 3-chloropyridine (1.0 mmol), p-tolylboronic acid (1.5 mmol), K PO (2.0 mmol), catalyst (2 mol %), THF (2 mL),
3
4
b
c
d
H O (4 mL). Determined by GC analysis. Run for 2 h. With 2 mol % of carbazole added.
2
The fast generation of the active “L-Pd(0)” catalyst using 3B has allowed a range of heteroaryl chlorides to be efficiently coupled with
1
3b
challenging aryl and heteroaryl boronic acids with uniformly high yields, including those which are prone to rapid protodeboronation, at
or slightly above room temperature (Table 5). For example, 2-thienylboronic acid, 2-furanboronic acid, and 2,6-difluorophenylboronic acid
(entries 16b, 16c, and 16d) were all coupled in high yields within 1 hour.
a
Table 5. Suzuki-Miyaura Coupling Reactions Using Precatalyst 3B.
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4
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9
0
1
2
3
4
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7
8
9
0
a
b
Reaction conditions: HetArCl (1.0 mmol), ArB(OH) (1.5 mmol), K PO (2.0 mmol), catalyst (2 mol %), THF (2 mL), H O (4 mL).
2
3
4
2
ArBr used, product isolated as the hydromethanesulfonate salt for ease of purification.
We also evaluated XPhos (L3) complexes 3A – 3C as well as the XPhos G3 palladacycle in the monoarylation of acetophenone (Fig-
4
3
ure 3). Rapid conversion (≥95%) within 1 hour to form 17a was observed using 3A – 3C, of which the allyl complex 3A was optimal
(98% conversion). Similar to what we observed in amination, the rate of conversion was significantly lower when G3 XPhos was em-
ployed as the precatalyst; 34% conversion was observed at 1 hour, and 4 hours were necessary to reach high conversion (93%). Carbazole
was again shown to retard the rate of the reaction as evidenced by the comparable lower activity of 3A with 1 mol% of carbazole added
relative to that of the XPhos G3 palladacycle. Four examples of ketone enolate arylations using 3A are highlighted in Table 6.
Figure 3. Catalyst comparison in the -arylation of acetophenone with 4-chloroanisole.
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Reaction conditions: 4-chloroanisole (1.0 mmol), ketone (1.2 mmol), KOt-Bu (2.4 mmol), Pd catalyst (1 mol %), toluene (4 mL), 60 °C, 4
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
h.
a
Table 6. Ketone Enolate Arylation Reactions Using 3A.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
b
Reaction conditions: Ar/HetArCl (1.0 mmol), ketone (1.2 mmol), KOt-Bu (2.4 mmol), 3A (1 mol %), toluene (4 mL), 60 °C, 2 – 4 h.
2
mol % of 3A used.
Catalyst systems based on very bulky tBuBrettPhos (L7), tBuXPhos (L9), RockPhos (L11), and BippyPhos (L12) exhibit excellent re-
activity in myriad challenging CX (X = heteroatom) cross-coupling reactions, particularly those with difficult reductive elimination
44
steps. Therefore, we evaluated our -allylpalladium catalysts 7 - 13 to effect such transformations utilizing known or modified reaction
4
4a
conditions, and the results are summarized in Table 7. The arylation of primary amides were highly efficient, giving aryl amide products
18a – 18e generally with high yields using 1.0 mol % of 8A. Notably, in the reaction to form 18a, the catalyst loading was lowered to 0.1
mol %, with no deleterious effect on yield, although a longer reaction time was required. Additionally, a cyclic secondary amide as well as
cyclic oxazolidinones proved to be excellent substrates with a catalyst loading of 1.5 mol %, for producing 19a – 19c in ≥ 95% yields.
Reported arylation reactions of 2-aminothiazoles using an L7-based catalyst required acetate additives to reach full conversion with unac-
4
5
tivated aryl electrophiles. However, our -allyl catalyst 8A provided a significant advantage: 2-aminothiazole was efficiently coupled
with 4-bromoanisole to produce N-aryl-2-aminothiazole 20 with 85% yield in the absence of acetate. Sulfonamides were also efficiently
coupled with nitrogen-containing heteroaryl halides in good yield at 1 mol% catalyst loading of 10A (entries 21a – 21c). Previous exam-
4
6
ples of sulfonamidation of heteroaryl electrophiles were limited to activated heteroaryl chlorides using high catalyst loadings (2 – 10
47
mol%) to achieve moderate yields, or required the use of aryl nonaflates. Various heterocycles were well tolerated in the CO coupling
4
4c
of heteroaryl halides with primary alcohols using 12A (entries 22a – 22b). Additionally the N-arylation of indoles proceeded in high
4
4d
yield using BippyPhos-based 13A (entries 23a – 23b).
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5
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6
a
Table 7. Challenging Cross-Coupling Reactions Using Various [Pd(allyl)(L)]OTf Complexes.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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8
9
0
1
2
3
4
5
6
7
8
9
0
a
b
General conditions: (hetero)aryl chloride (1.0 mmol), amide (1.2 mmol), 8A (1.0 mol %), K PO (1.4 mmol), t-BuOH (2 mL), 110 °C.
3
4
c
0.1 mol % of 8A used, 16 h reaction time. General conditions: (hetero)aryl chloride (1.0 mmol), amide (1.2 mmol), 8A (1.5 mol %),
d
K PO (1.4 mmol), t-BuOH (2 mL), 110 °C; Reaction conditions: 4-bromoanisole (1.0 mmol), 2-aminothiazole (1.2 mmol), 8A (1.5 mol
3
4
e
%
), K CO (1.4 mmol), t-BuOH (2 mL), 110 °C. General conditions: sulfonamide (1.0 mmol), heteroaryl chloride (1.2 mmol), 10A (1.0
2 3
f
mol %), K PO (1.5 mmol), 2-methyl-2-butanol (4 mL), 110 °C. General conditions: heteroaryl chloride (1.0 mmol), alcohol (1.5 mmol),
3
4
g
12A (1.0 mol %), K PO (1.5 mmol), toluene (1 mL), 100 °C. General conditions: (hetero)aryl chloride (1.0 mmol), indole (1.0 mmol),
3
4
h
1
3A (2.0 mol %), L12 (2.0 mol %), NaOt-Bu (1.4 mmol), toluene (4 mL), 110 °C. Aryl bromide used.
Mechanistic Studies on Carbazole Inhibition. In order to understand the negative effect of carbazole, we studied the cross-coupling of
morpholine with chlorobenzene as a model system using RuPhos G3 (Scheme 3A). Even after 1 hour at 80 °C, only 9 % GC conversion
3
1
was observed. P NMR analysis of the crude reaction mixture indicated the presence of a single phosphorus-containing species at 31 ppm.
An identical peak was also observed in the attempted cross-coupling of carbazole with chlorobenzene using 1B (Scheme 3B). Hence, we
48
postulated that this species was likely a stable L-Pd(Ar)carbazolyl complex, generated in catalysis via a competitive “transmetallation”
4
9-
between carbazole and the substrate (nucleophile) with the Pd(II)-oxidative addition intermediate. A high barrier to reductive elimination
5
1
from the resulting L-Pd(Ar)carbazolyl complex could be responsible for the observed diminished catalytic activity in the presence of
5
2
carbazole.
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Scheme 3. A) Cross-coupling of PhCl with Morpholine Catalyzed by RuPhos G3. B) Cross-Coupling of PhCl with
Carbazole Using by 1B. C) Preparation of L1-Pd(Ph)carbazol-9-yl (25).
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
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2
3
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3
4
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5
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5
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0
1
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0
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6
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8
9
0
1
2
3
4
5
6
7
8
9
0
5
3
To substantiate this hypothesis, we independently synthesized Pd-carbazol-9-yl complex 25 from 24 and carbazole as shown in Scheme
3
1
3C. The P NMR shift (31 ppm) of 25 confirms the presence of this species in the reactions of Scheme 3A and 3B. The X-ray crystal
structure of 25 was also determined, revealing that this complex contains a slightly distorted square planar Pd(II)-center (Figure 4), with a
36
stabilizing interaction between the Pd and the ipso-carbon of the nonphosphine-containing aryl ring. The Pd – N bond length (2.04 Å)
5
4
closely resembles those of other tricoordinate monoligated Pd-amido complexes reported by Hartwig (2.07 – 2.09 Å).
a
Figure 4. Crystal structure of 25. Thermal ellipsoid plot at 50% probability (hydrogen atoms, co-crystal, and solvent omitted for clarity).
a
Selected bond lengths: Pd – N: 2.04 Å; Pd – ipso C: 2.49 Å; Pd – C : 2.00 Å.
Ph
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55
The reductive elimination of 9-phenylcarbazole (26) from 25 was studied at 100 °C in toluene-d (using PhBr to trap L-Pd(0)), and first-
8
4
0
-4
-
order decay was observed (Figure 5). The half-life (t1/2) was found to be 91 minutes with a first-order rate constant of kobs = 1.17 10 sec
1
56
, indicating a relatively slow rate of reductive elimination. We note, however, that the rate of reductive elimination from complexes of
type 25 (as well as the extent of which carbazole inhibits reaction rates) will depend on several factors including temperature, ligand, and
substrate.
0
1
2
3
4
5
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9
0
1
2
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0
1
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5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 5. Thermal reductive elimination of 9-phenylcarbazole (26) from 25.
Mechanistic Study on Catalyst Activation Pathway. As previously mentioned, we hypothesized that the high reactivity of these al-
lylpalladium complexes containing biaryl/bipyrazolylphosphines may be a consequence of the suppression of -allyl-bridged Pd(I)-dimer
1
1,20
formation, a non-productive pathway by which active Pd(0) is sequestered from the reaction mixture.
