Evaluation of P-bridged biaryl phosphine ligands in palladium-catalysed Suzuki-Miyaura cross-coupling reactions

Article abstract of DOI:10.1039/d1ra04947j

A family of biaryl phosphacyclic ligands derived from phobane and phosphatrioxa-adamantane frameworks is described. The rigid biaryl phosphacycles are efficient for Suzuki-Miyaura cross-coupling of aryl bromides and chlorides. In particular, coupling reactions of the challenging sterically hindered and heterocyclic substrates were viable at room temperature.

Full text of DOI:10.1039/d1ra04947j

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Evaluation of P-bridged biaryl phosphine ligands in
palladium-catalysed Suzuki–Miyaura cross-
coupling reactions†‡
Cite this: RSC Adv., 2021, 11, 26883
a
a
a
Jairus L. Lamola,
Paseka T. Moshapo, Cedric W. Holzapfel§
ab
and Munaka Christopher Maumela*
Received 25th June 2021
Accepted 18th July 2021
A family of biaryl phosphacyclic ligands derived from phobane and phosphatrioxa-adamantane frameworks
is described. The rigid biaryl phosphacycles are efficient for Suzuki–Miyaura cross-coupling of aryl
bromides and chlorides. In particular, coupling reactions of the challenging sterically hindered and
heterocyclic substrates were viable at room temperature.
DOI: 10.1039/d1ra04947j
rsc.li/rsc-advances
4i,j
phosphines include ow chemistry, solvent-free reaction con-
ditions, and mechanochemically processes (ball milling). The
Introduction
4k
4l
For the past three decades, palladium-catalysed cross-coupling effectiveness of the well-known dialkylbiaryl phosphines is
reactions have revolutionised organic synthesis by providing believed to arise from the electron-rich and sterically hindered
easy and rapid access to compounds of varying levels of struc- characteristics of the dialkyl substituents on the phosphorus
1
a,b
4m
tural complexity.
Among these is the Suzuki–Miyaura reac- atom. The robustness and air stability of these classes of phos-
4n
tion, which has been identied as one of the most versatile phines is associated with the biaryl backbone.
methods for carbon–carbon (C–C) bond formation and is
Encouraged by the steric and electron donor properties of
pivotal to the synthesis of biaryl intermediates and building relatively air stable
5a–c
phosphines bearing phobane (Phob,
blocks for the ne chemical industry. Since its inception, the particularly [3.3.1] isomer) and phosphatrioxa-adamantane (Cg)
5g
2
a,b
5d
5e
5f
Suzuki–Miyaura reaction has received a great deal of attention moieties described by Pringle, Otto, Capretta, and Lautens,
in various elds of chemistry and has advanced signicantly. we report the synthesis and structural features of phosphine
The use of air stable dialkylbiaryl phosphines (Fig. 1) developed by ligands containing bicyclic Phob and Cg moieties (Fig. 1). The
the Buchwald's research group has resulted in a remarkable utility of the biaryl phosphacycles in palladium-catalysed Suzuki–
breakthrough in cross-coupling reactions. For example, Suzuki– Miyaura reactions of aryl bromides and chlorides is also described.
Miyaura reaction based on dialkylbiaryl phosphines has been
successfully used in the formation of C–C bonds in medicinal
chemistry; material science; process chemistry; and synthesis
Results and discussion
Ligand synthesis
3a
3b
3c
3
d
3e
3f
of heterocycles, natural products, and ligands. Interestingly,
Buchwald and other researchers have demonstrated that some of
Prior to the synthesis of the biarylphobane[3.3.1] systems (1 and
2), a separation of a racemic of isomers (1s,5s)-9-phospha-bicyclo
4a
these transformations can be conducted at low catalyst loadings,
room-temperature, short reaction times, using green sol-
vents, and deactivated substrates. Other advancements and
green approaches that have been demonstrated with dialkylbiaryl
4b
4c
4d,e
4f–h
a
Research Centre for Synthesis and Catalysis, Department of Chemical Sciences
University of Johannesburg, Kingsway Campus, Auckland Park 2006, South Africa.
E-mail: chris.maumela@sasol.com
b
Sasol (Pty) Ltd, Research and Technology (R & T), 1 Klasie Havenga Rd, Sasolburg
1
947, South Africa. E-mail: chris.maumela@sasol.com
†
Dedicated to the memory of Emeritus Professor Cedric Holzapfel (1935–2021).
We are eternally grateful for his mentorship and friendship.
Electronic supplementary information (ESI) available: CIFs, crystal data,
checkCif reports, NMR (1D & 2D), HRMS & GC-data. CCDC 2051924, 2051881,
051950 and 2051945. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/d1ra04947j
Deceased.
‡
2
Fig. 1 Biaryl phosphines with bridged bicyclic (1–4) and dialkyl (5–8)
moieties.
§
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2021 The Author(s). Published by the Royal Society of Chemistry
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Table 2 Selected bond lengths, angles, and torsional angles of
a
phosphines 1–4 and comparison with 6 (ref. 6h) and 11 (ref. 6i)
Biaryl torsion
angle ( )
b
ꢀ
ꢀ
˚
Ligand
P–CAr (A)
C–P–CAr ( )
1
2
3
4
6
1.841
1.844
1.839
1.839
1.850
1.875
104.34, 106.08
104.27, 107.45
103.94, 106.00
103.09, 106.51
102.96, 103.36
107.08, 110.65
52.74
72.47
61.89
65.78
73.79
91.41
Scheme 1 The synthesis of ligands 1 and 2, through reaction of
phosphine chloride 10 with (i) 2-biphenylmagnesium bromide, CuCl
ꢀ 0 0
mol%, LiBr 10 mol%, toluene, 110 C, 12 and Ar; or (ii) (2 ,6 -dime-
5
0
ꢀ
thoxy-[1,1 -biphenyl]-2-yl)lithium, THF, ꢁ80 C / RT, 24 h and Ar,
1
1
respectively.
a
The average values were employed for systems with more than one
b
molecule in the asymmetric unit. Bond angle generated between the
P-donor atom and its immediate neighbouring carbons (Ccyclic/alkyl–P–
[
3.3.1]nonane (s-Phob-H) and (1R,6S)-9-phospha-bicyclo[4.2.1]
C
Ar). The observed trigonal pyramidal geometries for 1–4 correlates to
5
e
ꢀ
ꢀ
nonane (a-Phob-H) was conducted. Otto and co-workers have the commonly accepted trigonal pyramidal angle (90 < q < 109.5 ).
shown that tertiary phosphines based on s-Phob exhibited superior
coordinating ability and catalytic potential than the a-Phob coun-
terpart. With compound 9 in hand, chlorination of the phosphine phosphines 1 and 2 were larger than CAr–P–CCy of phosphine 5,
by treatment with PCl afforded phobane[3.3.1] chloride 10 in 79% while the CAr–P–CCg bond angles of phosphines 3 and 4 were
3
isolated yield (Scheme 1). Lastly, phobane[3.3.1] chloride 10 was smaller than CAr–P–Ct-Bu of phosphine 11, Table 2. There is no
reacted with a suitable biaryl backbone to furnish the desired general correlation of bond lengths and angles of free ligands to
biarylphobane[3.3.1] ligands 1 and 2 in 64% and 49% isolated their catalytic potential, in contrast to studies of phosphine–
6b–e
6f
yields, respectively. The Cg-based systems 3 and 4 were synthesised metal complexes.
