Developing Chiral Dibenzazepine-Based S(O)-Alkene Hybrid Ligands for Rh(I) Complexation: Catalysts for the Base-Free Hayashi-Miyaura Reaction

Article abstract of DOI:10.1021/acs.organomet.8b00591

A stereodivergent synthesis using inexpensive reagents, i.e., dibenzazepine and glucose-derived t-Bu-sulfinate diastereomers (R_S)-6 or (S_S)-6, affords respective S(O)-alkene hybrid ligands (S)-7 and (R)-7 on gram scales and in excellent optical purity (ee > 99%). Phenyl substitution of the dibenzoazepine backbone generates planar chirality to give epimerization-resistant (pS,R_S)-10 diastereoisomer in high isomeric purity. Furthermore, the crystal structure of widely used sulfinate (R_S)-6 is disclosed for the first time since its discovery a quarter of a century ago. Ligands 7 and 10 coordinate Rh(I) in a bidentate fashion through the S atoms and the alkene functions as evidenced by the crystal structures of complexes (R)-11 and (S_N,S_S)-12. (R)-11 catalyzes the conjugate addition of arylboronic acids to enones with enantioselectivities of up to 77% ee. The reaction proceeds smoothly also under base-free conditions at 40 °C. The planar chirality in ligand (pS,R_S)-10 is shown to override and invert the sense of chiral induction predicted by the configuration of the sulfur donor atom.

Full text of DOI:10.1021/acs.organomet.8b00591

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Developing Chiral Dibenzazepine-Based S(O)-Alkene Hybrid Ligands
for Rh(I) Complexation: Catalysts for the Base-Free
Hayashi−Miyaura Reaction
Ahmed Chelouan, Siyuan Bao, Sibylle Frieß, Alberto Herrera, Frank W. Heinemann, Ana Escalona,
Alexander Grasruck, and Romano Dorta*
̈
̈
Department Chemie und Pharmazie, Anorganische und Allgemeine Chemie, Friedrich−Alexander−Universitat Erlangen−Nurnberg,
Egerlandstraße 1, 91058 Erlangen, Germany
S
* Supporting Information
ABSTRACT: A stereodivergent synthesis using inexpensive reagents, i.e., dibenzazepine and glucose-derived t-Bu-sulfinate
diastereomers (RS)-6 or (SS)-6, affords respective S(O)-alkene hybrid ligands (S)-7 and (R)-7 on gram scales and in excellent
optical purity (ee > 99%). Phenyl substitution of the dibenzoazepine backbone generates planar chirality to give epimerization-
resistant (pS,RS)-10 diastereoisomer in high isomeric purity. Furthermore, the crystal structure of widely used sulfinate (RS)-6 is
disclosed for the first time since its discovery a quarter of a century ago. Ligands 7 and 10 coordinate Rh(I) in a bidentate
fashion through the S atoms and the alkene functions as evidenced by the crystal structures of complexes (R)-11 and (SN,SS)-12.
(R)-11 catalyzes the conjugate addition of arylboronic acids to enones with enantioselectivities of up to 77% ee. The reaction
proceeds smoothly also under base-free conditions at 40 °C. The planar chirality in ligand (pS,RS)-10 is shown to override and
invert the sense of chiral induction predicted by the configuration of the sulfur donor atom.
the alkene coordinates to the metal or not, the N atom in 1 is
sp3 or sp2 hybridized,9 a property that further “spring-loads”
the alkene function toward hemilability. Here, we wish to com-
municate a simple procedure for the synthesis of a new class of
enantiopure dibenz[b,f ]azepine-based S(O)-alkene ligands.
We show that these diaryl, i.e., aprotic, sulfinamides10 are
indeed sp3−sp2 hybridization flexible at the azepine N atom
while remaining stereochemically stable. Furthermore, we
INTRODUCTION
■
Enantiopure sulfoxides, which are appreciated for their ease of
synthesis and high stability, are important auxiliaries in
asymmetric synthesis and excellent ligands for certain metal-
catalyzed asymmetric organic transformations,1 in which the
polarized R2 S−O− function appears to induce chirality also
+
through electrostatic effects.2 Inspired by Knochel’s effective
norbornene-derived sulfoxide-alkene 33 (see Table 1) and
highly flexible sulfinamido-alkene designs of type 44 and since
our laboratory has been developing chiral P-alkene ligands such
as 15 based on the dibenzo[b,f]azepine scaffold,6 we have been
interested to extend this architecture to S(O)-dibenzazepinyl
analogues7 by connecting the N atom with readily available
chiral sulfinyl electrophiles. The alkene functions in ligands 1−4
are expected to be hemilabile thus enhancing catalyst
performance. For example, complex [Rh(1)2]BF4 is a highly
active and stereoselective catalyst for the conjugate addition of
a wide range of arylboronic acids to enones.8 Structural studies
showed that the azepine N-function in ligand 1 is hybrid-
ization-flexible in contrast to the fixed sp3 hybridized methine
in tropylidenyl derivatives of type 2. Depending on whether
provide the proof-of-principle that in analogy to Grutzmacher’s
̈
tropylidenyl-based planar-chiral architecture of ligand 211 it is
possible to generate planar chirality by introducing a phenyl
group on the alkene function of the dibenz[b,f]azepine back-
bone, and we demonstrate that these S(O)-alkenes behave
as bidentate ligands for Rh(I). Rhodium complexes of chiral
bis-alkene,12 bis-sulfoxide,13 and in particular hybrid S(O)-
alkene14 ligands are emerging as the catalysts of choice for the
asymmetric conjugate addition of alkenyl and aryl boronic
acids to Michael acceptors (the Hayashi−Miyaura reaction).15
Received: August 20, 2018
© XXXX American Chemical Society
A
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Table 1. Inspiring Chiral P-Alkene and S-Alkene Ligands
However, mild, base-free protocols for this reaction still repre-
sent a challenge,16 which the new Rh−S(O)-alkene complexes
presented here partially address.
We recently introduced 10-phenyl-5H-dibenz[b,f]azepine for
the synthesis of a P-stereogenic/planar-chiral P-alkene ligand,23
and we found that its lithium salt 8 reacts with quinine-based
sulfinate (RS)-9 at −78 °C in THF solution to afford a 2:1
diastereomeric mixture of (pS,RS)- and (pR,RS)-10.24 The
diastereomers are best identified by the singlet resonances of the
RESULTS AND DISCUSSION
■
Dark blue Li-amide 517 is quenched in THF solution at −78 °C
with either diastereomers of the DAG-tert-butylsulfinate,18 (RS)-6
or (SS)-6, to afford gram quantities of the (R)-7 or the (S)-7
enantiomer, respectively, as white powders and in excellent opti-
cal purity (see Scheme 1). It should be noted that purification
1
t-Bu-groups in the H NMR spectrum at 1.09 ppm (major) and
1.04 ppm (minor), and the major one is separated by flash column
chromatography on K2CO3-impregnated silica19 and isolated as a
white crystalline material on a half-gram scale in excellent optical
purity.25 The absolute configuration (pS,RS) is assigned by single
crystal X-ray diffraction analysis (see Figure 2),26 the configu-
ration at sulfur being in accordance with the prediction based
on an SN2 type displacement reaction. As in 7, the sp2 N
atom shows average bond angles of 118.6(14)° and is slightly
pyramidalized, with the tip of the N atom pointing in endo
direction of the azepine chair. It is therefore possible, at least in
the solid state, to assign the N atom the absolute configuration
(R) instead of using the pS descriptor when dealing with an
ideal planar N atom. On the other side, the phenyl substituted
atom C8 is perfectly trigonal planar (averaged value of the
three bond angles: 120.0°). No epimerization of (pS,RS)-10
takes place in solution under acid-free conditions, even under
prolonged heating at 60 °C.
Scheme 1. Divergent Asymmetric Synthesis of the
Enantiomers of S(O)-Alkene 7
of these molecules by flash column chromatography is only
possible on K2CO3-impregnated silica,19 while on standard silica
G60 and even in humid, air-saturated CDCl3 solution they
racemize.20 In order to dispose of a standard for the determi-
nation of the optical purity of (R)-7 and (S)-7 by enantiontio-
selective HPLC (see Figure S4), the racemate rac-7 was
independently prepared by reacting racemic t-butyl-phenox-
ysulfinate with Li-amide 5 according to eq 1.21 Furthermore,
the improved crystallinity of rac-7 over its enantiopure conge-
ners allowed us to grow X-ray quality single crystals in a 1,2-
difluorobenzene/n-pentane solvent system, and the structure of
the (R)-enantiomer is depicted in Figure 1. The absolute
configurations of the enantiopure ligands 7 must therefore be
inferred from mechanistic considerations and most probably are
the ones outlined in Scheme 1.22 The stereogenic sulfur atom is
pyramidal with an average bond angle of 106.7°, while the
nitrogen atom is approximately trigonal planar (sp2-hybridized)
with average bond angles of 118.9° as also observed in corre-
sponding phosphoramidite ligands.5c,d,8 Similarly, the use of rac-7
also helped crystallization of the corresponding rhodium
complex (vide infra).
In a separate experiment, the racemic diastereomeric mixture
of 10 was prepared according to eq 3 in analogy to rac-7 (vide
supra). The crude product of rac-10 is a 1:1 diastereomeric
mixture, which after recrystallization displays a 83:17 bias in
favor of the (pR,RS)/(pS,SS)-10 pair of enantiomers. This
racemate served then as reference substance for the certifi-
cation of the enantio- and diastereomeric purity of (pS,RS)-10,
and Figure 3 shows the chiral stationary phase HPLC traces of
the reference rac-10 (top) along with a diastereomerically pure
sample of (pS,RS)-10 of medium optical purity (98% ee,
bottom trace).
