Application of Transmetalation to the Synthesis of Planar Chiral and Chiral-at-Metal Iridacycles

Article abstract of DOI:10.1021/acs.organomet.8b00905

Diastereoselective lithiation of (S)-2-ferrocenyl-4-(1-methylethyl)oxazoline, followed by addition of HgCl₂, resulted in the formation by transmetalation of an (S,S_p)-configured mercury substituted complex. Addition to this of [Cp?IrCl₂]₂ and tetrabutylammonium chloride resulted in a second transmetalation reaction and formation of an (S,S_p,R_Ir)-configured chloride-substituted half-sandwich iridacycle as exclusively a single diastereoisomer. By reversing the lithiation diastereoselectivity by use of a deuterium blocking group, an alternative (S,R_p,S_Ir)-configured iridacycle was synthesized similarly. Use of (R)-Ugi's amine as substrate in the lithiation/double transmetalation sequence gave an (R,S_p,S_Ir)-configured half-sandwich iridacycle, complexes of this type being previously unavailable by direct cycloiridation. Lithium to gold transmetalation was also demonstrated with the synthesis of an (S,S_p)-configured Au(I) ferrocenyloxazoline derivative. Use of the (S,R_p,S_Ir)-iridacycle as a catalyst for the formation of a chiral product by reductive amination with azeotropic HCO₂H/NEt₃ resulted in a racemate.

Full text of DOI:10.1021/acs.organomet.8b00905

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Application of Transmetalation to the Synthesis of Planar Chiral and
Chiral-at-Metal Iridacycles
Ross A. Arthurs,† David L. Hughes,† Peter N. Horton,‡ Simon J. Coles,‡
and Christopher J. Richards*,†
†School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, U.K.
‡EPSRC National Crystallography Service, School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ,
U.K.
S
* Supporting Information
ABSTRACT: Diastereoselective lithiation of (S)-2-ferrocenyl-4-(1-methyl-
ethyl)oxazoline, followed by addition of HgCl2, resulted in the formation by
transmetalation of an (S,Sp)-configured mercury substituted complex. Addition
to this of [Cp*IrCl2]2 and tetrabutylammonium chloride resulted in a second
transmetalation reaction and formation of an (S,Sp,RIr)-configured chloride-
substituted half-sandwich iridacycle as exclusively a single diastereoisomer. By
reversing the lithiation diastereoselectivity by use of a deuterium blocking
group, an alternative (S,Rp,SIr)-configured iridacycle was synthesized similarly.
Use of (R)-Ugi’s amine as substrate in the lithiation/double transmetalation
sequence gave an (R,Sp,SIr)-configured half-sandwich iridacycle, complexes of
this type being previously unavailable by direct cycloiridation. Lithium to gold
transmetalation was also demonstrated with the synthesis of an (S,Sp)-
configured Au(I) ferrocenyloxazoline derivative. Use of the (S,Rp,SIr)-iridacycle
as a catalyst for the formation of a chiral product by reductive amination with
azeotropic HCO2H/NEt3 resulted in a racemate.
loxazolines.7 In addition to a new element of planar chirality,
this also results in an iridium-based stereogenic center, the
configuration of the former controlling the configuration of the
latter as exemplified by the formation of (S,Sp,SIr)-2 from (S)-1
INTRODUCTION
■
Metallacycles derived from late transition metals have been
studied extensively as catalysts and precatalysts for use in
synthesis.1 Much of this work has focused on nonracemic
(Scheme 2). This methodology was subsequently extended to
metallacycles displaying planar chirality,2 including examples
that have found application in asymmetric catalysis.3 The
Scheme 2. Diastereoselective Cycloiridation of
element of planar chirality is typically generated with relative
ease by diastereoselecive ortho-C−H activation mediated by a
Ferrocenyloxazoline (S)-17
chiral auxiliary attached to a suitable substrate, such as
ferrocene (Scheme 1a).4 Transmetalation has also been used
for the synthesis of metallacycles,5 this providing an alternative
approach where direct access by C−H activation is not
possible. However, the use of transmetalation for the synthesis
of planar chiral metallacycles is rare (Scheme 1b).6
We recently reported the synthesis of planar chiral
iridacycles by diastereoselective C−H activation of ferroceny-
Scheme 1. General Approaches to the Synthesis of Planar
planar chiral iridacycles containing a bulky cobalt-based
Chiral Ferrocene-Based Metallacycles
sandwich complex.8 Although successful, C−H activation in
this way does limit the structure of the iridacycle with respect
to relative stereochemistry of the product, and the identity of
the auxiliary employed. Therefore, as a potentially more
versatile approach, transmetalation was investigated for the
Received: December 14, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00905
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
synthesis of planar chiral iridacycles. The results of this
investigation are reported in this article.
by the use of HgCl2 in the presence of excess NaOAc (Scheme
4). Both reactions resulted in mercury substituted complexes,
RESULTS AND DISCUSSION
Scheme 4. Mercuration of (S)-1 by Direct C−H Activation
■
Transmetalation typically involves the transfer of an alkyl or
aryl group from an electropositive metal to a metal with an
electronegativity closer to the value for carbon. Simultaneous
formation of a more polar byproduct, typically a halide salt,
from the electropositive metal provides the driving force for
the reaction.9 Use of lithium as the electropositive metal is
attractive given the ubiquity of lithiation as a method of C−H
activation, albeit that the use of organolithiums in this way may
alternatively result in reduction of the transmetalation
partner.10 As conditions have been reported for the highly
diastereoselective lithiation of ferrocenyloxazoline (S)-1,11 this
reaction was repeated, followed by the addition of [Cp*IrCl2]2,
in an attempted transmetalation reaction. No iridacycle was
observed, and the starting material (S)-1 was recovered from
the reaction. In contrast, diastereoselective lithiation, followed
by the addition of HgCl2, did lead to transmetalation and
isolation of mercury substituted ferrocenyl oxazoline (S,Sp)-3
(Scheme 3). The structure of this complex was confirmed by
albeit with no, or very low, diastereoselectivity. Use of cesium
pivalate in place of sodium acetate resulted in a 1:1 ratio of
diastereoisomers. The formation of both diastereoisomers by
C−H activation was used to confirm, using 1H NMR
spectroscopy, the absence of (S,Rp)-4 in the product of the
lithiation/transmetalation procedure. For this, the formation of
only (S,Sp)-3 confirms that transmetalation results in no
erosion of diastereoselectivity following highly selective
lithiation.
Addition of [Cp*IrCl2]2 to (S,Sp)-3 with either dichloro-
methane or acetone as solvent resulted only in the recovery of
starting material (S,Sp)-3. However, when tetrabutylammo-
nium chloride (TBAC) was included, the reaction in acetone
Scheme 3. Diastereoselective Lithiation of (S)-1 and
Transmetalation with HgCl2
1
resulted in clean transmetalation (Scheme 5). The broad H
Scheme 5. Synthesis of Iridacycles by Transmetalation of
(S,Sp)-3
an X-ray crystallographic analysis (Figure 1). A small quantity
of a second product was also isolated (16% yield) resulting
from double transmetalation of HgCl2 with 2 equiv of lithiated
ferrocenyl oxazoline (see Supporting Information).
Direct cyclomercuration of (S)-1 was investigated with
Hg(OAc)2, followed by acetate/chloride ligand exchange, or
NMR spectrum of the product matched that of chloride ligated
iridacycle (S,Sp,RIr)-5 synthesized previoulsy.7 The selectivity
of iridacycle formation was determined following addition of
KPF6 in acetonitrile and isolation of (S,Sp,SIr)-2. No other
diastereoisomers were observed in the sharp 1H NMR
spectrum obtained from this compound. As ligand substitution
reactions in these iridacycles have previously been shown to be
stereospecific, proceeding with retention of configuration, this
outcome confirms that only a single diastereoisomer of
(S,Sp,RIr)-5 was formed on transmetalation. The cationic
complex (S,Sp,SIr)-2 may alternatively be formed, again as a
single diastereoisomer, directly by performing the trans-
metalation reaction in acetonitrile in the presence of KPF6.