However, studies by Tyler's group
in a one-step palladium-catalysed C–P cross-coupling reaction of revealed the remarkably short P–M bond and strong s-donating
0
Cg-H with a suitable biaryl bromide, similar to the procedure character of [1,1 -biphenyl-2-yl]dimethylphosphine (MeJPhos)
5g
5h
described by Lautens and Shekhar. Ligands 3 and 4 were ob- as a manifest of its slightly distorted trigonal pyramid geometry
ꢀ
tained in 76% and 80% isolated yields, respectively.
(CAr–P–CMe, 100.3 ). According to Tyler, the slight distortion
3
Upon isolation, biaryl phosphacycles derived from s-Phob reduces “front strain”, allowing the P lone pair to occupy an sp -
and Cg moieties were recrystallised to obtain clear and white like orbital which has strong overlap with metal center. Simi-
crystals, respectively. Through X-ray crystallography, the larly, Otto and Bungu found strong s-donation to be a result of
6f
6g
˚
molecular structures and selected crystal data of the entire the correlation between short P–CPhob bond lengths (1.809 A,
˚
ligand library are described (Table 1).
phobane[3.3.1]-Ph contrary to 1.863 A, phobane[4.2.1]-Ph) and
The shorter P–CAr bond in bridged bicyclic systems 1–4 effective orbital overlap due to less geometry distortion.
t
compared to Buchwald congeners 6 and tetramethyl- BuXPhos
The observed magnitudes of the biaryl torsions increase with
(
11) (Table 2), was suspected to be a result of the inherent substituents on the o-aryl (bottom ring) (Table 2). The func-
t
freedom to rotation of the Cy and Bu, opposed to the “caged” tionalised biaryl phosphacycles 2 and 4 exhibited larger
Phob and Cg moieties. The CAr–P–CPhob bond angles of biaryl torsions (72.47 and 65.78 ) compared to the unsubstituted
6a
ꢀ
ꢀ
a
Table 1 Selected crystallographic data of the biaryl phosphacycles
Crystal structure
Ligand
1
2
3
4
CCDC no.
2051924
2051881
2051950
2051945
Empirical formula
Crystal system
Space group
C
20
H
23
P
C
44
H
54
O
4
P
2
C
22
H
25
O
3
P
24 3
C H30NO P
Monoclinic
C2/c
23.219(2)
8.4649(8)
24.795(2)
90
110.975(2)
90
Monoclinic
P2/n
14.554(2)
7.2220(11)
31.176(4)
90
Triclinic
P1ꢀ
Triclinic
P1ꢀ
˚
a/A
10.80490(10)
13.8758(2)
14.4304(2)
62.5460(10)
81.2320(10)
88.0550(10)
8.0873(7)
9.4963(9)
13.1468(12)
92.553(4)
105.035(4)
95.537(4)
˚
b/A
˚
c/A
ꢀ
ꢀ
a/
b/
97.878(5)
90
ꢀ
g/
Final R indexes [I $ 2s(I)]
R
wR
1
¼ 0.0413,
R
wR
1
¼ 0.0344,
R
wR
1
¼ 0.0446,
R
wR
1
¼ 0.0358,
2
¼ 0.0941
2
¼ 0.0914
2
¼ 0.1056
2
¼ 0.0910
a
Full data collection, renement parameters, and 50% probability ellipsoid plots in ESI.
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ꢀ
ꢀ
7h
7i
biaryl phosphacycles 1 (52.74 ) and 3 (61.89 ), respectively known bases such as TBAF, Cs
2 3 2 3
CO , and K CO (ref. 7c and
(
Table 2). A close correlation was observed between torsions of 7j) showed inferior results (Table S6, ESI‡).
ꢀ
ꢀ
0
biaryl phosphines 2 (72.47 ) and 5 (73.79 ), both bearing 2 ,6’-
(
With the optimal reaction conditions in hand, the scope and
OMe) substituents. Barder and Buchwald demonstrated the generality of this coupling system was investigated (Schemes 2
4
n
2
signicant role of substituents on the o-aryl group, revealing and 3). Selected well-known dialkylbiaryl phosphine ligands
ꢀ
enhanced stability to air and O
2
(at 100 C) for trisubstituted developed by Buchwald were also evaluated in this study for
0
0
0
ligands such as 2-di-tert-butylphosphino-2 ,4 ,6 -triisopropylbi- comparison purposes and to gauge the effectiveness of the
t
0
0
0
phenyl ( BuXPhos) and 2-(diphenylphosphino)-2 ,4 ,6 -triiso- biaryl phosphacycles. Our early experiments included
propylbiphenyl (PhXPhos), without correlations to biaryl comparing the catalytic potential of Pd catalyst systems derived
torsions. In addition to stability induced by the biaryl backbone, from biaryl phosphacycles 1 and 3 to those derived from dia-
Tyler's group also observed a contribution to steric effects from lkylbiaryl phosphines 5 and 7 (Scheme 2). Coupling reactions
ꢀ
6f
the MeJPhos biphenyl (torsion 66.8 ).
involving (i) monosubstituted 12a–b and (ii) naphthalene-based
2c–b aryl bromides were achieved at nearly quantitative yields
1
with catalysts based on ligands 1, 3, and 5, and at moderate
yields with ligand 7 (Scheme 2). The signicant steric bulk of
Catalytic activity
7o,p
Having successfully synthesised and authenticated the struc- ligand 7, as previously quantied by other authors,
is sus-
tures of ligands 1–4, catalytic evaluation commenced by estab- pected to have a negative impact on in this coupling system
lishing suitable conditions for the coupling of 4-bromotoluene (Scheme 2).
and phenylboronic acid as the model reaction (Table S6, ESI‡).
Distinct catalyst performances were observed from the
It was established that coupling proceeded in 100% conversion reactions entailing the synthesis of biaryl products 14f–k
and selectivity towards the desired biaryl product, in the pres- bearing ortho-substituent(s) (Scheme 2). In general, these
ence of 1 mol% Pd(OAc) , 2 mol% ligand (1 and 3), 3 equiv. KOH coupling reactions were sensitive to the ligand's steric bulk as
2
dissolved in MeOH (2 M base solution), THF as the solvent for demonstrated by the poor catalytic performances of catalysts
ꢀ
1
2 h at room temperature (25 C). Examining the optimal base based on ligands 3 and 7 (14f–i,k). It is worth mentioning that
7a,b
in other conventional solvents
such as DMA, DMF, and the synthesis of the sterically encumbered product 14i was
dioxane, afforded lower yields of the desired biaryl product. efficiently achieved by catalysts based on ligand 1. This is one of
Similarly, the use of traditional cross-coupling bases K PO (ref.
c–e) and KF in THF afforded cross-coupling in diminished
yields. Expansion of the optimisation by employing other
3
4
7f,g
7
a
Scheme 3 Substrate scope evaluation. Reaction conditions A: ArBr (1
equiv.), ArB(OH) (1.5 equiv.), 2 M KOH in MeOH (3 equiv.), Pd(OAc)
Scheme 2 Substrate scope evaluation. Reaction conditions: ArBr (1 (2 mol%), L (5 mol%), THF, Ar, 24 h, rt. Reaction conditions B: ArCl (1
2
2
b
equiv.), ArB(OH)
2
(1.5 equiv.), 2 M KOH in MeOH (3 equiv.), Pd(OAc)
2
equiv.), ArB(OH)
2
(1.5 equiv.), K
3
PO
4
(2 equiv.), Pd(OAc)
2
(1 mol%), L
a
ꢀ
c
d
(
1 mol%), L (2 mol%), THF, Ar, 12 h, rt. Isolated yields from an average (2 mol%), toluene, 100 C, 12 h, Ar. KF as a base. Isolated yields from
of two runs with <5% deviation. GC results included in Tables S5 and S6 an average of two runs with <5% deviation. GC results included in Table
ESI‡). S5 (ESI‡).
