Chiral monodentate phosphine ligands for the enantioselective α- And γ-arylation of aldehydes

Article abstract of DOI:10.1016/j.tet.2014.02.079

The synthesis of chiral variants of monodentate trialkyl and dialkylbiaryl phosphine ligands elaborated on the binepine scaffold is described. Their application in the Pd-catalyzed intramolecular asymmetric α-arylation of aldehydes and the intermolecular asymmetric γ-arylation of α,β-unsaturated aldehydes provides a mean of validating the design of these ligands. For the first reaction, excellent reactivities have been obtained while only modest enantioselectivities were measured. Aside from enantioselectivity, the second reaction offers additional challenges associated with intramolecularity and regioselectivity. With the formal chiral trialkyl monodentate phosphine ligands, good yield, high olefin stereocontrol, and perfect γ-selectivity were obtained while the enantioselectivity remained in the low but promising range.

Full text of DOI:10.1016/j.tet.2014.02.079

Tetrahedron 70 (2014) 4181e4190
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Chiral monodentate phosphine ligands for the enantioselective a-
and g-arylation of aldehydes
a
b
a,
*
ꢀ ꢀ
ꢀ
Ivan Franzoni , Laure Guenee , Clement Mazet
a Department of Organic Chemistry, University of Geneva, 30 quai Ernest Ansermet, 1211 Geneva 4, Switzerland
b Laboratoire de Cristallographie, University of Geneva, 24 quai Ernest Ansermet, 1211 Geneva 4, Switzerland
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of chiral variants of monodentate trialkyl and dialkylbiaryl phosphine ligands elaborated
on the binepine scaffold is described. Their application in the Pd-catalyzed intramolecular asymmetric
arylation of aldehydes and the intermolecular asymmetric -arylation of -unsaturated aldehydes
provides a mean of validating the design of these ligands. For the first reaction, excellent reactivities have
been obtained while only modest enantioselectivities were measured. Aside from enantioselectivity, the
second reaction offers additional challenges associated with intramolecularity and regioselectivity. With
the formal chiral trialkyl monodentate phosphine ligands, good yield, high olefin stereocontrol, and
Received 14 January 2014
Received in revised form 24 February 2014
Accepted 26 February 2014
Available online 5 March 2014
a
-
g
a,b
Dedicated to Professor Sarah Reisman on
the receipt of the Tetrahedron Young In-
vestigator Award
perfect
range.
g-selectivity were obtained while the enantioselectivity remained in the low but promising
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Chiral ligands
Phosphorus ligands
Asymmetric catalysis
Arylation
Palladium
1. Introduction
sight.2 In particular, there is to date only a limited number of chiral
analogues of the sterically demanding trialkyl or dialkylbiaryl
Electron-rich and sterically demanding trialkyl (A) and dia-
lkylbiaryl (B) monodentate phosphine ligands have had a tremen-
dous impact on cross-coupling reactions over the last two decades,
in particular in Pd-catalyzed CeC, CeN, and CeO bond forming
processes (Fig. 1).1 In several cases, coupling reactions that were
recognized as highly challenging have been achieved successfully
with these ligands under mild conditions, even with some of the
least reactive coupling partners (e.g., typically aryl chloride or
C(sp3) alkyl halides or pseudohalides). Interestingly, the design of
chiral ligands is often inspired by existing achiral structures that
have found widespread applications in a variety of reactions that
have the potential to be performed enantioselectively because they
lead to chiral (but racemic) products. Indeed, often little structural
modification of an existing scaffold by introduction of at least one
element of chirality allows chiral ligands to be readily elaborated
from an achiral motif. Despite some success story based on this
approach, maintaining catalytic efficiency while imparting high
level of enantioselectivity is not as trivial as it may appear at first
monodentate phosphine ligands (CeF).3e6 Furthermore, these
isolated examples have been employed in only a handful of cata-
lytic reactions and high levels of enantioinduction have been rarely
achieved.