To test this theory, we inde-
pendently synthesized the (-allyl)(-Cl)Pd (L) complex with biarylphosphine L2 (SPhos) using the method employed by Hazari for
2
2
2
0
synthesizing similar complexes with NHC ligands (Figure 6A). The X-ray structure of 27a, a (-allyl)(-Cl)-bridged Pd(I)-dimer derived
from L2 (SPhos), one of the smallest ligands in the biarylphosphine family (cone angle = 240°) , provides some insight into understanding
the catalyst activation pathway (Figure 6B). The complex crystallized in a conformation in which both cyclohexyl groups and the biaryl
groups are eclipsed, as they are oriented away from the -allyl group and the chlorine atom. Relatively short distances were observed be-
tween the cyclohexyl groups (3.867 Å) and between the non-phosphine containing aryl rings (3.922 Å) of the two SPhos ligands. Inspec-
tion of this structure reveals that replacement of cyclohexyl groups with more bulky groups (e.g. t-Bu) or increasing substitution on the
non-phosphine containing aryl ring (e.g. i-Pr) or the allyl moiety (e.g. Me) would result in increasingly unfavorable steric interactions. In
11b
contrast, in the X-ray crystal structure of (-allyl)(-Cl)Pd (AmPhos) 27b (Figure 6C) that we previously reported featuring the small-
2
2
er AmPhos ligand (cone angle 170°) , the closest points of contact between the two ligands are between the tert-butyl groups and are sig-
1
1a
nificantly more remote from one another (5.626 Å and 7.116 Å). Consistent with this trend, the -allyl-bridged Pd(I) dimer (27c) de-
rived from DTBNpP (not shown), a ligand which features a cone angle between those of SPhos and AmPhos (198°), has longer distances
between the ligands than the SPhos-derived 27a, but shorter than those of the AmPhos-derived 27b (closest contacts: 4.186 Å and 4.980
Å). Complex 27a is significantly bent as evidenced by the small Pd-Pd-P angles (∠ 154.7°), which is likely a result of minimization of the
steric interactions between the ligands. Analogous Pd-Pd-L angles for related (-allyl)(-Cl)-bridged Pd(I)-dimer complexes are compara-
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11b
11a
61
tively larger with AmPhos (∠ 168.8°), DTBNpP (∠ 156.3° – 161.3°), and the NHC ligand IPr (∠ 164.8°) (Table 8). Thus, we be-
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
lieve that (-allyl)(-Cl)Pd (L) complexes will become increasingly destabilized with increasing ligand size and/or substitution on the
2
2
allyl group due to steric strain, thereby retarding the non-productive comproportionation process.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 6. A. Synthesis of (-allyl)Pd (L) (-Cl) complex 27a. B. X-ray structure of 27a. Thermal ellipsoid plot at 50 % probability. Hy-
2
2
drogen atoms omitted for clarity. C. X-ray structure of 27b (from ref 11b). Thermal ellipsoid plot at 50% probability (hydrogen atoms, co-
crystals, and solvent omitted for clarity).
Table 8. Comparison of Pd-Pd-L Angles for -Allyl-Bridged Pd(I)-Complexes.
1
2
1
2
Entry
Ligand (L =L )
Ligand Cone
Angle (°)
Complex
Pd-Pd-L
∠
Pd-Pd-L ∠
(°)
(°)
1
SPhos (L2)
240
27a
154.7
154.7
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2
3
4
AmPhos (L13)
DTBNpP (L14)
IPr (L15)
170
198
-
27b
27c
27d
168.8
156.3
164.8
168.8
161.3
164.8
0
1
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9
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0
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9
0
1
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4
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8
9
0
To demonstrate the low reactivity of a -allyl-bridged Pd(I)-dimer in a catalytic application, the amination reaction of bromobenzene
with morpholine was studied using Pd(allyl)(SPhos)Cl (2A), Pd(crotyl)(SPhos)Cl (2B), and (-allyl)Pd (SPhos) (-Cl) (27a) as shown in
2
2
Table 9. The difference in reactivity between 2B and 27a was striking: after one hour at 40 °C the reaction employing Pd(I)-dimer 27a
only reached 8% (entry 1), while full conversion was observed in the reaction catalyzed by 2B (entry 2). Pd(allyl)(SPhos)Cl (2A) exhibited
intermediate reactivity with 49% conversion (entry 3), which is expected as 2A can comproportionate to form 27a upon activation.
a
Table 9. Comparison of Pd(R-allyl)(SPhos)Cl vs. (-allyl)(-Cl)Pd (SPhos) in Catalytic Aryl Amination.
2
2
b
Entry
Catalyst (2 mol% Pd)
(-allyl)(-Cl)Pd (SPhos) (27a)
GC Conversion
1
2
2
2
8%
Pd(crotyl)(SPhos)Cl (2B)
Pd(allyl)(SPhos)Cl (2A)
100%
49%
3
a
Reaction conditions: Bromobenzene (1.0 mmol), morpholine (1.2 mmol), NaOt-Bu (1.2 mmol), dodecane (GC standard, 0.2 mmol),
b
catalyst (2 mol% Pd), THF (1.5 mL), 40 °C, 1 hour. Determined by GC using dodecane as in internal standard.
In order to gain a better understanding of the catalyst activation process, a series of stoichiometric activation experiments were carried
out with selected R-allylpalladium complexes, and the results are summarized in Table 10. Thus, -allylpalladium complexes were activat-
ed with a slight excess of NaOt-Am at room temperature in the presence of PhBr to trap “L-Pd(0)”, and the relative amounts of oxidative
addition complex (A) and -allyl-bridged Pd(I)-dimer (B) were measured. In accord with our hypothesis, upon activation
Pd(allyl)(SPhos)Cl (2A) gave only 11% of the oxidative addition product A; instead the (-allyl)(-Cl)-bridged Pd(I)-dimer B was the
major product (44%), along with several as of yet unidentified species (entry 1). However, the analogous crotyl-complex of SPhos (2B)
reacted quickly to give 74% of the oxidative addition product (entry 2), demonstrating the significance of substitution on the allyl group for
precluding dimer formation. The presence of even larger ligands can override the necessity for substitution on the allyl group, as the
Pd(allyl)(BrettPhos)Cl complex (4A) is facilely activated with relatively clean formation (74%) of the oxidative addition product with no
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detectable amount of the (-allyl)-bridged dimer (entry 3). The analogous cationic complex to 4A, [Pd(allyl)(BrettPhos)]OTf (7A), formed
2
3
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6
7
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
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the oxidative addition product with higher efficiency (95%) (entry 4). -Allyl-complexes bearing the extremely bulky ligands tBuXPhos
and tBuBrettPhos rapidly and cleanly formed the oxidative addition products (92 – 100%) (entries 5-6) upon activation with NaOt-Am. In
these experiments, 4-bromobenzonitrile was used to trap the transient Pd(0) species. Similar experiments using bromobenzene did in fact
give rapid oxidative addition; however, the results were complicated by 3’-phenylation of the non-phosphine containing aryl ring of the
0
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ligand. These experiments substantiate our hypothesis that more sterically demanding phosphine ligands and substitution on the allyl
group hinder the formation of -allyl-bridged Pd(I)dimers, thereby allowing facile formation of the active “L-Pd(0)” species. Although we
have not studied the effects of cationic (OTf) vs neutral (Cl) complexes extensively, the enhanced reactivity with the former could be the
3
0k,
consequence of the increased electrophilicity of the cationic complexes,
bridged species with the more labile triflate counterion.
and/or the destabilization of the non-productive -allyl-
Table 10. Stoichiometric Activation of R-Allylpalladium Precatalysts.
a
a
Entry
Complex
A
B
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6
Pd(allyl)(SPhos)Cl (2A)
11%
74%
74%
95%
44%
0%
0%
0%
0%
0%
Pd(crotyl)(SPhos)Cl (2B)
Pd(allyl)(BrettPhos)Cl (4A)
[Pd(allyl)(BrettPhos)]OTf (7A)
[Pd(allyl)(tBuXPhos)]OTf (10A)
[Pd(allyl)(tBuBrettPhos)]OTf (8A)
b
92%
b
100%
a
31
b
Determined by relative P NMR integration. 4-Bromobenzonitrile was used to trap the L-Pd(0) intermediate.
CONCLUSIONS
In summary, we have developed two new classes of neutral and cationic -allylpalladium precatalysts featuring biar-
yl/bipyrazolylphosphines. A wide scope of Pd(R-allyl)(L)Cl complexes were synthesized with the less sterically encumbered members of
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this ligand class, while a cationic [Pd(R-allyl)(L)]OTf scaffold was engineered to accommodate extremely bulky ligands. These complexes
were easily prepared in high yields as air- and moisture-stable solids and exhibit excellent reactivity in several challenging CC and CX
cross-coupling processes, thus featuring key advantages over existing precatalyst technologies. Based on our mechanistic investigations,
the high activity observed in reactions catalyzed by these new precatalysts is rationalized by 1) the fast activation of these complexes to the
active “L-Pd(0)” catalyst under commonly employed catalytic conditions, 2) the release of non-inhibitory by-products, and 3) suppression
of the comproportionation pathway to form stable dinuclear (-allyl)-bridged Pd(I) dimers. Supported by mechanistic and crystallographic
studies, the diminished dimer formation is rationalized to be a consequence of the intrinsic steric demand of this ligand class in concert
with the fast rate of oxidative addition that biarylphosphine-based catalysts exhibit. Additionally, substitution on the -allyl group can
disfavor the comproportionation pathway with less sterically biased ligands. We believe that this comprehensive strategy can be applied to
generating precatalysts with many ligand systems which are not described in this report. Current studies aimed at exploring new reactions
using these precatalysts as well as further understanding of their structure-activity relationships, in particular the role of the -allyl-bridged
Pd(I)-complexes, are on-going in our laboratory.
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EXPERIMENTAL SECTION
General Information
All reactions were performed in glassware that was dried in a vacuum oven (55 – 65 °C, 80 Torr) using standard Schlenk techniques unless
noted otherwise. Anhydrous THF, toluene, 2-MeTHF, 2-methyl-2-butanol, and tert-butanol were purchased from commercial sources and
used as received. For use in a glove box, all solvents were further degassed by performing at least three freeze-pump-thaw cycles or by
sparging with nitrogen for 30 minutes. All aryl halides, boronic acids, ketones, and solid amines were purchased from commercial sources
and used as received unless otherwise noted. All liquid amines were passed through a plug of activated basic alumina prior to use in reac-
tions. [(allyl)PdCl] , [(crotyl)PdCl] , and [(cinnamyl)PdCl] , L1 – L12, RuPhos G1, RuPhos G2, RuPhos G3, and XPhos G3 were obtained
2
2
2
from our plant as most of them are commercially available from Johnson Matthey Catalysis and Chiral Technologies. AgOTf, NaOt-Bu,
K CO and anhydrous K PO were purchased from commercial sources and used as received. The bulk containers of these bases were
2
3
3
4
stored in a nitrogen-filled glove box. Small amounts up to 5 g were removed and stored on the bench top in a desiccator for up to 6 weeks.