(
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the few reports that demonstrates the room temperature derived from ligands 5 and 6 also exhibited high product yields
b
coupling of aryl bromide 12i since most reports achieved this at of 93–97% for the described products 17a–c,j . Combination of
ꢀ
7l–p
elevated temperatures (60–110 C).
Incorporation of bulky Pd(OAc) and dialkylbiaryl phosphine 7 formed inactive cata-
2
substituents on arylboronic acid 13c impeded coupling reac- lysts for Suzuki couplings of 2-chloro-N-heterocycles 16b,d and
tions using catalysts based on ligands 3 and 7, containing exhibited diminished efficiency for coupling of heteroaryl
t
sterically hindered Cg and Bu groups, respectively.
chloride 16c, with a product yield of 44%. Excess steric bulk of
Our attention was then directed to coupling reactions of ligand 7 appears to impede couplings of the selected 2-chlor-
selected heteroaryl bromides and chlorides (Scheme 3), with oheterocycles (Scheme 3). Catalysts based on PPh were inactive
a closer look at the most encountered therapeutic scaffolds in the coupling reactions of heteroaryl chlorides 16a,c, also
3
8
a,b
9d
which includes, (1) pyridine and its derivatives,
(
followed by observed by Tagata and Nishida.
8c
2) thiophene. Early experiments were carried out with the
entire ligand scope to gain better understanding of the role of
the ligand architecture in these coupling reactions, which are
well-known to be less straightforward due to potential catalyst
deactivation through undesirable coordination to metal
Conclusions
In summary, we have developed biaryl phosphines bearing
phobane (1 and 2) and phosphatrioxa-adamantane (3 and 4)
frameworks, which formed active catalysts in combination with
8d–f
centers.
In general, coupling reactions of heteroaryl bromides 15a–c
with arylboronic acid 13a were sensitive to the base used, KOH
appeared to be ideal for the ligands bearing the less hindered
Phob (1 and 2) and Cy (5 and 6) moieties. The use of KOH with
the sterically ligands 3, 4, 7, and 8 favoured side reactions (Table
S6, ESI‡). These side reactions were completely suppressed with
KF which proved to be the ideal base for the sterically hindered
ligands 3, 4, 7, and 8 (Scheme 3). This observation was also
2
Pd(OAc) for room temperature Suzuki–Miyaura reactions of
structurally diverse aryl bromides and boronic acids. These
catalyst systems were also effective in coupling reactions of
chloro-heteroarenes, with product yields of 88–100%. In
general, the catalytic performances of Pd-catalysts based on
biaryl phosphacycles ligands were comparable to those based
on dialkylbiaryl phosphines with a few examples of distinct
catalytic performances. Further application in other Pd-
catalysed transformations is in progress.
7g
noted by Amatore and co-workers. The authors demonstrated
the triple role of uoride ions in Pd-catalysed Suzuki–Miyaura
reaction, which includes: (i) formation of [ArPdFL ] which is the
reactive species for transmetalation; (ii) high uorophilicity of
2
Experimental section
aryl boron moieties which also enhances transmetalation; and General methods
(
iii) promoting reductive elimination via the reactive ve coor-
All chemicals and anhydrous solvents were purchased from
Sigma-Aldrich. All transformations that involve phosphorus
derivatives were performed using standard Schlenk line tech-
niques under argon. Secondary bridged phosphines, Phoban-H
0
ꢁ
7g
a
dinate [ArAr PdFL ] . The synthesis of biaryl product 17a
proceeded efficiently only with ligand 1 when KOH was used
a base (80% isolated yield, Scheme 3). This coupling appeared
to be facile with less hindered ligands
Furthermore, the synthesis of biaryl product 17b was favour-
able with KOH as the base for Pd-catalysts derived from biaryl
phosphacycles 1–2 and dialkylbiaryl phosphines 5–6, contain-
ing Phob and Cy groups, respectively. Catalyst systems based on
2
5c,6g
(Table S6, ESI‡).
(m/m in toluene, mixture of isomers [3.3.1] : [4.2.1]) and
a
phosphotrioxa-adamantane (Cg-H) were obtained from Sasol
Research & Technology (South Africa). NMR experiments were
conducted in CDCl solutions using Bruker Ultrashield 400 MHz
3
magnet, an Avance III 400 MHz Console or 500 MHz magnet
coupled to an Avance III HD 500 MHz Console. The spectra were
t
ligands 3–4 and 7–8 (containing sterically hindered Cg and Bu
groups, respectively) were effective with KF as the base.
Coupling reactions entailing arylboronic acid 13b employing
the narrowed ligand scope revealed that catalysts based on
phobane ligands 1 and 2 exhibited superior performances with
average product yields of 86% (17d–f ). Moderate performances
were exhibited by catalysts derived from ligands featuring the
Cg, Cy, and Bu moieties, with average product yields of 60%,
5
based on these ligands were inactive for the synthesis of biaryl
products 17g–i. Outstanding catalytic performance was ach-
ieved in the quantitative formation of biaryl product 17h (95%
isolated yield) using catalysts based on ligand 1.
1
13
calibrated relative to the solvent peaks for H and C. A SHI-
MADZU GC-FID was used for the quantication of compounds
present in a reaction mixture, using a RTX-1 column (L ¼ 100 m,
d ¼ 0.25 mm) with a lm thickness of 0.50 mm. Elemental analysis
was conducted on a Flash 2000 Organic Elemental Analyzer, were
samples were ran in triplicates and the average was recorded as the
a
t
nal measurement. For accurate mass, samples were analysed on
9%, and 54%, respectively (Scheme 3). Furthermore, catalysts
a Waters Synapt G2 quadrupole time-of-ight mass spectrometer,
equipped with an ESI probe (electrospray positive mode, 15 V).
Crystallography
Attempts to conduct facile room temperature couplings of X-ray analysis was conducted from two different diffractome-
aryl chlorides using the established reaction conditions were ters. (i) Single crystal of biaryl phosphacycle 2 was analysed on
unsuccessful. As a result, commonly employed reaction condi- a Rigaku XtaLAB Synergy R diffractometer, with a rotating-
3e,7c,d,9a–c
tions were adopted.
