The synthesis of a [2.2]paracyclophane-derived secondary phosphine oxide and a study of its reactivity

Article abstract of DOI:10.1016/j.tet.2018.05.013

A planar chiral secondary phosphine oxide based on [2.2]paracyclophane was synthesized and its chemistry investigated; it was shown to be a competent pre-ligand in palladium(0)-mediated reactions, and displayed promising activity in gold(I)-catalysed cyclisations. The secondary phosphine oxide could be transformed into a collection of P-stereogenic tertiary phosphine oxides. These are rare examples of the planar chirality of [2.2]paracyclophane being combined with a P-stereogenic centre. Unfortunately, epimerisation of the phosphorus stereocentre during reduction limits the use of this chemistry.

Full text of DOI:10.1016/j.tet.2018.05.013

Accepted Manuscript
The synthesis of a [2.2]paracyclophane-derived secondary phosphine oxide and a
study of its reactivity
Maulik N. Mungalpara, Jingjing Wang, Martyn P. Coles, Paul G. Plieger, Gareth J.
Rowlands
PII:
S0040-4020(18)30528-3
10.1016/j.tet.2018.05.013
TET 29520
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 27 February 2018
Revised Date: 2 May 2018
Accepted Date: 3 May 2018
Please cite this article as: Mungalpara MN, Wang J, Coles MP, Plieger PG, Rowlands GJ, The synthesis
of a [2.2]paracyclophane-derived secondary phosphine oxide and a study of its reactivity, Tetrahedron
(2018), doi: 10.1016/j.tet.2018.05.013.
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ACCEPTED MANUSCRIPT

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1

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The Synthesis of a [2.2]Paracyclophane-Derived Secondary Phosphine Oxide and a Study of
its Reactivity
a
a
b
a
Maulik N. Mungalpara, Jingjing Wang, Martyn P. Coles, Paul G. Plieger, Gareth J.
a*
Rowlands
a
Institute of Fundamental Sciences, Massey University, Private Bag 11 222, Palmerston
North, New Zealand. E-mail: g.j.rowlands@massey.ac.nz
b
School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box
6
00, Wellington, New Zealand
Abstract
A planar chiral secondary phosphine oxide based on [2.2]paracyclophane was synthesised
and its chemistry investigated; it was shown to be a competent pre-ligand in palladium(0)-
mediated reactions, and displayed promising activity in gold(I)-catalysed cyclisations. The
secondary phosphine oxide could be transformed into a collection of P-stereogenic tertiary
phosphine oxides. These are rare examples of the planar chirality of [2.2]paracyclophane
being combined with a P-stereogenic centre. Unfortunately, epimerisation of the phosphorus
stereocentre during reduction limits the use of this chemistry.
Introduction
Trivalent phosphine compounds are vital to modern synthesis acting as the quintessential
1
2
ligand in a variety of metal-catalysed reactions, and, to a lesser extent, as organocatalysts.
Even if we only consider chiral phosphines there are a staggering number of phosphorus(III)
compounds, and yet there is still a demand for even more phosphines in order to sate the
ever-increasing need for improved reactivity, improved selectivity, and/or more robust
catalysts.
2

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One of the major drawbacks with many phosphorus(III) compounds is their sensitivity to
3
4,3c
oxidation. Protection as borane adducts, or phosphonium salts offers a solution to this
problem. Another possibility is the use of secondary phosphine oxides (SPOs). These are
frequently air-stable pentavalent phosphorus species 1 that exist in equilibrium with the
5
trivalent phosphinous acid 2 as shown in Scheme 1. The equilibrium strongly favours the
P(V) species 1 until a transition metal is added then the equilibrium is driven towards
formation of the P(III) complex 3. SPOs offer a variety of binding modes making them
appealing pre-ligands; they can mimic trialkylphosphines and behave as monodentate ligands
3
. Alternatively, they can form bimetallic species (4 and 6) by coordinating late-transition
metals through the ‘soft’ phosphorus atom and early-transition metals through the ‘hard’
5
-6
oxygen atoms or they can ‘self-assemble’ into bidentate ligands through a hydrogen-bond
bridge 5 or as a bimetallic bidentate complex 6.
Scheme 1. Secondary phosphine oxides (SPOs) and their complexes.
A considerable body of work has been reported detailing the synthesis and application of
5
SPOs in catalysis. Notable applications of achiral SPOs have been the C–H activation and
7
8
direct arylation of oxazolines, and their use in gold-catalysed cyclopropanations. Most
9
chiral SPOs have not been resolved or applied to asymmetric transformations. The earliest
3

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example of a chiral SPO in an asymmetric transformation involved the reduction of an
10
11
imine; and this was followed by a limited number of other reductions, additions to
1
2
6
allenes, and a bimetallic hydrocarbamoylation.
1
3
[
2.2]Paracyclophane offers an intriguing scaffold for the formation of chiral ligands.
Unlike ferrocene, it only requires a single substituent on one of the aromatic rings to create
planar chirality. Its rigid structure restricts conformational freedom resulting in well-defined
structures. This has led to the development of a number of useful [2.2]paracyclophane-based
1
4
phosphine ligands, notably the isomeric diphosphines, PhanePhos (pseudo-ortho or 4,12-
1
5
disubstituted) and GemPhos (pseudo-gem 4,13-disubstituted).
1
6a-d,13g,16e
While many [2.2]paracyclophane-based phosphines have been reported,
there is
one glaring omission; there has, to the best of our knowledge, been no systematic research on
P-stereogenic [2.2]paracyclophane derivatives. There is a single reference to a P-stereogenic
1
7
[
2.2]paracyclophane derivative in a 2007 patent.
We have studied a range of planar chiral monophosphines, the majority of these
separated the [2.2]paracyclophane from the phosphine with a heteroaromatic ring such as
1
3g
18
16b
16c
imidazole, triazole, or indole. We have also studied the direct attachment of the
1
9,13g,16d
phosphine to [2.2]paracyclophane.
The monodentate phosphines showed too much
1
6d
conformational freedom to induce high enantioselectivities, while the bidentate ligand was
taxing to synthesise in high yield. We wanted a simpler route to bidentate planar chiral
ligands. We saw an opportunity in SPO chemistry to prepare enantiomerically enriched
bidentate ligands by the self-assembly of two SPOs. We anticipated that a menthol-derived
2
0
H-phosphinate would fix the P-stereocentre allowing installation of the SPO moiety with
simultaneous resolution of the planar chirality of [2.2]paracyclophane. This would mimic our
2
1
earlier successful sulfoxide chemistry. On coordination with the appropriate metal, we then
4