THF
8 + rac‐t‐BuS(O)OPh ⎯⎯⎯→⎯ rac‐10
(3)
0°C
On a side note, DAG-sulfinates28 represent an important class
of chiral sulfinylating agents, and (RS)-6 is one of the most
popular and practical tert-butyl sulfinates.29 It has been dis-
covered a quarter of a century ago,18a but so far has eluded
structural characterization for being described as an oil.18b
Structural information about DAG-sulfinates is in general
scarce.28d Thanks to a scaled-up procedure that affords very
pure material, we were able to isolate crystalline (RS)-6. The
THF
5 + rac‐t‐Bu(SO)OPh ⎯⎯⎯→⎯ rac‐7
(1)
0°C
B
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benzene or toluene solution to afford optically pure dinuclear
complexes (S)-11, (R)-11, and (SN,SS)-12, respectively, in high
yields as yellow-orange powders (see eq 4). The complexes are
soluble but unstable in chlorinated solvents and only sparingly
soluble in aromatic solvents. NMR spectra of (S)-11 and (R)-
11 reveal the exclusive formation of the anti-isomer, while
(SN,SS)-12 forms a syn/anti mixture of 1:2. The latter can be iso-
lated as the pure anti-isomer by recrystallization from benzene.
Figure 1. Molecular structure of the (R)-7 enantiomer in the crystal
of rac-7 plotted with 50% displacement ellipsoids. H atoms are
omitted. Selected distances (Å) and angles (deg): S1−O1 1.4884(9),
N1−C1 1.4333(15), S1−N1 1.6768(10), S1−C15 1.8498(13),
C7−C8 1.3432(10), O1−S1−N1 111.30(5), N1−S1−C15
103.10(5), O1−S1−C15 105.57(6), C1−N1−C14 117.17(9), C1−
N1−S1 115.64(8), C14−N1−S1 123.93(8).
Single crystal X-ray diffraction analyses of complexes 11
and 12 were necessary to prove the proposed bidentate coor-
dination mode of the new ligands and to gain precise structural
information, not least in view of the fact that structurally
authenticated chiral S-alkene complexes of rhodium are
rare.4a,14a Since crystallization of enantiopure (S)-11 proved
problematic and did not afford diffraction-quality single
crystals; racemic ligand rac-7 was used to synthesize complex
rac-11 in a bid to improve crystallinity. The resulting complex
exhibits NMR spectra identical to those of (S)-11 including
the observed anti-selectivity, which is an indication that only
homochiral dimers of rac-11 form. Indeed, well-shaped single
crystals of rac-11 are readily grown from a CH2Cl2/pentane
mixture (see the Experimental Section), in stark contrast to the
optically pure material of (S)-11. In contrast, X-ray quality
crystals of enantiopure (SN,SS)-12 are obtained without
problems by layering a C6D6 solution with n-hexane. The
X-ray diffraction analyses reveal in the case of rac-11 a centro-
symmetrical unit cell containing an enantiomeric pair of
homochiral dinuclear complexes and, in the case of (SN,SS)-12,
a chiral unit cell containing two independent molecules with
the expected absolute configurations. The respective structures
are depicted in Figures 5 and 6. Both show bidentate S-alkene
ligands and square planar coordination geometries around the
chloro-bridged Rh-centers. The Rh−Cl bonds located trans to
the S atoms are longer than those trans to the alkenes by ca.
0.01−0.06 Å, and the butterfly-shaped Rh2Cl2 cores in rac-11
and (SN,SS)-12 span wing angles of 120.7 and 122.7°,
respectively. Exclusive anti-coordination is observed in both
crystals, which in the case of rac-11 is the consequence of a
crystallographic C2-axis bisecting the Cl1−Cl1A and the Rh1−
Rh1A vectors. The Rh−S and Rh−alkene distances compare
well with values found in similar sulfoxide-alkene4a,14a and
P-alkene5c,8 complexes. The bite angles of ligands in the two com-
plexes are very similar at 91.8° in rac-11 and 92.0° in (SN,SS)-12
(average value of four independent molecules, measured
between the centroids of the alkene functions and the
S atoms). The coordinated alkene bonds (C7−C8 1.423(2)
in 11; C7−C8 1.427(11), C31−C32 1.436(11) in 12) are ca.
0.08 Å longer than those in respective free ligands 7 and 10
(1.3432(10) and 1.351(5) Å, see Figures 1 and 2). Further-
more, in complex 12 the C atom bearing the phenyl ring is
Figure 2. Molecular structure of (pS,RS)-10 in the chiral crystal
plotted with 50% displacement ellipsoids. H atoms are omitted.
Selected distances (Å) and angles (deg): S1−O1 1.483(2), N1−C1
1.441(4), S1−N1 1.680(3), N1−C14 1.440(4), S1−C21 1.849(3),
C7−C8 1.351(5), O1−S1−N1 112.47(14), N1−S1−C21
102.06(15), O1−S1−C21 105.95(15), C1−N1−S1 127.4(2), C14−
N1−S1 113.6(2), C14−N1−C1 114.8(3).
structure of one of four symmetry-independent molecules is
depicted in Figure 4 and confirms the expected absolute
configurations of the stereogenic sulfur and carbon atoms (the
other three molecules also correspond). In all four inde-
pendent molecules, the tert-butyl and glucose moieties are turned
away from each other in order to minimize steric repulsion, as
indicated by the torsion angle along C1−O2−S1−C13 of
−122.1° (in the other three molecules these angles measure
−141.6, −160.7, and −169.4°) and in opposite direction when
compared to the closely realted (SS)-DAG-cyclohexanesulfinate
(+157.2°).28d
The coordination chemistry of the new ligands with Rh(I)
was explored by reacting two equivalents of either (R)-7, (S)-7,
or (pS,RS)-10 with [RhCl(coe)2]2 (coe = cyclooctene) in
C
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Figure 3. Chiral stationary phase HPLC traces. Top: recrystallized rac-10 showing the four possible isomers with dr = 82.9:17.1. Bottom: sample of
(pS,RS)-10 having ee = 98% for illustrative purposes.27 Peak labels denote retention times and surface areas. Conditions: Chiralpak AD-H; flow
rate: 1 mL/min; n-hexane/i-PrOH = 95:5.
Figure 5. Molecular structure of the (S)-enantiomer in the racemic
crystal of rac-11 plotted with 50% displacement ellipsoids. H atoms
are omitted. Selected distances (Å) and angles (deg): Rh1−Cl1A(i)
2.4120 (5), Rh1−Cl1 2.3997(5), Rh1−S1 2.1792(5), Rh1−C7
2.1158(18), Rh1−C8 2.1394(18), C7−C8 1.423(2), S1−O1
Figure 4. Structure of one out of four symmetry-independent
1.4700(13), S1−N1 1.7334(15), C7−Rh1−S1 93.05(5), C8−Rh1−S1
molecules in the chiral crystal of (RS)-6 plotted with 50%
90.51(5), Cl1−Rh1−Cl1A 81.57(2), Rh1−Cl1−Rh1A 82.305(16),
displacement ellipsoids. H atoms are omitted for clarity. Selected
S1−Rh1−Cl1 97.973(17), N1−S1−Rh1 109.55(5). Symmetry code
distances (Å) and angles (deg): S1−O1 1.462(4), S1−O2 1.649(3),
(i): −x + 1, y, −z + 1/2.
S1−C13 1.827(4), O1−S1−O2 106.02(19), O1−S1−C13 106.7(2),
O2−S1−C13 96.87(16), C1−O2−S1 115.4(2).
N2 in 12). We note that the N atom in complex 12 is
slightly pyramidalized (sum of angles between C−C bonds at
C14:354.2°). Alkene bond elongation and pyramidalization are
the consequence of metal to alkene π-backbonding.30 Further-
more, the Rh−C distance to the phenyl-substituted carbon
atom is on average 5 pm longer than to the unsubstituted
carbon atoms, presumably due to steric repulsion. Another
important structural alteration of the coordinated ligands when
compared to their free state 7 and 10 is the pronounced sp3
character of the N atom, which may be quantified by the sum
of its bond angles (336.4° in 11; 335.8 and 334.6° for N1 and
stereogenic with (S)-configuration.