1
Chromatographic separations were performed using 12 g silica cartridges. All isolated materials were ≥95% pure as measured by H NMR
1
13
19
31
unless otherwise noted. Reactions were analyzed by gas chromatography using dodecane as an internal standard. H, C, F and P NMR
1
13
spectra were recorded on a 400 MHz NMR spectrometer. All chemical shifts are reported in ppm. H and C spectra were calibrated using
1
13
1
residual solvent as an internal reference (CDCl : 7.26 ppm for H NMR and 77.16 ppm for C NMR, C D : 7.16 ppm for H NMR and
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1
3
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1
1
28.06 ppm C NMR, DMSO-d6: 2.50 ppm for H NMR and 39.52 ppm for C NMR, toluene-d8: 2.08 ppm for H NMR and 20.43 ppm
13
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19
for C NMR). All P NMR spectra were externally referenced to H PO (0.00 ppm). All F NMR spectra were externally referenced to
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CFCl (0.00 ppm). The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet,
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quint = quintet, sept = septet, m = multiplet, b = broad, app t = apparent triplet, app d = apparent doublet, br = broad. High-resolution mass
spectrometry (HRMS) was obtained on an oa-TOF spectrometer.
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General Procedure for the Synthesis of 1A – 6B
A dry Schlenk flask equipped with a Teflon-coated magnetic stir bar was charged with [(R-allyl)PdCl] (0.50 equiv) followed by the ap-
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propriate ligand L1 – L6 (1.00 equiv). The flask was fitted with a rubber septum and it was evacuated and backfilled with nitrogen. This
evacuation/nitrogen backfill cycle was repeated two additional times. Solvent (THF or toluene) was added via syringe and the reaction
mixture was stirred at rt for the appropriate time. Pentane (or hexanes) was then added to fully precipitate the product. The solid materials
were then collected by suction filtration, washed with additional pentane (or hexanes), and dried in vacuo.
Pd(allyl)(RuPhos)Cl (1A)
The general procedure was followed using 503 mg (1.43 mmol) of [(allyl)PdCl] , 1.29 g (2.77 mmol) of RuPhos (L1), and 2 mL of anhy-
2
drous THF with a stir time of 30 minutes. The product was precipitated by the addition of 10 mL of pentane with cooling in an ice bath (0
°C) to give 1.52 g (2.34 mmol, 85%) of the title compound as a yellow solid. X-ray quality crystals were grown by slow vapor diffusion
1
(
THF / hexanes). H NMR (400 MHz, C D , ): 7.60 (t, J = 8.7 Hz, 1H), 7.18 – 7.05 (m, 3H), 6.96 – 6.86 (m, 1H), 6.92 (d, J = 7.7 Hz,
6
6
1
1

H), 6.48 (dd, J = 7.5 Hz, 1H), 6.32 (d, J = 7.5 Hz, 1H), 5.03 – 4.91 (m, 1H), 4.49 (t, J = 7.4 Hz, 1H), 4.46 – 4.30 (m, 1H), 4.22 – 4.08 (m,
13
1
H), 3.37 – 3.22 (m, 1H), 3.01 (dt, J = 9.7 Hz, 13.4 Hz, 1H), 2.55 – 2.04 (m, 5H), 2.03 – 0.80 (m, 29H). C{ H} NMR (100 MHz, C D ,
6
6
): 157.2, 156.7, 141.3 (two peaks), 134.4, 134.3, 132.7, 132.6, 132.4, 132.1, 128.7 (two peaks), 128.3, 127.9, 125.4, 125.3, 122.5, 122.4,
115.3 (two peaks), 106.4, 105.5, 80.1, 79.8, 70.2, 69.9, 55.8, 36.2, 36.0, 35.5, 35.3, 29.5, 29.4, 27.1, 27.0, 26.2, 22.3, 22.2, 21.6, 21.3 [Ob-
3
1
1
served complexity due to CP coupling]. P{ H} NMR (162 MHz, CDCl , ): 34.6 (br). Anal. Calcd. for C H ClO PPd: C, 61.02; H,
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33 48
2
7
.45. Found: C, 60.87; H, 7.42.
Pd(crotyl)(RuPhos)Cl (1B)
The general procedure was followed using 1.02 g (5.08 mmol) of [(crotyl)PdCl] , 2.37 g (10.2 mmol) of RuPhos (L1), and 2.5 mL of an-
2
hydrous THF with a stir time of 2 hours. The product was precipitated by the addition of 10 mL of pentane to give 2.93 g (4.42 mmol,
1
8
7%) of the title compound as a light yellow solid. X-ray quality crystals were grown by slow vapor diffusion (THF / hexanes). H NMR
(
400 MHz, C D , ): 7.64 (t, J = 8.4 Hz, 1H), 7.24 – 7.09 (m, 3H), 7.06 – 7.00 (m, 1H), 6.50 (d, J = 7.9 Hz, 1H), 6.34 (d, J = 7.6 Hz, 1H),
6 6
1
3
4.90 – 4.80 (m, 1H), 4.58 – 4.45 (m, 1H), 4.31 – 4.18 (m, 1H), 3.82 – 3.70 (m, 1H), 3.34 – 3.26 (m, 1H), 2.57 – 0.80 (m, 38H).
C
1
NMR{ H} (100 MHz, C D , ): 157.4, 156.9, 142.3, 142.2, 133.9, 133.8, 132.8 (two peaks), 132.5, 128.9 (two peaks), 128.2, 125.6, 125.5,
6
6
1
22.7 (two peaks), 114.7 (two peaks), 106.3, 105.4, 99.4, 99.1, 70.2, 70.0, 50.7, 37.5, 37.3, 36.7, 36.5, 30.0, 29.2, 27.4, 27.3, 27.1, 26.4,
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1
2
2.5, 22.4, 21.6, 21.4, 17.4 (two peaks) [Observed complexity due to CP coupling]. P NMR{ H} (162 MHz, C D , ): 33.2 (br). HRMS
6
6
+
(ESI) m/z [M – Cl] Calcd. for C H O PPd: 627.2583; Found: 627.2554.
34 50 2
Pd(cinnamyl)(RuPhos)Cl (1C)
The general procedure was followed using 1.00 g (1.93 mmol) of [(cinnamyl)PdCl] , 1.80 g (3.86 mmol) of RuPhos (L1), and 4 mL of
2
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anhydrous THF with a stir time of 2 hours. The product was precipitated by the addition of 24 mL of pentane and was triturated for 1 hour
1
to give 2.13 g (2.94 mmol, 76%) of the title compound as a yellow solid. H NMR (400 MHz, CDCl , ): 7.78 – 7.68 (m, 1H), 7.46 (d, J =
3
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1
.5 Hz, 1H), 7.35 – 7.18 (m, 7H), 6.92 – 6.87 (m, 1H), 6.55 (d, J = 8.2 Hz, 2H), 5.72 – 5.58 (m, 1H), 4.91 – 4.77 (m, 1H), 4.52 – 4.39 (m,
1
3
1
H), 3.00 – 2.50 (m, 1H), 2.31 – 2.19 (m, 2H), 2.05 – 1.94 (m, 2H), 1.74 – 1.49 (m, 8H), 1.44 – 0.89 (m, 24H). C{ H} NMR (100 MHz,
CDCl , ): 156.9, 140.1, 137.1 (two peaks), 135.1, 132.8, 132.7, 131.8, 131.5, 128.7, 128.4, 127.5 (two peaks), 127.4, 125.2, 125.1, 122.4
3
(
two peaks), 109.7, 109.6, 106.0, 100.3, 100.0, 70.4, 52.6, 35.0, 24.8, 30.0, 29.2. 27.0, 26.9, 26.8, 26.0, 22.4, 22.0, 21.8 [Observed com-
3
1
1
+
plexity due to CP coupling]. P{ H} NMR (162 MHz, CDCl , ): 44.0 (br). HRMS (ESI) m/z [M – Cl] Calcd. for C H O PPd:
3
39 52
2
6
89.2740; Found: 689.2739.
Pd(allyl)(SPhos)Cl (2A)
The general procedure was followed using 4.46 g (12.2 mmol) of [(allyl)PdCl] , 10.0 g (24.4 mmol) of SPhos (L2), and 30 mL of anhy-
2
drous THF with a stir time of 30 minutes. The product was precipitated by the addition of 30 mL of pentane to give 14.1 g (23.8 mmol,
1
9
7
–
8%) of the title compound as a white solid. H NMR (400 MHz, CDCl , ): 7.65 (t, J = 8.6 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.33 (t, J =
3
.8 Hz, 1H), 7.30 – 7.22 (m, 1H), 7.06 (dd, J = 3.5 Hz, 8.2 Hz, 1H), 6.70 – 6.44 (m, 2H), 5.24 – 5.08 (m, 1H), 4.47 (t, J = 7.1 Hz, 1H), 3.82
1
3
1
3.60 (m, 6H), 3.40 – 3.22 (m, 1H), 3.02 (dd, J = 9.4 Hz, 13.7 Hz, 1H), 2.41 – 2.00 (m, 3H), 2.00 – 0.90 (m, 20H). C{ H} NMR (100
MHz, CDCl , ): 257.7, 157.4, 140.3, 140.2, 132.6, 128.6, 125.5, 119.1 (two peaks), 115.6, 115.5, 103.8, 102.8, 81.7, 81.4, 67.6, 55.0,
3
3
1
1
54.5, 35.9, 35.6, 29.4, 28.7, 27.0, 26.9, 26.7, 25.8, 25.3 [Observed complexity due to CP coupling]. P{ H} NMR (162 MHz, CDCl , ):