We also investigated the mercuration of (η5-(S)-2-(4-methyl-
ethyl)oxazolinylcyclopentadienyl)(η4-tetraphenylcyclobuta-
diene)cobalt (a cobalt sandwich complex analogue of (S)-1),
which gave a 2:1 ratio of α-HgCl substituted complexes.
Mercury to iridium transmetalation was found to proceed in
Figure 1. A representation of the X-ray structure of (S,Sp)-3
(hydrogen atoms omitted for clarity). Principal bond lengths [Å]
include: Hg(1)−C(1) = 2.032(6), Hg(1)−N(1) = 2.948(6), Hg(1)−
Cl(1) = 2.295(2). Principal bond angles [deg] include: N(1)−
Hg(1)−C(1) = 71.63(2), Cl(1)−Hg(1)−C(1) = 178.1(2), Cl(1)−
Hg(1)−N(1) = 108.23(11). Thermal ellipsoids are drawn at the 50%
probability level. Flack parameter = −0.014(4).
B
DOI: 10.1021/acs.organomet.8b00905
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
low yield, giving a 2:1 ratio of iridacycles (see Supporting
Information).
Unlike direct cycloiridation, the lithiation-transmetalation
sequence provides (S,Sp,SIr)-2 free of small quantities of the
planar chiral diastereoisomer (S,Rp,RIr)-7, as well as avoiding
the formation of iridocenium cations.12 We then chose to
selectively synthesize this alternative isomer by utilizing a
deuterium blocking group to reverse the diastereoselectivity of
ferrocenyloxazoline lithiation (kH/kD ∼ 20).13 Accordingly,
(S)-1 was first lithiated as before, followed by the addition of
MeOH-d4, to give selectively deuterated (S,Rp)-2-d-1 (Scheme
6). Use of this in a second lithiation reaction with n-BuLi in
Scheme 6. Synthesis of (S,Rp)-5-d-4 and Subsequent
Transmetalation to give (S,Rp,SIr)-5-d-6 and (S,Rp,RIr)-5-d-7
Figure 2. A representation of the X-ray structure of (S,Sp)-5-d-4
(hydrogen and deuterium atoms omitted for clarity). Principal bond
lengths [Å] include: Hg(1)−C(1) = 2.030(6), Hg(1)−N(1) =
2.927(5), Hg(1)−Cl(1) = 2.303(2). Principal bond angles [deg]
include: N(1)−Hg(1)−C(1) = 71.7(2), Cl(1)−Hg(1)−C(1) =
177.1(2), Cl(1)−Hg(1)−N(1) = 107.88(11). Thermal ellipsoids
are drawn at the 50% probability level. Flack parameter = −0.015(4).
NOESY spectrum revealed an NOE between the Cp and Cp*
moieties in support of the RIr configurational assignment.7
Transmetalation of (S,Rp)-5-d-4 with [Cp*IrCl2]2 in the
presence of TBAC gave the neutral chloride ligated complex
(S,Rp,SIr)-5-d-6. As observed before with chloride ligated
iridacycles, the 1H NMR spectrum of this compound was very
broad, so its identity and stereochemical integrity were
confirmed by conversion into (S,Rp,RIr)-5-d-7.
An advantage of using mercuracycles as the transmetalation
intermediate in these reactions is the air and water stability of
these complexes, such that they may be purified readily to give
a single diastereoisomer. A disadvantage is the toxicity of
mercury, and this led us to briefly investigate the use of gold as
an alternative metal. Accordingly, diastereoselective lithiation
of (S)-1 as before, followed by the addition of ClAuPPh3, gave
1
(S,Sp)-8, the H NMR spectrum of which displayed three
THF, followed by the addition of HgCl2, resulted predom-
inantly in the formation of (S,Rp)-5-d-4 (d.r. = 10:1). The pure
diastereoisomer was obtained readily by recrystallization, and
the identity confirmed by X-ray crystallographic analysis
(Figure 2). The X-ray structures of both mercury-containing
complexes reveal an essentially linear coordination about this
metal [C(1)−Hg−Cl = 178.1(2)° in (S,Sp)-3 and 177.1(2)° in
(S,Rp)-5-d-4]. In both structures, the nitrogen is oriented
toward mercury such that the distance between this metal and
nitrogen [2.948(6) Å in (S,Sp)-3 and 2.927(5) Å in (S,Rp)-5-d-
4] is less than the estimated sum of their van der Waals radii
(∼3.6 Å).14 As such these complexes are designated as
mercuracycles, albeit with a weak and labile Hg···N bond as
determined for related complexes.14 This is supported by the
similarity of the oxazoline CN stretch in (S)-1 and (S,Sp)-3
(1657 and 1645 cm−1, respectively).
cyclopentadienyl hydrogen signals for the disubstituted ring at
4.89, 4.42, and 4.23 ppm, in addition to characteristic signals
for a triphenylphosphine ligand (Scheme 7). A related
Scheme 7. Synthesis of Planar Chiral Au(I) Complex (S,Sp)-
8
Transmetalation of (S,Rp)-5-d-4 with [Cp*IrCl2]2 in the
presence of KPF6 gave iridacycle (S,Rp,RIr)-5-d-7 as a single
diastereoisomer. The identity of this compound was confirmed
synthesis of planar chiral Au(I) and Au(II) species derived
from ferrocenyloxazoline(S)-1 was reported recently.15 At-
tempted transmetalation with [Cp*IrCl2]2 was unsuccessful, an
outcome that is likely due to the preference for halogen ligands
to be present in both transmetalation partners.
1
by comparison of its H NMR spectrum to that of the minor
diastereoisomer formed on cycloiridation of (S)-1.7 The only
difference was the absence of a cyclopentadienyl proton signal
at 4.85 ppm due to the presence of deuterium. In addition, a
Ugi’s amine 9 is the most widely used starting material for
the synthesis of planar chiral ferrocene derivatives,16 but a
C
DOI: 10.1021/acs.organomet.8b00905
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
previous attempt by us to use this as a substrate for
cycloiridation with [Cp*IrCl2]2 was unsuccessful.7 These
reactions led only to the isolation of ferrocene derivatives
formed as a result of α-substitution, α-oxidation or elimination.
Transmetalation was therefore investigated as an alternative
approach starting with the synthesis of (R,Sp)-10 (Scheme
8).17 This was obtained with a small quantity of the alternative
Scheme 8. Synthesis of Iridacycle (R,Sp,SIr)-11 via
Mercurated Complex (R,Sp)-10
Figure 3. A representation of the X-ray structure of (R,Sp,SIr)-11
(hydrogen atoms omitted for clarity). Principal bond lengths [Å]
include: Ir(1)−C(1) = 2.039(4), Ir(1)−N(1) = 2.220(3), Ir(1)−
Cl(1) = 2.4257(10), Ir(1)-Cp* (center of mass) = 1.822. Principal
bond angles [deg] include: N(1)−Ir(1)−C(1) = 76.90(17), Cl(1)−
Ir(1)−C(1) = 93.42(13), Cl(1)−Ir(1)−N(1) = 85.82(14), N(1)−
Ir(1)−Cp* = 134.05, C(1)−Ir(1)−Cp* = 132.06. Thermal ellipsoids
are drawn at the 50% probability level. Flack parameter = −0.024(4).
epimer.20 Iridacycle (R,Sp,SIr)-11 also displays this syn
relationship. All attempts at ligand substitution with (R,Sp,-
SIr)-11, for example, by treating this complex with KPF6 in
MeCN, were unsuccessful and resulted in decomposition. This
outcome is compatible with our previous inability to synthesize
this complex by base promoted cycloiridation.7 That trans-
metalation is successful is a result of this procedure not
requiring the formation of a coordinatively unsaturated, and in
this case unstable, intermediate complex. In light of this
successful transmetalation, we sought to extend this chemistry
following modification of the dimethylamino group of (R,Sp)-
10. However, all attempts to replace this with a methylamino
group by α-substitution were unsuccessful (see Supporting
Information).