With well-characterized enantiopure complexes 11 and 12 in
hand, their catalytic performance was benchmarked in the
Hayashi−Miyaura conjugate addition of arylboronic acids 14
to enones 13 (Table 2). First, enantiomeric catalysts (R)-11
and (S)-11 were tested under standard biphasic dioxane/water
2:1 conditions in the presence of K3PO4 base at 40 °C. The
respective product ketones (R)-15aa and (S)-15aa were
obtained as opposite enantiomers in 75% ee in very close
agreement, thus demonstrating stereochemical consistency
D
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(entries 1 and 2). The use of KOH as additive led to complete
erosion of enantioselectivity (entry 3) and is probably due to
decomposition of the ligand. It was then found that the reac-
tion also proceeds smoothly in the absence of base additives in
a toluene/water 2:1 solvent system (entry 4). However, the
base-free protocol requires higher catalyst loadings to ensure
full conversion and ee values drop by 5−14% depending on
the reaction (compare entries 1/4, 6/7, 8/9, and 10/11). While
cyclopentenone (13b) gives similar results, the addition of 14a
to chalcone 13c under base-free condition proceeds swiftly but
with disappointing enantioselectivity (entry 18). Complex
(SN,SS)-12, in comparison with (R)-11, returned lower chemi-
cal and optical yields in the standard reaction between 13a and
14a (cf. entries 4 and 5). It should be noted that even though
(SN,SS)-12 bears an inversely configured sulfur donor com-
pared to (R)-11 it shows the same (R) selectivity for the prod-
uct. Clearly, the planar chirality of the alkene function in ligand
(pS,RS)-10 (and not the chirality of the sulfur donor) controls
the stereochemical outcome in this reaction, which is consistent
with observations made by Knochel and co-workers3 and Liao
and co-workers14a with their respective planar chiral S(O)-
alkene ligand systems. The stereochemical model in Figure 7
rationalizes the observed enantioselectivities for the proto-
typical reaction of 13a with 14a.31 In the case of catalyst
(S)-11 bearing ligand (R)-7, enone 13a is oriented “up” and anti
with respect to the bulky tert-butyl group, thereby presenting
Figure 6. Molecular structure of one of two symmetry-independent
molecules of anti-(SN,SS)-12 in the chiral crystal plotted with 50%
displacement ellipsoids. H atoms are omitted. Selected distances (Å)
and angles (deg): Rh1−Cl1 2.400(2), Rh1−Cl2 2.382(2), Rh2−Cl1
2.370(2), Rh2−Cl2 2.4320(19), Rh1−S1 2.155(2), Rh2−S2
2.156(2), Rh1−C7 2.115(8), Rh1−C8 2.165(2), Rh2−C31
2.120(8), Rh2−C32 2.171(8), C7−C8 1.427(11), C31−C32
1.436(11), S1−O1 1.461(6), S1−N1 1.728(7), S1−C21 1.864(8),
N1−C1 1.449(9), N1−C14 1.428(9), N2−C25 1.425(11), N2−C38
1.458(10), Cl1−Rh1−Cl2 79.79(7), S1−Rh1−C8 89.7(2), S1−Rh1−
C7 93.4(2).
Table 2. Complexes 11 and 12 Catalyze the Hayashi−Miyaura Conjugate Addition Reaction
a
b
c
entry
catalyst (mol %)
additive
enone
boronic acid
isolated yield (%)
ee (%)
major isomer
1
2
3
4
5
6
7
8
(R)-11 (1.5)
(S)-11 (1.5)
(R)-11 (5)
(R)-11 (5)
(SN,SS)-12 (5)
(S)-11 (5)
(S)-11 (1.5)
(R)-11 (5)
(R)-11 (1.5)
(R)-11 (5)
(R)-11 (1.5)
(S)-11 (5)
(S)-11 (5)
(S)-11 (5)
(S)-11 (5)
(S)-11 (5)
(S)-11 (5)
(S)-11 (5)
(SN,SS)-12 (5)
K3PO4
K3PO4
KOH
none
none
none
K3PO4
none
K3PO4
none
K3PO4
none
none
none
none
none
none
none
none
13a
13a
13a
13a
13a
13a
13a
13a
13a
13a
13a
13a
13a
13a
13a
13b
13b
13c
13c
14a
14a
14a
14a
14a
14b
14b
14c
14c
14d
14d
14e
14f
14g
14h
14a
14b
14b
14b
96 (15aa)
98 (15aa)
98 (15aa)
97 (15aa)
67 (15aa)
97 (15ab)
97 (15ab)
97 (15ac)
98 (15ac)
96 (15ad)
97 (15ad)
95 (15ae)
95 (15af)
96 (15ag)
97 (15ah)
98 (15ba)
98 (15bb)
98 (15cb)
traces
75.2
74.9
0
(R)
(S)
70
60
69
76
52
66
68
77
70
67
60
40
68
66
36
n.d.
(R)
(R)
(S)
(S)
(R)
(R)
(R)
(R)
(S)
(S)
(S)
(S)
(S)
(S)
(S)
9
10
11
12
13
14
15
16
17
18
19
a
b
With KOH additive and without additive, the organic solvent is toluene; with K3PO4 additive, the organic solvent is 1,4-dioxane. Commercial
aryl boronic acids were used as received. Ar = Ph (14a), 4-CH3C6H4 (14b), 4-t-Bu-C6H4 (14c), 2-naphthyl (14d), 4-FC6H4 (14e), 4-CH3OC6H4
c
(14f), 3-CH3OC6H4 (14g), 2-CH3OC6H4 (14h). Determined by enantioselective HPLC (see the Supporting Information); absolute
configurations are assigned by comparison with reported data.
E
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show that preformed rhodium complexes 11 and 12 withstand
the aqueous reaction conditions commanded by the Hayashi−
Miyaura C−C coupling protocol and indeed operate also with-
out base additives. However, the use of these ligands in aqueous
solvent systems represents a potential source of erosion of
enantioselectivity, and water-free protocols are currently being
developed in our laboratory. Finally, planar chirality in ligand
(pS,RS)-10 is found to be the overwhelming stereochemical
factor defining the sense of chiral induction, and therefore
diastereomeric forms such as (pR,RS)-10 represent worthwhile
synthetic targets.
EXPERIMENTAL SECTION
■
Experiments involving sensitive compounds were carried out under
anaerobic and anhydrous conditions, using standard Schlenk and
glovebox techniques. Technical grade EtOAc, hexanes, and MeOH for
flash column chromatography were purified by rotary evaporation.
Solvents were distilled as follows: THF, Et2O, and benzene from
purple Na/Ph2CO solutions; toluene from Na; pentane, C6D6, and
THF-D8 from Na2K alloy; CH3CN, CH2Cl2, and CD2Cl2 from CaH2;
NEt3 and 1,4-dioxane from K. CD3CN and CDCl3 were degassed with
three freeze−pump−thaw cycles and then kept in a glovebox over
activated molecular sieves (3 and 4 Å, respectively). K3PO4 (99%,
Aldrich) and diacetone-D-glucose (DAG, 98%, Carbosynth) were
used as received. 5,23 (SS)-6,18b 8,23 PhLi,33 (R)-9,18 [RhCl(COE)2]2,34
were prepared according to published procedures. Elemental analyses
(EA) were performed on a Euro EA 3000 analyzer, and air-sensitive
samples were handled and prepared in a glovebox. NMR spectra were
recorded on Jeol EX 270, ECP 400, or ECX 400 instruments
Figure 7. Top: stereochemical model (top view) for the prediction of
the sense of addition of 14a to 13a when using catalysts 11 (left) or
12 (right). Bottom: steric maps (head-on view) of Rh(I)-coordinated
ligands (R)-7 (left) and (pS,RS)-10 (right) generated from crystallo-
graphic data of complexes 11 and 12 with SambVca32 freeware.
Sphere radii are 5.0 Å, and bondi radii are scaled at 1.17. Metal atoms
and secondary ligands were excluded, and H atoms were included in
the calculations. Red: more bulk; blue: less bulk.
the si face to the phenyl nucleophile in a [2 + 2] transition
state leading to the (S)-configured product 15aa. In support of
this model, the head-on view of the steric map around rhodium
(Figure 7, left diagram) illustrates the pronounced steric bulk of
the t-Bu in the lower right quadrant (red and orange contours
denote the methyl groups, which in solution rotate freely).
In contrast, the green contours representing the coordinated
ligand alkene function indicate free space for the keto function
in the upper left quadrant. The inverted sense of chiral induc-
tion observed with the complex bearing ligand (pS,RS)-10
(sporting a sulfur donor with the same chirality as in (R)-7) is
explained by the steric bulk of the phenyl group of the alkene
donor that generates a pseudo-C2 symmetric coordination
environment around Rh(I) and obstructs the upper left quad-
rant (Figure 7, right diagram), thereby forcing coordination of
the re side of the enone. Apparently, the planar chirality of the
alkene donor is the determining stereochemical factor, over-
riding the opposite influence of the tert-butyl group of the sulfur
donor. Consequently, the (pR,RS)-diastereomer of ligand 10
(with the phenyl group pointing into the lower left quadrant)
promises to be the better proposition for this reaction.
To conclude, we present a simple protocol that combines
inexpensive dibenzazepine with readily available glucose-based
sulfinates to afford optically pure S(O)-alkene hybrid ligands.
Phenyl-substitution on the dibenzazepine backbone is shown
to introduce stable planar chirality. This additional element of
chirality gives rise to four possible isomers, and our synthesis of
(pS,RS)-10 yields material of excellent enantiopurity. The syn-
thetic methodology outlined here opens the possibility to tune
sterics and electronics by modular combination of a variety of
aryl-dibenzoazepines (readily accessible by Suzuki cross
coupling methodology from dibenzazepine)23 with a range of
well-known chiral sulfinates. The new ligands coordinate Rh(I)
in a bidentate fashion and feature sp2−sp3 hybridization flexible
azepine N atoms upon coordination. Even though the S−N
functionality is rather pH-sensitive, preliminary catalysis results
1
operating at 269.71, 399.78, and 400.18 MHz for H; 67.82, 100.52,
and 100.62 MHz for 13C; and at 161.83 and 162.00 MHz for 31P,
respectively. Chemical shifts are given in ppm and are reported
relative to residual solvent peaks as secondary standard.35 Delta NMR
Processing and Control Software was used to process and visualize the
NMR data.36 HPLC was performed on a Shimadzu LC10 series
instrument.
Synthesis of 10 wt % K2CO3-Impregnated Silica.25 A 2 L
round-bottomed flask was loaded with silica G60 (700 g) and K2CO3
(70 g). To this mixture MeOH (1.5 L) was added and then refluxed
at 80 °C for 12 h while stirring. The solid was filtered off over a
Buchner funnel, washed with MeOH (3 × 500 mL), and dried under
̈
vacuum at 40 °C for 48 h.