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hoped that two planar chiral SPOs would interact through either hydrogen bonding or a
bridging metal to give the desired bidentate complex analogous to 5 or 6.
Such a route would also enable the synthesis of new planar chiral phosphines by P-
arylation of the SPO. The resulting tertiary phosphine would allow the first systematic study
of P-stereogenic [2.2]paracyclophane derivatives. In this paper we outline the synthesis and
reactivity of a planar chiral SPO, highlighting the potential of this chemistry and delineating
current limitations.
Results and Discussion
The chemistry started smoothly, addition of 4-lithio[2.2]paracyclophane, generated by
halogen-metal exchange of 7, to tert-butyldichlorophosphine followed by hydrolysis gave the
desired tert-butyl secondary phosphine oxide 8 as essentially one diastereomer (> 95:5 d.r.)
1
(
Scheme 2). The H NMR spectrum indicates that the unlike (RS ,SR ) diastereomer was
p
P
*
formed. The downfield shift of a proton at C2 is characteristic of the anisotropic influence of
the proximal oxygen of the SPO. The same observation was made in the analogous sulfoxide
2
1d,21e,21a
chemistry.
The stereochemistry was confirmed by single X-ray crystallography
2
2
(Figure 1).
*
For compounds possessing both a stereogenic plane and a stereogenic centre we use a
nomenclature where S (lowercase p) refers to the planar chirality as defined from the C1
p
pilot atom (a good description of defining the stereochemistry of [2.2]paracyclophane can be
1
3b
found in the Gibson review ) and S (uppercase P) refers to the phosphorus stereochemistry.
P
2
3
We have used Cahn-Ingold-Prelog labelling for racemates (RS,SR = R*,S*).
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Scheme 2. Synthesis of [2.2]paracyclophane-based SPO. Reagents and conditions (a) i. n-
BuLi; ii. t-BuPCl ; iii. H O, 30 - 55%, > 95:5 dr.
2
2
Figure 1. X-ray of secondary phosphine oxide (RS ,SR )-8. Ellipsoids are drawn at a 50%
p
P
2
2
probability level.
The origin of the diastereoselectivity is unclear. Arguably, (RS ,SR )-8 is the more
p
P
sterically congested diastereomer as the oxygen is forced into close proximity with the
ethylene bridge. In our earlier sulfoxide chemistry, oxidation of 4-tert-
2
1e
butylsulfanyl[2.2]paracyclophane always furnished the like (RS ,RS ) diastereomer and we
p
S
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suggested that the lone pair facing C5 was more accessible. Based on this observation, it is
plausible that addition to tert-butyldichlorophosphine results in formation of a single
diastereomer of chlorophosphine (9) with the chlorine atom orientated towards the ortho
proton. Hydrolysis then occurs with inversion of the stereochemistry to give the more
congested phosphine oxide (Scheme 2).
The synthesis of other [2.2]paracyclophane-based SPOs proved impossible. A
2
4a-c,11f,20d,24d,20c,24e-g
comprehensive array of reactions were attempted
but all to no avail. We
were able to prepare alkyl [2.2]paracyclophane-H-phosphinates but could not displace the
9
f
alkoxy substituent. It is unclear why these reactions failed; our experience with
[
2.2]paracyclophane suggests that the bulk, and the high basicity of this scaffold can impede
seemingly simple transformations.
Fortunately, the chemistry of the planar chiral SPO (RS ,SR )-8 was more rewarding. It
p
P
proved to be a competent pre-ligand in a number of metal-catalysed transformations. A
catalyst formed from SPO 8 promoted Suzuki-Miyaura couplings, such as that of 2-
bromotoluene and 2-methoxyphenylboronic acid (Scheme 3), but it should be noted that
2
5
simpler SPO ligands, such as POPd [(t-Bu P(O)H) PdCl ], or analogous ligands such as
2
2
2
9
e
(
tert-butylphosphinyl)ferrocene, give better yields. The Buchwald_Hartwig arylation of
2
5b,26
various anilines were more promising (Scheme 4).
Electron rich and electron poor aryl
bromides and chlorides could be coupled to various anilines including sterically demanding
examples.
7

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Scheme 3. Suzuki-Miyaura coupling catalysed by Pd(0) and SPO-8. Reagents and
Conditions (a) Pd(OAc) (1 mol%), 8 (1 mol%), NaOt-Bu (200 mol%), EtOH, 80 °C, 64%
2
(gc yield).
Scheme 4. Buchwald-Hartwig coupling of aryl bromides (unless otherwise noted) and
anilines catalysed by SPO-8. Reagents and Conditions (a) [Pd (dba) ] (2.5 mol%), 8 (10
2
3
mol%), NaOt-Bu (150 mol%), toluene, 105 °C, (isolated yields).
In an effort to gain greater insight into the palladium-mediated reactions we tried to
prepare a Pd(II) complex of SPO-8. While we were unable to isolate a pure complex,
presumably due to the racemic SPO furnishing a mixture of diastereomers along with
potential geometric isomers, we made one pertinent observation; treating SPO-8 with
Pd(OAc) in various solvents at room temperature, or higher, resulted in the clean
2
decomposition of the SPO into [2.2]paracyclophane 10 (Scheme 5).
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Scheme 5. Protodephosphinylation of SPO-8. Reagents and conditions (a) Pd(OAc)2,
toluene at 50 °C or CH Cl or CDCl at rt, > 95%.
2
2
3
Pd-mediated cleavage of C–P bonds is unusual but not unheard of. There have been
reports of triarylphosphines acting as sources of the aryl moiety in cross coupling reactions
2
7
2
8
and such reactions have been performed with sub-stoichiometric quantities of Pd(OAc)2.
Recently analogous methodology was used to prepare a P,N-[2.2]paracyclophane
1
6e
derivative. While there have been no reports of palladium insertion into the C–P bond of a
2
9
secondary phosphine oxide, Pfaltz has reported the insertion of iridium into such a bond,
while it has also been shown that palladium will insert into the C–P bond of arylphosphonic
3
0
acids. It is clear that the combination of the tert-butyl secondary phosphine oxide and
[
2.2]paracyclophane activates the C–P bond. This may prove an interesting method to
functionalise paracyclophane if the SPOs can be synthesized in enantiomerically pure form.
Concerned with the instability of SPO 8 in Pd-catalysed reactions, we turned our attention
to Au-mediated cyclisations. At the outset of this research there had been only a single report
8
of an Au(I)-SPO complex being used in catalysis. Formation of the gold complex, as judged
1
31
by H and P NMR, was readily achieved by treating the SPO with chloro(dimethyl
sulfide)gold(I) in dichloromethane at room temperature.
9

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Scheme 6. Cycloisomerisation of 11. Regents and conditions (a) 8-AuCl (2 mol%),
AgSbF (2 mol%), CH Cl , rt, 10 hrs, 73%.
6
2
2
Scheme 7. Methoxycyclisation of enynes. Reagents and conditions (a) 8-AuCl (2 mol%),
AgSbF (2 mol%), CH Cl , rt, 12 hrs, 14 = 72%; 15 = 97%.
6
2
2
Three cyclisations were examined, the cycloisomerisation of the dimethyl malonate-
derived enyne 11 (Scheme 6) and the methoxycyclisation of 11 and the sulfonamide analogue
1
3 (Scheme 7). The reactions proceeded smoothly to give the excepted products, the diene 12
or the ethers 14 and 15, in good yield. Comparing our results with those for the published
SPO catalyst there is little difference; this result shows promise for future studies should we
be able to resolve the racemate.
C–P bond formation by the arylation of P–H bonds is a powerful method for the
3
1
formation of phosphines, phosphinates, and other other phosphorus containing species. . The
arylation of the SPO (RS ,SR )-8 would provide a general route to P-stereogenic
p
P
[
2.2]paracyclophane-derived phosphines. This is an unstudied area of [2.2]paracyclophane
1
7
chemistry with only a single example reported in a patent. Such a target is attractive as it
might permit the tuning of steric properties on a planar chiral phosphine derivative.
3
1a
Based on Bloomfield’s methodology, we investigated the Pd-mediated arylation of
SPO 8. Optimisation led to conditions that permitted a variety of electron rich and electron
poor aryl iodides to be coupled to the SPO to give the tertiary phosphine oxides 16a-e in
good yield (Scheme 8). Unlike Bloomfield’s original couplings, the reaction required
10

ACCEPTED MANUSCRIPT
elevated temperatures, suggesting that the sterically demanding nature of the
[
2.2]paracyclophane SPO impedes reaction.
Scheme 8 – (a) Ar–I (150 mol%), Pd(OAc) (2 mol%), dppf (2.2 mol%), Cs CO (130
2
2
3
mol%), 1,4-dioxane:DCE (9:1), 100 °C.
In each case, the new tertiary phosphine oxides were formed as a single diastereomer as
1
judged by H NMR spectroscopy. As before, the characteristic downfield shift of one of the
H2 protons indicates that the unlike diastereomer is favoured as we would expect (except in
the 2-pyridyl example where the like diastereomer is formed due to a change in priorities
according the Cahn-Ingold-Prelog guidelines). This was later confirmed by X-ray
2
2
crystallography (Figure 2).
11