R,Rp isomer, and the 10:1 ratio of diastereoisomers obtained is
similar to the ratio of diastereoisomers resulting initially from
lithiation under the conditions used (14:1).18 Transmetalation
of (R,Sp)-10 in the presence of excess TBAC proceeded to give
a new complex that was purified by recrystallization. That a
new iridacycle had been formed was supported by its 1H NMR
spectrum containing three cyclopentadienyl hydrogen signals
for the disubstituted ring (4.20, 4.12, and 3.76 ppm), and a
singlet integrating to 15 hydrogens for the Cp* group at 1.71
ppm. Confirmation of the product as (R,Sp,SIr)-11 was
achieved by an X-ray crystallographic analysis (Figure 3).
The relative configuration of the planar and iridium-centered
elements of chirality in (R,Sp,SIr)-11 is different to that
observed previously in related imine- and oxazoline-containing
ferrocene and cobalt-sandwich based complexes obtained by
cycloiridation.7,8 The chloride ligand of (R,Sp,SIr)-11 is
oriented toward rather than away from iron, changing the
configuration of the pseudo-tetrahedral stereogenic center. A
previous study on imine-containing iridacycles similar to 5
revealed little difference in energy between the (Sp*,RIr*) and
(Sp*,SIr*)-configured diastereoisomers.7 The selective forma-
tion of the former on cycloiridation was ascribed to a
stereoelectronic effect dictating facile dissociative ligand
substitution along a trajectory opposite to iron, such that
base assisted concerted metalation deprotonation, followed by
introduction of a chloride ligand by substitution, resulted in
the relative configuration Sp*,RIr*. As discussed above,
transmetalation of lithiated ferrocenyloxazolines with [Cp*-
IrCl2]2 results in the same outcome.
In an attempt to extend this methodology, we also
investigated the lithiation and subsequent transmetalation of
(R)-12, a bulky cobalt sandwich complex analogue of Ugi’s
amine (Scheme 9).18 As was found with its ferrocene-based
Scheme 9. Synthesis of Cobalt Sandwich Complex Based
Mercury Derivative (R,Sp)-13
There are a number of ruthenium, iridium, and rhodium
half-sandwich Cp*-containing metallacycles derived from α-
methylbenzylamine, and related derivatives, that have been
synthesized using a variety of procedures.19 In almost all of
these, the cyclopentadienyl moiety is exclusively or predom-
inantly syn to the α-methyl group such that this would appear
to be the kinetically and thermodynamically preferred
equivalent, (R)-12 underwent α-substitution, α-oxidation or
elimination on attempted direct cycloiridation (see Supporting
Information). Thus, following highly diastereoselective lith-
iation of (R)-12 (>99:1),18 addition of excess HgCl2 led to the
isolation by chromatography of (R,Sp)-13 together with
recovered (R)-12. The 1H NMR spectrum of the new
compound displayed a single set of three characteristic
D
DOI: 10.1021/acs.organomet.8b00905
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
from calcium hydride. Methanol was dried over 4 Å molecular sieves.
All cycloiridation reactions and reactions involving the use of dry
solvents were carried out under an inert atmosphere of either nitrogen
or argon. Silica gel (60 Å pore size, 40−63 μm technical grade) and
neutral aluminum oxide (Brockmann I, 50−200 μm) were used for
chromatography.
cyclopentadienyl hydrogen signals at 4.79, 4.64, and 4.27 ppm.
Attempted transmetalation of (R,Sp)-13 with [Cp*IrCl2]2,
under the room temperature conditions used previously, or on
heating at reflux, was unsuccessful and resulted only in the
recovery of starting material (R,Sp)-13. The low reactivity of
bulky cobalt-based sandwich complexes in related metalation
reactions has been noted previously.21
In light of the extensive application of half-sandwich
iridacycles derived from ketimines as catalysts for transfer
hydrogenation,22 it was anticipated that the ferrocenyloxazo-
line derived iridacycles of this study could also be applied to
such reactions. In a preliminary investigation, a mixture of
acetophenone and benzylamine underwent reductive amina-
tion when heated with an azeotropic mixture of formic acid
and triethylamine in the presence of 1 mol % (S,Rp,SIr)-5-d-6
(Scheme 10). Following acetylation (see Supporting Informa-
Synthesis of (S,Sp)-3. (S)-125 (0.15 g, 0.51 mmol) was added to a
flame-dried Schlenk tube under an atmosphere of argon and dissolved
in dry diethyl ether (6 mL). TMEDA (0.10 mL, 0.66 mmol) was
added and the subsequent orange solution was cooled to −78 °C and
stirred for 5 min, after which sec-butyllithium (1.4 M in hexanes)
(0.47 mL, 0.66 mmol) was added slowly. In a separate Schlenk tube,
mercury(II) chloride (0.2741 g, 1.01 mmol) was dried by heating
under high vacuum and allowed to cool. After the reaction had stirred
for 2 h, the mixture was warmed to 0 °C and a partial suspension of
mercury(II) chloride was added (using dry diethyl ether (6 mL)) to
the reaction mixture and stirred for 10 min. The reaction was allowed
to warm to room temperature, and after an additional 30 min, was
quenched with saturated sodium hydrogen carbonate solution. The
organics were separated with H2O, washed with brine, dried over
MgSO4 and upon removal of the solvent in vacuo gave a crude
product. Column chromatography (SiO2, 10% EtOAc/hexane)
yielded a yellow solid as a single diastereoisomer (0.1748 g, 65%).
Scheme 10. Iridacycle Catalyzed Reductive Amination
Rf 0.51 (10% EtOAc in hexane). Mp: 149−152 °C. [α]D22.5°C = −312
1
(c 0.2, CHCl3). IR (film): 3093, 2957, 2924, 2869, 1645 (CN). H
3
4
NMR (500 MHz, CDCl3): 4.84 (1H, dd, JHH = 2.6, JHH = 1.1 Hz,
3+3
2
CpH), 4.52 (1H, apt,
J
HH
= 2.4 Hz, CpH), 4.45 (1H, dd, JHH =
tion), the product of this reaction was determined by chiral
HPLC to be racemic. On the basis of an experimental and
computational study, the mechanism of intermediate imine
reduction is proposed to proceed by rate determining
iridacycle hydride formation, followed by outer-sphere hydride
transfer to the imino bond.23 In light of this, it is notable that
the use of a related chiral nonracemic iridacycle as a catalyst for
reductive amination resulted in a complete absence of
stereoinduction.24
3
3
4
9.6, JHH = 8.4 Hz, CHH), 4.31 (1H, dd, JHH = 2.4, JHH = 1.1 Hz,
2+3
CpH), 4.21 (5H, s, CpH), 4.14 (1H, apt,
J
HH
= 8.2 Hz, CHH),
3
3.90−3.85 (1H, m, CH), 1.76−1.71 (1H, m, CH), 1.06 (3H, d, JHH
= 6.7 Hz, CH3), 1.02 (3H, d, JHH = 6.7 Hz, CH3). 13C NMR (125
3
MHz, CDCl3): 168.6 (CN), 85.8 (CpCC), 75.5 (CpCH), 74.5
(CpCHg), 73.0 (CpCH), 72.0 (CH2), 71.8 (CH), 70.2 (C5H5), 70.1
(CpCH), 33.0 (CH), 19.2 (CH3), 18.8 (CH3). High resolution MS
(m/z, APCI+): found for [M + H]+ = 534.0189, calcd for
C16H18ClFeHgNO + H+ 534.0199.