Improved Synthesis of Crystalline (R)-3-Deoxy-1,2:5,6-di-O-
isopropylidene-α-D-glucofuranos-3-yl-tert-butanesulfinate
((RS)-6).18b To a cooled solution of tert-butanesulfinyl chloride (28.0 g,
199 mmol) in anhydrous THF (350 mL) at −78 °C was added
dropwise Et3N (21.1 g, 209 mmol) over 15 min followed by slow
addition over 60 min of a solution of DMAP (4.86 g, 39.8 mmol) in
THF (50 mL). The resulting mixture was stirred for 60 min at −78 °C,
to which then a solution of diacetone glucose (25.9 g, 99.6 mmol) in
THF (300 mL) was added dropwise over 7 h. The reaction mixture was
stirred overnight and then quenched with HCl (10% aqueous). The
mixture was extracted with CH2Cl2 (3 × 400 mL), and the organic
phase washed with saturated aqueous NaHCO3 and brine. After drying
over Na2SO4 the volatiles were removed in vacuo to give products (RS)-6
and (SS)-6 (96:4 dr). This mixture was purified by column chroma-
tography (hexane/diethyl ether, 9:1) and cooled to −5 °C to afford
pure (RS)-6 as a white solid (35.2 g, 94%), which contained single
crystals suitable for X-ray diffraction analysis. [α]2D0 + 11.3 (c = 1.30,
acetone). 1H NMR (500 MHz, CDCl3): δ = 5.89 (d, J = 3.5 Hz, 1 H),
4.81 (d, J = 3.57 Hz, 1 H), 4.69 (d, J = 2.3 Hz, 1 H), 4.16−4.13 (m,
3 H), 4.95−3.93 (m, 1 H), 1.50, 1.41 (2 s, 6 H), 1.30 (s, 6 H), 1.22
(s, 9 H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 112.3, 109.4,
105.3, 83.6, 82.6, 81.3, 71.8, 67.9, 58.5, 26.7, 26.2, 25.2, 21.5 ppm.
(R)-5-(tert-Butylsulfinyl)-5H-dibenzo[b,f ]azepine ((R)-7).
A deep blue solution of 5 (3.58 g, 18.0 mmol) in THF (40 mL)
was cooled to −78 °C and then added dropwise to a stirred solution
of (R)-6 (5.95 g, 16.3 mmol) in THF (40 mL) at −78 °C. The
F
DOI: 10.1021/acs.organomet.8b00591
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
reaction mixture was allowed to rise slowly to 0 °C overnight and then
was stirred another 48 h at this temperature. The volatiles were
removed under reduced pressure, giving a brownish solid that was
taken up in THF (100 mL) and K2CO3-silica-G60 (6 sp) and then
stripped to an off-white powder. This mixture was subjected to flash
column chromatography (K2CO3-silica-G60; d = 5 cm; l = 12 cm;
EtOAc/n-hexane 1:9). Recrystallization from THF/n-pentane (1:5)
afforded white crystals, which were recrystallized a second time from
THF/n-pentane (1:3) and dried in vacuo. This procedure gives white
crystals of excellent optical purity (3.33 g, 69%). ee = 99.3% by HPLC
(column: Chiralpak AD-H; flow rate: 1 mL/min; n-hexane/i-PrOH =
95:5, t = 9.63 min, 11.04 min (major, (R)-isomer). [α]2D0 − 105°
(c = 1.0, in THF). EA: C, 72.85; H, 6.35; N, 4.73; S, 10.02; calcd for
(s, 9H) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ 147.88, 143.96,
143.29, 135.99, 134.43, 130.44, 130.39, 130.00, 129.42, 129.05,
128.89, 128.44, 127.5, 127.38, 126.05, 59.83, 23.85 ppm.
rac-5-(tert-Butylsulfinyl)-10-phenyl-5H-dibenzo[b,f]azepine
((rac-10). A deep blue solution of 8 (650 mg, 2.36 mmol) in THF
(20 mL) was added dropwise to a stirred solution of phenyl tert-
butylsulfinate (428 mg, 2.15 mmol) in THF (40 mL), which was kept
at −30 °C. The reaction mixture was allowed to slowly rise to RT over
the course of 24 h. The mixture was quenched with water (30 mL),
slurried for 0.5 h, the organic phase separated, and the aqueous phase
extracted with EtOAc (3 × 15 mL). The combined organic phases
were dried over MgSO4, filtered, and stripped to a yellowish solid.
Recrystallization in EtOAc/n-pentane yielded an off-white micro-
crystalline solid (237 mg, 41%). Enantioselective HPLC: see upper
trace of Figure 3. The 1H NMR (270 MHz, CDCl3) spectrum shows a
ca. 85:15 diastereomeric mixture of {(pS,SS)-9 + (pR,RS)-9}: {(pS,RS)-
9 + (pR,SS)-9}: δ 8.00 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H),
7.72 (d, J = 7.9 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.50−6.90 (m, 22H),
1.13 (s, 9H, major diastereomer), 1.04 (s, 9H, minor diastereomer)
ppm.
1
C18H19NOS: C, 72.69; H, 6.44; N, 4.71; S, 10.78. Mp = 118 °C. H
NMR (400 MHz, CDCl3) δ 8.44 (d, J = 8 Hz, 1H), 7.91 (d, J = 8 Hz,
1H), 7.16−7.10 (m, 2H), 7.00−6.91 (m, 4H), 6.58−6.64 (m, 2H),
1.06 (s, 9H) ppm. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8 Hz,
1H), 7.65 (d, J = 8 Hz, 1H), 7.38−7.21 (m, 2H), 7.20−7.17 (m, 4H),
6.82 (m, 2H), 1.00 (s, 9H) ppm. 13C{1H} NMR (101 MHz, CDCl3)
δ 146.79, 142.74, 134.63, 131.70, 131.65, 130.28, 129.66, 129.41,
129.32, 129.19, 128.19, 127.03, 126.42, 125.81, 59.85, 24.06.
(S)-5-(tert-Butylsulfinyl)-5H-dibenzo[b,f ]azepine ((S)-7).
A deep blue solution of 5 (1.11 g, 5.58 mmol) in THF (20 mL)
was cooled to −78 °C and then added dropwise to a stirred solution
of (S)-6 (1.85 g, 5.08 mmol) in THF (20 mL) at −78 °C. The
reaction mixture was allowed to rise slowly to 0 °C overnight and was
then stirred another 48 h at this temperature. The volatiles were
removed under reduced pressure, giving a brownish solid that was
taken up in THF (100 mL) and K2CO3-silica-G60 (6 sp) and then
stripped to an off-white powder. This mixture was subjected to flash
column chromatography (K2CO3-silica-G60; d = 5 cm; l = 12 cm;
EtOAc/n-hexane 1:9). Recrystallization from 1:3 THF/n-pentane
afforded yellowish crystals, which were recrystallized a second time
from 2:5 THF/n-pentane and dried in vacuo. This procedure gives
white crystals of excellent optical purity (1.05 g, 70%). ee = 99.5% by
HPLC (column: Chiralpak AD-H; flow rate: 1 mL/min; n-hexane/i-
PrOH = 95:5, t = 8.90 min (major, (S)-isomer), 10.44 min. NMR
spectra are identical to (R)-7.
[RhCl((R)-7)]2 ((S)-11). A solution of (R)-7 (640 mg, 2.15 mmol)
in benzene (5 mL) was added dropwise to an orange slurry of
[RhCl(coe)2]2 (772 mg, 1.07 mmol) in benzene (5 mL). The
resulting deep-red solution was stirred for 15 h. Then, the volatiles
were removed in vacuo, and the crude was slurried and washed with
cold n-pentane (2 × 8 mL) and dried in vacuo to yield an orange
powder (905 mg, 97%). EA: C 49.16, H 4.40, N 3.58; calcd for
C36H38N2O2S2Cl2Rh2: C 49.61, H 4.39, N 3.21. 1H NMR (400 MHz,
3
3
C6D6): δ 7.56 (d, 1H, JHH = 7.6 Hz), 7.41 (d, 1H, JHH = 7.6 Hz),
3
7.12−7.01 (3H, m), 6.84−6.75 (3H, m), 6.09 (d, 1H, JHH = 9 Hz),
4.93 (d, 1H, JHH = 9 Hz), 1.24 (9H, s) ppm. 13C{1H} NMR
3
(101 MHz, C6D6) δ 142.03, 140.69, 140.55, 138.83, 130.55, 130.08,
129.30, 129.31, 128.57, 129.93, 127.81, 127.69, 127.57, 127.45, 16.80,
126.35, 66.95, 65.82 (d, JC−Rh = 15 Hz), 57.31 (d, JC−Rh = 15 Hz),
24.76 ppm.
[RhCl((S)-7)]2 ((R)-11). The same procedure as that for the synthesis
of (S)-11 was followed. Spectroscopic data and yields correspond.
Single Crystals of rac-11. rac-11 was synthesized by analogy to
(S)-11 (vide supra) by using the racemic ligand rac-7. Vapor diffusion
of n-pentane into a filtered solution of rac-11 (60 mg) in CH2Cl2
(1.5 mL) afforded diffraction-quality single crystals.
rac-5-(tert-Butylsulfinyl)-5H-dibenzo[b,f ]azepine (rac-7).
A deep blue solution of 5 (500 mg, 2.59 mmol) in THF (20 mL)
was added dropwise to a solution of phenyl-tert-butylsulfinate (428 mg,
2.16 mmol) in THF (40 mL) at −30 °C. The reaction mixture was
allowed to reach RT over the course of 24 h. The volatiles were then
removed under reduced pressure giving a brownish solid that was taken
up in THF (30 mL) and K2CO3-silica (2 sp) and then stripped to an
off-white powder. This mixture was subjected to flash column chro-
matography (K2CO3-silica; d = 5 cm; l = 12 cm; EtOAc/hexane
15:85) affording an off-white powder (487 mg, 76%). NMR spectra
are identical with spectra of (R)-7 and (S)-7. HPLC conditions:
Chiralpak AD-H; flow rate: 1 mL/min; n-hexane/i-PrOH = 95:5, t =
11.34 min, 12.99 min.