In general, catalysts based on anode X-ray source and a HyPix CCD detector. Data reduction
ligands 1–3 consistently exhibited high efficacies in couplings and absorption were carried out using the CrysAlisPro (version
10a
of aryl chlorides 16a–d, with product yields of 80–97%. Catalysts 1.171.40.23a) soware package. (ii) Single crystals of biaryl
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phosphacycles 1, 3 and 4 were analysed on a Bruker Apex II DUO through a celite plug, and concentrated to give yellow solids of s-
diffractometer with a CCD area detector, using a multilayer Phob-Cl (0.51 g, 79%, 90% purity). To improve the purity the
˚
ꢀ
monochromated Mo-Ka radiation (l ¼ 0.71073 A). Data reduc- solids were either (i) sublimed at 90 C, 2 mmHg or (ii) dissolved
tion was carried out by means of a standard procedure using the in degassed pentane, passed through a plug of silica/alumina
Bruker soware package SAINT, absorption corrections and (1 : 1) and concentrated. Both methods improved the purity to
10b
10c,d
31
35
other systematic errors were accounted for using SADABS.
>98%. P NMR (202 MHz, CDCl
3
) d ¼ 89.94 ppm ( Cl iso-
3
7
All X-ray diffraction measurements were performed at 100–298 topomer), 89.90 ppm ( Cl, isotopomer). NMR data in agree-
5
d
6g
K, using an Oxford Cryogenics Cryostat. All structures were ment with Pringle and Otto's groups, also see ESI.‡
0
solved by direct methods with SHELXS and SHELXL sowar-
Synthesis of (1s,5s)-9-([1,1 -biphenyl]-2-yl)-9-phosphabicyclo-
using the OLEX2 (ref. 10g) interface. All H atoms were [3.3.1]nonane (ligand 1). In a glovebox, CuCl (0.014 g, 0.14
10e,f
es
placed in geometrically idealised positions and constrained to mmol) and LiBr (0.025 g, 0.28 mmol) were transferred to a ame
3
ride on their parent atoms. For data collection and renement dried Schlenk tube containing degassed toluene (1.00 cm ). The
ꢀ
parameters, see (Table S1‡). The X-ray crystallographic coordi- reaction mixture was stirred at ꢁ70 C, while a 0.50 M solution
3
nates for all structures have been validated through the free of 2-biphenylmagnesium bromide in diethyl ether (5.10 cm ,
online checkCIF platform and later deposited at the Cambridge 2.55 mmol) was added dropwise for 30 minutes. This was fol-
Crystallographic Data Centre (CCDC), with deposition numbers lowed by the addition of s-Phob-Cl (0.50 g, 2.83 mmol) dissolved
3
CCDC: biaryl phosphacycles 1 (2051924), 2 (2051881), 3 in degassed toluene (3.00 cm ). The reaction mixture was
(
2051950), and 4 (2051945). The attached crystal data folder allowed to warm-up to room temperature, evacuated and
ꢀ
contains all CIFs, checkCIF reports, and crystal data tables.
backlled with argon (10 times) and reuxed (110 C) for 12 h
under argon. The reaction mixture was then cooled to room
3
temperature and diluted with degassed EtOAc (200 cm ). The
solution was poured into a mixture of degassed 28% aqueous
Characterisation data
3
3
4
Separation of s-Phob-H isomer [3.3.1] by selective oxidation NH OH (50 cm ), degassed brine (50 cm ), and degassed water
5
d
3
of the a-Phob-H isomer [4.2.1]. A methodology reported by (50 cm ), allowed to stir for 10 min. The blue biphasic mixture
5d
Pringle and co-workers was adopted. A 2 : 1 mixture of Phob-H was separated, and the aqueous layer was kept on the side. The
3
[
3.3.1] : [4.2.1] in toluene (50 cm , 158 mmol) was concentrated organic layer was washed three times with degassed 28%
3
under argon and reduced pressure to give a colourless oily solid aqueous NH OH (50 cm ), i.e. until all unreacted Cu was
4
3
with a very strong order. Aqueous HCl (12 M, 41.5 cm ) was removed (transition from blue to clear). All aqueous fractions
slowly added over 2 h at 30 C, under argon. The oily solids were were combined and further extracted with degassed EtOAc (200
ꢀ
3
entirely solubilised in the HCl media, in which s-Phob-H was cm ꢂ 3), dried over Na
2 4
SO and the solvent was removed under
ꢀ
selectively protonated. The solution was then cooled to 0 C and argon. The resulting oil was recrystallised in hot-degassed
3
3
stirred vigorously while H
2 2
O (10.9 cm , 30 wt%) was slowly MeOH (1.00 cm ), to obtain clear crystalline material which
ꢀ
3
added over 45 min, maintaining the temperature at 0 C. This was washed with cold-degassed MeOH (10 cm ꢂ 3), affording
3
1
was performed to selective oxidize a-Phob-H, leaving the the title compound (0.53 g, 64%, 100% pure based on P NMR).
1
protonated s-Phob-H unscathed. To ensure full consumption of
H O
2 2
H NMR (400 MHz, CDCl
) d ¼ 7.48 (d, J ¼ 6.8 Hz, 2H(ar)), 7.31
3
, the mixture was stirred for another 30 min at room (m, 6H(ar)), 7.21–7.15 (m, 1H(ar)), 2.08–1.90 (m, 4H, P–CH–
3
temperature. Degassed hexane (25 cm ) was added and the CH2(2eq+2ax), P–CH–CH(4ax), P–CH–CH
2
–CH(5eq)), 1.88 (bs, 1H, P–
ꢀ
mixture was cooled to 0 C. To this was added an ice-cold CH–CH(4eq)), 1.85–1.78 (m, 3H, P–CH–CH(6eq), P–CH–CH
2
–
solution of NaOH (16 g) in water dropwise. When the addition CH(1eq) and P–CH–CH(8eq)), 1.60 (bs, 3H, P–CH(3ax), P–CH(7eq)
was completed (i.e. neutralization of the protonated s-Phob-H), and P–CH–CH –CH(5ax)), 1.49–1.43 (m, 2H, P–CH–CH(6ax) and
2
1
3
the hexane layer was separated, and the water layer was P–CH–CH(6ax)), 1.29–1.21 (m, 1H, P–CH–CH
2
–CH(1ax)). C NMR
3
1
extracted with degassed hexane (2 ꢂ 25 cm ). The combined (101 MHz, CDCl
) d ¼ 145.11 (d, JCP ¼ 10.1 Hz, P–C(quat)), 142.70
3
organic extracts were dried over MgSO
4
and the solvent was (C(quat)), 131.01 (d, JCP ¼ 9.1 Hz, P–CH(ar)), 130.32 (CH(ar)), 128.46
removed under argon and reduced pressure to give s-Phob-H as (d, JCP ¼ 3.0 Hz, P–CH(ar)), 128.31 (CH(ar)), 127.21 (CH(ar)), 126.71
3
1
2
a colourless solid (9.25 g, 90%, 97% pure). P NMR (202 MHz, (JCP ¼ 11.1 Hz, P–CH(ar)), 31.75 (d,
J
CP ¼ 15.1 Hz, P–CH–
5
d
2
1
CDCl ) d ¼ ꢁ54.17 ppm. NMR data in agreement with Pringle
C
(2+4)
H
2
), 25.49 (d, JCP ¼ 5.0 Hz, P–CH–C(6+8)
H
2
), 24.54 (d, JCP
3
6
g
3
and Otto's groups, also see ESI.‡
Synthesis of (1s,5s)-9-chloro-9-phosphabicyclo[3.3.1]nonane
¼ 12.1 Hz, P–C(3+7)H), 22.79 (d,
J
H
CP ¼ 4.0 Hz, P–CH–CH
2
–
C
(5)
H
2
), 21.91 (bs, P–CH–CH
2
–C(1)
2
). Peak assignment was
5
d,6g
31
(
s-Phob-Cl).