In 2012 our group reported the synthesis of a novel class of
chiral (P,N) ligands (G) elaborated on the ubiquitous binepine
scaffold (H) (one of the few examples of chiral monodentate trialkyl
phosphine ligand).7,8 Originally inspired by the work of Wildhalm
and Zhang,9 these chelating ligands revealed particularly efficient
in the Pd-catalyzed asymmetric intramolecular a-arylation of al-
dehydes and the Ir-catalyzed asymmetric hydrogenation of allylic
alcohols. Importantly, during optimization of the ligand synthesis,
we found that a single primary alkyl substituent could be in-
troduced at the most accessible benzylic position with high levels
of diastereoselectivity when a large secondary or tertiary alkyl
group was attached to the phosphorus atom. Building on this ob-
servation, we set out to synthesize two novel and complementary
classes of chiral monodentate phosphine ligands (I and J) articu-
lated around a common binepine core structure. Whereas the
first class (I) would represent a formal version of some of the
ubiquitous electron-rich and sterically demanding trialkyl phos-
phine ligands, such as Cy3P and tBu3P (A), the second class (J) would
* Corresponding author. Tel.: þ41 22 379 62 88; fax: þ41 22 379 32 15; e-mail
address: clement.mazet@unige.ch (C. Mazet).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.079

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I. Franzoni et al. / Tetrahedron 70 (2014) 4181e4190
Fig. 1. Prototypical trialkyl (A) and dialkylbiaryl (B) phosphine ligands used in Pd-catalyzed cross-coupling. Representative chiral versions (CeF). Binepine (H) as a pivotal scaffold
for the development of (P,N) ligands (G) and chiral trialkyl phosphine (I) and diarylalkyl phosphine (J) analogs of ligands of type A and B.
formally constitute a chiral version of the monodentate dia-
lkylbiaryl phosphines (B).
purification by column chromatography as white crystalline solids.
Ligand precursor (Ra)-2c.BH3 was prepared after in situ generation
of the biaryl moiety starting from 1c, followed by Cu-catalyzed
coupling of the corresponding Grignard intermediate with chlor-
ophosphepine (Ra)-3 and subsequent borane protection. All three
borane adducts were deprotected by refluxing in diethylamine for
a 3e4 days period of time and the corresponding ligands (Ra)-2aec
were isolated in good yields as white crystalline solids (68e78%)
(Fig. 2).
2. Results and discussion
Over the years, the Buchwald group has developed a catalog of
dialkylbiaryl monodentate phosphines, the design of which has
been validated in an impressive number of Pd-catalyzed cross-
coupling reactions.10 Some key features that contribute to catalyst
Fig. 2. Synthesis of three chiral monodentate dialkylbiaryl phosphine ligands (type B/J).
efficiency in mechanistically distinct transformations have been
identified. For instance, large alkyl or alkoxy substituents on the
ortho position of the lower aryl ring are thought to simultaneously
promote reductive elimination, increase ligand stability, and pre-
vent from undesired cyclometallation. Therefore, we commenced
our synthesis from the commercially available 20-bromo-2,6-
dialkoxy-1,10-biphenyl 1a (R¼Me) and 1b (R¼iPr) according to
protocols reported in the literature.11 In a one-pot operation, lith-
ium/halogen exchange at low temperature followed by addition of
1 equiv of chlorophosphepine (Ra)-312 and final protection with an
excess of BH3$THF adduct delivered the corresponding ligand
precursors (Ra)-2a.BH3 and (Ra)-2b.BH3 in moderate yields after
Chiral analogs of trialkyl monodentate phosphine ligands were
prepared according to the protocol developed in our laboratory for
the synthesis of (P,N) ligands of type H starting from (Ra)-4.BH3.7a,12
Seven different primary alkyl halides were selected to access
a structurally varied library of these ligands (Fig. 3). Hence meth-
ylcyclohexyl (2d), benzyl (2e), mesitylmethyl (2f), 1,3,5-tris-iso-
propylbenzyl (2g), 2-methylnaphthalene (2h), 3,5-dimethylbenzyl
(2i), and 3,5-di-tert-butylbenzyl (2j) fragments were all in-
troduced using the corresponding commercially available iodo-,
bromo- or chloroalkyl precursors. The ligands were obtained in two
steps as described on Fig. 3 in usually useful overall yields and
essentially as single diastereoisomers (dr>50:1). As for their (P,N)

I. Franzoni et al. / Tetrahedron 70 (2014) 4181e4190
4183
Fig. 3. Two-step synthesis of seven chiral monodentate trialkyl phosphine ligands (type A/I). Yields over two steps, diastereoselectivity determined by 1H NMR of the crude
reaction mixture after the first step. Bottom right: X-ray structure analysis of the borane-protected ligand precursor (Ra,R,RP)-2j.BH3.13
congeners, these compounds are characterized by three distinct
Table 1
elements of chirality: the axial chirality of the binepine core, the
central chirality at the benzylic position and the central chirality at
the phosphorus atom; the latter two being stereoselectively in-
stalled in the first step of the synthetic sequence. An X-ray dif-
fraction study performed on (Ra,R,RP)-2j.BH3 confirmed the
absolute configuration of the borane-protected ligand and showed
that the bulky aryl moiety projects away from the binaphthyl
backbone in the solid state. Careful analysis by 2D NMR suggests
that this arrangement is also conserved in solution.