Synthesis of (S,Sp,RIr)-5. (S,Sp)-3 (0.033 g, 0.06 mmol),
(pentamethylcyclopentadienyl)iridium(III) chloride dimer (0.025 g,
0.03 mmol), and tetrabutylammonium chloride (0.087 g, 0.31 mmol)
were added to a flame-dried Schlenk tube under an inert atmosphere.
Acetone (2 mL) was added and the resulting red solution was allowed
to stir at room temperature overnight. The reaction mixture was
filtered through Celite using dichloromethane as the eluent and the
solvent removed in vacuo. Excess tetrabutylammonium chloride was
removed by redissolving the orange residue in hexane and separating
with brine (4 × 50 mL). The organics were dried by filtering through
a glass wool pad loaded with magnesium sulfate and removing the
solvent in vacuo to give a tacky orange solid (0.03 g, 74%). Data as
previously reported.7
Synthesis of (S,Sp,SIr)-2. (S,Sp)-3 (0.033 g, 0.06 mmol),
(pentamethylcyclopentadienyl)iridium(III) chloride dimer (0.025 g,
0.03 mmol), and potassium hexafluorophosphate (0.047 g, 0.25
mmol) were added to a flame-dried Schlenk tube under an inert
atmosphere. Acetonitrile (3 mL) was added and the resulting red
solution was allowed to stir at room temperature overnight. The
reaction mixture was washed with hexane until the hexane layer
became colorless. The solvent from the acetonitrile layer was reduced
in vacuo. Purification was achieved by filtering through a 30 cm pad of
neutral alumina, using acetonitrile as the eluent, and collecting the
first bright orange fractions (subsequent pale yellow fractions
contained starting material and decomposition products). Removal
of the solvent in vacuo yielded the desired product as an amorphous
air sensitive orange solid (0.02 g, 34%). Data as previously reported.7
Synthesis of (S,Rp)-5-d-4. (S)-2-d-113 (0.260 g, 0.87 mmol) was
added to a flame-dried Schlenk tube under an atmosphere of argon
and dissolved in dry tetrahydrofuran (2 mL). The subsequent orange
solution was cooled to −78 °C and stirred for 5 min after which n-
butyllithium (2.5 M in hexanes) (0.45 mL, 1.13 mmol) was added
slowly. In a separate Schlenk tube, mercury(II) chloride (0.355 g, 1.32
CONCLUSION
■
Transmetalation is a viable alternative to cycloiridation as a
method for the synthesis of ferrocene-based planar chiral
iridacycles. Although lithium to iridium transmetalation did
not prove possible, lithium to mercury, followed by mercury to
iridium, transmetalation reactions were successful. This process
provided access to iridacycles that were previously unavailable
by direct introduction of iridium by C−H activation. In the
first example, the reversal of ferrocenyloxazoline lithiation
diastereoselectivity by use of a deuterium blocking group led to
the exclusive synthesis of the minor diastereoisomer generated
previously by cycloiridation. In the second example, the
transmetalation approach gave access to an iridacycle derived
from Ugi’s amine, whereas previously attempted cycloiridation
had resulted in substrate degradation. The intermediate
mercuracycles generated in this study are air and water stable,
and may be purified to remove any minor diastereoisomer
arising from incomplete selectivity on substrate lithiation. Gold
was investigated as an alternative to mercury, transmetalation
providing access to a planar chiral Au(I) species. A preliminary
investigation into the use of an enantiomerically and
diastereomerically pure iridacycle as a catalyst for reductive
amination resulted in the formation of a racemic product.
EXPERIMENTAL SECTION
■
General Remarks. Caution! All organomercurials are highly toxic.
Extreme care is necessary when handling all products and their solutions.
Diethyl ether and THF were distilled over sodium and benzophenone
ketyl. Acetonitrile and dichloromethane were dried by distillation
E
DOI: 10.1021/acs.organomet.8b00905
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
mmol) was dried by heating under high vacuum and allowed to cool.
After the reaction had stirred for 2 h, the mixture was warmed to 0 °C
and a partial suspension of mercury(II) chloride was added (using dry
THF (2 mL)) to the reaction mixture and stirred for 10 min. The
reaction was allowed to warm to room temperature, and after an
additional 20 min was diluted with diethyl ether and then quenched
with saturated sodium hydrogen carbonate. The organics were
separated with water, washed with brine, dried over magnesium
sulfate, and upon removal of the solvent in vacuo gave a crude product
(14:1 mixture of diastereoisomers). Column chromatography (SiO2,
10% EtOAc/hexane) yielded an orange solid that was recrystallized
from diethyl ether and hexane, giving the product as a single
diastereoisomer (0.206 g, 44%, 99% D-incorp.). Rf 0.54 (20% EtOAc/
22.5°C
became colorless. The acetonitrile layer was reduced in vacuo.
Purification was achieved by filtering through a 30 cm pad of neutral
alumina, using acetonitrile as the eluent, and collecting the first bright
orange fractions. Removal of the solvent in vacuo yielded the desired
product as an amorphous air sensitive orange solid (0.01 g, 46%).
Synthesis of (S,Sp)-8. (S)-125 (0.100 g, 0.34 mmol) was added to
a flame-dried Schlenk tube under an atmosphere of argon and
dissolved in dry diethyl ether (5 mL). TMEDA (0.070 mL, 0.44
mmol) was added and the subsequent orange solution was cooled to
−78 °C and stirred for 5 min, after which sec-butyllithium (1.4 M in
hexanes) (0.310 mL, 0.44 mmol) was added slowly. After stirring for
2 h, the mixture was warmed to 0 °C and a suspension of
chloro(triphenylphosphine)gold(I) (0.250 g, 0.51 mmol) in dry
diethyl ether (10 mL) was added via syringe and the resulting mixture
stirred vigorously for 1 h at room temperature. The reaction was
quenched with saturated sodium hydrogen carbonate solution,
washed with water, dried over magnesium sulfate, followed by
removal of the solvent in vacuo, to give an orange residue. This was
taken up in hexane and filtered through a glass frit, leaving a white
solid behind. The orange filtrate was concentrated and a
recrystallization performed from boiling hexane, followed by washing
with ice cooled hexane, to yield an orange solid as a single
24.0°C
hexane). Mp: 129 °C. [α]D
= +222 (c 0.9, CHCl3). IR (film):
1
3090, 2958, 2898, 2871, 1640 (CN). H NMR (500 MHz, CDCl3):
2+3
4.53 (1H, brs, CpH), 4.46 (1H, apt,
J
HH
= 8.6 Hz, CHH), 4.30
2+3
(1H, brs, CpH), 4.22 (5H, s, CpH), 4.03 (1H, apt,
J
HH
= 7.7 Hz,
CHH), 3.91−3.81 (1H, m, CH), 1.71−1.62 (1H, m, CH), 1.01 (3H,
d, 3JHH = 6.5 Hz, CH3), 0.92 (3H, d, 3JHH = 6.5 Hz, CH3). 13C NMR
(125 MHz, CDCl3): 168.5 (CN), 86.4 (CpCC), 75.5 (CpC), 74.2
(CpCHg), 72.9 (CpCH), 72.3 (CH2 & CH), 70.2 (C5H5), 33.3 (CH),
19.1 (2CH3). High resolution MS (m/z, ASAP+): found for [M + H]+
= 535.0276, calcd for C16H17DClFeHgNO + H+ 535.0267.