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Figure 2. X-ray structure of tertiary phosphine oxide 16b. Ellipsoids are drawn at a 50%
2
2
probability level.
The disadvantage of this route to chiral phosphines is that it requires reduction of a
3
2
phosphine oxide. This is always a challenging reaction but past precedent suggested it
would be possible; a number of [2.2]paracyclophane phosphine oxides have been
1
4a,15b,33
reduced.
Our confidence was misplaced. We attempted a comprehensive cross section
3
4
of reduction methodologies but with no success. The only conditions that furnished any of
the desired compound was prolonged heating at 145 °C with excess trichlorosilane or use of
phenylsilane for excessive reaction times (Scheme 9). Reduction of a single diastereomer of
1
tertiary phosphine oxide gave two major compounds as revealed by H NMR spectroscopy of
the crude reaction mixture. The phosphines are unstable and this has made identification
challenging. They could be ‘protected’ as the phosphonium salt by reaction with
tetrafluoroboric acid or by complexation with chloro(tetrahydrothiophene)gold(I) or
chloro(dimethyl sulfide)gold(I) to give, in each case, two inseparable products. Spectroscopic
evidence shows that reduction and complexation was possible for all derivatives but 17a, 17c
or 17d could not be isolated as pure samples. Crude NMR have been included in the
supplementary data.
12

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Scheme 9. Reduction of phosphine oxides. Reagents and conditions (a) Cl SiH (28 eq.),
3
xylene, 145 °C, 24 hrs or neat PhSiH , 140 °C for 3-5 days; crude reaction mixtures used
3
without purification in step (b). (b) HBF (15 eq.), H O, CH Cl or Au(dms)Cl (1.0 eq.),
4
2
2
2
*
1
CH Cl or Au(tht)Cl (1.2 eq.), CH CN. Overlapping peaks in the H NMR spectrum
2
2
3
*
*
prevented the diastereomeric ratio of 17a/17d being determined. 17a, 17c, 17d could be
reduced and complexes formed but it proved impossible to remove all impurities.
We believe that the reduction occurs with epimerisation at the phosphorus stereocentre to
generate two diastereomeric phosphines. We have ruled out epimerisation of the planar
chirality by conducting the reduction at 110 °C. This yields the same products in the same
ratio but at a temperature unlikely to cause homolytic scission of the [2.2]paracyclophane
ethylene bridge.
Curiously, the pyridine derivative 16e gives a single diastereomer on reduction.
1
Inspection of the H NMR of the gold complex suggests that reduction occurs with retention
of stereochemistry at phosphorus; there are two downfield signals that can be assigned to the
2
2
ethylene bridge. This was later confirmed by X-ray crystallography (Figure 3). It is unclear
why the pyridine alters the stereochemical course of the reduction. It is possible that a
pyridine-silane adduct delivers the hydride in an intramolecular fashion causing
stereoselective reduction. Ideally, we would prepare a regioisomeric pyridine tertiary
phosphine oxide and see if clean reduction is still observed.
13

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Figure 3. X-ray of the gold complex of phosphine 17e•AuCl. Ellipsoids are drawn at a
2
2
5
0% probability level.
Conclusion
This project set out to investigate the synthetic utility of [2.2]paracyclophane-derived
secondary phosphine oxides. It is clear that the unusual properties of [2.2]paracyclophane has
adversely affected the chemistry. The tert-butyl secondary phosphine oxide is readily
prepared as a single diastereomer. It is a capable pre-ligand, facilitating both Suzuki-Miyaura
cross coupling reactions and Buchwald-Hartwig aminations. More promising is its
complexation with gold, which results in the formation of a complex capable of catalysing
cycloisomerisations and methoxycyclisations.
It was noted that Pd(OAc) inserts into the C[2.2]paracyclophane–P bond causing
2
protodephosphinylation. Should it be possible to prepare enantiomerically enriched
[
2.2]paracyclophane SPOs, this could offer a new route to planar chiral motifs.
The [2.2]paracyclophane SPO was readily transformed into a variety of tertiary
phosphine oxides. These molecules are promising candidates for ligand synthesis as they are
14

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both planar chiral and chiral at phosphorus. During the reduction of the phosphine oxide
epimerisation of all but the pyridine derivative was observed leading to the isolation of a
mixture of diastereomers.
Planar chiral SPOs show potential in asymmetric catalysis, but more research is required
before they can fulfil their potential.
Experimental
All starting compounds and solvents were used as received from commercial sources
without further purification unless otherwise noted. All reactions were performed in oven-
dried glassware under an atmosphere of argon or nitrogen unless otherwise stated. Column
chromatography was carried out on silica gel (grade 60, mesh size 230-400, Scharlau).
Visualisation techniques employed included using ultraviolet light (254 nm), potassium
permanganate, ethanolic phosphomolybdic acid or ninhydrin when applicable. NMR spectra
were recorded at room temperature on Bruker-400 and Bruker-500 Avance instruments, with
the use of the residual solvent proton as an internal standard (CHCl = 7.26 ppm). Melting
3
points were recorded on a Gallenkamp melting point apparatus and are uncorrected. Mass
spectra and high-resolution mass spectrometry were performed at Massey University, using a
ThermoScientific Q Exactive Focus Hybrid Quadrupole-Orbitrap Mass Spectrometer.
(
SR , RS )-tert-butyl([2.2]paracyclophan-4-yl)phosphine oxide (8)
P p
A solution of n-BuLi (1.2 M in hexanes; 18.3 ml, 21.9 mmol, 1.05 eq.) was added
dropwise over 30 min. to a solution of (±)-4-bromo[2.2]paracyclophane (6.0 g, 20.9 mmol,
1
.0 eq.) in THF (60 ml), at -78 °C. The resulting yellow solution was stirred at -78 °C for 40
min. tert-Butyldichlorophosphine (1M in Et O; 21.9 ml, 21.9 mmol, 1.05 eq.) was added
2
dropwise over 20 min. The solution was warmed to room temperature overnight. H O (75 ml)
2
15

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was added to the reaction mixture and the resulting organic phases were separated. The
aqueous phase was extracted with EtOAc (3 × 50 ml), the combined organics dried (MgSO4)
and concentrated under reduced pressure to yield a yellow residue. Purified by column
chromatography on silica gel (EtOAc:Hex 6:4) followed by recrystallization (CH Cl :Pentane
2
2
2
:8) to give white crystals of 8 (3.3 g, 55%).
Rf (4:6 Hex:EtOAc) 0.40.
mp: 142 – 144 °C
IR νmax 2959, 2930, 2865, 1700, 1594, 1499, 1473, 1431, 1410, 1392, 1358, 1263, 1129,
-1
1
094, 1069, 1022, 994, 925, 900 cm .
1
H NMR (CDCl , 500 MHz): δ 7.42 (1H, d, J = 398.1 Hz), 6.92 (1H, d, J = 7.7 Hz), 6.67
3
P-H
(
1H, d, J = 8.1 Hz), 6.61-6.58 (2H, m, H-7), 6.53-6.52 (2H, m), 6.45 (1H, d, J = 8.1 Hz), 3.94
1H, t, J = 11.5 Hz), 3.45 (1H, td, J = 12.1, 4.6 Hz), 3.22-3.18 (2H, m), 3.13-2.99 (4H, m),
(
1
.00 (9H, d, J = 16.3 Hz).
1
3
C NMR (CDCl , 125 MHz) δ 173.7, 145.3, 140.02, 139.6 (d, JP-C = 54.1 Hz), 135.5 (d, JP-C
3
=
71.3 Hz), 134.2 (d, JP-C = 133.8 Hz), 133.2 (d, JP-C = 105.2 Hz), 132.2, 126.3 (d, JP-C =
3
75.7 Hz) 39.53, 36.2, 35.2, 32.6 (d, JP-C = 273.0 Hz), 23.5.
3
1
P NMR (CDCl , 200 MHz) δ 57.81.
3
+
+
HRMS-EI: m/z found: [M] , 312.1747. C H OP requires [M] 312.1643.
25
25
(
RS ,RS )-chloro(tert-butyl([2.2]paracyclophan-4-yl)phosphinous acid)gold(I)
P p
8
•AuCl
To a solution of secondary phosphine oxide 8 (30 mg, 0.01 mmol, 1eq.) in CH Cl (5 mL)
2
2
was added chloro(dimethyl sulfide)gold(I) (28 mg, 0.01 mmol, 1eq.). The mixture was stirred
at room temperature overnight in the absence of light. The crude mixture was concentrated
16