A methodology reported by Otto and Bungu achieved by 2D NMR data. P NMR (162 MHz, CDCl
3
) d ¼
6
g
3
+
was adopted. PCl
3
(0.32 cm , 3.67 mmol) was added dropwise ꢁ19.05. HR-ESI-MS ¼ Calculated m/z ¼ 295.1616 [M + H] ,
+
to a degassed toluene solution of s-Phob-H (0.62 g, 4.36 mmol) Found m/z ¼ 295.1624 [M + H] . Elemental analysis ¼ calcu-
at room temperature under argon. Aer the addition was lated: C, 81.60%; H, 7.88%; found: C, 81.38%; H, 7.83%.
0
0
0
complete, the reaction mixture was stirred for 1 h to give
Synthesis of (1s,5s)-9-(2 ,6 -dimethoxy-[1,1 -biphenyl]-2-yl)-9-
a bright yellow solution. The reaction mixture was concentrated phosphabicyclo[3.3.1]nonane (ligand 2). In a glovebox, 2 -
under argon and reduced pressure, to give a yellow oily solid, bromo-2,6-dimethoxy-1,1 -biphenyl (1.99 g, 6.79 mmol) was
0
0
which was extracted repeatedly with degassed diethyl ether (3 ꢂ transferred to a ame dried Schlenk tube containing super-dry
3
3
1
5 cm ). The diethyl ether fractions were combined, ltered and degassed THF (10 cm ). The reaction mixture was stirred
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ꢀ
ꢁ
80 C, while a 2.5 M solution of n-butyllithium in hexanes obtained as white crystals (0.13 g, 76%) which were 100% pure
3
(
2.72 cm , 6.87 mmol) was added dropwise for 1 h with vigorous (pure based on NMR) in most cases. To improve purity where
stirring. The resulting white reaction mixture was thick and applicable, the solids were recrystallised in degassed ethyl
1
oen required hand-assisted stirring. The reaction mixture was acetate and degassed hexane (1 : 3). H NMR (500 MHz, CDCl ) d ¼
3
ꢀ
1
warmed to 0 C, followed by the slow addition of (1s,5s)-9- 8.37 (d, J ¼ 7.0 Hz, 1H, ArH ), 7.43–7.35 (m, 6H, ArH(2,5,6)), 7.34–
chloro-9-phosphabicyclo[3.3.1]nonane (s-Phob-Cl, 1.00 g, 5.66 7.30 (m, 1H, ArH(4)), 7.29–7.25 (m, 1H, ArH(3)), 2.03 (m, 1H,
3
mmol) in super-dry and degassed THF, for 15 min. The reaction CgH(Dax)), 1.90 (m, 2H, CgH(Deq) and CgH(Ceq)), 1.53 (d, JP–H
¼
mixture was evacuated and backlled with argon (10 times) and 12.4 Hz, 3H, CgH(A2)), 1.44 (s, 3H, CgH(B2)), 1.40 (d, J ¼ 3.6 Hz, 1H,
3
allowed to slowly warm up to room temperature for 24 h, to give CgH(Cax)), 1.33 (s, 3H, CgH(B1)), 0.92 (d,
J
P–H ¼ 11.9 Hz, 3H,
13
1
a clear yellow solution. This mixture was quenched with satu- CgH(A1)). C NMR (126 MHz, CDCl ) d ¼ 151.06 (d, J ¼ 28.6 Hz,
3
CP
3
2
2
rated and degassed aqueous ammonium chloride (10 cm ), ArC(Ipso1)), 141.83 (d, J ¼ 6.1 Hz, ArC
), 133.83 (d, J
CP
¼
¼
CP
3
(Ipso2)
3
4
diluted with degassed ethyl acetate (50 cm ), and transferred 3.1 Hz, ArC ), 132.33 (d, J ¼ 33.3 Hz, ArC
), 131.01 (d, J
CP
(1)
CP
4
(Ipso3)
into a separatory funnel. The layers were separated, and the 4.8 Hz, ArC(5)), 130.89 (d, JCP ¼ 5.2 Hz, ArC(3)), 129.11 (ArC(2)),
3
aqueous layer was kept on the side. The organic layer washed 127.56 (ArC(6)), 127.05 (d, JCP ¼ 4.5 Hz, ArC(4)), 96.75 (CgC(Q4)),
1
1
with saturated and degassed aqueous ammonium chloride (3 ꢂ 95.97 (CgC(Q3)), 73.94 (d, JCP ¼ 7.2 Hz, CgC(Q1)), 73.79 (d, JCP
¼
3
3
2
1
0 cm ) and degassed brine (10 cm ). All aqueous fractions were 21.6 Hz, CgC(Q2)), 45.99 (d, JCP ¼ 19.4 Hz, CgC(D)), 36.04 (CgC(C)),
3
2
extracted with fresh and degassed ethyl acetate (200 cm ). The 28.10 (CgC(B2)), 27.96 (d, JCP ¼ 20.6 Hz, CgC(A1)), 27.70 (CgC(B1)),
2
31
organic fractions were dried over Na SO and the solvent was 26.78 (d, J ¼ 11.4 Hz, CgC ). P NMR (202 MHz, CDCl ) d ¼
2
4
CP
(A2)
3
+
removed under argon. The resulting yellow oil was recrystallised ꢁ39.06. HR-ESI-MS ¼ calculated m/z ¼ 369.1620 [M + H] , found
3
+
in hot-degassed acetone (4.00 cm ), to obtain clear crystals m/z ¼ 369.1624 [M + H] . Elemental analysis ¼ calculated: C,
3
which were washed with cold-degassed acetone (10 cm ꢂ 3), 71.72%; H, 6.84%; found: C, 71.82%; H, 6.93%.