[RhCl(pS,RS)-10)]2 ((SN,SS)-12). A solution of (pS,Rs)-10 (214 mg,
0.573 mmol) in benzene (3 mL) was added dropwise to an orange
solution of [RhCl(coe)2]2 (206 mg, 0.287 mmol) in benzene (3 mL).
The resulting dark red solution was stirred for 15 h, and then the
volatiles were removed under HV. The crude solid was slurried and
washed in cold pentane (2 × 5 mL) and dried in vacuo to afford an
orange powder (270 mg, 92%). This analytically pure material is a
1:2 mixture of cis/trans-isomers. EA: C 56.28, H 4.59, N 2.44;
1
calcd for C48H46N2O2S2Cl2Rh2: C 56.32, H 4.53, N 2.74. H NMR
(400 MHz, C6D6) δ 8.84 (s, br, 2H, trans), 8.56 (s, br, 2H, cis), 7.55−
6.95 (m, 20H), 6.85−6.70 (m, 4H), 5.62 (s, br, 2H, cis), 5.15 (s, br,
2H, trans), 1.61 (s, br, 18H, cis), 1.40 (s, br, 18H, trans) ppm. Recrys-
tallization from C6D6 affords a microcrystalline precipitate in ca. 60%
yield, which is the pure trans-isomer. Diffraction quality single crystals
were obtained by layering a filtered solution of (SN,SS)-12 (20 mg) in
C6D6 (0.6 mL) with n-hexane.
General Procedures for Rhodium-Catalyzed 1,4-Addition
Reaction. Method A (Base-Free Protocol). In a glovebox, [RhCl-
(SO-alkene)]2 (0.050 mmol), ArB(OH)2 (1.50 mmol), and enone
(1.00 mmol) were added to an oven-dried 20 mL scintillation vial
equipped with a magnetic stir bar. Then, toluene (3.0 mL) and water
(1.5 mL) were added and the vial sealed with a Teflon-lined screw
cap. After stirring for 15 h at 40 °C the volatiles were removed in vacuo
and the residue directly purified by flash chromatography (hexane/
EtOAc 9:1) to afford the desired product as a colorless liquid. For
spectroscopic data and determination of enantiomeric excesses, see
the Supporting Information.
(pS,RS)-5-(tert-Butylsulfinyl)-10-phenyl-5H-dibenzo[b,f ]-
azepine ((pS,RS)-10). A deep blue solution of 8 (1.411 g,
5.124 mmol) in THF (30 mL) was stirred for 1 h at 0 °C and
then added dropwise to a stirred colorless solution of (R)-9 (1.99 g,
4.65 mmol) in THF (40 mL), which was kept at −78 °C. After com-
pleted addition, the temperature of the reaction mixture was allowed
to rise slowly to RT overnight. The volatiles were then removed under
vacuum to give a brownish solid, which was slurried in Et2O
(100 mL) for 4 h. The white solid was separated by filtration, dried,
mixed with K2CO3-silica (6 sp) in THF (50 mL), and dried again.
This mixture was subjected to flash column chromatography (K2CO3-
silica; d = 5 cm; l = 15 cm; EtOAc/n-hexane = 1:9) affording white
crystalline material (539 mg, 31%). Mp = 178 °C. EA: C 73.30, H
5.96, N 3.51, S 8.01; calcd for C24H23NOS·0.03CH2Cl2: C 73.15, H
5.96, N 3.51, S 8.04. [α]2D0 − 50.4° (c = 1.00, THF). ee = 99.6% by
HPLC (column: Chiralpak AD-H; flow rate: 1 mL/min; n-hexane/i-
1
PrOH 95:5, t = 14.9 min (major), 19.6 min). H NMR (400 MHz,
CDCl3) δ 7.97 (d, J = 7.9 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.43−
7.26 (m, 9H), 7.17 (d, J = 7.3 Hz, 1H), 7.02 (d, J = 7.3 Hz, 1H), 1.07
Method B (with K3PO4 Additive). In a glovebox, [RhCl(SO-alkene)]2
(0.015 mmol), ArB(OH)2 (1.50 mmol), and enone (1.00 mmol) were
G
DOI: 10.1021/acs.organomet.8b00591
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added to an oven-dried 20 mL scintillation vial equipped with a magnetic
stir bar. After adding 1,4-dioxane (3.0 mL) and water (1.0 mL) and
stirring the mixture for 0.5 h, aqueous K3PO4 (1.0 M, 0.5 mL) was
added by syringe to the vial. Stirring was then continued at 40 °C for
3 h, after which the reaction mixture was cooled to room temperature,
quenched with water, and extracted with ethyl acetate (3 × 15 mL).
The combined organic phases were dried over anhydrous MgSO4, the
volatiles evaporated, and the residue purified by flash chromatography
(hexane/EtOAc 9:1) to afford the desired product as a colorless
liquid. For spectroscopic data and determination of enantiomeric
excesses, see the Supporting Information.
(75 MHz, CDCl3) δ 25.5, 30.9, 37.9, 41.3, 47.5, 55.2, 110.5, 120.6,
126.5, 127.5, 132.4, 156.7, 211.6 ppm. HPLC: Daicel Chiralpak AD-H,
n-hexane/iPrOH = 96/4, 1.0 mL/min, 254 nm, tR: 6.30 min, 7.44 min
(major).
3-Phenylcyclopentanone (15ba).39 Yield 98%, colorless oil, 69% ee.
1H NMR (300 MHz, CDCl3) δ 1.98−2.02 (m, 1H), 2.30−2.49 (m, 4H),
2.62−2.71 (m, 1H), 3.40−3.48 (m, 1H), 7.23−7.28 (m, 3H), 7.34−7.38
(m, 2H) ppm. 13C NMR (75 MHz, CDCl3) δ 31.0, 38.7, 42.0, 45.6,
126.51, 126.54, 128.5, 142.9, 218.2 ppm. HPLC: Daicel Chiralpak,
AS-H, n-hexane/iPrOH = 98/2, 0.7 mL/min, 254 nm, tR: 27.03 min
(major), 28.59 min.
3-Phenyl-cyclohexanone (15aa)..5c,37 Yield 98%, colorless oil, for
74.9% ee. 1H NMR (300 MHz, CDCl3): δ 1.80−1.89 (m, 2H), 2.07−
2.16 (m, 2H), 2.37−2.59 (m, 4H), 3.00−3.01 (m, 1H), 7.21−7.26
(m, 3H), 7.31−7.36 (m, 2H) ppm. 13C NMR (75 MHz, CDCl3): δ
25.4, 32.7, 41.1, 44.6, 48.8, 126.5, 126.6, 128.6, 144.3, 210.8 ppm.
HPLC: Daicel Chiralpak OD-H, n-hexane/iPrOH = 98/2, 0.5 mL/min,
254 nm, tR: 23.90 min ((S)-isomer), 25.59 min ((R)-isomer).
3-(4-Methylphenyl)cyclohexanone (15ab)..5c,39 Yield 97%, white
3-(4-Methylphenyl)cyclopentanone (15bb).42 Yield 98%, color-
less oil, 68% ee. 1H NMR (300 MHz, CDCl3) δ 1H NMR (300 MHz,
CDCl3) δ 1.90−2.04 (m, 1H), 2.27−2.51 (m, 4H), 2.34 (s, 3H), 2.66
(dd, J = 18.0, 7.5 Hz, 1H), 3.33−3.45 (m, 1H), 7.16 (s, 4H). HPLC:
Daicel Chiralpak AS-H, n-hexane/iPrOH = 90/10, 0.7 mL/min,
254 nm, tR: 13.07 min (major), 13.99 min.
(+)-1,3-Diphenyl-3-(para-tolyl)propan-1-one (15cb).43 Yield
98%, white solid, 36% ee. 1H NMR (300 MHz, CDCl3) δ 2.30
(s, 3 H), 3.74 (d, JH,H = 7.2 Hz, 2 H), 4.82 (t, JH,H = 7.2 Hz, 1 H),
7.08−7.11 (m, 2 H), 7.15−7.22 (m, 3 H), 7.25−7.63 (m, 8 H), 7.94−
7.96 (m, 2 H). 13C NMR (75 MHz, CDCl3) δ 20.9, 44.8, 45.6, 126.3,
127.7 (2 C), 127.8 (2 C), 128.0 (2 C), 128.5 (2 C), 129.3 (2 C),
133.0, 135.9, 137.1, 141.1, 144.4, 198.1. HPLC: Diacel Chiralcel AD-H,
n-hexane/2-propanol = 98/2, 0.5 mL/min, 270 nm, tR: 24.96 min,
29.87 min (major).
1
solid, 76% ee. H NMR (300 MHz, CDCl3): δ 1.79−1.86 (m, 2H),
2.05−2.16 (m, 2H), 2.33 (s, 3H), 2.37−2.57 (m, 4H), 2.97−2.98
(m, 1H), 7.10−7.16 (m, 4H) ppm. 13C NMR (75 MHz, CDCl3):
δ 20.9, 25.5, 32.9, 41.2, 44.3, 49.0, 126.4, 129.3, 136.2, 141.4, 211.1 ppm.
HPLC: Daicel Chiralpak AD-H, n-hexane/iPrOH = 95/5,
0.7 mL/min, 254 nm, tR: 9.14 min (major), 9.96 min.