ACCEPTED MANUSCRIPT
under reduced pressure to give a greyish solid of the gold complex. Due to the instability of
the complex only limited data could be collected.
1
H NMR (CDCl , 500 MHz): δ 7.33 (1H, dd, J = 20.1, 1.7 Hz), 6.96 (2H, d, J = 7.7 Hz), 6.65
3
(2H, d, J = 8.0 Hz), 6.55 (2H, dd, J = 7.7, 3.2 Hz), 6.52 (1H, dd, J = 7.8, 1.7 Hz), 4.01 (1H, t,
1
1.2 Hz), 3.29-3.21 (2H, m), 3.22-3.16 (2H, m), 3.15-3.11 (1H, m), 3.10-3.02 (2H, m), 1.00
(9H, d, J = 17.3 Hz).
3
1
P NMR (CDCl , 200 MHz) δ 125.63.
3
3
5
(±)-Dimethyl 3-(2-methylprop-1-en-1-yl)cyclopent-3-ene-1,1-dicarboxylate 12
To a solution of 8•AuCl (3 mg, 0.007 mmol, 0.02 eq.) in CH Cl (2 ml) was added
2
2
AgSbF (4 mg, 0.007 mmol, 0.02 eq.) and suspension stirred for 10 min. During this time
6
AgCl precipitates as a white solid. A solution of 1,6-enyne 11 (90 mg, 0.37 mmol, 1eq.) in
CH Cl (5.5 ml). The mixture was stirred at room temperature and was monitored by TLC.
2
2
After 10 hrs, the mixture was filtered through a short pad of silica (CH Cl , 10 ml) and
2
2
concentrated under reduced pressure. Subsequent purification by column chromatography on
silica gel (EtOAc:Hex 0.2:9.8) afforded product 12 as colourless oil (66 mg, 73%).
1
H NMR (CDCl , 500 MHz): δ 5.75 (1H, s), 5.41 (1H, s), 3.76 (6H, s), 3.22 (2H, s), 3.07
3
3
6
(2H, s), 1.84 (3H s), 1.80 (3H, s). Data comparable to that reported in the literature.
(±)-Dimethyl 3-(2-methoxypropan-2-yl)-4-methylenecyclopentane-1,1-dicarboxylate 14
To a solution of 8•AuCl (3 mg, 0.008 mmol, 0.02 eq.) in CH Cl (2 ml) was added
2
2
AgSbF (5 mg, 0.008 mmol, 0.02 eq.) and suspension stirred for 10 min. During this time
6
AgCl precipitates as a white solid. A solution of 1,6 enyne 11 (100 mg, 0.41 mmol, 1.0 eq.)
in CH OH (8.3 ml) was added. The mixture was stirred at room temperature and was
3
monitored by TLC. After 12 hrs, the mixture was filtered through a short pad of silica
17

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(
CH Cl , 10 ml) and concentrated under reduced pressure. Subsequent purification by column
2
2
chromatography on silica gel (EtOAc:Hex 0.2:9.8) afforded product 14 as colorless oil (81
mg, 72%).
1
H NMR (CDCl , 500 MHz): δ 5.04 (1H, bs), 4.98 (1H, bs), 3.73 (3H, s), 3.72 (3H, s), 3.19
3
(3H, s), 2.94-2.83 (3H, m), 2.55 (1H, ddd, J = 13.5, 9.4, 1.7 Hz), 2.00 (2H, dd, J = 13.5, 9.4
3
7
Hz), 1.18 (3H, s), 1.12 (3H, s). Data comparable to that reported in the literature.
(±)-3-(2-methoxypropan-2-yl)-4-methylene-1-tosylpyrrolidine 15
To a solution of 8•AuCl (3 mg, 0.005 mmol, 0.02 eq.) in CH Cl (2 ml) was added
2
2
AgSbF (2 mg, 0.005 mmol, 0.02 eq.) and suspension stirred for 10 min. During this time
6
AgCl precipitates as a white solid. A solution of 1,6-enyne 13 (75 mg, 0.27 mmol, 1eq.) in
CH OH (3.4 ml) was added. The mixture was stirred at room temperature and was monitored
3
by TLC. After 12 hrs, the mixture was filtered through a short pad of silica (CH Cl , 10 ml)
2
2
and concentrated under reduced pressure. Subsequent purification by column
chromatography on silica gel (EtOAc:Hex 0.1:9.9) afforded product 15 as a white solid (81
1
mg, 97%); H NMR (CDCl , 500 MHz): δ 7.74 (2H, d, J = 6.1 Hz), 7.35 (2H, d, J = 7.9 Hz),
3
5
.04 (2H, m), 3.80 (2H, m), 3.43 (1H, dd, J = 9.9, 4.2 Hz), 3.32-3.29 (1H, m), 2.74 (3H, s),
2
.45 (3H, s), 1.14 (3H, s), 1.14 (3H, s), 1.03 (3H, s). Data comparable to that reported in the
8
literature.
General procedure for P-arylation
To a flame dried 25 ml round bottom flask was added Pd(OAc) (2 mol%), dppf (2.2
2
mol%), Cs CO (1.3 eq.). The reaction vessel was degassed and dioxane (2 ml) added. The
2
3
resulting suspension was stirred under a flow of argon for 10 min. A solution of SPO 8 (1.0
eq.) and aryl iodide (1.5 equiv.) in dioxane:DCE (7:1) (8 ml) was added by syringe. The
18

ACCEPTED MANUSCRIPT
reaction mixture was heated at 100 °C until the starting material had been completely
consumed as judged by TLC (24 hrs). The mixture was cooled to room temperature, passed
through celite pad and purified by column chromatography on silica gel (EtOAc:Hex 4:6) to
obtain the appropriate tertiary phosphine oxide.
(
RS ,RS )-tert-Butyl([2.2]paracyclophan-4-yl)(phenyl)phosphine oxide 16a
P p
Pd(OAc) (1 mg, 0.004 mmol, 0.02 eq.), dppf (2 mg 0.004 mmol, 0.022 eq.), Cs CO (81
2
2
3
mg, 0.25 mmol, 1.3 eq.), 8 (60 mg, 0.19 mmol, 1 eq.), phenylbromide (0.03 ml, 47.53 mg,
.30 mmol, 1.5 eq.) to give a yellow solid of 16a (45 mg, 61%).
0
mp: 166 – 168 °C.
IR: νmax 2924, 2856, 1586, 1497, 1474, 1433, 1409, 1393, 1365, 1263, 1209, 1165, 1153,
-1
1
129, 1100, 1074, 1066, 1020, 996, 941, 916, 902 cm .
1
H NMR (CDCl , 500 MHz): δ 8.20-8.16 (2H, m), 7.69-7.61 (3H, m), 6.68 (1H, dd, J = 7.8,
3
1
.7 Hz), 6.60-6.58 (3H, m), 6.56 (1H, dd, J = 7.8, 1.5 Hz), 6.47 (1H, dd, J = 7.8, 1.8 Hz),
.76 (1H, dd, J = 7.8, 1.8 Hz), 4.49 (1H, t, J = 10.9 Hz), 3.50 (1H, td, J = 8.3, 5.6 Hz), 3.13-
.06 (2H, m), 3.02-2.96 (2H, m), 2.94- 2.90 (1H, m), 2.82-2.76 (1H, m), 1.07 (9H , d, J =
6.1 Hz).
5
3
1
1
3
C NMR (CDCl , 125 MHz) δ 146.6 (d, JP-C = 27.4 Hz), 140.4, 138.7, 138.6 (d, JP-C = 47.7
3
Hz), 136.7 (d, JP-C = 47.8 Hz), 136.2 (d, JP-C = 47.7 Hz), 135.9 (d, JP-C = 11.5 Hz), 134.0,
1
33.0 (d, JP-C = 27.9 Hz), 132.2 (d, JP-C = 40.5 Hz), 131.8, 131.3 (d, JP-C = 10.1 Hz), 131.1,
28.3, 127.3, 126.6, 36.8, 36.2, 35.2 (d, JP-C = 25.5 Hz), 35.0, 34.6, 25.1.
1
3
1
P NMR (CDCl , 200 MHz) δ 41.93.
3
+
+
HRMS-EI: m/z found: [M+H] , 389.2024. C H OP requires 389.2034; [M+Na] 411.1846
26
30
C H NaOP requires 411.1854.
26
29
19