0
affording the title compound (0.98 g, 49%, 100% pure based on
Synthesis of N,N-dimethyl-2 -((1R,3S,5S,7R)-1,3,5,7-tetra-
1
0
NMR). H NMR (500 MHz, CDCl
3
) d ¼ 7.36–7.29 (m, 1H, ArH(3)), methyl-2,4,6-trioxa-8-phospha-adamantan-8-yl)[1,1 -biphenyl]-
7
.21 (m, 3H, ArH(4–6)), 7.09 (bd, J ¼ 7.0 Hz, 1H, ArH(2)), 6.51 (d, J 2-amine (ligand 4). In a glovebox, 1,3,5,7-tetramethyl-2,4,6-
¼
8.4 Hz, 2H, ArH(1)), 3.64 (s, 6H, OMe ), 1.94 (m, 6H, P–CH– trioxa-8-phospha-adamantane (Cg-H, 0.5 g, 2.31 mmol),
0
CH2(2ax+eq), P–CH–CH –CH(5ax), P–CH–CH(4eq) and P–CH– Pd(PPh3)4 (0.08 g, 0.069 mmol, 3 mol%), 2 -bromo-N,N-
CH(6eq) and P–CH–CH(8eq)), 1.84–1.74 (m, 2H, P–CH–CH2– dimethyl-[1,1 -biphenyl]-2-amine (0.64 g, 2.31 mmol), and
2
0
CH(1ax) and P–CH–CH(4ax)), 1.60 (bs, 2H, P–CH(3ax) and P– K PO (1.47 g, 6.94 mmol) were transferred in a amed dried
3
4
3
CH(7eq)), 1.51 (m, 1H, P–CH–CH
CH(6ax) and P–CH–CH(8ax)), 1.28 (m, 1H, P–CH–CH
2
–CH(5eq)), 1.43 (bs, 2H, P–CH– Schlenk tube containing degassed toluene (5.00 cm ). The
–CH(1eq)). reaction mixture was evacuated and backlled with argon (10
2
1
3
1
ꢀ
C NMR (126 MHz, CDCl
3
) d ¼ 157.89 (C(q1)), 139.65 (d, JCP
¼
times) and reuxed (110 C) for 48 h under argon. The reaction
2
3
1
1
3
1.5 Hz, C(q4)), 137.36 (d, JCP ¼ 11.3 Hz, C(q3)), 131.83 (ArC(2)), mixture was cooled to rt, diluted with degassed ethyl acetate
2
3
30.48 (d, JCP ¼ 7.7 Hz, ArC(3)), 129.06 (ArC(6)), 126.67 (ArC(5)), (150 cm ), and washed with (i) saturated and degassed ammo-
3
3
26.04 (ArC ), 119.47 (C(q2)), 103.92 (Ar(C1)), 55.83 (OCH ), nium chloride (50 cm ꢂ 2), (ii) degassed water (50 cm ), and
(
4)
3
2
2
3
2.02 (d, J ¼ 15.3 Hz, P–CH–C
H ), 25.64 (d, J ¼ 4.2 Hz, (iii) degassed brine (50 cm ). The resulting deep brown oil was
CP
(2+4)
2
CP
1
P–CH–C
H ), 25.17 (d, J ¼ 13.4 Hz, P–C
2
H), 22.79 (d, puried by column chromatography on silica gel (10% v/v
(3+7)
(
6+8)
CP
3
J
CP ¼ 4.6 Hz, P–CH–CH
Peak assignment was achieved by 2D NMR data. P NMR (202 tained as white crystals (0.76 g, 80%) which were 100% pure
MHz, CDCl
) d ¼ ꢁ16.26. HR-ESI-MS ¼ calculated m/z ¼ (pure based on NMR) in most cases. To improve purity where
55.1827 [M + H] , found m/z ¼ 355.1837 [M + H] . Elemental applicable, the solids were recrystallised in degassed THF and
2 2 2 2
–C(5)H ), 22.18 (bs, P–CH–CH –C(1)H ). degassed ethyl acetate/hexane). The desired product was ob-
3
1
3
+
+
3
1
analysis ¼ calculated: C, 74.55%; H, 7.68%; found: C, 74.16%; degassed acetone (1 : 3). H NMR (500 MHz, CDCl
H, 7.60%.
J ¼ 7.8 Hz, 1H, ArH ), 7.41 (t, J ¼ 7.4 Hz, 1H, ArH ), 7.33–7.24
Synthesis of (1R,3S,5S,7R)-8-([1,1 -biphenyl]-2-yl)-1,3,5,7- (m, 3H, ArH
3
) d ¼ 8.28 (d,
(
1)
(3)
0
), 7.09–7.04 (m, 1H, ArH ), 7.00–6.94 (m, 2H,
(
2,4,7)
(5)
5
h
tetramethyl-2,4,6-trioxa-8-phospha-ada-mantane (ligand 3).
In
ArH(6, 8)), 2.42 (s, 6H, NMe ), 1.99–1.91 (m, 2H, CgH(Ceq),
2
a
glovebox, 1,3,5,7-tetramethyl-2,4,6-trioxa-8-phospha- CgH(Dax)), 1.85 (dd, J ¼ 26.1, 13.0 Hz, 1H, CgH(Deq)), 1.44–1.38
adamantane (Cg-H, 0.10 g, 0.46 mmol), Pd(PPh
0
3
)
4
(0.016 g, (m, 7H, CgH(B2), CgH(A2), CgH(Cax)), 1.30 (s, 3H, CgH(B1)), 0.86 (d,
0
3
13
.014 mmol, 3 mol%), 2-bromo-1,1 -biphenyl (0.08 cm , 0.46 J ¼ 11.9 Hz, 3H, CgH(A1)). C NMR (126 MHz, CDCl
3
) d ¼ 151.34
mmol), and K
2
CO
3
(0.19 g, 1.40 mmol) were transferred in (d, J ¼ 2.4 Hz, ArC(Ipso4)), 150.28 (d, J ¼ 32.5 Hz, ArC(Ipso1)), 135.22
a amed dried Schlenk tube containing degassed toluene (5.00 (d, J ¼ 6.0 Hz, ArC(Ipso3)), 133.84 (d, J ¼ 4.0 Hz, ArC(1)), 133.57
3
cm ). The reaction mixture was evacuated and backlled with (ArC
), 131.89 (ArC ), 130.66 (d, J ¼ 6.4 Hz, ArC(4)), 129.63
(
Ipso2)
(5)
ꢀ
argon (10 times) and reuxed (110 C) for 24 h under argon. The (ArC(3)), 128.54 (ArC(7)), 126.51 (ArC ), 121.31 (ArC(6)), 118.15
(2)
reaction mixture was cooled to rt, diluted with degassed ethyl (ArC(8)), 96.85 (CgC(Q4)), 95.97 (CgC(Q3)), 74.10 (d, J ¼ 17.9 Hz,
3
acetate (50 cm ), and washed with (i) saturated and degassed CgC(Q2)), 73.95 (d, J ¼ 1.4 Hz, CgC(Q1)), 46.17 (d, J ¼ 20.4 Hz,
3
3
ammonium chloride (10 cm ꢂ 2), (ii) degassed water (10 cm ), CgC(D)), 42.90 (NMe
2
), 36.26 (CgC(C)), 28.18–27.97 (CgC(B2),
3
31
and (iii) degassed brine (10 cm ). The resulting deep brown oil CgC(A1)), 27.78 (CgC(B1)), 26.22 (d, J ¼ 11.4 Hz, CgC(A1)). P NMR
was puried by column chromatography on silica gel (5% v/v (202 MHz, CDCl
) d ¼ ꢁ34.93. HR-ESI-MS ¼ calculated m/z ¼
3
+
+
degassed ethyl acetate/hexane). The desired product was 412.2042 [M + H] , found m/z ¼ 412.2046 [M + H] .
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1
1a
1
General procedure for room temperature Suzuki–Miyaura
An oven-dried ace pressure tube was evacuated and backlled with
4-Methoxy-biphenyl.