Ligand screen for the intramolecular a-arylation of aldehydes
Entry
Ligand
Yield (%)a
ee (%)b
1
2
3
4
5
6
7
8
9
(Ra)-2a
(Ra)-2b
(Ra)-2c
(Ra,R,RP)-2d
(Ra,R,RP)-2e
(Ra,R,RP)-2f
(Ra,R,RP)-2g
(Ra,R,RP)-2h
(Ra,R,RP)-2i
96
91
97
87
10
95
97
97
89
29
10
<5
9
The Pd-catalyzed intramolecular a-arylation of aldehydes was
elected as benchmark reaction to evaluate the potential of ligands
2aej in asymmetric catalysis.14 Among the various enantioselective
14c
35
24
<5
12
a
-arylation of carbonyl compounds reported, this reaction appears
as one of the most challenging. This has been attributed to the
inherent instability of aldehydes and to their tendency to undergo
a variety of side-reactions under the necessary basic reaction con-
ditions. Moreover, in contrast to amides, esters or ketones the
carbon atom of the carbonyl group lacks gearing elements that may
be needed to impart high levels of enantioinduction.15
a
Determined by 1H NMR analysis of crude reaction mixture.
Determined by chiral GC or chiral HPLC.
In toluene for 24 h.
b
c
To identify the best performer out of the library of 10 mono-
dentate
phosphine
ligands
2aej,
4-(2-bromophenyl)-2-
increase in electron density of the aromatic fragment had only
minimal impact on the reaction outcome (58% yield and 28% ee for
methylbutanal aldehyde 5a was used as a model substrate under
the reaction conditions optimized for the related (P,N) ligands
(Cs2CO3 (1.2 equiv), DMF, 80 ꢀC, 48 h) with a twofold excess of
monodentate ligand relative to Pd(OAc)2 (10 and 5 mol %, re-
spectively). With the chiral dialkylbiaryl ligands (Ra)-2aec, the
cyclized product 6a was obtained in excellent yield throughout the
series while the enantioselectivity decreased with the increasing
steric demand of the lower biaryl moiety (Table 1, Entry 1e3). In the
chiral trialkyl series (Ra,R,RP)-2dej, conversions to product 6a were
usually excellent and the best level of enantioselectivitydalbeit
still modestdwas obtained with ligand (Ra,R,RP)-2f (95% conv., 35%
ee). The scope was explored next using ligand (Ra,R,RP)-2f and the
corresponding cyclization product 6aeh are all displayed on Fig. 4.
Whereas variation of the alkyl substituent in the substrate or an
6b; 80% yield and 39% ee for 6c), the use of an
afforded product 6d in good yield but as a racemic mixture and the
use of an -phenyl substituent did not provide any cyclization
product. In contrast, a 2-anisole -substituent restored significant
a-benzyl substituent
a
a
catalytic activity, 6f being isolated in 75% yield and 15% ee. Similar
selectivities were measured for the naphthyl derived aldehyde 6g
and the tetrahydronaphthalene product 6h. Of note, no product
formation could be detected in trying to develop an intermolecular
version of this reaction (see Supplementary data).
We recently reported a very general protocol for the in-
termolecular Pd-catalyzed
g-arylation of g-branched a,b-un-
saturated aldehydes with electron-rich, electron-neutral, and
electron-poor bromoarenes to efficiently forge remote quaternary

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I. Franzoni et al. / Tetrahedron 70 (2014) 4181e4190
Table 2
Ligand screen for the intermolecular g-arylation of aldehydes
Entry
Ligand
Yield (%)a,b
E/Zc
ee (%)d
1
2
3
4
5
6
7
8
9
(Ra)-2ae
nrf
nr
nr
76 (68)
71 (64)
87 (74)
91
66 (59)
61 (57)
82 (70)
ndg
nd
nd
30:1
25:1
14:1
12:1
30:1
>50:1
20:1
nd
nd
nd
12
17
ꢂ8
<5
14
23
26
(Ra)-2be
(Ra)-2ce
(Ra,R,RP)-2d
(Ra,R,RP)-2e
(Ra,R,RP)-2f
(Ra,R,RP)-2g
(Ra,R,RP)-2h
(Ra,R,RP)-2i
(Ra,R,RP)-2j
10
a
Determined by 1H NMR analysis of crude reaction mixture.