ACCEPTED MANUSCRIPT
(
RS ,RS )-tert-Butyl([2.2]paracyclophan-4-yl)(p-tolyl)phosphine oxide 16b
P
p
Pd(OAc) (1 mg, 0.004 mmol, 0.02 eq.), dppf (2 mg, 0.004 mmol, 0.02 eq.), Cs CO (81
2
2
3
mg, 0.25 mmol, 1.3 eq.), 8 (60 mg, 0.191 mmol), 4-iodotoulene (49.24 mg, 0.287 mmol, 1.5
eq.) in dioxane:DCE (7:1) (8 ml), to give a white solid of 16b (52 mg, 68%).
Rf (7:3 Hex:EtOAc) 0.50.
mp: 216 – 218 °C
IR: νmax 2925, 2851, 1725, 1598, 1500, 1466, 1433, 1394, 1365, 1293, 1259, 1205, 1162,
-1
1
150, 1111, 1066, 1013, 942, 919, 906, 906, 813, 799, 720 cm .
1
H NMR (CDCl , 500 MHz): δ 8.05 (2H, t, J = 8.5 Hz), 7.46 (2H, d, J = 8.0 Hz), 6.68 (1H, d,
3
J = 5.7 Hz), 6.59 (3H, m), 6.56 (1H, dd, J = 7.8, 1.7 Hz), 6.46 (1H, dd, J = 7.7, 1.8 Hz), 5.79
(1H, dd, J = 7.7, 1.8 Hz), 4.48 (1H, t, J = 10.8 Hz), 3.50 (1H, td, J = 10.7, 5.4 Hz), 3.12-3.07
(2H, m), 3.01- 2.91 (3H, m), 2.85-2.78 (1H, m), 2.54 (3H, s), 1.04 (9H, d, J = 16.9 Hz).
1
3
C NMR (CDCl , 125 MHz) δ 138.6 (d, JP-C = 47.9 Hz), 136.7 (d, JP-C = 47.5 Hz), 136.2 (d,
3
JP-C = 48.8 Hz), 135.9 (d, JP-C = 12.7 Hz), 135.9, 134.0, 133.0 (d, JP-C = 29.4 Hz), 132.2 (t, JP-
=
37.60 Hz), 129.0 (d, JP-C = 42.05 Hz), 128.6, 127.5, 126.7, 36.8, 36.2, 35.2, 35.0, 25.1,
C
2
1.6.
3
1
P NMR (CDCl , 200 MHz) δ 42.19.
3
+
+
HRMS-EI: m/z found: [M+H] , 403.2178. C H OP requires 403.2191; [M+Na] 425.2003.
27
32
C H NaOP requires 425.2010.
27
31
(
RS ,RS )-tert-Butyl(4-methoxyphenyl)([2.2]paracyclophan-4-yl)phosphine oxide 16c
P p
Pd(OAc) (1 mg, 0.004 mmol, 0.02 eq.), dppf (2 mg, 0.004 mmol, 0.022 eq.), Cs CO (81
2
2
3
mg, 0.25 mmol, 1.3 eq.), 8 (60 mg, 0.19 mmol, 1 eq.), 4-iodoanisole (67 mg, 0.29 mmol, 1.5
eq.) in dioxane:DCE (7:1) (8 ml) to give a yellow solid of 16c (48 mg, 60 %).
Rf (7:3 Hex:EtOAc) 0.50.
20

ACCEPTED MANUSCRIPT
mp: 137 – 139 °C.
IR: νmax 2925, 2851, 1725, 1598, 1500, 1466, 1433, 1394, 1365, 1293, 1259, 1205, 1162,
-1
1
150, 1111, 1066, 1013, 942, 919, 906, 906, 813, 799, 720 cm .
1
H NMR (CDCl , 500 MHz): δ 8.09 (2H, t, J = 8.7 Hz), 7.18 (2H, d, J = 7.2 Hz), 6.66 (1H, d,
3
J = 13.2 Hz), 6.60-6.54 (4H, m), 6.47 (1H, d, J = 7.5 Hz), 5.81 (1H, d, J = 7.4 Hz), 4.45 (1H,
d, J = 11.4 Hz), 3.98 (3H, s), 3.50 (1H, dd, J = 11.8, 5.3 Hz), 3.10 (2H, t, J = 4.4 Hz), 3.01-
2
.89 (3H, m), 2.84-2.78 (1H, m), 1.04 (9H, d, J = 14.8 Hz).
1
3
C NMR (CDCl , 125 MHz) δ 162.0 (d, JP-C = 10.3 Hz), 146.4 (d, JP-C = 28.8 Hz), 140.5,
3
138.7, 138.6 (d, JP-C = 48.1 Hz), 136.7 (d, JP-C = 47.7 Hz), 136.3 (d, JP-C = 48.6 Hz), 135.9,
134.7 (d, JP-C = 32.9 Hz), 134.0, 132.2 (d, JP-C = 40.1 Hz), 132.1, 127.5, 126.8, 122.5, 121.7,
113.9 (d, JP-C = 44.9 Hz), 64.1, 55.3, 36.8, 36.2, 35.2 (d, JP-C = 27.5 Hz), 35.2, 35.0, 25.1.
3
1
P NMR (CDCl , 200 MHz) δ 42.37.
3
+
+
HRMS-EI: m/z found: [M+H] , 419.2132. C H O P requires 419.2140; [M+Na] 441.1952
27
32
2
C H NaO P requires 441.1959.
27
31
2
(
RS ,RS )-tert-Butyl(4-cyanophenyl)([2.2]paracyclophan-4-yl)phosphine oxide 16d
P p
Pd(OAc) (1 mg, 0.004 mmol, 0.02 eq.), dppf (2 mg, 0.004 mmol, 0.022 eq.), Cs CO (81
2
2
3
mg, 0.25 mmol, 1.3 eq.), 8 (60 mg, 0.19 mmol, 1 eq.), 4-iodobenzonitrile (66 mg, 0.29 mmol)
in dioxane:DCE (7:1) (8 ml), to give a white solid of 16d (50 mg, 64%).
mp: 118 – 120 °C.
IR: νmax 3430, 2960, 2926, 2855, 2230, 1669, 1500, 1476, 1465, 1394, 1367, 1263, 1200,
-1
1
156, 1130, 1091, 1065, 1017, 942, 915 cm .
1
H NMR (CDCl , 500 MHz): δ 8.31 (2H, t, J = 5.7 Hz), 7.95 (2H, d, J = 8.2 Hz), 6.62 (2H,
3
s), 6.56 (1H, dd, J = 7.7, 1.6 Hz), 6.53-6.47 (3H, m), 5.74 (1H, dd, J = 1.8, 7.8 Hz), 4.40 (1H,
21