3-(4-tert-Butylphenyl)-cyclohexanone (15ac).5c Yield 98%, white
1
solid, 66% ee. H NMR (400 MHz, CDCl3): δ 7.39 (d, J = 8.3 Hz,
Crystallographic Information. CCDC-1845166 ((R)-6), CCDC-
1845167 (rac-7), CCDC-1845168 ((S,R)-10), CCDC-1845169 (rac-11),
and CCDC-1845170 ((S,S)-12) contain the supplementary crystallo-
graphic data for this paper. Collection and refinement parameters are
summarized in Table S1.
2H), 7.19 (d, J = 8.3 Hz, 2H), 3.03 (tt,J = 11.7, 3.9 Hz, 1H), 2.66−
2.39 (m, 4H), 2.22−2.08 (m, 2H), 1.92−1.75 (m, 2H), 1.35 (s, 9H).
13C NMR (100 MHz, CDCl3): δ 211.4, 149.5, 141.3, 126.2, 125.6,
49.0, 44.3, 41.3, 34.4, 32.8, 31.4,25.6. HPLC: Daicel Chiralpak AS-H,
n-hexane/iPrOH = 98/2, 0.6 mL/min, 254 nm, tR: 18.60 min, 23.98 min
(major).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.organomet.8b00591.
■
3-(2-Naphtyl)-cyclohexanone (15ad).38 Yield 97%, white solid,
S
1
77% ee. H NMR (400 MHz, CDCl3): δ 7.80 (dd, J = 8.7, 4.2 Hz,
3H), 7.63 (s, 1H), 7.50−7.41 (m, 2H), 7.35 (dd, J = 8.5, 1.7 Hz, 1H),
3.22−3.10 (m, 1H), 2.72−2.57 (m, 2H), 2.45 (dddd, J = 26.8, 19.6,
8.5, 3.8 Hz, 2H), 2.17 (tdd, J = 9.8, 6.9, 3.3 Hz, 2H), 2.01−1.73
(m, 2H). 13C NMR (100 MHz, CDCl3): δ 211.0, 141.8, 133.6, 132.4,
128.4, 127.7, 126.2, 125.7, 125.4, 124.8, 48.9, 44.8, 41.3, 32.7, 25.6.
HPLC: Daicel Chiralpak AD-H Column, n-hexane/iPrOH = 98/2,
0.5 mL/min, 250 nm, tR: 26.88 min, 29.12 min (major).
NMR spectra of ligands and complexes, HPLC traces of
ligands (PDF)
Accession Codes
CCDC 1845166−1845170 contain the supplementary crys-
tallographic 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.
3-(4-Fluorophenyl)cyclohexanone (15ae).39 Yield 95%, white
1
solid, 70% ee. H NMR (300 MHz, CDCl3): δ 1.77−1.85 (m, 2H),
2.05−2.17 (m, 2H), 2.38−2.56 (m, 4H), 2.98−3.00 (m, 1H), 6.98−
7.04 (m, 2H), 7.15−7.20 (m, 2H). 13C NMR (75 MHz, CDCl3):
δ 25.3, 32.8, 41.0, 43.9, 48.9, 115.3 (d, J = 21.1 Hz), 127.9 (d, J =
7.8 Hz), 140.0 (d, J = 3.2 Hz), 161.4 (d, J = 243.2 Hz), 210.6 ppm.
HPLC: Daicel Chiralpak AD-H, n-hexane/iPrOH = 99/1, 1.0 mL/min,
254 nm, tR: 27.51 min (major), 37.55 min.
AUTHOR INFORMATION
Corresponding Author
*E-mail: romano.dorta@fau.de.
■
3-(4-Methoxyphenyl)cyclohexanone (15af.).40 Yield 95%, yellow-
ish solid, 68% ee. 1H NMR (300 MHz, CDCl3): δ 1.76−1.83
(m, 2H), 2.03−2.15 (m, 2H), 2.35−2.55 (m, 4H), 2.95−2.96
(m, 1H), 3.79 (s, 3H), 6.86 (d, J = 8.6 Hz, 2H), 7.14 (d, J = 8.6 Hz,
2H) ppm. 13C NMR (75 MHz, CDCl3) δ 25.4, 32.9, 41.1, 43.9, 49.1,
55.2, 114.0, 127.4, 136.5, 158.2, 210.9 ppm. HPLC: Daicel Chiralpak
OD-H, n-hexane/iPrOH = 98/2, 0.5 mL/min, 254 nm, tR: 33.57 min
(major), 35.60 min.
ORCID
Frank W. Heinemann: 0000-0002-9007-8404
Romano Dorta: 0000-0001-5986-9729
Notes
3-(3-Methoxyphenyl)cyclohexanone (15ag).5c Yield 96%, color-
less oil, 60% ee. 1H NMR (300 MHz, CDCl3) δ 1.80−1.88 (m, 2H),
2.07−2.19 (m, 2H), 2.40−2.45 (m, 2H), 2.52−2.59 (m, 2H), 2.98−
2.99 (m, 1H), 3.82 (s, 3H), 6.78−6.84 (m, 3H), 7.24−7.29 (m, 1H)
ppm. 13C NMR (75 MHz, CDCl3) δ 18.5, 25.7, 34.2, 37.7, 41.9, 48.2,
104.6, 105.7, 111.9, 122.6, 139.0, 152.8, 203.9 ppm. HPLC: Daicel
Chiralpak AD-H, n-hexane/iPrOH = 95/5, 1.0 mL/min, 254 nm, tR:
9.26 min, 9.92 min (major).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Ms. Christina Wronna for carrying out the elemental
analyses and Ms. Cordula Ruppenstein and Mr. Rami Alahmar
for performing catalytic tests. Financial support by Friedrich−
Alexander University is acknowledged.
3-(2-Methoxyphenyl)cyclohexanone (15ah).41 Yield 97%, color-
less oil, 40% ee. 1H NMR (300 MHz, CDCl3) δ 1.72−1.90 (m, 2H),
2.01−2.15 (m, 2H), 2.36−2.57 (m, 4H), 3.38−3.43 (m, 1H), 3.82
(s, 3H), 6.86−6.97 (m, 2H), 7.17−7.26 (m, 2H) ppm. 13C NMR
REFERENCES
■
(1) (a) Trost, B. M.; Rao, M. Development of Chiral Sulfoxide
Ligands for Asymmetric Catalysis. Angew. Chem., Int. Ed. 2015, 54,
H
DOI: 10.1021/acs.organomet.8b00591
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
5026. (b) Sipos, G.; Drinkel, E.; Dorta, R. The emergence of
sulfoxides as efficient ligands in transition metal catalysis. Chem. Soc.
Rev. 2015, 44, 3834−3860. (c) Otocka, S.; Kwiatkowska, M.;
Madalinska, L.; Kielbasinski, P. Chiral Organosulfur Ligands/
Catalysts with a Stereogenic Sulfur Atom: Applications in Asymmetric
Synthesis. Chem. Rev. 2017, 117, 4147−4181.
(2) Poater, A.; Ragone, F.; Mariz, R.; Dorta, R.; Cavallo, L.
Comparing the Enantioselective Power of Steric and Electrostatic
Effects in Transition-Metal-Catalyzed Asymmetric Synthesis. Chem. -
Eur. J. 2010, 16, 14348−14353.
(3) The diastereomer of 3 is also readily accessible. Thaler, T.; Guo,
L.-N.; Steib, A. K.; Raducan, M.; Karaghiosoff, K.; Mayer, P.; Knochel,
P. Sulfoxide−Alkene Hybrids: A New Class of Chiral Ligands for the
Hayashi-Miyaura Reaction. Org. Lett. 2011, 13, 3182−3185.
(8) Drinkel, E.; Bricen
̃
o, A.; Dorta, R.; Dorta, R. Hemilabile P-
Alkene Ligands in Chiral Rhodium and Copper Complexes: Catalytic
Asymmetric 1,4 Additions to Enones. 2. Organometallics 2010, 29,
2503−2514.
(9) (a) Refs 5b−d. (b) Linden, A.; Llovera, L.; Herrera, J.; Dorta,
R.; Agrifoglio, G.; Dorta, R. “Chiral-at-Metal” Hemilabile Nickel
Complexes with a Latent d10-ML2 Configuration: Receiving
Substrates with Open Arms. Organometallics 2012, 31, 6162−6171.
(10) Examples of chiral secondary aprotic sulfinamide ligands are
rare. For a diaryl-sulfinamide, see (a) Yuan, S.; Zeng, Q.; Wang, J.;
Zhou, L. Chiral N-aryl tert-butanesulfinamide-olefin ligands for
rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to
cyclic enones. ARKIVOC 2017, 2017, 32−42. For aziridine
derivatives, see (b) Chen, Q.; Chen, C.; Guo, F.; Xia, W. Chem.
Commun. 2013, 49, 6433. For phosphorylated derivatives, see
(4) (a) Feng, X.; Wang, Y.; Wei, B.; Yang, J.; Du, H. Simple N-
Sulfinyl-Based Chiral Sulfur−Olefin Ligands for Rhodium-Catalyzed
Asymmetric 1,4-Additions. Org. Lett. 2011, 13, 3300−3303.
(b) Khiar, N.; Salvador, A.; Chelouan, A.; Alcudia, A.; Fernandez, I.