Synthesis of (S,Rp,SIr)-5-d-6. (S,Rp)-5-d-4 (0.0425 g, 0.085
mmol), (pentamethylcyclopentadienyl)iridium(III) chloride dimer
(0.0336 g, 0.042 mmol), and tetrabutylammonium chloride (0.1174
g, 0.422 mmol) were added to a flame-dried Schlenk tube under an
inert atmosphere. Acetone (3 mL) was added and the resulting red
solution was allowed to stir at room temperature overnight. The
reaction mixture was filtered through Celite using dichloromethane as
the eluent and the solvent removed in vacuo. Excess tetrabutylammo-
nium chloride was removed by redissolving the orange residue in
hexane (a small amount of acetone was added to aid dissolution) and
separating with brine (4 × 50 mL). The organics were dried by
filtering through a glass wool pad loaded with magnesium sulfate and
removing the solvent in vacuo to give an orange solid (0.05 g, 90%).
diastereoisomer (0.14 g, 53%) Mp: 63−64 °C. [α]D
= −168 (c
0.1, CHCl3). IR (film): 3067, 2958, 2892, 1642 (CN). 1H NMR (500
MHz, CDCl3): 7.72−7.67 (6H, m, PPh3), 7.49−7.46 (9H, m, PPh3),
4.90−4.88 (1H, m, CpH), 4.44−4.41 (1H, m, CpH), 4.25−4.20 (2H,
m, CpH + CHH), 4.16 (5H, s, CpH), 4.01 (1H, apt, 2+3JHH = 7.5 Hz,
CHH), 3.97−3.92 (1H, m, CH), 1.81−1.64 (1H, m, CH), 0.87 (3H,
d, 3JHH = 6.8 Hz, CH3), 0.80 (3H, d, 3JHH = 6.8 Hz, CH3). 13C NMR
2
(125 MHz, CDCl3): 169.0 (CN), 134.6 (d, JCP = 13.9 Hz, ArC),
131.7 (d, 1JHH = 50.0 Hz, ArC), 131.1 (d, 4JCP = 2.0 Hz, ArC), 129.0
(d, 3JCP = 10.7 Hz, ArC), 103.2 (d, 2JCP = 122.6 Hz, CpCAu), 79.4 (d,
3
4JCP = 4.1 Hz, CpCH), 77.8 (d, JCP = 4.6 Hz, CpCC), 72.4 (CH),
4
3
72.1 (d, JCP = 5.8 Hz, CpCH), 71.0 (d, JCP = 5.1 Hz, CpCH), 69.0
(CH2), 68.9 (C5H5), 32.5 (CH), 19.2 (CH3), 17.9 (CH3). 31P NMR
(202 MHz, CDCl3): 44.06 (PPh3). High resolution MS (m/z,
APCI+): found for [M + H]+ = 756.1390, calcd for C34H33AuFeNOP
+ H+ 756.1387.
Mp: 165−167 °C. [α]D21.5°C = +778 (c 0.20, CHCl3). IR (film): 2953,
2923, 2853, 1607. High resolution MS (m/z, NSI+): found for [M −
Cl]+ = 625.1599, calcd for C26H32FeIrNO+ 625.1599.
Synthesis of (R,Sp,)-10. (R)-916 (0.2572 g, 1.00 mmol) was
dissolved in diethyl ether (2 mL) in a flame-dried Schlenk tube under
an inert atmosphere. n-Butyllithium (0.86 mL, 1.20 mmol) was added
dropwise and the solution stirred at room temperature for 2 h. In a
separate dry vessel, mercury(II) chloride (0.407 g, 1.50 mmol) was
heated under high vacuum to ensure it was completely dry and
dissolved in the minimum quantity of diethyl ether once cool. After 2
h, the mercury(II) chloride solution was added rapidly to the reaction
mixture which was then stirred at room temperature for 30 min. The
resulting cloudy orange suspension was quenched with saturated
sodium hydrogen carbonate, followed by the addition of water and
diethyl ether. The organic layer was separated and dried with
potassium carbonate, followed by removal of the solvent in vacuo.
Column chromatography (SiO2, 1% NEt3/Et2O) gave the product as
23°C
Synthesis of (S,Rp,RIr)-5-d-7. (S,Rp)-5-d-4 (0.034 g, 0.06 mmol),
(pentamethylcyclopentadienyl)iridium(III) chloride dimer (0.025 g,
0.03 mmol), and potassium hexafluorophosphate (0.047 g, 0.25
mmol) were added to a flame-dried Schlenk tube under an inert
atmosphere. Acetonitrile (5 mL) was added and the resulting red
solution was allowed to stir at room temperature overnight. The
reaction mixture was separated with hexane until the hexane layer
became colorless. The acetonitrile layer was reduced in vacuo.
Purification was achieved by filtering through a 30 cm pad of neutral
alumina, using acetonitrile as the eluent, and collecting the first bright
orange fractions. Removal of the solvent in vacuo yielded the desired
product as an amorphous air sensitive orange solid (0.028 g, 54%).
[α]D25.7°C = +665 (c 1.89, MeCN). 1H NMR (500 MHz, MeCN-d3):
4.82−4.75 (2H, m, CHH + CHH), 4.54 (1H, d, 3JHH = 1.5 Hz, CpH),
4.46 (1H, d, 3JHH = 2.0 Hz, CpH), 4.12 (5H, s, CpH), 4.10 (1H, ddd,
3JHH = 8.9, 3JHH = 4.9, 3JHH = 2.4 Hz, CH), 1.91 (15H, s, C5(CH3)5),
1.89−1.87 (1H, m, CH), 0.98 (3H, d, 3JHH = 7.2 Hz, CH3), 0.68 (3H,
an orange solid (0.16 g, 33%). Mp: 98−100 °C. [α]D
= +26.9 (c
1.04, CHCl3). IR (film): 3090, 2968, 2935, 2825, 2779, 1446, 920.82.
1H NMR (500 MHz, CDCl3): 4.37 (1H, d, 3JHH = 1.8 Hz, CpH), 4.24
(1H, apt, 3+3JHH = 2.3 Hz, CpH), 4.10 (5H, s, CpH), 4.08−4.07 (1H,
3
m, CpH), 3.94 (1H, q, JHH = 6.7 Hz, CH), 2.14 (6H, s, N(CH3)2),
3
d, JHH = 6.7 Hz, CH3). 13C NMR (125 MHz, MeCN-d3): 183.7
3
1.14 (3H, d, JHH = 6.8 Hz, CH3). 13C NMR (125 MHz, CDCl3):
(CN), 91.4 (C5(CH3)5), 90.4 (CpCIr), 74.4 (CpCC), 74.0
95.4 (CpCC), 84.0 (CpCHg), 72.5 (CpCH), 69.5 (C5H5), 69.2
(CpCH), 68.1 (CpCH), 60.0 (CH), 39.4 (N(CH3)2), 9.2 (CH3).
High resolution MS (m/z, APCI+): found for [M]+ = 493.0171, calcd
for C14H18ClFeHgN 493.0171.
Synthesis of (R,Sp,SIr)-11. (R,Sp)-10 (0.080 g, 0.16 mmol),
(pentamethylcyclopentadienyl)iridium(III) chloride dimer (0.065 g,
0.08 mmol), and tetrabutylammonium chloride (0.226 g, 0.81 mmol)
were added to a flame-dried Schlenk tube under an inert atmosphere.
Acetone (5 mL) was added and the resulting brown/orange
suspension was allowed to stir at room temperature overnight. The
reaction mixture was filtered through Celite using dichloromethane as
(CpCH), 73.7 (CH2), 72.6 (CpCH), 70.7 (C5H5), 67.5 (CH), 65.9
’
(CpCD), 30.1 (CH), 19.3 (CH3 ), 14.5 (CH3), 9.9 (C5(CH3)5). High
resolution MS (m/z, NSI+): found for [M − (PF6 + MeCN)]+
=
625.1586, calcd for C26H32DFeIrNO+ 625.1599.