3
3
1.9. Anal. Calcd. for C H ClO PPd: C, 58.69; H, 6.79. Found: C, 58.68; H, 6.92.
29 40 2
Pd(crotyl)(SPhos)Cl (2B)
The general procedure was followed using 501 mg (1.27 mmol) of [(crotyl)PdCl] , 1.05 g (2.56 mmol) of SPhos (L2), and 5 mL of anhy-
2
drous THF with a stir time of 6 hours (reaction time not optimized). The product was precipitated by the addition of 10 mL of pentane to
1
give 1.28 g (2.11 mmol, 82%) of the title compound as a light yellow solid. H NMR (400 MHz, C D , ): 7.58 (t, J = 7.7 Hz, 1H), 7.47 –
6
6
7
.04 (m, 4H), 6.42 (d, J = 8.5 Hz, 1H), 6.28 (d, J = 8.3 Hz, 1H), 4.69 – 4.58 (m, 1H), 3.77 – 3.62 (m, 1H), 3.53 (s, 3H), 3.25 (s, 3H), 3.20
1
3
1
(d, J = 6.6 Hz, 1H), 2.52 – 2.29 (m, 2H), 2.20 – 1.15 (m, 24H). C{ H} NMR (100 MHz, C D , ): 158.0, 157.7, 141.8, 141.7, 133.4 (two
6
6
peaks), 133.2, 133.1, 132.0, 131.7, 129.1 (two peaks), 128.2, 125.6, 125.5, 119.8, 119.7, 114.1 (two peaks), 103.7, 102.8, 99.8, 99.6, 54.8,
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4.6, 48.4, 38.0, 37.8, 37.3, 37.1, 29.9, 28.5, 28.3, 27.4 (two peaks), 27.3, 27.1, 27.0 (two peaks), 26.9, 26.1, 17.1 (two peaks) [Observed
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complexity due to CP coupling]. P{ H} NMR (162 MHz, C D , ): 28.9. Anal. Calcd. for C H ClO PPd: C, 59.31; H, 6.97. Found: C,
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59.15; H, 7.17.
Pd(cinnamyl)(SPhos)Cl (2C)
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The general procedure was followed using 1.00 g (1.93 mmol) of [(cinnamyl)PdCl] , 1.59 g (3.86 mmol) of SPhos (L2), and 4.3 mL of
2
anhydrous toluene with a stir time of 1 hour. The product was precipitated by the addition of 10 mL of pentane to give 2.56 g (3.82 mmol,
1
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7
1
9%) of the title compound as a bright yellow solid. H NMR (400 MHz, CDCl , ): 7.68 (t, J = 8.5 Hz, 1H), 7.48 – 7.20 (m, 8H), 7.08 –
3
.02 (m, 1H), 6.60 (d, J = 8.3 Hz, 2H), 5.53 – 5.42 (m, 1H), 4.78 – 4.67 (m, 1H), 3.67 (s, 6H), 3.43 – 2.20 (m, 4H), 2.01 – 1.88 (m, 2H),
13
1
.80 – 1.51 (m, 8H), 1.46 – 1.05 (m, 10H). C{ H} NMR (100 MHz, CDCl , ): 157.8, 140.3, 140.2, 136.9, 136.8, 135.0, 134.9, 133.0
3
(
two peaks), 131.3, 131.0, 129.3, 129.0, 128.4, 128.4, 128.1, 127.6 (two peaks), 127.5, 125.7, 125.6, 119.4 (two peaks), 109.3, 109.2,
103.6, 101.7, 101.4, 55.3, 50.0, 36.1, 35.9, 29.8, 29.7, 29.2, 27.3, 27.2, 27.0, 26.9, 26.1 [Observed complexity due to CP coupling].
3
1
1
P{ H} NMR (162 MHz, CDCl , ): 37.4. Anal. Calcd. for C H ClO PPd: C, 62.78; H, 6.62. Found: C, 62.66; H, 6.54.
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2
Pd(allyl)(XPhos)Cl (3A)
The general procedure was followed using 858 mg (2.36 mmol) of [(allyl)PdCl] , 2.26 g (4.74 mmol) of XPhos (L3), and 5 mL of anhy-
2
drous THF with a stir time of 3 hours. The product was precipitated by the addition of 10 mL of pentane to give 3.04 g (4.62 mmol, 97%)
1
of the title compound as a light yellow solid. Product contains ~5 mol % of THF. H NMR (400 MHz, CDCl , ): 7.98 – 7.84 (m, 1H),
3
7
1
1
.40 – 7.27 (m, 2H), 7.07 – 6.99 (m, 3H), 5.47 – 5.26 (m, 1H), 4.54 (t, J = 7.1 Hz, 1H), 3.51 (dd, J = 9.3 Hz, 13.6 Hz, 1H), 3.12 – 3.01 (m,
13
1
H), 3.00 – 2.88 (m, 1H), 2.70 – 2.42 (m, 2H), 2.41 – 2.10 (m, 3H), 1.92 – 0.73 (m, 38H). C{ H} NMR (100 MHz, CDCl , ): 148.7,
3
46.2, 142.1, 136.6, 136.4, 136.3, 133.7, 133.6, 131.8, 131.6, 128.0 (two peaks), 125.5, 125.4, 120.7, 116.0, 116.0, 79.3, 79.0, 55.7, 34.4,
34.1, 33.9, 31.3, 30.4, 29.0, 27.1, 27.0, 26.8, 26.7, 25.6, 25.4, 23.9, 22.3 [Observed complexity due to CP coupling], peaks attributable to
3
1
1
THF were observed at 67.7, 25.8. P{ H} NMR (162 MHz, CDCl , ): 48.2 (br). Anal. Calcd. for C H ClPPd: C, 65.55; H, 8.25. Found:
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36 54
C, 65.79; H, 8.01.
Pd(crotyl)(XPhos)Cl (3B)
The general procedure was followed using 1.00 g (2.54 mmol) of [(crotyl)PdCl] , 2.42 g (5.08 mmol) of XPhos (L3), and 30 mL of anhy-
2
drous toluene with a stir time of 3 hours. 60 mL of pentane was added and the mixture was concentrated in vacuo. The residue was dis-
solved in 5 mL of toluene and precipitated by the addition of 20 mL of pentane to give 3.11 g (4.61 mmol, 91%) of the title compound as
1
an off-white solid. H NMR (400 MHz, CDCl , ): 7.99 – 7.86 (m, 1H), 7.38 – 7.29 (m, 2H), 7.18 – 6.99 (m, 3H), 5.19 – 5.03 (m, 1H),
3
1
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4.32 – 4.13 (m, 1H), 3.00 – 2.80 (m, 2H), 2.71 – 2.42 (m, 2H), 2.31 – 2.02 (m, 3H), 1.95 – 0.74 (m, 41H). C{ H} NMR (100 MHz,
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CDCl , ): 148.7, 146.3, 142.1, 136.9, 136.7, 136.5, 133.7, 133.6, 132.3, 132.0, 128.8, 128.0 (two peaks), 125.5, 125.4, 120.8, 115.0 (two
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peaks), 98.5, 98.2, 50.9, 34.8, 34.2, 31.4, 30.5 (two peaks), 29.2, 27.2, 27.1, 27.0, 26.9, 26.8, 25.8, 25.7, 24.0, 22.4, 17.2, 17.1 [Observed
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complexity due to CP coupling]. P{ H} NMR (162 MHz, CDCl , ): 50.8 (br). HRMS (ESI) m/z [M – Cl] Calcd. for C H PPd:
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637.3154; Found: 637.3153.
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Pd(cinnamyl)(XPhos)Cl (3C)
The general procedure was followed using 1.00 g (1.93 mmol) of [(cinnamyl)PdCl] , 1.84 g (3.86 mmol) of XPhos (L3), and 5 mL of an-
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hydrous toluene with a stir time of 1 hour. The product was precipitated by the addition of 10 mL of pentane to give 2.27 g (3.09 mmol,
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0%) of the title compound as a bright yellow solid. Product contains trace residual toluene. H NMR (400 MHz, CDCl , ): 8.10 – 7.95
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(m, 1H), 7.52 (d, J = 7.5 Hz, 2H), 7.42 – 7.23 (m, 5H), 7.11 – 7.01 (m, 3H), 5.87 – 5.69 (m, 1H), 5.20 – 5.06 (m, 1H), 3.08 – 2.90 (m, 2H),
13
1
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.73 – 0.70 (m, 43H), peaks attributable to toluene were observed at 7.17 and 2.36. C{ H} NMR (100 MHz, CDCl , ): 148.9, 146.4,
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142.1, 137.2, 136.9, 136.8, 136.7, 136.6, 133.8, 133.7, 132.4, 132.2, 129.0, 128.6, 128.4, 128.1, 127.6 (two peaks), 125.7, 125.6, 125.2,
21.0, 109.7, 109.6, 99.4, 99.1, 51.9, 34.5, 34.3, 31.7, 30.6, 29.2, 27.3, 27.2, 27.0, 26.9, 26.0, 25.7, 24.1, 22.5 [Observed complexity due to
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CP coupling], peaks attributable to toluene were observed at 137.7, 21.4. P{ H} NMR (162 MHz, CDCl , ): 54.3 (br). Anal. Calcd. for
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C H ClPPd: C, 68.56; H, 7.95. Found: C, 68.85; H, 7.93.
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Pd(allyl)(BrettPhos)Cl (4A)
The general procedure was followed using 502 mg (1.38 mmol) of [(allyl)PdCl] , 1.48 g (2.76 mmol) of BrettPhos (L4), and 6 mL of an-
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hydrous THF with a stir time of 1.5 hours. The product was precipitated by the addition of 6 mL of pentane to give 1.81 g (2.52 mmol,
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1%) of the title compound as an off-white solid. H NMR (400 MHz, CDCl , ): Complex spectrum, see supporting information. C{ H}
3
NMR (101 MHz, CDCl , ): 154.8, 153.4, 152.2, 151.6, 151.4, 150.9, 135.0, 134.8, 131.3, 124.8, 124.1, 123.8, 119.3, 119.2, 115.4, 113.8,
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113.0, 112.9, 100.5, 100.2, 56.04, 54.8, 51.9, 38.5, 38.3, 33.8, 32.2, 31.6, 30.5, 30.1, 27.2, 27.1, 26.8, 26.7, 25.8, 25.6, 25.0, 24.2, 23.9
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[
Observed complexity due to CP coupling]. P{ H} NMR (162 MHz, CDCl , ): 51.5. Anal. Calcd. for C H ClO PPd: C, 63.42; H,
3 38 58 2
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.12. Found: C, 63.31; H, 8.31.