Sulfolefin”: Highly modular mixed S/Olefin ligands for enantiose-
lective Rh-catalyzed 1,4-addition. Org. Biomol. Chem. 2012, 10, 2366−
2368. (c) Chen, G.; Gui, J.; Cao, P.; Liao, J. Chiral sulfoxide-olefin
ligands: tunable stereoselectivity in Rh-catalyzed asymmetric 1,4-
additions. Tetrahedron 2012, 68, 3220−3224. (d) Jin, S.-S.; Wang, H.;
Zhu, T.-S.; Xu, M.-H. Design of N-cinnamyl sulfinamides as new
sulfur-containing olefin ligands for asymmetric catalysis: achieving
structural simplicity with a categorical linear framework. Org. Biomol.
Chem. 2012, 10, 1764. (e) Wang, H.; Jiang, T.; Xu, M.-H. Simple
Branched Sulfur−Olefins as Chiral Ligands for Rh-Catalyzed
Asymmetric Arylation of Cyclic Ketimines: Highly Enantioselective
Construction of Tetrasubstituted Carbon Stereocenters. J. Am. Chem.
Soc. 2013, 135, 971−974. (f) Khiar, N.; Valdivia, V.; Salvador, A.;
̀
́
(c) Sola, J.; Reves, M.; Riera, A.; Verdaguer, X. N-Phosphino
Sulfinamide Ligands: An Efficient Manner To Combine Sulfur
Chirality and Phosphorus Coordination Behavior. Angew. Chem., Int.
́
̀
Ed. 2007, 46, 5020−5023. (d) Reves, M.; Achard, T.; Sola, J.; Riera,
A.; Verdaguer, X. N-Phosphino-p-tolylsulfinamide Ligands: Synthesis,
Stability, and Application to the Intermolecular Pauson-Khand
Reaction. J. Org. Chem. 2008, 73, 7080−7087. (e) Benetskiy, E. B.;
Bolm, C. Synthesis of phosphorylated sulfoximines and sulfinamides
and their application as ligands in asymmetric metal catalysis.
Tetrahedron: Asymmetry 2011, 22, 373−378. (f) Doran, S.; Achard,
T.; Riera, A.; Verdaguer, X. Neutral vs. cationic rhodium (I)
complexes of bulky N-phosphino sulfinamide ligands: Coordination
modes and its influence in the asymmetric hydrogenation of Z-MAC.
J. Organomet. Chem. 2012, 717, 135−140.
̈
̈
̈
(11) Piras, E.; Lang, F.; Ruegger, H.; Stein, D.; Worle, M.;
Grutzmacher, H. Chiral Phosphane Alkenes (PALs): Simple Syn-
thesis, Applications in Catalysis, and Functional Hemilability. Chem. -
Eur. J. 2006, 12, 5849−5858.
̈
́
Chelouan, A.; Alcudia, A.; Fernandez, I. Adv. Synth. Catal. 2013, 355,
1303. (g) Zhu, D.-X.; Chen, W.-W.; Xu, M.-H. Rhodium-catalyzed
asymmetric intramolecular addition of arylboronic acids to ketones:
(12) (a) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. A
Chiral Chelating Diene as a New Type of Chiral Ligand for Transition
Metal Catalysts: Its Preparation and Use for the Rhodium-Catalyzed
Asymmetric 1,4-Addition. J. Am. Chem. Soc. 2003, 125, 11508−11509.
(b) Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. M. Chiral [2.2.2]
Dienes as Ligands for Rh(I) in Conjugate Additions of Boronic Acids
to a Wide Range of Acceptors. Org. Lett. 2004, 6, 3873−3876.
(c) Paquin, J. F.; Stephenson, C. R. J.; Defieber, C.; Carreira, E. M.
Catalytic Asymmetric Synthesis with Rh-Diene Complexes: 1,4-
Addition of Arylboronic Acids to Unsaturated Esters. Org. Lett. 2005,
7, 3821−3824. (e) Paquin, J.-F.; Defieber, C.; Stephenson, C. R. J.;
Carreira, E. M. Asymmetric Synthesis of 3,3-Diarylpropanals with
Chiral Diene-Rhodium Catalysts. J. Am. Chem. Soc. 2005, 127, 10850.
(f) Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. Preparation
of C2-Symmetric Bicyclo[2.2.2]octa-2,5-diene Ligands and Their Use
for Rhodium-Catalyzed Asymmetric 1,4-Addition of Arylboronic
Acids. J. Org. Chem. 2005, 70, 2503−2508. (g) Wang, Z.-Q.; Feng, C.-
G.; Xu, M.-H.; Lin, G.-Q. Design of C2-Symmetric Tetrahydropenta-
lenes as New Chiral Diene Ligands for Highly Enantioselective Rh-
Catalyzed Arylation of N-Tosylarylimines with Arylboronic Acids. J.
Am. Chem. Soc. 2007, 129, 5336−5337. (h) Melcher, M.-C.; Ivsic, T.;
3
catalytic enantioselective access to -hydroxy-2,3-dihydrobenzofurans
bearing a tetrasubstituted carbon stereocenter. Tetrahedron 2016, 72,
2637−2642. (h) Revu, O.; Uphade, M. B.; Prasad, K. R. Synthesis and
evaluation of C2-symmetric bis-sulfinamides as effective ligands in
rhodium catalyzed addition of arylboronic acids to cycloalkenones.
Tetrahedron 2016, 72, 5355−5362.
(5) (a) Defieber, C.; Ariger, M. A.; Moriel, P.; Carreira, E. M.
Iridium-Catalyzed Synthesis of Primary Allylic Amines from Allylic
Alcohols: Sulfamic Acid as Ammonia Equivalent. Angew. Chem., Int.
Ed. 2007, 46, 3139−3143. For the structural authentication of 1, see
(b) Briceno, A.; Dorta, R. cis-Dichloridobis{[(S)-N-(3,5-dioxa-4-
̃
phosphacyclohepta[2,1-a;3,4-a′]-dinaphthalen-4-yl]dibenz[b,f]aze-
pin-κP}-palladium(II) deuterochloroform disolvate. Acta Crystallogr.,
Sect. E: Struct. Rep. Online 2007, 63, m1718−m1719. For closely
related variants of 1, see (c) Mariz, R.; Briceno, A.; Dorta, R.; Dorta,
̃
R. Chiral Dibenzazepine-Based P-Alkene Ligands and Their Rhodium
Complexes: Catalytic Asymmetric 1,4 Additions to Enones. Organo-
metallics 2008, 27, 6605−6613. (d) Herrera, A.; Linden, A.;
Heinemann, F.; Brachvogel, R.-C.; von Delius, M.; Dorta, R.
Optimized Syntheses of Optically Pure P-Alkene Ligands; Crystal
Structures of a Pair of P-Stereogenic Diastereomers. Synthesis 2016,
48, 1117−1123.
Olagnon, C.; Tenten, C.; Lutzen, A.; Strand, D. Control of
̈
Enantioselectivity in Rhodium(I) Catalysis by Planar Chiral Dibenzo-
[a,e]cyclooctatetraenes. Chem. - Eur. J. 2018, 24, 2344−2348.
(13) (a) Mariz, R.; Luan, X.; Gatti, M.; Linden, A.; Dorta, R. J. Am.
Chem. Soc. 2008, 130, 2172−2173. (b) Burgi, J. J.; Mariz, R.; Gatti,
M.; Drinkel, E.; Luan, X. J.; Blumentritt, S.; Linden, A.; Dorta, R.
Angew. Chem., Int. Ed. 2009, 48, 2768. (c) Chen, J.; Chen, J.; Lang, F.;
Zhang, X.; Cun, L.; Zhu, J.; Deng, J.; Liao, J. A C2-Symmetric Chiral
Bis-Sulfoxide Ligand in a Rhodium-Catalyzed Reaction: Asymmetric
1,4-Addition of Sodium Tetraarylborates to Chromenones. J. Am.
Chem. Soc. 2010, 132, 4552−4553.
(6) [5H]dibenzo[b,f ]azepine is an inexpensive building block for the
synthesis of essential medicines, such as the anticonvulsant drug
carbamazepine. Schindler, W.; New N-Heterocyclic Compounds, U.S.
Patent 2,948,718A, 1960.
(7) For reviews on S(O)-alkene ligands, see (a) Dong, H.-Q; Xu,
M.-H.; Feng, C.-G.; Sun, X.-W.; Lin, G.-Q. Recent applications of
chiral N-tert-butanesulfinyl imines, chiral diene ligands and chiral
sulfur−olefin ligands in asymmetric synthesis. Org. Chem. Front. 2015,
2, 73. (b) Li, Y.; Xu, M.-H. Simple sulfur−olefins as new promising
chiral ligands for asymmetric catalysis. Chem. Commun. 2014, 50,
3771. (c) Feng, X.; Du, H. Synthesis of Chiral Olefin Ligands and
their Application in Asymmetric Catalysis. Asian J. Org. Chem. 2012,
1, 204.
(14) See ref 7, as well as (a) Chen, G.; Gui, J.; Li, L.; Liao, J. Chiral
Sulfoxide-Olefin Ligands: Completely Switchable Stereoselectivity.
Angew. Chem., Int. Ed. 2011, 50, 7681−7685. (b) Xue, F.; Li, X.; Wan,
B. A Class of Benzene Backbone-Based Olefin−Sulfoxide Ligands for
I
DOI: 10.1021/acs.organomet.8b00591
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Rh-Catalyzed Enantioselective Addition of Arylboronic Acids to
Enones in Rhodium-Catalyzed Asymmetric Conjugate Additions. J.
Org. Chem. 2011, 76, 7256−7262.
Pouchot, M. 1,2:5,6-Di-O-isopropylidene-α-D-glucofuranosyl (S)-
cyclohexanesulfinate. Acta Crystallogr., Sect. C: Cryst. Struct. Commun.
1999, 55, 262−264.