Conversion of (S,Rp,SIr)-5-d-6 into (S,Rp,RIr)-5-d-7. (S,Rp,SIr)-5-
d-6 (0.0170 g, 0.026 mmol) and potassium hexafluorophosphate
(0.0048 g, 0.026 mmol) were added to a flame-dried Schlenk tube
under an inert atmosphere. After dissolving in dry acetonitrile, the
reaction mixture was stirred for 2 h at room temperature. The
reaction mixture was washed with hexane until the hexane layer
F
DOI: 10.1021/acs.organomet.8b00905
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
the eluent and the solvent removed in vacuo. Excess tetrabutylammo-
nium chloride was removed by redissolving the orange residue in
hexane (with a small amount of dichloromethane added to aid
dissolution), followed by washing with brine (4 × 50 mL). The
organic layer was dried by filtering through a glass wool pad loaded
with magnesium sulfate. Removal of the solvent in vacuo gave a red
solid that was recrystallized from hot dichloromethane and hexane,
26.4°C
thermal parameters. Hydrogen atoms were included in idealized
positions and their Uiso values were set to ride on the Ueq values of the
parent carbon atoms.
In the final difference map, the highest peaks were close to the
mercury atoms.
Scattering factors for neutral atoms were taken from “International
Tables”.30 Computer programs used in this analysis have been noted
above, and were run through WinGX31 at the University of East
Anglia.
Crystal Structure Analysis - (R,Sp,SIr)-11. A suitable crystal
(0.130 × 0.120 × 0.005) mm3 was selected and mounted on a
MITIGEN holder in perfluoroether oil on a Rigaku FRE+ equipped
with VHF Varimax confocal mirrors and an AFC12 goniometer and
HyPix 6000 detector diffractometer. The crystal was kept at T =
100(2) K during data collection. Using Olex2,32 the structure was
solved with the ShelXT28 structure solution program, using the
Intrinsic Phasing solution method. The model was refined with
version 2014/7 of ShelXL29 using Least Squares minimization.
CCDC 1873232, 1873231, and 1862175 contain supplementary X-
ray crystallographic data for (S,Sp)-3, (S,Sp)-5-d-4, and (R,Sp,SIr)-11,
respectively.
yielding red crystals (0.05 g, 50%). Mp: 145−147 °C. [α]D
=
+720 (c 0.10, CHCl3). IR (film): 3048, 2966, 2922, 1698, 1458, 1262,
1
3+3
800. H NMR (500 MHz, CDCl3): 4.13 (1H, apt,
J
HH
= 2.0 Hz,
3
CpH), 4.06 (1H, d, JHH = 1.2 Hz, CpH), 3.94 (5H, s, CpH), 3.69
(1H, d, 3JHH = 1.6 Hz, CpH), 3.53 (1H, brq, 3JHH = 6.8 Hz, CH), 3.21
(3H, s, N(CH3)), 3.01 (3H, s, N(CH3)), 1.63 (15H, s, C5(CH3)5),
1.22 (3H, d, JHH = 6.8 Hz, CH3). 13C NMR (125 MHz, CDCl3):
3
102.3 (CpCC), 90.1 (CpCIr), 87.2 (C5(CH3)5), 68.5 (CpCH), 68.1
(C5H5), 67.6 (CpCH), 63.5 (CH), 60.7 (CpCH), 50.5 (N(CH3)),
49.4 (N(CH3)), 9.6 (C5(CH3)5), 9.3 (CH3). High resolution MS (m/
z, NSI+): [M − Cl]+ = 584.1581, calcd for C24H33FeIrN+ 584.1586.
Synthesis of (R,Sp)-13. (R)-1218 (0.100 g, 0.18 mmol) was added
to a flame-dried Schlenk tube under an inert atmosphere and
dissolved in dry diethyl ether (5 mL). sec-Butyllithium (1.4 M in
hexanes) (1.23 mL, 1.8 mmol) was added and the reaction was heated
to 40 °C and allowed to stir for 3 h. In a separate dry vessel,
mercury(II) chloride (0.543 g, 2.0 mmol) was heated under high
vacuum to ensure it was completely dry and dissolved in the
minimum quantity of diethyl ether once cool. After 3 h, the
mercury(II) chloride solution was added rapidly to the reaction
mixture, followed by heating at 40 °C for 15 min. The resulting
cloudy orange suspension was allowed to cool to room temperature,
diluted with diethyl ether, and then quenched with saturated sodium
hydrogen carbonate. The organic layer was separated and washed
with water and then brine, dried over potassium carbonate, and the
solvent removed in vacuo. Purification by column chromatography
(SiO2, 50% EtOAc/hexane) yielded the product as a yellow solid
(0.0395 g, 28%). Rf 0.18 (50% EtOAc/hexane). Mp: 68.8−71.4 °C.
22.6°C
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00905.
Copies of the 1H, 13C, 31P NMR and X-ray
crystallography details (PDF)
Accession Codes
CCDC 1862175, 1873231, and 1873232 contain the
supplementary crystallographic data for this paper. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
[α]D
= +16 (c 0.2, CHCl3). IR (film): 3080, 3058, 3029, 2971,
1
2938, 2868, 2828, 2784, 1597, 1498, 908, 736, 699. H NMR (500
MHz, CDCl3): 7.49−7.45 (8H, m, ArH), 7.27−7.24 (12H, m, ArH),
4.79 (1H, dd, 3JHH = 2.4, 4JHH = 1.2 Hz, CpH), 4.27 (1H, dd, 3JHH
=
2.4, 4JHH = 1.2 Hz, CpH), 4.64 (1H, apt, 3+3JHH = 2.4 Hz, CpH), 3.04
3
(1H, brq, JHH = 6.7 Hz, CH), 1.96 (6H, s, N(CH3)2), 0.87 (3H, d,
AUTHOR INFORMATION
Corresponding Author
*E-mail: Chris.Richards@uea.ac.uk.
■
3JHH = 6.7 Hz, CH3). 13C NMR (125 MHz, CDCl3): 136.2 (ArC),
128.8 (ArC), 128.5 (ArC), 126.7 (ArC), 106.7 (CpCC), 104.7
(CpCHg), 88.9 (CpCH), 84.5 (CpCH), 81.9 (CpCH), 75.23
(C4Ph4), 55.6 (CH), 39.1 (N(CH3)2), 9.8 (CH3). High resolution
MS (m/z, ASAP+): [M + H]+ = 788.1413, calcd for C37H33ClCoHgN
+ H+ 788.1414.
ORCID
Simon J. Coles: 0000-0001-8414-9272
Christopher J. Richards: 0000-0001-7899-4082
Iridacycle Catalyzed Reductive Amination. To a Schlenk tube
were added acetophenone (0.12 mL, 1.00 mmol), benzylamine (0.13
mL, 1.20 mmol), and (S,Rp,SIr)-5-d-6 (0.007 g, 0.01 mmol), followed
by dissolution in methanol (3 mL). A 5:2 mixture of formic acid and
triethylamine (0.5 mL) was then added and the reaction heated to 80
°C and stirred at this temperature overnight following sealing of the
Schlenk tube. After cooling, the reaction was quenched with water,
made basic with potassium hydroxide, and extracted with ethyl
acetate. The organic solvent was removed in vacuo and the residue
purified by column chromatography (SiO2, 10% EtOAc/hexane),
yielding a colorless oil (0.068 g, 32%, 0% ee). Data as previously
reported.26 Enantiomeric excess determined following acetylation (see
Supporting Information).
Crystal Structure Analyses - (S,Sp)-3 and (S,Sp)-5-d-4. For
each sample, a single crystal was mounted on a glass fiber and fixed in
the cold nitrogen stream on an Oxford Diffraction Xcalibur-3/
Sapphire3-CCD diffractometer (at UEA). Intensity data were
measured by thin-slice ω- and φ-scans. Data were processed using
the CrysAlisPro-CCD and -RED27 programs. The structures were
determined by the intrinsic phasing routines in the SHELXT
program28 and refined by full-matrix least-squares methods, on F2’s,
in SHELXL.29 The non-hydrogen atoms were refined with anisotropic
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The AI-Chem Channel is thanked for financial support. We
also thank the EPSRC National Mass Spectrometry Centre
(University of Wales, Swansea).