Pd(allyl)(JohnPhos)Cl (5A)
The general procedure was followed using 1.00 g (2.75 mmol) of [(allyl)PdCl] , 1.64 g (5.50 mmol) of JohnPhos (L5), and 13 mL of an-
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hydrous toluene with a stir time of 1.25 hours. The product was precipitated by the addition of 26.5 mL of pentane to give 2.46 g (5.11
1
mmol, 93%) of the title compound as a yellow solid. H NMR (400 MHz, CDCl , ): 7.93 – 7.82 (m, 1H), 7.71 – 7.57 (m, 2H), 7.50 – 7.19
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m, 6H), 4.85 – 2.60 (br m, 5H), 1.90 – 1.10 (m, 18H). C{ H} NMR (100 MHz, CDCl , ): 149.0, 148.8, 142.2 (two peaks), 134.8, 134.6,
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133.6 (two peaks), 130.4, 129.8, 129.7, 129.6, 128.1, 126.3, 125.4, 125.3, 113.3, 113.2, 81.7 (br), 57.6 (br), 37.2, 30.9 [Observed complex-
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ity due to CP coupling]. P{ H} NMR (162 MHz, CDCl , ): 57.3. Anal. Calcd. for C H ClPPd: C, 57.39; H, 6.70. Found: C, 57.35; H,
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.53.
Pd(crotyl)(JohnPhos)Cl (5B)
The general procedure was followed using 1.00 g (2.54 mmol) of [(crotyl)PdCl] , 1.52 g (5.08 mmol) of JohnPhos (L5), and 12.5 mL of
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anhydrous toluene with a stir time of 1.25 hours. The product was precipitated by the addition of 25 mL of pentane to give 2.40 g (4.84
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mmol, 95%) of the title compound as a yellow solid. H NMR (400 MHz, CDCl , ): 7.87 (s, 1H), 7.75 – 7.50 (m, 2H), 7.50 – 7.10 (m,
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H), 4.23 – 3.98 (m, 1H), 3.83 – 3.60 (m, 1H), 3.11 – 2.99 (m, 1H), 1.76 – 1.20 (m, 22H). C{ H} NMR (101 MHz, CDCl , ): 149.0,
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48.8, 142.1 (two peaks), 135.0, 133.9 (two peaks), 130.4, 130.0, 129.8, 129.7, 127.9, 126.4, 125.2 (two peaks), 112.7 (two peaks), 100.3,
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00.0, 52.2, 37.7, 37.6, 37.3, 37.2, 31.7, 31.6, 30.5, 30.4, 17.7, 17.6 [Observed complexity due to CP coupling]. P{ H} NMR (162
MHz, CDCl , ): 57.1. Anal. Calcd. for C H ClPPd: C, 58.19; H, 6.92. Found: C, 57.91; H, 6.74.
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Pd(allyl)(CyBippyPhos)Cl (6A)
A dry 20 mL scintillation vial was charged with 245 mg (0.67 mmol) of [(allyl)PdCl] and transferred into a nitrogen-filled glove box. The
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vial was then charged with 750 mg (1.34 mmol) of CyBippyPhos (L6). 4 mL of toluene was added and the mixture was stirred at rt for 30
minutes. During the stir time, the mixture became thick and stirring was difficult. An additional 4 mL of toluene was added to allow stir-
ring to continue. The product was fully precipitated by the addition of 8 mL of hexanes. The solid was collected by vacuum filtration in air
and washed with 3 x 10 mL of hexanes. The solid was dried in vacuo to give 913 mg (1.23 mmol, 92%) of the title compound as an off-
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white solid. The product contains < 2 wt % of residual toluene. H NMR (400 MHz, CDCl , ): 7.99 (s, 1H), 7.44 – 7.18 (m, 15H), 6.68 –
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.55 (m, 1H), 5.30 – 4.99 (m, 1H), 4.60 – 4.50 (m, 1H), 3.54 – 3.33 (m, 1H), 2.88 – 2.78 (m, 1H), 2.20 – 0.77 (m, 22H), 0.48 – 0.30 (m,
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1H). C{ H} NMR (100 MHz, CDCl , ): 147.8, 147.5, 141.9, 140.6, 139.9, 139.8, 137.9, 137.1, 131.3, 131.1, 130.3, 129.3, 129.2, 129.1
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(two peaks), 128.7, 128.4, 128.3, 127.6, 127.4, 126.2, 126.1, 125.9, 125.3, 120.1, 117.2, 117.0, 116.8, 116.6, 80.6, 80.3, 57.5, 56.2, 34.2,
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3.9, 33.5, 33.3, 31.6, 30.7, 29.7, 29.5, 28.4, 28.2, 27.7, 27.1, 27.0, 26.9, 26.8, 26.6, 25.8, 25.3[Observed complexity due to CP coupling].
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P{ H} NMR (162 MHz, CDCl , ): 22.7 (br), 20.6 (br). Anal. Calcd. for C H ClN PPd: C, 63.16; H, 5.98; N, 7.55. Found: C, 63.13; H,
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.93; N, 7.30.
Pd(crotyl)(CyBippyPhos)Cl (6B)
A dry Schlenk flask was charged with 264 mg (0.67 mmol) of [(crotyl)PdCl] and transferred into a nitrogen-filled glove box. The flask
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was then charged with 750 mg (1.34 mmol) of CyBippyPhos (L6). 8 mL of toluene was added and the mixture was stirred at rt for 1 hour.
The product was precipitated by the addition of 20 mL of pentane with cooling in an ice bath. The solid was collected by vacuum filtration
in air, washed with 3 x 10 mL of hexanes, and dried in vacuo to give 904 mg (1.10 mmol, 83%) of the title compound as an off-white sol-
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id. The product is a 2/3 toluene adduct, which was broken by the dissolution in CH Cl and evaporating the solvent under reduced pressure
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at 60 °C. In solution 10 exists as a 1:1 mixture of diastereomers. H NMR (400 MHz, CDCl , ): 8.03 (app s, 1H, both diastereomers), 7.49
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– 7.12, m, 15H, both diastereomers), 6.62 – 6.55 (m, 1H, both diastereomers), 5.10 – 4.90 (m, 1H), 4.75 – 4.67 (m, 1H), 4.30 – 4.10 (m,
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H, both diastereomers), 2.75 – 2.70 (m, 1H, both diastereomers), 2.20 – 0.75, m, 25H, both diastereomers), 0.70 – 0.40 (m, 1H, both dia-
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stereomers). C{ H} NMR (101 MHz, CDCl , ): 147.2, 142.2, 142.0, 140.5, 140.4, 140.0, 139.9, 137.9, 137.6, 137.3, 137.1, 131.4,
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31.3, 130.4, 129.1 (two peaks), 129.0, 128.7, 128.6 (two peaks), 128.5, 128.2 (two peaks), 127.6, 127.5, 126.2 (two peaks), 126.1, 125.3,
20.1, 119.8, 116.9, 116.8, 116.4, 116.3, 115.8 (two peaks), 115.3 (two peaks), 100.9, 100.6, 100.4, 52.0, 50.6, 34.9, 34.7, 34.4, 34.1, 30.6,
29.9 (two peaks), 29.6, 29.5, 28.5, 28.3, 27.9, 27.7, 27.2, 27.0, 26.9, 26.8, 26.7, 26.6, 26.0, 25.8, 22.4, 21.5 [Observed complexity due to
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+
CP coupling]. P{ H} NMR (162 MHz, CDCl , ): 22.6 (br), 19.8 (br). HRMS (ESI) m/z [M – Cl] Calcd. for C H N PPd: 719.2495;
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Found: 719.2510.
General Procedures for the Synthesis of 7A – 13A
A dry Schlenk flask equipped with a Teflon-coated magnetic stir bar was charged with [(R-allyl)PdCl] (0.50 mmol, 0.50 equiv) followed
2
by AgOTf (257 mg, 1.00 mmol, 1.00 equiv). The flask was fitted with a rubber septum evacuated and backfilled with nitrogen. This evac-
uation/nitrogen backfill cycle was repeated two additional times. Solvent (10 mL THF or 2-MeTHF) was added and the reaction mixture
was stirred at rt for 30 min while protected from light. A second dry Schlenk flask was equipped with a magnetic stir bar, fitted with a
Schlenk frit, and charged with the appropriate ligand L4, L7 – L12 (1.00 mmol, 1.00 equiv). The flask was fitted with a rubber septum and
it was evacuated and backfilled with nitrogen. This evacuation/nitrogen backfill cycle was repeated two additional times. The solution
from the first Schlenk flask was transferred via cannula through the Schlenk frit (to remove AgCl) and into the second Schlenk flask con-
taining the ligand, rinsing with 5 mL of additional solvent (THF or 2-MeTHF). This mixture was stirred at rt for 2h. 30 mL of hexanes was
then added to fully precipitate the product. The solid materials were then collected by suction filtration, washed with additional pentane (or
hexanes), and dried in vacuo.