In parenthesis: isolated yield of geometrically pure E isomer.
Determined by 1H NMR analysis of crude reaction mixture.
Determined by chiral HPLC.
4-Bromoanisole 2b was employed.
No reaction.
b
c
d
e
f
g
Not determined.
Fig. 4. Substrate scope using ligand (Ra,R,RP)-2f and the optimized conditions of Table
1. Yields were assessed after purification by chromatography and ee values were de-
termined using a chiral HLPC.
Using a ligand/metal stoichiometry similar to that employed for
in situ catalysis, ligand (Ra,R,RP)-2i was reacted with 0.5 equiv of
[(CH3CN)2PdCl2] at room temperature in dichloromethane in order
to obtain structural information on the coordination mode of this
ligand to palladium (Fig. 6). After 2 h, evaporation of the volatiles
and purification by silica gel chromatography, an air-stable yellow
solid was isolated. Mass spectrometric analyses showed molecular
ion and fragmentation pics consistent with the formation of
a complex of general formula [((Ra,R,RP)-2i)2PdCl2], while NMR
analyses indicated the presence of two distinct and non-
centers.16,17 With the optimal protocol, the products were usually
isolated in good yield with excellent
g regioselectivity and high
levels of stereoselectivity (typically E/Z>9:1).
As a direct continuation of this study, we set out to develop an
enantioselective version of this difficult cross-coupling reaction
with aldehyde 7a and 2- or 4-bromoanisole (8a and 8b, re-
spectively) in a model transformation using our initially optimized
reaction conditions. A preliminary evaluation of a vast array of
commercially available chiral ligands revealed that chelating (P,P)
or (P,N) ligands were not suitable for this transformation as the
cross-coupling products were usually isolated in low yield and
marginal enantioselectivity (See Supplementary data for details).
Surprisingly, when the dialkylbiaryl ligands (Ra)-2aec were
employed, the coupling between 7a and 4-bromoanisole 8b did not
yield any product (Table 2, Entry 1e3). In contrast, good to very
good conversions were obtained with the trialkyl ligands (Ra,R,RP)-
2dej for the coupling between 7a and 8a (Table 2, Entry 4e10). We
tentatively attribute this marked reactivity difference to an in-
creased steric environment around the phosphorus atom in ligands
2dej when compared to ligands 2aec. The best results were ob-
tained with ligands (Ra,R,RP)-2i and (Ra,R,RP)-2j, which delivered
9aa in 57% yield and 23% ee and 70% yield and 26% ee, respectively;
both with excellent stereoselectivity (E/Z>50:1 and 20:1, re-
spectively). Although the enantioselectivities obtained with these
two ligands are still modest, it is worth mentioning that the re-
activity and stereoselectivity surpass those of the best achiral li-
exchangeable isomers in a 2:1 ratio (31P{1H}:
d
¼70.71 ppm (s)
and 69.25 ppm (s) in CDCl3). The coordination chemistry of mon-
odentate binepine ligands to palladium has not been studied ex-
tensively. Among the very few examples reported, the trans-[((Sa)-
4)2Pd(C6H5)Br] complex has been crystallographically character-
ized by Baudoin and co-workers.18,19 The singlet observed by 31P
{1H} NMR (
d
¼67.6 ppm) was also consistent with the persistence of
trans arrangement of the C2-symmetric binepine (Sa)-4 in solution.