H NMR (400 MHz, CDCl
3
) d ¼ 7.61–
7
4
.53 (m, 4H), 7.44 (dd, J ¼ 10.5, 4.8 Hz, 2H), 7.32 (dd, J ¼ 10.5,
1
3
.2 Hz, 1H), 7.04–6.97 (m, 2H), 3.86 (s, 3H). C NMR (101 MHz,
2
argon. Pd(OAc) (0.01 mmol, 1 mol%) and ligand (0.02 mmol,
CDCl
3
) d ¼ 159.20, 140.88, 133.82, 128.78, 128.21, 126.79,
2
mol%), were added and the tube was evacuated and backlled
1
26.71, 114.26, 55.37.
with argon. THF (2.00 mL), aryl halide (1 mmol), boronic acid (1.5
mmol), 2 M KOH dissolved in MeOH (3 mmol), and n-decane
11b
1
2-Methoxy-biphenyl.
H NMR (400 MHz, CDCl ) d ¼ 7.56
3
(
4
dd, J ¼ 5.3, 3.1 Hz, 2H), 7.45–7.40 (m, 2H), 7.34 (ddd, J ¼ 7.3,
(0.5 mmol, internal standard), were added to the tube. The tube
1
3
.3, 1.4 Hz, 3H), 7.08–6.98 (m, 2H), 3.82 (s, 3H). C NMR (101
) d ¼ 156.51, 138.59, 130.93, 130.78, 129.59, 128.80,
28.65, 128.02, 127.21, 126.95, 120.87, 111.29, 55.58.
underwent a nal evacuation/backll cycle, sealed with a screw cap,
ꢀ
MHz, CDCl
3
and allowed to stir at room temperature (25 C) for the specied
1
times. Conversion, selectivity and GC yield were quantied from an
aliquot (0.20 mL) of the reaction mixture using GC-FID. Upon
completion, the GC sample was transferred back into the main
0
11a
1
2
,6-Dimethoxy-1 -biphenyl.
.46–7.29 (m, 3H), 6.68 (d, J ¼ 8.4 Hz, 1H), 3.75 (s, 3H). C NMR
) d ¼ 157.74, 134.21, 130.95, 128.69, 127.71,
26.81, 119.65, 104.29, 55.96.
,4 -Dimethyl-1,1 -biphenyl.
.34–7.27 (m, 3H), 2.48 (s, 1H), 2.35 (s, 1H). C NMR (126 MHz,
) d ¼ 141.94, 139.10, 136.37, 135.41, 130.29, 129.87,
29.10, 128.79, 127.08, 125.75, 21.18, 20.51.
H NMR (500 MHz, CDCl
3
) d ¼
1
3
7
(
1
101 MHz, CDCl
3
reaction mixture, an aqueous work-up was performed (EtOAc : H
2
O,
1
: 1). The organic layer was dried over MgSO , ltered through
4
0
0
11e
1
2
H NMR (500 MHz, CDCl ) d ¼
3
a cotton wool plug and concentrated on a rotary evaporator. The
isolated yield was obtained by purication of the crude product
through column chromatography using silica gel (EtOAc–hexane).
13
7
CDCl
3
1
0
0
11e
1
2
,4 ,6-Trimethyl-1,1 -biphenyl.
3
H NMR (500 MHz, CDCl )
Characterisation data
d ¼ 7.23 (d, J ¼ 7.6 Hz, 2H), 7.17–7.13 (m, 1H), 7.10 (d, J ¼
11a
1
13
4-Methyl-biphenyl.
H NMR (400 MHz, CDCl
3
) d ¼ 7.66– 7.3 Hz, 2H), 7.04 (d, J ¼ 7.7 Hz, 2H), 2.41 (s, 3H), 2.04 (s, 6H).
C
7
7
.61 (m, 2H), 7.55 (d, J ¼ 8.2 Hz, 2H), 7.51–7.44 (m, 2H), 7.41– NMR (126 MHz, CDCl ) d ¼ 141.86, 138.06, 136.22, 136.06,
3
1
3
.34 (m, 1H), 7.30 (d, J ¼ 8.0 Hz, 2H), 2.45 (s, 3H). C NMR (101 129.11, 128.90, 127.24, 126.87, 21.23, 20.87.
11f
1
MHz, CDCl
3
) d ¼ 141.24, 138.44, 137.09, 129.57, 128.80, 127.08,
3-Phenyl-pyridine.
H NMR (500 MHz, CDCl ) d ¼ 8.82 (s,
3
127.06, 21.18.
1H), 8.55 (d, J ¼ 4.7 Hz, 1H), 7.81 (d, J ¼ 7.8 Hz, 1H), 7.53 (d, J ¼
11b
1
3-Methyl-biphenyl.
H NMR (400 MHz, CDCl
3
) d ¼ 7.62– 8.0 Hz, 2H), 7.43 (t, J ¼ 7.6 Hz, 2H), 7.36 (t, J ¼ 7.0 Hz, 1H), 7.30
1
3
7
7
1
1
.57 (m, 2H), 7.46–7.38 (m, 4H), 7.37–7.30 (m, 2H), 7.17 (d, J ¼ (dd, J ¼ 7.6, 4.9 Hz, 1H). C NMR (126 MHz, CDCl ) d ¼ 148.47,
3
1
3
.5 Hz, 1H), 2.43 (s, 3H). C NMR (101 MHz, CDCl
3
) d ¼ 141.40, 148.33, 137.83, 137.82, 136.58, 134.25, 129.05, 128.07, 127.12,
41.27, 138.35, 128.72, 128.69, 128.02, 128.01, 127.21, 127.18, 123.49.
24.30, 21.57.
2-Phenyl-pyridine.
-Phenylnaphthalene.
1
1g
1
H NMR (500 MHz, CDCl ) d ¼ 8.68 (d, J
3
1
1c
1
2
H NMR (500 MHz, CDCl ) d ¼ 8.09 ¼ 4.3 Hz, 1H), 7.99 (d, J ¼ 7.7 Hz, 2H), 7.70 (s, 2H), 7.46 (t, J ¼
3
1
3
(
3
d, J ¼ 0.6 Hz, 1H), 7.92 (dt, J ¼ 8.8, 4.9 Hz, 3H), 7.81–7.75 (m, 7.5 Hz, 2H), 7.40 (t, J ¼ 7.2 Hz, 1H), 7.19 (s, 1H). C NMR (126
1
3
H), 7.56–7.49 (m, 4H), 7.45–7.39 (m, 1H). C NMR (101 MHz, MHz, CDCl ) d ¼ 157.49, 149.69, 139.45, 136.71, 128.96, 128.75,
3
CDCl
3
) d ¼ 141.21, 138.64, 133.77, 132.71, 128.94, 128.50, 126.93, 122.08, 120.53.
11h
1
1
28.29, 127.73, 127.51, 127.43, 126.36, 126.01, 125.89, 125.68.
2-Phenyl-quinoline.
H NMR (500 MHz, CDCl ) d ¼ 8.23–
3
11c
1
2-Methoxy-6-phenylnaphthalene.