[Pd(allyl)(BrettPhos)]OTf (7A)
The general procedure was followed using 183 mg (0.50 mmol) of [(allyl)PdCl] , 257 mg (1.00 mmol) of AgOTf, 537 mg (1.00 mmol) of
2
BrettPhos (L4) in anhydrous THF to give 803 mg (0.94 mmol, 94%) of the title compound as a yellow solid. The material contains ~3 wt%
1
of THF. H NMR (400 MHz, CDCl , ): 7.34 (s, 1H), 7.23 (s, 1H), 7.07 – 6.98 (m, 1H), 6.96 – 6.87 (m, 1H), 5.45 (sept, J = 7.52 Hz, 1H),
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.14 (d, J = 6.8 Hz, 1H), 3.84 (s, 3H), 3.42 (dd, J = 8.2, 13.1 Hz, 1H), 3.29 (s, 3H), 2.90 (sept, J = 8.2 Hz, 1H), 2.79 – 2.63 (m, 1H), 2.59
(d, J = 13.2 Hz, 1H), 2.55 – 2.41 (m, 1H), 2.40 – 2.25 (m, 2H), 2.14 (sept, J = 7.8 Hz, 1H), 1.98 – 1.82 (m, 2H), 1.81 – 0.93 (m, 29H), 0.92
1
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–
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0.66 (m, 7H). C{ H} NMR (100 MHz, CDCl , ): 154.8 (two peaks), 153.3, 151.4, 150.5, 135.0, 134.8, 125.6, 124.9, 124.8, 124.2,
3
23.9, 122.4, 119.5, 119.4, 119.3, 115.2, 113.7, 112.7 (two peaks), 100.7, 100.5, 55.8, 54.7, 52.0, 38.5, 38.4, 38.3, 38.1, 33.7, 32.5, 31.5,
0.0, 27.2, 26.7, 26.6, 24.3, 24.0, 23.9, 23.8 [Observed complexity due to C–P and C–F coupling]; peaks attributable to THF were ob-
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served at 67.7 and 25.4. P{ H} NMR (162 MHz, CDCl , ): 51.4. F NMR (376 MHz, CDCl , ): ─78.4 (s, 3F). Anal. Calcd. for
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C H F O PPdS: C, 56.21; H, 7.02. Found: C, 56.46; H, 7.05.
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[Pd(crotyl)(BrettPhos)]OTf (7B)
The general procedure was followed using 1.97 g (5.00 mmol) of [(crotyl)PdCl] , 2.57 g (10.0 mmol) of AgOTf, 5.37 g (10.0 mmol) of
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BrettPhos (L4) in anhydrous THF (100 mL) to give 8.04 g (9.48 mmol, 95%) of the title compound as a yellow solid. The material con-
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tains ~2 wt% of THF. In solution 7B exists as a mixture of 4 isomers in a 57:26:13:4 ratio as judged by P NMR (X-ray crystallographic
analysis indicates the presence of both trans-crotyl and cis-crotyl isomers). 7.35 – 7.00 (m, 3H), 6.80 (d, J = 9.5 Hz, 1H), 5.48 – 5.37 (m,
0
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.09 H), 5.37 – 5.19 (m, 0.39 H), 4.90 – 4.78 (m, 0.50 H), 4.23 (d, J = 6.7 Hz, 0.51H), 3.97 (d, J = 7.7 Hz, 0.30 H), 3.90 – 3.80 (m, 3H),
.53 – 3.25 (m, 4H), 3.20 – 3.05 (m, 0.70 H), 3.04 – 2.75 (m, 1.44 H), 2.74 – 2.20 (m, 3H), 2.20 – 1.50 (m, 11H), 1.49 – 0.84 (m, 24 H),
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0.83 – 0.68 (m, 8 H) (observed complexity due to the presence of multiple isomers). C{ H} NMR (100 MHz, CDCl , ): 154.7 (two
3
peaks), 152.7, 152.5, 152.1, 151.8 (two peaks), 151.6, 148.9, 148.6, 125.2, 125.1, 122.8, 122.6, 115.2, 113.8 (two peaks), 112.7 (two
peaks), 108.4, 108.1, 55.9 (two peaks), 54.8, 54.7 (two peaks), 50.9, 39.2, 39.0 (two peaks), 38.8, 33.9, 33.6, 32.5, 32.4, 32.0, 31.7, 31.3,
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0.3, 30.2, 30.1, 27.3 (two peaks), 27.2 (two peaks), 27.1, 27.0, 26.9 (three peaks), 26.8 (three peaks), 26.7, 25.7, 25.5, 25.4, 25.3, 25.0,
4.2 (two peaks), 24.1, 24.0 (two peaks), 23.9, 23.8, 23.6, 23.0, 15.6, 15.5 (observed complexity due to C–P coupling, C–F coupling, and
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the presence of multiple isomers). P{ H} NMR (162 MHz, CDCl , ): 54.0, 52.2, 45.7, 43.3. F NMR (376 MHz, CDCl , ): ─78.2 (s,
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3F). Anal. Calcd. for C H F O PPdS: C, 56.70; H, 7.14. Found: C, 56.86; H, 7.42.
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[Pd(cinnamyl)(BrettPhos)]OTf (7C)
The general procedure was followed using 259 mg (0.50 mmol) of [(cinnamyl)PdCl] , 257 mg (1.00 mmol) of AgOTf, 537 mg (1.00
2
mmol) of BrettPhos (L4) in anhydrous 2-MeTHF to give 884 mg (0.97 mmol, 97%) of the title compound as a yellow solid. The structure
1
was confirmed by X-ray crystallographic analysis. H NMR (400 MHz, CDCl , ): 7.60 – 7.20 (m, 4H), 7.16 – 6.80 (m, 4H), 6.48 (s, 0.71
3
H), 5.91 – 5.77 (m, 0.17 H), 5.50 – 5.39 (m, 0.73 H), 4.80 (d, J = 10.5 Hz, 0.16 H), 4.51 (app t, J = 10.5 Hz, 0.74 H), 4.26 (d, J = 5.5 Hz,
0
.76 H), 4.13 – 4.02 (m, 0.24 H), 4.00 – 3.77 (m, 3H), 3.40 – 3.29 (m, 3H), 3.10 – 2.92 (m, 1H), 2.78 – 2.28 (m, 3 H), 2.20 – 0.45 (m, 38.2
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H) (observed complexity due to the presence of isomers). C{ H} NMR (100 MHz, CDCl , ):155.1, 154.8, 154.1, 152.8, 152.0, 151.8,
3
151.7, 148.4, 136.3, 136.1, 133.3, 133.2, 130.0, 129.9, 129.5, 125.9, 125.3, 124.7, 124.4, 124.2, 122.7, 121.8, 119.5, 116.2, 115.3, 115.1,
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13.9, 113.6, 112.8, 112.7 (two peaks), 112.4, 109.0, 108.9, 56.1, 55.6, 54.8, 49.2, 39.5, 39.3 (two peaks), 39.1, 34.1, 33.1, 32.7, 31.9,
1.7, 31.4, 31.1, 30.5, 30.3, 29.2, 28.9, 28.6, 27.6, 27.4, 27.3, 27.2 (two peaks), 27.1, 27.0, 26.5, 26.0, 25.8, 25.7, 24.3, 24.2, 22.4, 21.0
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(observed complexity due to CP and C–F coupling and presence of multiple isomers). P{ H} NMR (162 MHz, CDCl , ): 57.6, 39.5.
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F NMR (376 MHz, CDCl , ): ─78.1 (s, 3F). Anal. Calcd. for C H F O PPdS: C, 59.43; H, 6.87. Found: C, 59.26; H, 6.68.
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5
5
5
5
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6
[
Pd(allyl)(tBuBrettPhos)]OTf (8A)
The general procedure was followed using 183 mg (0.50 mmol) of [(allyl)PdCl] , 257 mg (1.00 mmol) of AgOTf, 485 mg (1.00 mmol) of
2
1
tBuBrettPhos (L7) in anhydrous THF to give 653 mg (0.84 mmol, 84%) of the title compound as a light yellow solid. H NMR (400 MHz,
CDCl , ): .7.34 (d, J = 2.5 Hz, 1H), 7.27 (d, J = 1.8 Hz, 1H), 7.09 (dd, J = 2.9 Hz, 9.0 Hz, 1H), 6.97 (d, J = 9.4 Hz, 1H), 5.53 (sept, J =
3
7
.1 Hz, 1H), 4.37 (app d, J = 6.3 Hz, 1H), 3.83 (s, 3H), 3.35 (dd, J = 9.2 Hz, 13.9 Hz, 1H), 3.32 (s, 3H); 2.96 (sept, J = 6.9 Hz, 1H), 2.79
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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7
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9
0
1
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7
8
9
0
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6
7
8
9
0
1
2
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7
8
9
0
(
(
app d, J = 12.4 Hz, 1H), 2.55 (sept, J = 6.7 Hz, 1H), 2.31 – 2.12 (m, 2H), 1.44 – 1.26 (m, 24H), 1.22 (dd, J = 6.9 Hz, 11.8 Hz, 6H), 0.85
13
1
d, J = 6.9 Hz, 3H), 0.71 (d, J = 6.9 Hz, 3H). C{ H} NMR (100 MHz, CDCl , ): 156.3, 154.6 (two peaks), 154.5, 152.2, 151.5, 151.4,
3
1
36.5, 136.2, 125.8, 125.7, 125.6, 125.4, 125.2, 122.6, 119.7, 119.6, 119.4, 116.2, 115.5 (two peaks), 112.8, 112.0 (two peaks), 99.8, 99.5,
58.4 (two peaks), 54.7, 54.6, 39.9, 39.8, 39.3, 39.1, 34.0, 32.1, 32.0, 31.9, 31.8, 31.6 (two peaks), 25.7, 25.5, 24.6, 24.5, 24.2 [Observed
3
1
1
19
complexity due to C–P and C–F coupling]. P{ H} NMR (162 MHz, CDCl , ): 86.8. F NMR (376 MHz, CDCl , ): ─77.9 (s, 3F). Anal.
3
3
Calcd. for C H F O PPdS: C, 53.81; H, 6.97. Found: C, 53.79; H, 7.10.