(29) The crystal structure of Lu-Senanayake sulfinate 9 is discussed
in the following: Seidel, F.; Frieß, S.; Heinemann, F.; Chelouan, A.;
Scheurer, A.; Grasruck, A.; Herrera, A.; Dorta, R. C2-Symmetric
(SO)N(SO) Sulfoxide Pincer Complexes of Mg and Pd: Helicity
Switch by Ambidentate S/O-Coordination and Isolation of a Chiral
Pd-Sulfenate. Organometallics 2018, 37, 1160−1171.
(30) (a) Dewar, M. J. S. Bull. Chem. Soc. Fr. 1951, 18, C71.
(b) Chatt, J.; Duncanson, L. A. Olefin Co-ordinution Compounds.
Part III. * Infra-red Spectra and Structure: Attempted Preparation of
Acetylene Complexes. J. Chem. Soc. 1953, 2939−2947.
(31) For similar stereochemical models featuring S(O)-alkene
ligands, see refs 3, 4c,4d, and 10b.
(15) (a) Sakai, M.; Hayashi, H.; Miyaura, N. Rhodium-Catalyzed
Conjugate Addition of Aryl- or 1-Alkenylboronic Acids to Enones.
Organometallics 1997, 16, 4229−4231. (b) Takaya, Y.; Ogasawara,
M.; Hayashi, T.; Sakai, M.; Miyaura, M. Rhodium-Catalyzed
Asymmetric 1,4-Addition of Aryl- and Alkenylboronic Acids to
Enones. J. Am. Chem. Soc. 1998, 120, 5579−5580. (c) Takaya, Y.;
Ogasawara, M.; Hayashi, T. Asymmetric 1,4-Addition of Phenyl-
boronic Acid to 2-Cyclohexenone Catalyzed by Rh(I)/binap
Complexes. Chirality 2000, 12, 469.
(16) (a) Lee, A.; Kim, K. Chiral Bicyclic Bridgehead Phosphor-
amidite (Briphos) Ligands for Asymmetric Rhodium-Catalyzed 1,2-
and 1,4-Addition. J. Org. Chem. 2016, 81, 3520−3527. (b) Dou, X.;
Lu, Y.; Hayashi, T. Base-Free Conditions for Rhodium-Catalyzed
Asymmetric Arylation To Produce Stereochemically Labile α-Aryl
Ketones. Angew. Chem., Int. Ed. 2016, 55, 6739−6743. (c) Miyamura,
H.; Nishino, K.; Yasukawa, T.; Kobayashi, S. Rhodium-catalyzed
asymmetric 1,4-addition reactions of aryl boronic acids with
nitroalkenes: reaction mechanism and development of homogeneous
and heterogeneous catalysts. Chem. Sci. 2017, 8, 8362−8372.
(17) Freitag, B.; Elsen, H.; Pahl, J.; Ballmann, B.; Herrera, A.; Dorta,
R.; Harder, S. s-Block Metal Dibenzoazepinate Complexes: Evidence
for Mg−Alkene Encapsulation. Organometallics 2017, 36, 1860−1866.
(32) Falivene, L.; Credendino, R.; Poater, A.; Petta, A.; Serra, L.;
Oliva, R.; Scarano, V.; Cavallo, L. SambVca 2. A Web Tool for
Analyzing Catalytic Pockets with Topographic Steric Maps. Organo-
metallics 2016, 35, 2286−2293.
(33) Schlosser, M.; Ladenberger, V. Notiz uber die Darstellung
̈
reiner Lithiumaryle. J. Organomet. Chem. 1967, 8, 193−197.
(34) Van Der Ent, A.; Onderdelinden, A. L.; Schunn, R. A. Inorg.
Synth. 2007, 28, 90−91.
(35) Fulmer, G. R.; Miller, A. J. M.; Sherden, N. H.; Gottlieb, H. E.;
Nudelman, A.; Stoltz, B. M.; Bercaw, J. E.; Goldberg, K. I.
Organometallics 2010, 29, 2176−2179.
́
(18) (a) Khiar, N.; Fernandez, I.; Alcudia, F. Asymmetric synthesis
(36) Delta NMR Processing and Control Software, version 4.3.6; JEOL
USA, Inc.: Peabody, MA, 2006.
of optically pure tert-butyl sulfoxides using the “DAG methodology.
Tetrahedron Lett. 1994, 35, 5719−5722. (b) Chelouan, A.; Recio, R.;
(37) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura, N.
Rhodium-Catalyzed Asymmetric 1,4-Addition of Aryl- and Alkenyl-
boronic Acids to Enones. J. Am. Chem. Soc. 1998, 120, 5579−5580.
(38) Takaya, Y.; Ogasawara, M.; Hayashi, T. Rhodium-catalyzed
asymmetric 1,4-addition of arylboron compounds generated in situ
from aryl bromides. Tetrahedron Lett. 1999, 40, 6957−6961.
(39) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M.
Catalytic Cycle of Rhodium-Catalyzed Asymmetric 1,4-Addition of
Organoboronic Acids. Arylrhodium, Oxa-π−allylrhodium, and
Hydroxorhodium Intermediates. J. Am. Chem. Soc. 2002, 124,
5052−5058.
(40) Cho, C. S.; Motofusa, S.; Ohe, K.; Uemura, S.; Shim, S. C. A
New Catalytic Activity of Antimony(III) Chloride in Palladium(0)-
Catalyzed Conjugate Addition of Aromatics to α,β−Unsaturated
Ketones and Aldehydes with Sodium Tetraphenylborate and
Arylboronic Acids. J. Org. Chem. 1995, 60, 883−888.
(41) Boiteau, J.; Imbos, R.; Minnaard, A.; Feringa, B. Rhodium-
Catalyzed Asymmetric Conjugate Additions of Boronic Acids Using
Monodentate Phosphoramidite Ligands. Org. Lett. 2003, 5, 681−684.
(42) Feng, C.-G.; Wang, Z.-Q.; Tian, P.; Xu, M.-H.; Lin, G.-Q. Easily
Accessible C2-Symmetric Chiral Bicyclo[3.3.0] Dienes as Ligands for
Rhodium-Catalyzed Asymmetric 1,4-Addition. Chem. - Asian J. 2008,
3, 1511−1516.
(43) Wong, J.; Gan, K.; Chen, H. J.; Pullarkat, S. A. Evaluation of
Palladacycles as a Non-Rhodium Based Alternative for the
Asymmetric Conjugate 1,4-Addition of Arylboronic Acids to α,β-
Unsaturated Enones. Adv. Synth. Catal. 2014, 356, 3391−3400.
́
Alcudia, A.; Khiar, N.; Fernandez, I. DMAP-Catalysed Sulfinylation of
Diacetone-D-Glucose: Improved Method for the Synthesis of
Enantiopure tert-Butyl Sulfoxides and tert-Butanesulfinamides. Eur.
J. Org. Chem. 2014, 2014, 6935−6944.
(19) Harrowven, D. C.; Curran, D. P.; Kostiuk, S. L.; Wallis-Guy, I.
L.; Whiting, S.; Stenning, K. J.; Tang, B.; Packard, E.; Nanson, L.
Potassium carbonate−silica: a highly effective stationary phase for the
chromatographic removal of organotin impurities. Chem. Commun.
2010, 46, 6335−6337.
(20) No racemization is observed in dry deoxygenated CDCl3.
(21) García Ruano, J. L.; Parra, A.; Yuste, F.; Mastranzo, V. M. Mild
and General Method for the Synthesis of Sulfonamides. Synthesis
2008, 2008, 311−319.
(22) Efforts in our laboratory to obtain diffraction quality single
crystals of enantiopure 7 are ongoing.
(23) Herrera, A.; Grasruck, A.; Heinemann, F.; Scheurer, A.;
Chelouan, A.; Frieß, S.; Seidel, F.; Dorta, R. Developing P-
Stereogenic, Planar−Chiral P-Alkene Ligands: Monodentate, Biden-
tate, and Double Agostic Coordination Modeson Ru(II). Organo-
metallics 2017, 36, 714−720.
(24) The use of sulfinate 9 instead of 6 in this reaction is beneficial
in terms of product purity and easier separation of the chiral auxiliary.
(25) The isolation of (pR,RS)-10 isomer in pure form is the subject
of ongoing efforts in our laboratory.
(26) Sulfur is chosen as the lead atom. For the determination of
descriptors of planar chirality, see for example Eliel, E. L.; Wilen, S. H.
Stereochemistry of Organic Compounds; Wiley-Interscience, 1994; p
1121−1122.
(27) Traces have been generated sequentially under strictly identical
conditions. For a trace of a representative sample with ee = 99.6% but
with slightly differing retention time, see Figure S9.
(28) For the first DAG-derived sulfinates, see (a) Ridley, D. D.;
Smal, M. A. Use of Carbohydrates in the Preparation of Optically
Active Sulfoxides. J. Chem. Soc., Chem. Commun. 1981, 505−506.
(b) Ridley, D. D.; Smal, M. A. Preparation of Arenesulfinic Esters of
1,2:5,6-Di-0-cyclohexylidene-α-D-glucofuranose, and Their Conver-
sion into Optically Active Sulfoxides. Aust. J. Chem. 1982, 35, 495.
́
(c) Llera, J. M.; Fernandez, I.; Alcudia, F. An efficient synthesis of
both enantiomers of chiral non racemic methylsulfoxides from DAG.
Tetrahedron Lett. 1991, 32, 7299−7302. For a structural report, see
́
(d) Alayrac, C.; Saint-Clair, J.; Lemarie, M.; Metzner, P.; Averbuch-
J
DOI: 10.1021/acs.organomet.8b00591
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