ACCEPTED MANUSCRIPT
t, J = 11.2 Hz), 3.46 (1H, td, J = 10.9, 5.4 Hz), 3.13-3.05 (2H, m), 3.00-2.96 (1H, m), 2.98-
2
.90 (2H, m), 2.81-2.75 (1H, m), 1.05 (9H, d, J = 15.2 Hz).
1
3
C NMR (CDCl , 125 MHz) δ 146.7 (d, JP-C = 26.7 Hz), 140.3, 139.0 (d, JP-C = 48.1 Hz),
3
1
38.6, 137.1 (d, JP-C = 47.2 Hz), 136.5, 135.9 (d, JP-C = 47.9 Hz), 133.7, 133.6 (d, JP-C = 25.4
Hz), 132.3 (d, JP-C = 58.1 Hz), 132.0, 131.7 (d, JP-C = 38.1 Hz), 118.1, 115.2, 36.7, 36.2,35.0,
2
5.0.
3
1
P NMR (CDCl , 200 MHz) δ 41.75.
3
+
+
HRMS-EI: m/z found: [M+H] , 414.1979. C H NOP requires [M+H] 414.1989. m/z found:
2
7
29
+
+
[
M+Na] , 436.1800. C H NNaOP requires [M+Na] 436.1806.
27 28
(
SR ,RS )-tert-Butyl([2.2]paracyclophan-4-yl)(pyridine-2-yl)phosphine oxide 16e
P p
Pd(OAc) (1 mg, 0.004 mmol, 0.02 eq.), dppf (2 mg, 0.004 mmol, 0.022 eq.), Cs CO (81
2
2
3
mg, 0.25 mmol, 1.3 eq.), 8 (60 mg, 0.19 mmol, 1 eq.), 2-iodopyridine (59 mg, 0.29 mmol, 1.5
eq.) in dioxane:DCE (7:1) (8 ml), brown solid of 16e (43 mg, 58%).
mp: 136 – 137 °C.
IR: νmax 3042, 2953, 2928, 2852, 1726, 1573, 1564, 1500, 1473, 1450, 1431, 1420, 1391,
-1
1
364, 1262, 1177, 1152, 1134, 1081, 1064, 1045, 1021, 991, 945, 918, 882 cm .
1
H NMR (CDCl , 500 MHz): δ 8.93 (1H, d, J = 3.9 Hz), 8.64 (1H, t, J = 6.5 Hz), 8.03 (1H,
3
tdd, J = 7.7, 3.1, 1.7 Hz), 7.53-7.50 (1H, m), 7.34 (1H, d, J = 12.4 Hz), 6.60-6.54 (3H, m),
6
.45 (1H, d, J = 7.8 Hz), 6.37 (1H, d, J = 7.8 Hz), 4.52 (1H, t, J = 10.8 Hz), 3.44 (1H, td, J =
0.5, 5.9 Hz), 3.16-3.08 (2H, m), 2.96-2.85 (4H, m), 1.06 (9H, d, J = 15.1 Hz).
1
1
3
C NMR (CDCl , 125 MHz) δ 149.0 (d, JP-C = 65.5 Hz), 146.4 (d, JP-C = 24.9 Hz), 140.5,
3
1
38.9, 138.3 (d, JP-C = 47.2 Hz), 136.7 (d, JP-C = 41.8 Hz), 136.4 (d, JP-C = 47.2 Hz), 138.3 (d,
JP-C = 41.8 Hz), 136.2 (d, JP-C = 47.9 Hz), 135.8 (d, JP-C = 13.2 Hz), 133.4, 132.6, 132.3,
22

ACCEPTED MANUSCRIPT
1
2
31.9, 130.0 (d, JP-C = 65.8 Hz), 124.7 (d, JP-C = 12.1 Hz), 35.2 (d, JP-C = 48.1 Hz), 34.9, 34.4,
4.4.
3
1
P NMR (CDCl , 200 MHz) δ 36.12.
3
+
+
HRMS-EI: m/z found: [M+H] , 390.1978. C H NOP requires 390.1987; [M+Na] 412.1798
25
29
C H NaOP requires 412.1806.
25
28
(
RS ,RS )-tert-Butyl([2.2]paracyclophan-4-yl)(p-tolyl)phosphine and (SR ,RS )-tert-
P
p
P
p
butyl([2.2]paracyclophan-4-yl)(p-tolyl)phosphine 17b
Trichlorosilane (0.73 ml, 7.30 mmol, 28 eq.) was added to a stirred suspension of 16b
105 mg, 0.26 mmol, 1.0 eq.) in p-xylene (2 ml) and heated to 140 °C in a pressure tube for
(
2
0 hrs. The reaction mixture was cooled to 0 °C and carefully quenched by the addition of
0% aqueous NaOH (10 ml) (Care: exothermic reaction). The aqueous layer was extracted
3
with EtOAc (3 x15 ml), dried (MgSO ) and the solvent was remove under reduced pressure.
4
The crude material (80 mg, approximately 80% yield) as a 60:40 diastereomeric mixture was
used without further purification.
1
H NMR (CDCl , 500 MHz): δ 7.76 (2H, t, J = 7.9 Hz), 7.21 (2H, d, J = 7.6 Hz), 7.10 (1H, d,
3
J = 7.7 Hz), 7.03-6.99 (3H, m), 6.93 (1H, d, J = 7.8 Hz), 6.73 (1H, d, J = 6.4 Hz), 6.51 (1H,
d, J = 7.7 Hz, 1H), 6.46-6.43 (3H, m), 6.39-6.33 (5H, m), 6.23-6.20 (1H, m), 5.67 (1H, d, J =
7
2
1
.8 Hz), 4.12-4.07 (1H, m), 3.35-3.30 (2H, m), 3.19-3.14 (1H, m), 3.11-3.05 (2H, m), 3.00-
.91 (3H, m), 2.90-2.84 (3H, m), 2.82-2.77 (2H, m), 2.76 (2H, m), 2.39 (3H, s), 2.21 (3H, s),
.15 (6H, d, J = 12.2 Hz), 0.90 (9H, d, J = 12.5 Hz).
3
1
P NMR (CDCl , 200 MHz) δ 16.21, 8.40.
3
23

ACCEPTED MANUSCRIPT
(
RS ,RS )-tert-Butyl([2.2]paracyclophan-4-yl)(p-tolyl)phosphinium tetrafluoroborate
P
p
and (SR ,RS )-tert-butyl([2.2]paracyclophan-4-yl)(p-tolyl)phosphinium
P
p
tetrafluoroborate 17b•H
7b (80 mg, 0.21 mmol, 1.0 eq.), HBF .OEt (54% solution in Et O; 0.52 ml, 3.22 mmol,
1
4
2
2
1
5.0 eq.) and CH Cl (7 ml) were combined at 0 °C. After 2 hrs, the reaction mixture was
2 2
warmed to 22 °C and aqueous tetrafluoroboric acid (5 ml) was added. The reaction mixture
was allowed to stir for more 2 hrs. The aqueous phase was separated with EtOAc (3 x15 ml),
dried (MgSO ) and the solvent was removed under reduced pressure. The crude product
4
1
7b•H was obtained as a 57:43 mixture of diastereomers as a fluffy white powder (55 mg,
6
9%).
-1
IR: νmax 2956, 2851, 1598, 1467, 1407, 1317, 1180, 1031, 919, 857, 809, 719 cm .
1
H NMR (CDCl , 500 MHz): δ 8.68 (1H, s), 8.55 (1H, s), 8.22-8.18 (2H, m), 7.78-7.74 (1H,
3
m), 7.68 (2H, s), 7.45-7.44 (1H, m), 7.40 (1H, d, J = 14.8 Hz, 1H), 7.00 (1H, d, J = 12.8 Hz,
1
H), 6.87-6.79 (3H, m), 6.68-6.65 (1H, m), 6.62-6.60 (2H, m), 6.55-6.47 (2H, m), 5.96 (1H,
d, J = 7.6 Hz, 1H), 5.78 (1H, d, J = 7.3 Hz, 1H), 3.92 (1H, t, J = 11.4 Hz), 3.53-3.49 (1H, m),
3
.41-3.37 (1H, m), 3.30-3.25 (3H, m), 3.22 (2H, d, J = 10.2 Hz), 3.17 (2H, d, J = 9.2 Hz),
.06-3.00 (4H, m), 2.59 (3H, s), 2.48 (2H, s), 1.59 (6H, d, J = 18.0 Hz), 1.31 (9H, d, J = 16.1
3
Hz).
1
3
C NMR (CDCl , 125 MHz) δ 146.7, 146.5 (d, J = 30.6 Hz), 146.2, 145.6, 141.9, 141.5 (d, J
3
=
46.1 Hz), 140.0, 139.6, 139.5, 139.1 (d, J = 60.0 Hz), 138.8, 137.9 (d, J = 45.5 Hz), 137.3
(d, J = 47.0 Hz), 136.0 (d, J = 32.5 Hz), 134.6 (d, J = 37.0 Hz), 134.4 (d, J = 41.2 Hz), 133.0
(d, J = 34.1 Hz), 132.8, 132.6 (d, J = 42.7 Hz), 132.2, 131.9, 131.7 (d, J = 50.2 Hz), 131.05
(d, J = 51.1 Hz), 35.51, 35.2 (d, J = 21.2 Hz), 35.1, 34.6, 33.5, 33.1, 29.7, 26.1, 25.2, 22.01
(d, J = 65.5 Hz).
3
1
P NMR (CDCl , 200 MHz) δ 18.5, 11.6.
3
24