We propose that in the present study, the C1-symmetry of ligand
(Ra,R,RP)-2i accounts for the formation of two air-stable, non-sep-
arable, isomeric palladium complexes where the monodentate li-
gands are trans disposed but in either a ‘head-to-tail’ (10i) or ‘head-
to-head’ (11i) arrangement (Fig. 6). Slow evaporation of a concen-
trated solution of a mixture of the isomeric complexes gave crystals
of suitable quality for an X-ray diffraction study for 10i only. The
nature of the ‘head-to-tail’ arrangement initially postulated was
thus confirmed (Fig. 7).20
The neutral palladium complex is also characterized by
a strongly distorted square planar geometry around the metal
center as indicated by the angles between the mutually trans dis-
posed donor atoms (PePdeP¼168.27(8)ꢀ; ClePdeCl¼168.48(8)ꢀ)
and the torsion angle PeClePePd¼8.32ꢀ.
t
gand (i.e., Bu3P) identified in our previous study.16 Furthermore,
examples of asymmetric intermolecular
a and g-arylations of car-
bonyls are still scarce (presumably due to reactivity issues prior to
any selectivity consideration).15
A small set of other linear and cyclic
a,
b-unsaturated aldehydes
3. Conclusion
was investigated with ligands (Ra,R,RP)-2i and (Ra,R,RP)-2j with ei-
ther 2- or 4-bromoanisole as electrophilic component. The results
The design of novel chiral ligands and catalysts for asymmetric
synthesis remains a formidable and contemporary challenge. Some
categories of achiral ligands, such as sterically demanding and
electron-rich trialkyl and dialkylbiaryl monodentate phosphines
are still in need for efficient and broadly applicable chiral versions
of these investigations are summarized on Fig. 5. While the
g
regioselectivity, the yield (average yield¼74%; 5 examples) and the
stereoselectivity (E/Zꢁ16:1) were consistently high, the enantio-
selectivities varied between 9 and 26%.

I. Franzoni et al. / Tetrahedron 70 (2014) 4181e4190
4185
Fig. 5. Substrate scope using either ligand (Ra,R,RP)-2i or ligand (Ra,R,RP)-2j and the conditions described on Table 2. The E/Z ratio was determined by 1H NMR of the crude reaction
mixture. Yields of pure isomer E were assessed after purification by chromatography and ee values were determined using a chiral HLPC.
Fig. 6. Complexation of (Ra,R,RP)-2i to palladium: formation of isomeric trans-coordinated Pd complexes 10i and 11i.
discovery of efficient chiral monodentate phosphine ligands for
these transformations in a near future. Work in this direction is
currently ongoing in our laboratories.
4. Experimental section
4.1. General
All reactions were carried out under an inert atmosphere of
nitrogen using either two-manifold vacuum/inert gas lines or an
MBraun glove-box, unless otherwise noted. Solvents were dried
over activated alumina columns or by distillation from metallic
sodium and further degassed by three successive ‘freeze-pump-
thaw’ cycles. NMR spectra were recorded on AMX-400 and AMX-
500 Bruker Avance spectrometers at 298 K unless otherwise
Fig. 7. CYLview representation of the crystal structure of complex 10i.13b All hydrogen
atoms have been omitted for clarity (color code: C gray; P orange; Cl green; Pd cyan).
noted. Deuterated solvents were purchased from Cambridge Iso-
tope Laboratories. Spin multiplicities are reported as a singlet (s),
to be developed. In this article we have presented our efforts in this
direction using the ubiquitous binepine scaffold as the common
core structure for the design of two novel classes of chiral ligands.
The potential of these ligands was evaluated in two reputedly
challenging cross-coupling reactions that enable the construction
doublet (d), triplet (t), quartet (q), and heptet (h) with coupling
constants (J) given in Hertz, or multiplet (m). Broad signals are
indicated as ‘br’. 1H and 13C resonances were assigned with the aid
of additional information from 1D and 2D NMR experiments (H,H-
COSY, DEPT 135, HSQC, HMBC, and ROESY). 1H and 13C NMR
chemical shifts are given in parts per million relative to SiMe4, with
the solvent resonance used as internal reference. 1H NMR spectra
were referenced to CDCl3 (7.26 ppm) and 13C NMR spectra were
referenced to CDCl3 (77.36 ppm) unless otherwise indicated. 31P
{1H} NMR chemical shifts are reported in ppm relative to H3PO4.