REFERENCES
■
(1) (a) Dupont, J.; Consorti, C. S.; Spencer, J. The Potential of
Palladacycles: More Than Just Precatalysts. Chem. Rev. 2005, 105,
2527−2571. (b) Djukic, J.-P.; Sortais, J.-B.; Barloy, L.; Pfeffer, M.
Cycloruthenated Compounds - Synthesis and Applications. Eur. J.
Inorg. Chem. 2009, 2009, 817−853. (c) Michon, C.; MacIntyre, K.;
Corre, Y.; Agbossou-Niedercorn, F. Pentamethylcyclopentadienyl
Iridium(III) Metallacycles Applied to Homogeneous Catalysis for
Fine Chemical Synthesis. ChemCatChem 2016, 8, 1755−1762.
(d) Wang, C.; Xiao, J. Iridacycles for Hydrogenation and
Dehydrogenation Reactions. Chem. Commun. 2017, 53, 3399−3411.
(e) Hazari, N.; Melvin, P. R.; Beromi, M. M. Well-Defined Nickel and
G
DOI: 10.1021/acs.organomet.8b00905
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Palladium Precatalysts for Cross-Coupling. Nat. Rev. Chem. 2017, 1,
0025.
(2) Djukic, J.-P.; Hijazi, A.; Flack, H. D.; Bernardinelli, G. Non-
Racemic (Scalemic) Planar-Chiral Five-Membered Metallacycles:
Routes, Means, and Pitfalls in their Synthesis and Characterization.
Chem. Soc. Rev. 2008, 37, 406−425.
(3) (a) Richards, C. J. In Chiral Ferrocenes in Asymmetric Catalsis:
Synthesis and Applications; Dai, L.-X., Hou, X.-L., Eds.; Wiley-VCH:
Weinheim, 2010; pp 337−368. (b) Nomura, H.; Richards, C. J. Allylic
Imidate Rearrangements Catalyzed by Planar Chiral Palladacycles.
Chem. - Asian J. 2010, 5, 1726−1740.
Ferrocenyloxazoline Gold(I) and Gold(II) Complexes. Dalton Trans.
2018, 47, 3880−3905.
(16) Marquarding, D.; Klusacek, H.; Gokel, G.; Hoffmann, P.; Ugi, I.
Correlation of Central and Planar Chirality in Ferrocene Derivatives.
J. Am. Chem. Soc. 1970, 92, 5389−5393.
(17) Reported previously but lacking a detailed experimental
procedure and characterization data. See: Sokolov, V. I.; Troitskaya,
L. L.; Reutov, O. A. Asymmetric Induction in the Course of Internal
Palladation of Enantiomeric 1-Dimethylaminoethylferrocene. J.
Organomet. Chem. 1977, 133, C28−C30.
(18) Arthurs, R. A.; Horton, P. N.; Coles, S. J.; Richards, C. J.
Stereoselective and Stereospecific Reactions of Cobalt Sandwich
Complexes: Synthesis of a New Class of Single Enantiomer Bulky
Planar Chiral P-N and P-P Ligands. Chem. - Eur. J. 2018, 24, 4310−
4319.
(19) (a) Martin, G. C.; Boncella, J. M. Nucleophilic Addition to
Coordinated Imines: Diastereoselective Synthesis of the Ruthenium
Amide Complexes (η6-C6Me6)RuN(Ph)CRR’C6H4(PMe3). Organo-
metallics 1989, 8, 2968−2970. (b) Martin, G. C.; Boncella, J. M.;
Wucherer, E. J. Synthesis of Ruthenium Amide Complexes by
Nucleophilic Attack on Ortho-Metalated Imine Ligands. Organo-
metallics 1991, 10, 2804−2811. (c) Attar, S.; Nelson, J. H.; Fischer, J.;
de Cian, A.; Sutter, J.-P.; Pfeffer, M. Metallacycles with Stereogenic
Metal Centers: Synthesis and Characterization of Diastereomeric
Cycloruthenated Chiral Amines. Organometallics 1995, 14, 4559−
4569. (d) Attar, S.; Catalano, V. J.; Nelson, J. H. Diastereoselectivity
of Chloride Substitution Reactions of Cycloruthenated (R)C-(+)- and
(S)C-(−)-Dimethyl(1-phenylethyl)amine. Organometallics 1996, 15,
2932−2946. (e) Hansen, H. D.; Maitra, K.; Nelson, J. H. Chloride
Substitution Reactions of Cycloruthenated (R)C-(+)-N,N-Dimethyl-
(1-phenylethyl)amine with Pseudohalides: Ruthenium Atom Stereo-
(4) (a) Stevens, A. M.; Richards, C. J. Synthesis and Highly
Diastereoselective Palladation of (η5-(S)-2-(4-Methylethyl)-
oxazolinylcyclopentadienyl) (η4-tetraphenylcyclobutadiene)cobalt.
Organometallics 1999, 18, 1346−1348. (b) Xia, J.-B.; You, S.-L.
Carbon-Carbon Bond Formation through Double sp2 C-H
Activations: Synthesis of Ferrocenyl Oxazoline Derivatives. Organo-
metallics 2007, 26, 4869−4871. (c) Cassar, D. J.; Roghzai, H.;
Villemin, D.; Horton, P. N.; Coles, S. J.; Richards, C. J. Chirality
Control in Planar Chiral Cobalt Oxazoline Palladacycles. Organo-
metallics 2015, 34, 2953−2961.
(5) (a) Wehman-Ooyevaar, I. C. M.; Vedral, J. A.; Jastrzebski, J. T.
B. H.; Grove, D. M.; van Koten, G. Novel Rhodate and Iridate
Complexes Containing C,N Chelating Arylamine Ligand Systems. J.
́
Organomet. Chem. 1993, 451, 195−204. (b) Perez, J.; Riera, V.;
Rodríguez, A.; Miguel, D. Synthesis and Structure of the First
Ruthenated Benzodiazepines. Organometallics 2002, 21, 5437−5438.
(6) (a) Meneghetti, M. R.; Grellier, M.; Pfeffer, M.; Dupont, J.;
Fischer, J. Synthesis of Configurationally Stable, Optically Active
Organocobalt Compounds. Organometallics 1999, 18, 5560−5570.
(b) Djukic, J.-P.; Berger, A.; Duquenne, M.; Pfeffer, M.; de Cian, A.;
Kyritsakas-Gruber, N.; Vachon, J.; Lacour, J. Syntheses of Nonracemic
Ortho-Mercurated and Ortho-Ruthenated Complexes of 2-
[Tricarbonyl(η6-phenyl)chromium]pyridine. Organometallics 2004,
23, 5757−5767.
chemistry. Inorg. Chem. 1999, 38, 2150−2156. (f) Gul, N.; Nelson, J.
̈
H. Synthesis, Characterization, and Diastereoselectivity of Chloride
Substitution Reactions of Cycloruthenated (R)C-(+)-N,N-Dimethyl-
α-(2-naphthyl) Ethylamine. Organometallics 1999, 18, 709−725.
(g) Gul, N.; Nelson, J. H. Ruthenacycles with Stereogenic Metal
̈
(7) Arthurs, R. A.; Ismail, M.; Prior, C. C.; Oganesyan, V. S.;
Horton, P. N.; Coles, S. J.; Richards, C. J. Enantiopure Ferrocene-
Based Planar-Chiral Iridacycles: Stereospecific Control of Iridium-
Centred Chirality. Chem. - Eur. J. 2016, 22, 3065−3072.
(8) Arthurs, R. A.; Prior, C. C.; Hughes, D. L.; Oganesyan, V. S.;
Richards, C. J. Enantiopure Planar Chiral and Chiral-at-Metal
Iridacycles Derived from Bulky Cobalt Sandwich Complexes.
Organometallics 2018, 37, 4204−4212.
Centers: Synthesis and Characterization of Cycloruthenated (R)C-
(+)-N,N-Dimethyl-α-(2-naphthyl) ethylamine (TMNA); Crystal
Structure of [(η6-C6H5Me)Ru(TMNA)(X)], (X = Cl, Br, I).