ACCEPTED MANUSCRIPT
(
SR ,RS )-Chloro[(tert-butyl([2.2]paracyclophan-4-yl)(p-tolyl)phosphine]gold(I) and
P
p
(
RS ,RS )-chloro[(tert-butyl([2.2]paracyclophan-4-yl)(p-tolyl)phosphine]gold(I)
P p
1
7b•AuCl
To a flame dried two necked 25 ml RBF was added 17b (80 mg, 0.20 mmol, 1.0 eq.) and
chloro(tetrahydrothiophene)gold(I) (66.3 mg, 0.20 mmol, 1.0 eq.) in dry CH CN (5 ml). The
3
mixture was heated to refluxed for 2 hrs. The crude mixture was concentrated under reduced
pressure. The resulting yellow solid was dissolved in CH Cl (1 ml) before pentane (10 ml)
2
2
was added to precipitate the desired complex as a yellow solid, which was isolated by
decantation to obtain desired complex as a mixture of diastereomers (62:38 dr) (20 mg, 16%
yield).
-1
IR: νmax 2961, 2920, 1710, 1600, 1498, 1460, 1394, 1261, 1090, 805, 713 cm .
1
H NMR (CDCl , 500 MHz): δ 8.05-8.01 (2H, m), 7.66 (1H, d, J = 7.7 Hz), 7.44 (2H, d, J =
3
6
6
.4 Hz), 7.38-7.34 (1H, m), 7.16-7.15 (1H, m), 7.10-7.09 (1H, m), 7.04-6.98 (2H, m), 6.65-
.60 (3H, m), 6.58-6.54 (3H, m), 6.42-6.37 (1H, m), 6.34 (1H, d, J = 12.8 Hz, 1H), 5.91 (1H,
dd, J = 7.8, 1.5 Hz), 4.81-4.76 (1H, m), 4.28-4.17 (1H, m), 3.86-3.71 (2H, m), 3.23-3.09 (5H,
m), 3.14-3.03 (6H, m), 2.98-2.95 (3H, m), 2.89 (1H, d, J = 7.2 Hz), 2.78-2.73 (2H, m), 2.54
(3H, s), 2.38 (2H, s), 1.36 (6H, d, J = 16.4 Hz), 1.17 (9H, d, J = 16.8 Hz).
1
3
C NMR (CDCl , 125 MHz) δ 144.1 (d, JP-C = 48.2 Hz), 142.9, 139.2 (d, JP-C = 33.3 Hz),
3
1
39.0, 136.9 (d, JP-C = 36.8 Hz), 136.7, 136.6, 136.4, 136.1, 135.6 (d, JP-C = 50.9 Hz), 133.0
(d, JP-C = 35.1 Hz), 132.6, 132.3 (d, JP-C = 40.5 Hz), 132.0, 129.9 (d, JP-C = 46.4 Hz), 129.0 (d,
JP-C = 47.3 Hz), 42.1, 36.6, 36.5 (d, JP-C = 22.8 Hz), 36.2, 35.6, 35.1, 30.0, 34.9, 30.1, 28.3 (d,
JP-C = 23.6 Hz), 21.5 (d, JP-C = 79.7 Hz), 1.0.
3
1
P NMR (CDCl , 200 MHz) δ 47.8, 46.7.
3
+
HRMS-EI: m/z found: [M + Na] 641.1402 C H ClNaP requires 641.1415.
27
31
25

ACCEPTED MANUSCRIPT
(
SR ,RS )-Chloro[tert-butyl([2.2]paracyclophan-4-yl)(pyridin-2-yl)phosphine]gold(I)
P
p
1
7e•AuCl
To a solution of 17e (40 mg, 0.10 mmol, 1.0 eq.) in dry CH Cl (3 ml) was added
2
2
chloro(dimethyl sulfide)gold(I) (31.57 mg, 0.10 mmol, 1.0 eq.). The mixture was stirred at
room temperature in the absence of light. The crude mixture was concentrated after 2 hrs
under reduced pressure. The resulting grey solid was dissolved in CH Cl (1 ml) and pentane
2
2
(10 ml) was added to precipitate the desired complex as a white solid, which was isolated by
decantation. The solid was dissolved in CH Cl (1 ml) and pentane was slowly added to get a
2
2
biphasic solution. Slow crystallization furnished crystals of the desired complex (15 mg,
3%).
mp: 223 - 224 °C
2
-1
IR: νmax 2958, 2920, 1568, 1446, 1413, 1359, 1258, 1134, 1093, 805, 716 cm .
1
H NMR (CDCl , 500 MHz): δ 8.90 (1H, d, J = 4.1 Hz), 8.69-8.65 (1H, m), 8.00-7.99 (1H,
3
m), 7.57-7.53 (1H, m), 6.82 (1H, d, J = 7.8 Hz), 6.62 (1H, dd, J = 7.8, 1.9 Hz), 6.59-6.58
(1H, m), 6.54 (1H, dd, J = 7.8, 1.8 Hz), 6.49 (1H, d, J = 12.1 Hz), 5.80 (1H, dd, J = 7.8, 1.8
Hz), 4.89-4.82 (1H, m), 3.84-3.75 (1H, m), 3.22-3.16 (2H, m), 3.11-3.03 (1H, m), 2.99-2.90
(2H, m), 2.76-2.71 (1H,m), 1.21 (9H, d, J = 17.4 Hz).
1
3
C NMR (CDCl , 125 MHz) δ 150.3 (d, J = 50.6 Hz), 144.2 (d, J = 49.5 Hz), 139.8 (d, J =
3
3
4.8 Hz), 139.3, 139.1, 137.2 (d, J = 11.3 Hz), 136.8, 136.7 (d, J = 16.7 Hz), 136.58, 136.51
(d, J = 11.7 Hz), 134.8, 134.6, 133.0, 132.7, 132.4, 132.0, 125.4 (d, J = 8.9 Hz), 124.0, 36.6,
3
6.5 (d, J = 31.2 Hz), 36.3, 35.7, 35.0 (d, J = 21.7 Hz), 34.1, 27.4 (d, J = 21.6 Hz), 22.3, 14.0.
3
1
P NMR (CDCl , 200 MHz) δ 40.6.
3
+
HRMS-EI: m/z found: [M + Na] 628.1193 C H AuClNNaP requires 628.1211.
25
28
26