3
5
54
3
5
[Pd(crotyl)(tBuBrettPhos)]OTf (8B)
The general procedure was followed using 197 mg (0.50 mmol) of [(crotyl)PdCl] , 257 mg (1.00 mmol) of AgOTf, 485 mg (1.00 mmol) of
2
tBuBrettPhos (L7) in anhydrous 2-MeTHF to give 784 mg (0.99 mmol, 99%) of the title compound as a light yellow solid. A minor impu-
31
rity detected at 44.0 ppm integrating to 1% was observed in the P NMR spectrum. In solution 8B exists as a mixture of 3 isomers in a
3
1
1
5
5:31:14 as judged by P NMR. H NMR (400 MHz, CDCl , ): 7.38 – 7.05 (m, 3H), 6.95 (d, J = 7.6 Hz, 1H), 5.52 – 5.31 (m, 0.77 H),
3
4.98 – 4.85 (m, 0.29 H), 4.45 – 4.38 (m, 0.25 H), 4.18 (d, J = 7.7 Hz, 0.50 H), 3.71 – 3.68 (m, 3H), 3.39 – 3.22 (m, 3.75 H), 3.11 (d, J =
2.6 Hz, 0.86 H), 3.06 – 2.85 (m, 0.79 H), 2.65 – 2.45 (m, 1.36 H), 2.30 – 2.03 (m, 1H), 1.48 – 0.67 (m, 35.5 H) [observed complexity due
1
1
3
1
to the presence of multiple isomers]. C{ H} NMR (100 MHz, CDCl , ): 155.8, 155.4, 154.6 (two peaks), 154.5 (two peaks), 153.3,
3
1
51.7, 151.5, 151.4, 151.2, 149.1, 136.7, 136.5, 126.0, 125.9, 125.6, 125.1, 124.9, 123.7, 122.6, 121.3, 121.1, 119.4, 115.4, 114.6 (two
peaks), 113.2 (two peaks), 112.7 (two peaks), 112.6, 54.7, 54.6 (two peaks), 54.5, 50.6, 50.5, 40.6, 39.4, 39.3, 39.2, 39.1, 34.1, 33.8, 32.2,
32.1 (two peaks), 32.0, 31.9 (two peaks), 31.8 (two peaks), 31.6, 31.4, 31.3 (two peaks), 31.2, 26.3, 26.1, 25.6, 25.4, 25.1, 24.6, 24.4, 24.4,
3
1
1
2
4.3, 24.1, 24.0, 23.6, 17.1 (two peaks) (observed complexity due to C–P and C–F coupling and the presence of multiple isomers. P{ H}
1
9
NMR (162 MHz, CDCl , ): 90.1, 88.4, 83.9. F NMR (376 MHz, CDCl , ): ─78.0 (s, 3F). Anal. Calcd. for C H F O PPdS: C, 54.37;
3
3
36 56
3
5
H, 7.10. Found: C, 54.58; H, 7.01.
[Pd(cinnamyl)(tBuBrettPhos)]OTf (8C)
The general procedure was followed using 259 mg (0.50 mmol) of [(cinnamyl)PdCl] , 257 mg (1.00 mmol) of AgOTf, 485 mg (1.00
2
1
mmol) of tBuBrettPhos (L7) in anhydrous 2-MeTHF to give 812 mg (0.95 mmol, 95%) of the title compound as a dark yellow solid. H
NMR (400 MHz, CDCl , ): 7.60 – 7.47 (m, 1H), 7.36 – 7.27 (m, 2H), 7.15 – 6.80 (m, 5H), 6.50 – 4.30 (m, 3H), 3.85 (s, 3H), 3.28 (s, 3H),
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.95 – 1.98 (m, 3H), 1.90 – 1.66 (m, 1H), 1.61 – 0.50 (m, 37 H). C{ H} NMR (100 MHz, CDCl , ): 161.8, 154.5, 153.7, 151.7, 151.6,
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2
3
4
5
6
7
8
9
1
1
1
1
1
1
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1
1
2
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2
2
2
2
2
2
2
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49.9, 143.6, 137.5, 137.2, 133.4, 129.5, 125.7, 122.6, 119.4, 115.4, 112.9, 112.6 (two peaks), 110.6, 109.0, 88.9, 72.8, 55.0, 54.6, 54.4,
41.2, 41.1, 40.3, 40.1, 32.1, 30.9, 25.8, 25.5, 25.1, 24.7, 24.4, 24.3, 22.3 [observed complexity due to C–P coupling and C–F coupling].
3
1
1
19
P{ H} NMR (162 MHz, CDCl , ): 94.5. F NMR (376 MHz, CDCl , ): ─77.9 (s, 3F). Anal. Calcd. for C H F O PPdS: C, 57.44; H,
3
3
41 58
3
5
6
.82. Found: C, 57.04; H, 6.77.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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7
8
9
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7
8
9
0
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9
0
[Pd(allyl)(AdBrettPhos)]OTf (9A)
The general procedure was followed using 57.1 mg (0.156 mmol) of [(allyl)PdCl] , 80.2 mg (0.312 mmol) of AgOTf, 200 mg (0.312
2
mmol) of AdBrettPhos (L8) in anhydrous THF to give 265 mg (0.281 mmol, 90%) of the title compound as a tan solid. The product con-
1
tained ~ 2 wt% of THF. H NMR (400 MHz, CDCl , ): 7.40 (s, 1H), 7.35 (s, 1H), 7.17 (dd, J = 2.3 Hz, 8.7 Hz, 1H), 7.04 (app d, J = 9.1
3
Hz, 1H), 5.60 (sept, J = 6.8 Hz, 1H), 4.54 (d, J = 6.2 Hz, 1H), 3.94 (s, 3H), 3.45 – 3.35 (m, 4H), 3.04 (quint, J = 7.0 Hz, 1H), 2.85 (d, J =
12.0 Hz, 1H), 2.63 (quint, J = 6.3 Hz, 1H), 2.39 – 1.91 (m, 18H), 1.81 – 1.60 (m, 12H), 1.42 – 1.19 (m, 13H), 0.99 – 0.82 (m, 4H), 0.78 (d,
1
3
1
J = 6.7 Hz, 3H). Resonances attributable to THF were observed at 3.76 and 1.83 ppm. C{ H} NMR (100 MHz, CDCl , ): 157.1, 154.8,
3
1
9
54.6, 152.6, 151.7, 151.5, 137.1, 136.8, 125.9, 125.3, 124.6, 124.4, 119.3 (two peaks), 115.4, 112.9, 112.8, 112.0 (two peaks), 100.2,
31
1
9.9, 58.1, 54.7, 45.6, 44.8, 44.7, 42.0, 36.3, 36.2, 34.4, 31.7, 29.2, 26.0, 25.6, 25.5, 24.9, 24.6, 24.3 (two peaks). P{ H} NMR (162
19
+
MHz, CDCl , ): 88.9. F NMR (376 MHz, CDCl , ): ─77.9 (s, 3F). HRMS (ESI) m/z: [M – OTf + H] Calcd. for C H O PPd:
3
3
46 66
2
7
87.3835. Found: 787.3832.
[Pd(allyl)(tBuXPhos)]OTf (10A)
A dry Schlenk flask equipped with a Teflon-coated magnetic stir bar was charged with 3.66 g (10.0 mmol) of [(allyl)PdCl] , 5.14 g (20.0
2
mmol) of AgOTf. The flask was fitted with a rubber septum and evacuated and backfilled with nitrogen. This evacuation/backfill cycle
was repeated two additional times. Anhydrous THF (40 mL) was added and the mixture was stirred at rt for 30 min while protected from
light. A second dry Schlenk flask was charged with 8.49 g (20.0 mmol) of tBuXPhos (L9), and fitted with a rubber septum. The flask was
evacuated and backfilled with nitrogen. This evacuation/backfill cycle was repeated two additional times. Anhydrous THF (40 mL) was
added and the contents were swirled and all of L9 had dissolved. This solution was transferred into the first Schlenk flask via cannula rins-
ing with 5 mL of additional anhydrous THF. The mixture was stirred at rt for 1.5 hours, and the contents were then filtered through a dis-
posable frit (to remove AgCl) into a round-bottomed flask. To the resulting clear solution was added 170 mL of hexanes with agitation as
solids precipitated The solid was collected by vacuum filtration, washed (2 x 50 mL of hexanes), and dried in vacuo to give 12.5 g (17.2
1
mmol, 86%) of the title compound as a light yellow solid. Product contains ~0.5 wt % of THF. H NMR (400 MHz, CDCl , ): 7.92 (t, J =
3
7.3 Hz, 1H), 7.59 – 7.45 (m, 3H), 7.42 (s, 1H), 6.80 (dd, J = 3.2 Hz, 7.5 Hz, 1H), 5.71 (sept, J = 7.2 Hz, 1H), 4.49 (d, J = 6.7 Hz, 1H), 3.54
(dd, J = 9.0 Hz, 14.0 Hz, 1H), 3.03 (quint, J = 7.1 Hz, 1H), 2.93 (d, J = 12.9 Hz, 1H), 2.69 – 2.61 (m, 1H), 2.50 (quint, J = 7.1 Hz, 1H),
1
3
1
2
.26 (J = 6.9 Hz, 1H), 1.52 – 1.41 (m, 9H), 1.41 – 1.27 (m, 21H), 0.96 (d, J = 6.7 Hz, 3H), 0.86 (d, J = 6.7 Hz, 3H). C{ H} NMR (100
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MHz, CDCl , ): 153.6, 152.7, 149.2, 146.0, 145.8, 135.1 (two peaks), 134.9, 133.7, 133.6, 131.7, 131.6, 128.3, 128.2, 126.6, 126.2, 125.8,
3
1
22.6, 120.3 (two peaks), 120.1 (two peaks), 119.4, 116.2, 101.3, 101.1, 55.5, 38.3 (two peaks), 38.2, 38.1, 33.9, 32.0, 31.7, 31.2, 31.1,
3
1
1
30.9, 30.8, 25.9, 25.4, 24.9, 24.5 (two peaks), 24.1 [Observed complexity due to C–P and C–F coupling]. P{ H} NMR (162 MHz,
1
9
CDCl , ): 70.1. F NMR (376 MHz, CDCl , ): ─78.1 (s, 3F). Anal. Calcd. for C H F O PPdS: C, 54.96; H, 6.99. Found: C, 54.72; H,
3
3
33 50
3
3
6
.79.