Polyhedron 1999, 18, 1835−1843. (h) Ritleng, V.; Bertani, P.;
Pfeffer, M.; Sirlin, C.; Hirschinger, J. Optically Active Ortho-
Metalated Half-Sandwich Ruthenium Complexes: Solid-State NMR
as a Convenient Tool To Analyze Mixtures of Diastereomers. Inorg.
Chem. 2001, 40, 5117−5122. (i) Sortais, J.-B.; Ritleng, V.; Voelklin,
A.; Holuigue, A.; Smail, H.; Barloy, L.; Sirlin, C.; Verzijl, G. K. M.;
Boogers, J. A. F.; de Vries, A. H. M.; de vries, J. G.; Pfeffer, M.
Cycloruthenated Primary and Secondary Amines as Efficient Catalyst
Precursors for Asymmetric Transfer Hydrogenation. Org. Lett. 2005,
7, 1247−1250. (j) Sortais, J.-B.; Pannetier, N.; Holuigue, A.; Barloy,
L.; Sirlin, C.; Pfeffer, M.; Kyritsakas, N. Cyclometalation of Primary
Benzyl Amines by Ruthenium(II), Rhodium(III), and Iridium(III)
Complexes. Organometallics 2007, 26, 1856−1867. (k) Sortais, J.-B.;
(9) Hegedus, L. S. In Comprehensive Organometallic Chemistry II;
Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford,
U.K., 1995; Vol. 12, pp 1−8.
(10) Abbenhuis, H. C. L.; Pfeffer, M.; Sutter, J. P.; de Cian, A.;
Fischer, J.; Ji, H. L.; Nelson, J. H. Carbon-Carbon and Carbon-
Nitrogen Bond Formation Mediated by Ruthenium(II) Complexes:
Synthesis of (1H)-Isoquinolinium Derivatives. Organometallics 1993,
12, 4464−4472.
(11) Sammakia, T.; Latham, H. A. Ligand Effects on the
Stereochemistry of the Metalation of Chiral Ferrocenyloxazolines. J.
Org. Chem. 1995, 60, 6002−6003.
́
Pannetier, N.; Clement, N.; Barloy, L.; Sirlin, C.; Pfeffer, M.;
Kyritsakas, N. Cyclometalation of Secondary Benzyl Amines by
Ruthenium(II) Complexes. Organometallics 2007, 26, 1868−1874.
(l) Pannetier, N.; Sortais, J.-B.; Dieng, P. S.; Barloy, L.; Sirlin, C.;
Pfeffer, M. Kinetics and Mechanism of Ruthenacycle-Catalyzed
Asymmetric Hydrogen Transfer. Organometallics 2008, 27, 5852−
5859. (m) Arthurs, R. A.; Horton, P. N.; Coles, S. J.; Richards, C. J.
Phenyl vs. Ferrocenyl Cyclometallation Selectivity: Diastereoselective
Synthesis of an Enantiopure Iridacycle. Eur. J. Inorg. Chem. 2017,
2017, 229−232. (n) Chen, H. J.; Teo, R. H. X.; Li, Y.; Pullarkat, S. A.;
Leung, P.-H. Stereogenic Lock in 1-Naphthylethanamine Complexes
for Catalyst and Auxiliary Design: Structural and Reactivity Analysis
for Cycloiridated Pseudotetrahedral Complexes. Organometallics
2018, 37, 99−106.
(12) Arthurs, R. A.; Horton, P. N.; Coles, S. J.; Richards, C. J.
Metallocene to Metallocene Conversion. Synthesis of an Oxazoline-
Substituted Pentamethyliridocenium Cation from a Ferrocenyloxazo-
line. Chem. Commun. 2016, 52, 7024−7027.
(13) Arthurs, R. A.; Richards, C. J. Deuterium as a Stereochemically
Invisible Blocking Group for Chiral Ligand Synthesis. Org. Lett. 2017,
19, 702−705.
(14) Gorunova, O. N.; Novitskiy, I. M.; Grishin, Y. K.; Gloriozov, I.
P.; Roznyatovsky, V. A.; Khrustalev, V. N.; Kochetkov, K. A.; Dunina,
V. V. When Applying the Mercury Poisoning Test to Palladacycle-
Catalyzed Reactions, One Should Not Consider the Common
Misconception of Mercury(0) Selectivity. Organometallics 2018, 37,
2842−2858.
(20) The exceptions are N-heterocyclic ligated iridacycles. See:
Sabater, S.; Baya, M.; Mata, J. A. Highly Active Cp*Ir Catalyst at Low
Temperatures Bearing an N-Heterocyclic Carbene Ligand and a
(15) Holz, J.; Garcia, M. A.; Frey, W.; Krupp, F.; Peters, R.
Diastereoselective Synthesis, Structure and Reactivity Studies of
H
DOI: 10.1021/acs.organomet.8b00905
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Chelated Primary Benzylamine in Transfer Hydrogenation. Organo-
metallics 2014, 33, 6830−6839.
́
(21) Arrayas, R. G.; Mancheno, O. G.; Carretero, J. C. First Planar
̃
Chiral Bidentate Ligand Based on a (η5-Cyclopentadienyl)(η4-
cyclobutadiene)cobalt Backbone: High Efficiency in Enantioselective
Palladium-Catalyzed Allylic Substitutions. Chem. Commun. 2004,
1654−1655.
(22) Wang, C.; Xiao, J. Iridacycles for Hydrogenation and
Dehydrogenation Reactions. Chem. Commun. 2017, 53, 3399−3411.
(23) Chen, H.-Y. T.; Wang, C.; Wu, X.; Jiang, X.; Catlow, C. R. A.;
Xiao, J. Iridicycle-Catalysed Imine Reduction: An Experimental and
Computational Study of the Mechanism. Chem. - Eur. J. 2015, 21,
16564−16577.
(24) In additional investigations, the attempted reduction of
acetophenone was investigated with (a) KOt-Bu in i-PrOH in the
presence of 1 mol % of (S,Sp,RIr)-5 at 80 °C and (b) Et3SiH in
CH2Cl2 in the presence of 0.5 mol % (S,Sp,RIr)-5 and 1 mol %
NaBArF24 at RT and then 40 °C. Both resulted in essentially no
reaction (<1%).
(25) Sammakia, T.; Latham, H. A.; Schaad, D. R. Highly
Diastereoselective Ortho Lithiations of Chiral Oxazoline-Substituted
Ferrocenes. J. Org. Chem. 1995, 60, 10−11.
(26) Wang, C.; Pettman, A.; Basca, J.; Xiao, J. A Versatile Catalyst
for Reductive Amination by Transfer Hydrogenation. Angew. Chem.,
Int. Ed. 2010, 49, 7548−7552.
(27) Programs CrysAlisPro; Oxford Diffraction Ltd.: Abingdon, U.K.,
2010.
(28) Sheldrick, G. M. SHELXT - Integrated space-group and crystal-
structure determination. Acta Crystallogr., Sect. A: Found. Adv. 2015,
A71, 3−8.
(29) Sheldrick, G. M. Crystal Structure Refinement with SHELXL.
Acta Crystallogr., Sect. C: Struct. Chem. 2015, C71, 3−8.
(30) International Tables for X-ray Crystallography; Kluwer Academic
Publishers: Dordrecht, 1992; Vol. C, pp 500, 219, and 193.
(31) Farrugia, L. J. WinGX and ORTEP for Windows: an Update. J.
Appl. Crystallogr. 2012, 45, 849−854.
(32) Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A.
K.; Puschmann, H. OLEX2: A Complete Structure Solution,
Refinement and Analysis Program. J. Appl. Crystallogr. 2009, 42,
339−341.
I
DOI: 10.1021/acs.organomet.8b00905
Organometallics XXXX, XXX, XXX−XXX