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Acknowledgements
The authors thank Massey University for financial support and the Institute of
Fundamental Sciences (Massey University) for a Graduate Assistant (MNM) position.
References
1.
2.
3.
(a) Li, W; Zhang, X. In Phosphorus(III) Ligands in Homogeneous Catalysis: Design
and Synthesis; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Eds.; Wiley-VCH:
Weinheim, 2012; pp. 27-80; (b) Fleckenstein, CA; Plenio, H. Chem. Soc. Rev.
2
010;39:694-711.
(a) Wei, Y; Shi, M. Chem. Asian J. 2014;9:2720-2734; (b) Xiao, Y; Sun, Z; Guo, H;
Kwon, O. Beilstein J. Org. Chem. 2014;10:2089-2121; (c) Xiao, Y; Guo, H; Kwon,
O. Aldrichchim. Acta 2016;49:3-13; (d) Wang, T; Han, X; Zhong, F; Yao, W; Lu, Y.
Acc. Chem. Res. 2016;49:1369-1378.
(a) Staubitz, A; Robertson, APM; Sloan, ME; Manners, I. Chem. Rev. 2010;110:4023-
4
078; (b) Pellon, P. Tetrahedron Lett. 1992;33:4451-4452; (c) Denmark, SE; Werner,
NS. Org. Lett. 2011;13:4596-4599.
4
5
.
.
Netherton, MR; Fu, GC. Org. Lett. 2001;3:4295-4298.
(a) Achard, T. Chimia 2016;70:8-19; (b) Ackermann, L. Synthesis 2006;2006:1557-
1
571; (c) Shaikh, TM; Weng, C-M; Hong, F-E. Coord. Chem. Rev. 2012;256:771-
8
03.
6
7
.
.
Donets, PA; Cramer, N. J. Am. Chem. Soc. 2013;135:11772-11775.
Ghorai, D; Muller, V; Keil, H; Stalke, D; Zanoni, G; Tkachenko, BA; Schreiner, PR;
Ackermann, L. Adv. Synth. Catal. 2017;359:3137-3141.
8
.
.
Schroder, F; Tugny, C; Salanouve, E; Clavier, H; Giordano, L; Moraleda, D; Gimbert,
Y; Mouries-Mansuy, V; Goddard, JP; Fensterbank, L. Organometallics
2
014;33:4051-4056.
9
(a) Wellala, NPN; Guan, H. Org. Biomol. Chem. 2015;13:10802-10807; (b) Chang,
Y-C; Chang, W-C; Hu, C-Y; Hong, F-E. Organometallics 2014;33:3523-3534; (c)
Hu, D-F; Weng, C-M; Hong, F-E. Organometallics 2011;30:1139-1147; (d)
Ackermann, L; Kapdi, AR; Schulzke, C. Org. Lett. 2010;12:2298-2301; (e) Jung, L-
Y; Tsai, S-H; Hong, F-E. Organometallics 2009;28:6044-6053; (f) Xu, H; Ekoue-
Kovi, K; Wolf, C. J. Org. Chem. 2008;73:7638-7650.
1
0.
1.
Jiang, X-b; Minnaard, AJ; Hessen, B; Feringa, BL; Duchateau, ALL; Andrien, JGO;
Boogers, JAF; de Vries, JG. Org. Lett. 2003;5:1503-1506.
1
(a) Jiang, X-b; van den Berg, M; Minnaard, AJ; Feringa, BL; de Vries, JG.
Tetrahedron: Asymmetry 2004;15:2223-2229; (b) Landert, H; Spindler, F; Wyss, A;
Blaser, H-U; Pugin, B; Ribourduoille, Y; Gschwend, B; Ramalingam, B; Pfaltz, A.
Angew. Chem. Int. Ed. 2010;49:6873-6876; (c) Li, Y; Dong, K; Wang, Z; Ding, K.
Angew. Chem. Int. Ed. 2013;52:6748-6752; (d) Dong, K; Li, Y; Wang, Z; Ding, K.
Angew. Chem. Int. Ed. 2013;52:14191-14195; (e) Dong, K; Wang, Z; Ding, K. J. Am.
Chem. Soc. 2012;134:12474-12477; (f) Wang, X-B; Goto, M; Han, L-B. Chem. Eur.
J. 2014;20:3631-3635.
1
2.
(a) Xu, K; Thieme, N; Breit, B. Angew. Chem. Int. Ed. 2014;53:7268-7271; (b)
Haydl, AM; Xu, K; Breit, B. Angew. Chem. Int. Ed. 2015;54:7149-7153.
27

ACCEPTED MANUSCRIPT
1
3.
(a) David, ORP. Tetrahedron 2012;68:8977-8993; (b) Gibson, SE; Knight, JD. Org.
Biomol. Chem. 2003;1:1256-1269; (c) Gleiter, R; Hopf, H, Eds. Modern Cyclophane
Chemistry; Wiley-VCH: Weinheim, 2004; (d) Paradies, J. Synthesis 2011:3749-3766;
(e) Fulton, JR; Glover, JE; Kamara, L; Rowlands, GJ. Chem. Commun. 2011;47:433-
4
35; (f) Glover, JE; Plieger, PG; Rowlands, GJ. Aust. J. Chem. 2014;67:374-380; (g)
Rowlands, GJ. Isr. J. Chem. 2012;52:60-75.
1
4.
5.
(a) Pye, PJ; Rossen, K; Reamer, RA; Tsou, NN; Volante, RP; Reider, PJ. J. Am.
Chem. Soc. 1997;119:6207-6208; (b) Dyer, PW; Dyson, PJ; James, SL; Martin, CM;
Suman, P. Organometallics 1998;17:4344-4346; (c) Pye, PJ; Rossen, K; Reamer, RA;
Volante, RP; Reider, PJ. Tetrahedron Lett. 1998;39:4441-4444.
(a) Bestgen, S; Seidl, C; Wiesner, T; Zimmer, A; Falk, M; Koberle, B; Austeri, M;
Paradies, J; Brase, S; Schepers, U; Roesky, PW. Chem. Eur. J. 2017;23:6315-6322;
1
(
b) Falk, FC; Frohlich, R; Paradies, J. Chem. Commun. 2011;47:11095-11097; (c)
Falk, FC; Oechsle, P; Thiel, WR; Daniliuc, C-G; Paradies, J. Eur. J. Org. Chem.
014;2014:3637-3645; (d) Sarcher, C; Bestgen, S; Falk, FC; Lebedkin, S; Paradies, J;
2
Roesky, PW. J. Organomet. Chem. 2015;795:11-17.
1
6.
(a) Austeri, M; Enders, M; Nieger, M; Bräse, S. Eur. J. Org. Chem. 2013;2013:1667-
1
2
670; (b) Glover, JE; Martin, DJ; Plieger, PG; Rowlands, GJ. Eur. J. Org. Chem.
013:1671-1675; (c) Thennakoon, N; Kaur, G; Wang, JJ; Plieger, PG; Rowlands, GJ.
Aust. J. Chem. 2015;68:566-575; (d) Jayasundera, KP; Engels, TGW; Lun, DJ;
Mungalpara, MN; Plieger, PG; Rowlands, GJ. Org. Biomol. Chem. 2017;15:8975-
8
984; (e) Braun, C; Nieger, M; Bräse, S. Chem. Eur. J. 2017;23:16452-16455.
1
1
7.
8.
Hou, X; Zhang, T; Dai, L. (2007) Chinese Patent CN101003549A.
Seacome, RJ; Coles, MP; Glover, JE; Hitchcock, PB; Rowlands, GJ. Dalton Trans.
2
010;39:3687-3694.
1
2
9.
0.
Wang, JJ, M.Sc. Thesis, Massey University, New Zealand, 2011.
(a) Gatineau, D; Giordano, L; Buono, G. J. Am. Chem. Soc. 2011;133:10728-10731;
(b) Achard, T; Giordano, L; Tenaglia, A; Gimbert, Y; Buono, G. Organometallics
2
010;29:3936-3950; (c) Leyris, A; Bigeault, J; Nuel, D; Giordano, L; Buono, G.
Tetrahedron Lett. 2007;48:5247-5250; (d) Xu, Q; Zhao, C-Q; Han, L-B. J. Am. Chem.
Soc. 2008;130:12648-12655; (e) Berger, O; Montchamp, J-L. Angew. Chem. Int. Ed.
2
013;52:11377-11380.
(a) Parmar, R; Coles, MP; Hitchcock, PB; Rowlands, GJ. Synthesis 2010:4177-4187;
b) Rowlands, GJ. Org. Biomol. Chem. 2008;6:1527-1534; (c) Rowlands, GJ;
2
1.
(
Seacome, RJ. Beilstein J. Org. Chem. 2009;5:doi:10.3762/bjoc.3765.3769; (d)
Hitchcock, PB; Rowlands, GJ; Parmar, R. Chem. Commun. 2005:4219-4221; (e)
Hitchcock, PB; Rowlands, GJ; Seacome, RJ. Org. Biomol. Chem. 2005;3:3873-3876;
(f) Morisaki, Y; Hifumi, R; Lin, L; Inoshita, K; Chujo, Y. Chem. Lett. 2012;41:990-
992; (g) Morisaki, Y; Hifumi, R; Lin, L; Inoshita, K; Chujo, Y. Polym. Chem.
2012;3:2727-2730; (h) Morisaki, Y; Inoshita, K; Chujo, Y. Chem. Eur. J.
2014;20:8386-8390; (i) Morisaki, Y; Inoshita, K; Shibata, S; Chujo, Y. Polym. J.
2015;47:278-281; (j) Reich, HJ; Yelm, KE. J. Org. Chem. 1991;56:5672-5679; (k)
Wada, N; Morisaki, Y; Chujo, Y. Macromolecules 2009;42:1439-1442; (l) Enders, D;
Ludwig, M; Raabe, G. Chirality 2012;24:215-222.
2
2.
3.
CCDC-1824735 contains the supplementary crystallographic data for compound 8;
CCDC-1824734 for compound 16b and CCDC-1824733 for compound 17e•AuCl.
This data can be obtained free of charge from The Cambridge Crystallographic Data
Centre via https://www.ccdc.cam.ac.uk/structures/?
2
Cahn, RS; Ingold, C; Prelog, V. Angew. Chem. Int. Ed. Engl. 1966;5:385-415.
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