H NMR (500 MHz, 8.14 (m, 4H), 7.84 (d, J ¼ 8.6 Hz, 1H), 7.79 (d, J ¼ 8.1 Hz, 1H),
CDCl
3
) d ¼ 7.98 (s, 1H), 7.80 (dd, J ¼ 8.3, 6.7 Hz, 2H), 7.74–7.69 7.73 (dd, J ¼ 8.1, 7.2 Hz, 1H), 7.56–7.49 (m, 3H), 7.48 (dd, J ¼
1
3
(
(
m, 3H), 7.48 (t, J ¼ 7.7 Hz, 2H), 7.37 (t, J ¼ 7.4 Hz, 1H), 7.21–7.15 10.8, 3.7 Hz, 1H). C NMR (126 MHz, CDCl ) d ¼ 157.35, 148.36,
3
1
3
m, 2H), 3.94 (s, 3H). C NMR (101 MHz, CDCl ) d ¼ 157.81, 139.72, 136.77, 129.81, 129.67, 129.36, 128.87, 127.63, 127.50,
3
1
1
41.24, 136.42, 133.82, 129.75, 129.22, 128.86, 127.29, 127.26, 127.24, 126.30, 118.98.
11f
1
27.10, 126.07, 125.65, 119.19, 105.62, 55.36.
2-Phenyl-thiophene. H NMR (500 MHz, CDCl ) d ¼ 7.42 (d,
3
0
11b
1
3
,5-Dimethyl-1,1 -biphenyl.
H NMR (500 MHz, CDCl
3
) d ¼ J ¼ 5.6 Hz, 1H), 7.34 (bs, 1H), 7.28–7.22 (m, 3H), 7.11–7.07 (m,
1
3
7
1
.61–7.57 (m, 2H), 7.45–7.41 (m, 2H), 7.34 (dd, J ¼ 13.2, 5.9 Hz, 2H), 2.44 (s, 3H). C NMR (101 MHz, CDCl ) d ¼ 143.16, 136.16,
3
1
3
H), 7.22 (s, 2H), 7.01 (s, 1H), 2.39 (s, 6H). C NMR (101 MHz, 134.22, 130.79, 130.54, 127.85, 127.15, 126.45, 125.96, 125.18,
CDCl
3
) d ¼ 141.51, 141.30, 138.27, 128.92, 128.78, 128.66, 21.25.
11i
1
127.28, 127.22, 127.20, 127.10, 125.14, 21.44.
3-(o-Tolyl)pyridine.
H NMR (500 MHz, CDCl ) d ¼ 8.62–
3
0
11d
1
2,4-Dimethyl-1,1 -biphenyl.
H NMR (500 MHz, CDCl ) d ¼ 8.55 (m, 2H), 7.66–7.61 (m, 1H), 7.33 (m, 1H), 7.30–7.24 (m, 3H),
3
13
7
7
2
1
1
.46 (dd, J ¼ 10.4, 4.4 Hz, 2H), 7.41–7.35 (m, 3H), 7.20 (d, J ¼ 7.20 (d, J ¼ 7.2 Hz, 1H), 2.26 (s, 3H). C NMR (101 MHz, CDCl3)
.7 Hz, 1H), 7.16 (s, 1H), 7.12 (d, J ¼ 7.7 Hz, 1H), 2.43 (s, 3H), d ¼ 149.93, 148.09, 138.09, 137.49, 136.50, 135.60, 130.57,
1
3
.31 (s, 3H). C NMR (101 MHz, CDCl
36.94, 135.21, 131.17, 129.84, 129.37, 128.84, 128.11, 127.25,
26.67, 126.57, 21.13, 20.46.
3
) d ¼ 142.04, 139.20, 129.87, 128.12, 126.08, 123.02, 20.35.
11j
1
2-(o-Tolyl)-thiophene.
H NMR (400 MHz, CDCl ) d ¼ 7.48–
3
7.44 (m, 1H), 7.37 (d, J ¼ 5.0 Hz, 1H), 7.32–7.26 (m, 3H), 7.13 (m,
0
7n
1
13
2,4,6-Trimethyl-1,1 -biphenyl.
H NMR (400 MHz, CDCl
3
)
2H), 2.48 (s, 3H). C NMR (101 MHz, CDCl ) d ¼ 143.16, 136.16,
3
d ¼ 7.48 (t, J ¼ 7.4 Hz, 2H), 7.40 (d, J ¼ 7.4 Hz, 1H), 7.22 (t, J ¼ 134.22, 130.79, 130.54, 127.85, 127.15, 126.45, 125.96, 125.18, 21.25.
1
3
11k
1
6.3 Hz, 2H), 7.03 (s, 2H), 2.41 (s, 3H), 2.09 (s, 6H). C NMR (126
2-(2,6-Dimethylphenyl)pyridine.
H NMR (500 MHz,
MHz, CDCl
3
) d ¼ 141.19, 139.16, 136.64, 136.06, 129.39, 128.47, CDCl ) d ¼ 8.75–8.64 (m, 1H), 7.73 (t, J ¼ 7.6 Hz, 1H), 7.25–7.14
3
128.16, 126.61, 21.14, 20.86.
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1
3
(
m, 3H), 7.08 (d, J ¼ 7.5 Hz, 2H), 2.02 (s, 6H). C NMR (101
MHz, CDCl ) d ¼ 159.94, 149.75, 140.52, 136.31, 135.79, 127.88,
B. U. W. Maes and S. Ballet, Catalysts, 2017, 7, 1–32; (f)
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3
1
27.55, 124.46, 121.69, 20.26.
-(2,6-Dimethylphenyl)pyridine.
CDCl
) d ¼ 8.59 (dd, J ¼ 4.9, 1.7 Hz, 1H), 8.43 (dd, J ¼ 2.2, 0.9 Hz,
H), 7.52–7.47 (m, 1H), 7.36 (m, 1H), 7.19 (dd, J ¼ 8.5, 6.5 Hz,
11l
1
3
H NMR (400 MHz,
3
1
1
1
3
3
H), 7.13–7.10 (m, 2H), 2.02 (s, 6H). C NMR (101 MHz, CDCl )
d ¼ 150.04, 148.11, 137.85, 136.78, 136.69, 136.31, 127.89,
27.58, 123.41, 20.91.
-(2,6-Dimethylphenyl)-thiophene.
CDCl ) d ¼ 7.40 (d, J ¼ 5.1 Hz, 1H), 7.24–7.19 (m, 1H), 7.14 (d, J
1
11l
1
2
H NMR (400 MHz,
3
1
3
¼
7.7 Hz, 3H), 6.86 (d, J ¼ 2.8 Hz, 1H), 2.19 (s, 6H). C NMR (101
MHz, CDCl
) d ¼ 141.40, 138.51, 134.13, 128.15, 127.33, 127.13,
26.33, 125.36, 20.88.
3
1
129, 5096–5101.
5
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Conflicts of interest
There are no conicts to declare.
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Acknowledgements
We are grateful for nancial support from Research Centre for
Synthesis and Catalysis (University of Johannesburg) and Sasol
(Pty) Ltd. We thank Mr Mutshinyalo Nwamadi (NMR) as well as
Dr Banele Vatsha and Dr Frederick Malan for assistance with X-
Ray crystallography. The authors also thank Sasol Research &
Technology (South Africa) for providing secondary phosphines
phobane-H and Cg-H. Stellenbosch University Central Analyt-
ical Facilities is acknowledged for mass spectrometry analysis.
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2021 The Author(s). Published by the Royal Society of Chemistry
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