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[Pd(crotyl)(tBuXPhos)]OTf (10B)
A dry Schlenk flask equipped with a Teflon-coated magnetic stir bar was charged with 1.97 g (5.00 mmol) of [(crotyl)PdCl] , 2.57 g (10.0
2
mmol) of AgOTf. The flask was fitted with a rubber septum and evacuated and backfilled with nitrogen. This evacuation/backfill cycle
was repeated two additional times. Anhydrous 2-MeTHF (20 mL) was added and the mixture was stirred at rt for 30 min while protected
from light. A second dry Schlenk flask was charged with 4.25 g (10.0 mmol) of tBuXPhos (L9), and fitted with a rubber septum. The flask
was evacuated and backfilled with nitrogen. This evacuation/backfill cycle was repeated two additional times. Anhydrous 2-MeTHF (20
mL) was added and the contents were swirled and all of L9 had dissolved. This solution was transferred into the first Schlenk flask via
cannula rinsing with 5 mL of additional anhydrous 2-MeTHF. The mixture was stirred at rt for 2 hours, and the contents were then filtered
through a disposable frit (to remove AgCl) into a round-bottomed flask. To the resulting clear solution was added 90 mL of heptane with
agitation as solids precipitated over 1 hour. The solid was collected by vacuum filtration, washed (2 x 20 mL of heptane), and dried in
vacuo to give 6.55 g (8.90 mmol, 89%) of the title compound as a yellow solid. In solution, 10B exists as a mixture of 3 isomers in a
3
1
1
1
6
7:24:9 ratio as judged by P NMR and H NMR. H NMR (400 MHz, CDCl , ): 7.99 – 7.89 (m, 1H), 7.60 – 7.28 (m, 4H), 6.87 – 6.74
3
(m, 1H), 5.71 – 5.53 (m, 0.81 H), 5.23 – 5.10 (m, 0.32 H), 4.62 – 3.89 (m, 0.26 H), 4.38 (d, J = 6.8 Hz, 0.59 H), 3.89 – 3.79 (m, 0.62 H),
3
.75 – 3.59 (m, 0.33 H), 3.30 – 3.14 (m, 1H), 3.13 – 3.03 (m, 0.72H), 2.80 (d, J = 8.2 Hz, 0.39H), 2.60 – 2.49 (m, 0.41 H), 2.47 – 2.34 (m,
1
3
1
0.57 H), 2.33 – 2.11 (m, 1H), 1.61 – 0.75 (m, 39 H) [observed complexity due to presence of multiple isomers]. C{ H} NMR (100 MHz,
CDCl , ): 153.7, 153.4, 152.8, 152.3, 151.9, 146.4, 146.2, 146.0, 145.8, 144.1, 135.0, 134.9, 134.7, 134.4, 134.1, 133.7, 133.5, 133.3,
3
1
1
2
33.2, 131.5, 131.4 (two peaks), 128.1 (two peaks), 128.0, 126.4, 125.7, 124.1, 122.9, 121.4, 120.4, 119.7, 119.3, 117.4, 116.1, 112.9,
12.8, 48.3, 38.9, 38.8, 38.1, 37.5, 37.3, 33.8, 33.5, 32.9, 31.6, 31.3, 31.1 (two peaks), 31.0 (two peaks), 30.7 (two peaks), 26.2, 24.9, 24.8,
4.5, 24.3, 24.2, 24.0 (two peaks), 23.7, 23.4, 22.8, 20.8, 17.0, 16.4 (two peaks) [observed complexity due to C–P coupling, C–F coupling,
3
1
1
19
and the presence of multiple isomers]. P{ H} NMR (162 MHz, CDCl , ): 72.1, 71.7, 66.7. F NMR (376 MHz, CDCl , ): ─77.9 (s,
3
3
3F). Anal. Calcd. for C H F O PPdS: C, 55.54; H, 7.13. Found: C, 55.71; H, 6.96.
3
4
52
3
3
[Pd(cinnamyl)(tBuXPhos)]OTf (10C)
The general procedure was followed using 259 mg (0.50 mmol) of [(cinnamyl)PdCl] , 257 mg (1.00 mmol) of AgOTf, 485 mg (1.00
2
mmol) of tBuXPhos (L9) in anhydrous THF to give 725 mg (0.91 mmol, 91%) of the title compound as a yellow solid. The structure was
1
confirmed by X-ray crystallographic analysis. H NMR (400 MHz, CDCl , ): 7.91 (t, J = 6.7 Hz, 1H), 7.50 (t, J = 7.7 Hz, 2H), 7.42 (t, J =
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.7 Hz, 1H), 7.29 (t, J = 7.7 Hz, 2H), 7.22 – 6.98 (m, 3H), 6.61 (dd, J = 3.2 Hz, 7.6 Hz, 2H), 5.71 – 4.00 (m, 2H), 3.20 – 2.11 (m, 2H), 1.95
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
1
–
0.55 (m, 39H).. C{ H} NMR (100 MHz, CDCl , ): 153.1, 151.5, 146.8, 146.6, 135.4, 135.11, 135.0, 134.1, 133.6, 133.5, 131.5, 130.3
3
(two peaks), 129.6 (two peaks), 128.1, 128.0, 125.2, 123.3, 122.6, 119.4, 118.9, 116.2, 110.2, 39.3, 39.1, 32.1, 31.5, 31.3 (two peaks), 31.0,
3
1
1
2
7
5.7, 25.5, 24.9, 24.8, 24.4, 22.6, 22.5, 14.1 [Observed complexity due to C–P and C–F coupling]. P{ H} NMR (162 MHz, CDCl , ):
3
1
9
6.0. F NMR (376 MHz, CDCl , ): ─78.6 (s, 3F). Anal. Calcd. for C H F O PPdS: C, 58.75; H, 6.83. Found: C, 58.81; H, 6.76.
3
39 54
3
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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6
7
8
9
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7
8
9
0
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3
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7
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9
0
[Pd(allyl)(Me tBuPhos)]OTf (11A)
4
The general procedure was followed using 183 mg (0.50 mmol) of [(allyl)PdCl] , 257 mg (1.00 mmol) of AgOTf, 485 mg (1.00 mmol) of
2
Me tBuXPhos (L10) in anhydrous THF to give 727 mg (0.94 mmol, 94%) of the title compound as a pale yellow solid. The product con-
4
1
tains ~0.5 wt% THF. H NMR (400 MHz, CDCl , ): 7.42 (s, 1H), 7.32 (s, 1H), 5.58 (sept, J = 7.1 Hz, 1H), 4.53 (d, J = 6.5 Hz, 1H), 3.31
3
(
dd, J = 9.5, 13.4 Hz, 1H), 3.00 (sept, J = 7.3 Hz, 1H), 2.91 (d, J = 12.8 Hz, 1H), 2.61 (sept, J = 6.8 Hz, 1H), 2.60 (s, 3H), 2.31 (sept, J =
6.6 Hz, 1H), 2.25 (s, 3H), 2.16 – 2.08 (m, 4H), 1.52 – 1.37 (m, 18H), 1.32 (d, J = 7.0 Hz, 6H), 1.24 (t, J = 7.6 Hz, 6H), 0.88 (d, J = 6.8 Hz,
1
3
1
3H), 0.82 (s, 3H), 0.74 (d, J = 6.6 Hz, 3H), peaks attributable to THF were observed at 3.76 and 1.85 ppm. C{ H} NMR (100 MHz,
CDCl , ): 155.1, 154.6, 151.4, 143.3, 143.0, 141.5 (two peaks), 139.2, 138.5, 138.4, 137.1, 137.0, 133.6, 133.4, 125.8, 125.6, 125.5,
3
1
3
22.6, 120.0, 119.9, 119.4, 116.2, 116.1, 98.3, 98.0, 62.7 (two peaks), 40.9, 40.8, 40.1, 40.0, 34.0, 33.4 (two peaks), 32.9 (two peaks), 32.2,
2.0, 26.9, 26.3, 26.2, 24.8, 24.6, 24.3 (two peaks), 18.7, 17.5, 17.3 [Observed complexity due to C–P and C–F coupling], peaks attributa-
3
1
1
19
ble to THF were observed at 67.9 and 25.6 ppm. P{ H} NMR (162 MHz, CDCl , ): 93.5. F NMR (376 MHz, CDCl , ): ─78.1 (s, 3F).
3
3
Anal. Calcd. for C H F O PPdS: C, 57.17; H, 7.52. Found: C, 57.19; H, 7.64.
3
7
58
3
3
[Pd(allyl)(RockPhos)]OTf (12A)
The general procedure was followed using 183 mg (0.50 mmol) of [(allyl)PdCl] , 257 mg (1.00 mmol) of AgOTf, 469 mg (1.00 mmol) of
2
RockPhos (L11) in anhydrous THF to give 744 mg (0.97 mmol, 97%) of the title compound as a yellow solid. The product contains ~0.8
1
wt% THF. H NMR (400 MHz, CDCl , ): 7.44 (d, J = 1.3 Hz, 1H), 7.37 (d, J = 1.3 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 7.01 (dd, J = 2.2,
3
8
2
.4 Hz, 1H), 5.57 (sept, J = 6.9 Hz, 1H), 4.44 (d, J = 6.6 Hz, 1H), 3.88 (s, 3H), 3.38 (dd, J = 9.4, 13.7 Hz, 1H), 3.01 (sept, J = 7.1 Hz, 1H),
.86 (d, J = 12.7 Hz, 1H), 2.63 (sept, J = 6.7 Hz, 1H), 2.31 (sept, J = 6.8 Hz, 1H), 2.23 (dt, J = 2.3, 7.5 Hz, 1H), 1.45 – 1.20 (m, 30H) 1.08
1
3
1
(s, 3H), 0.97 (d, J = 6.5 Hz, 3H), 0.84 (d, J = 6.8 Hz, 3H), peaks attributable to THF were observed at 3.76 and 1.85 ppm. C{ H} NMR
(100 MHz, CDCl , ): 160.0, 159.9, 154.8, 154.7, 151.4, 146.8, 146.5, 137.2, 137.1, 132.2, 132.1, 125.9, 125.8, 125.7, 124.1, 123.9, 122.6,
3
1
20.0, 119.9, 119.4, 116.2, 116.1, 112.0 (two peaks), 99.0, 98.8, 59.2 (two peaks), 54.6, 40.2, 40.1, 39.6, 39.4, 34.1, 32.3 (two peaks), 32.0
(
two peaks), 31.8, 27.0, 26.7, 24.7, 24.6, 24.3, 24.2, 19.0, [Observed complexity due to C–P and C–F coupling], peaks attributable to THF
31
1
19
were observed at 67.9 and 25.6 ppm. P{ H} NMR (162 MHz, CDCl , ): 84.8. F NMR (376 MHz, CDCl , ): ─78.2 (s, 3F). Anal.
3
3
Calcd. for C H F O PPdS: C, 54.93; H, 7.11. Found: C, 54.92; H, 7.25.
3
5
54
3
4
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