Infrared spectra were obtained on a PerkineElmer 1650 FT-IR
spectrometer using neat samples on a diamond ATR Golden Gate
sampler. Optical rotations were measured on a PerkineElmer 241
polarimeter equipped with a Na-lamp. The mass spectrometric data
were obtained at the mass spectrometry facility of the University of
of congested quaternary stereocenters: (i) the intramolecular
a
g
-
-
arylation of
arylation of
a
-branched aldehydes and (ii) the intermolecular
g-branched
a,
b-unsaturated aldehydes. In the first case,
excellent reactivity was observed while the enantioselectivities
remained modest for both ligand classes. In the second case,-
dwhich is by far more challenging (intermolecular process,
regioselectivity issues)dexcellent yields, regio- and stereo-
selectivities were observed in the chiral trialkyl series while again
the ee were relatively low. We are nevertheless confident that the
high degree of modularity of the binepine platform will allow the

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I. Franzoni et al. / Tetrahedron 70 (2014) 4181e4190
Geneva (http://www.unige.ch/sciences/sms/index.html). Chiral
HPLC analyses were performed on Shimadzu CTO-20AA. Retention
times are given in minutes. Chiral GC analyses were performed on
HP6890 gas chromatograph. Commercial reagents were purchased
from Aldrich, Acros or Strem and used without further purification,
unless otherwise noted. Liquid reagents were transferred with
stainless steel syringes or cannula. Thin layer chromatography
(TLC) was performed on plates of silica pre-coated with 0.25 mm
Kieselgel 60 F254. Flash chromatography was performed using silica
gel 60 (230e400 mesh ASTM) from SiliCycle. Precursor (Ra)-3 and
(Ra)-4.BH3 were prepared according to the procedure reported in
the literature (J. Am. Chem. Soc. 2003, 125, 5139; Org. Process Res.
Dev. 2007, 11, 568; Angew. Chem., Int. Ed. 2012, 51, 3826). Aldehydes
7a and 7b were prepared according to the procedure reported in
the literature (Chem. Sci. 2013, 4, 2619). For additional experimental
details (i.e., ligand screen, substrate synthesis) and for the precise
assignments of all NMR signals, see the Supplementary data
Files. Abbreviations used: THF (tetrahydrofuran), DMF (N,N-
dimethylformamide).
afford the desired compound as a white foamy solid (30% yield). 1H
NMR (CDCl3, 500 MHz)
d
(ppm)¼0.41 (br q, 3H), 0.49 (d,
3JHH¼6.0 Hz, 3H), 0.86 (d, JHH¼6.0 Hz, 3H), 1.11 (d, JHH¼6.0 Hz,
3H), 1.34 (d, 3JHH¼6.0 Hz, 3H), 2.56 (dd, 2JHP¼2.8 Hz, 2JHH¼13.0 Hz,
1H), 2.79 (dd, 2JHP¼7.2 Hz, 2JHH¼14.5 Hz,1H), 3.01 (dd, 2JHP¼17.1 Hz,
3
3
2JHH¼13.0 Hz, 1H), 3.36 (dd, JHP¼5.8 Hz, JHH¼14.5 Hz, 1H), 4.12
2
2
3
and 4.45 (2hept, JHH¼6.0 Hz, 2ꢃ1H), 6.36 and 6.57 (2d,
3JHH¼8.3 Hz, 2ꢃ1H), 7.07 (ddd, J¼1.0 Hz, J¼3.4 Hz, 3JHH¼7.5 Hz, 1H),
7.12e7.14 (m, 2H), 7.17e7.21 (m, 4H), 7.28e7.31 (m, 1H), 7.39e7.44
3
3
(m, 4H), 7.47 (d, JHH¼8.4 Hz, 1H), 7.72 (d, JHH¼8.4 Hz, 1H),
7.85e7.90 (m, 3H); 13C{1H} NMR (CDCl3, 125 MHz)
d
(ppm)¼21.7,
22.1, 22.5, 22.8, 29.4 (d, 1JCP¼32.2 Hz), 32.7 (d, 1JCP¼30.7 Hz), 70.1,
71.5, 105.9, 106.5, 102.9 (d, 3JCP¼2.6 Hz), 125.7, 126.2, 126.3, 126.4 (d,
3JCP¼8.3 Hz), 127.0, 127.3, 128.1 (d, 3JCP¼2.5 Hz), 128.2, 128.4, 128.5,
128.6, 128.6 (d, 1JCP¼42.4 Hz), 129.7, 130.1 (d, 3JCP¼3.6 Hz), 130.3 (d,
4JCP¼6.0 Hz), 131.5e131.6 (m), 132.3 (d, JCP¼2.4 Hz), 132.4e132.5
4
3
5
(m), 133.1, 133.3 (d, JCP¼8.3 Hz), 133.4 (d, JCP¼2.1 Hz), 133.9 (d,
3
2
3JCP¼4.2 Hz), 134.0 (d, JCP¼2.7 Hz), 141.0 (d, JCP¼8.7 Hz), 157.2,
157.3; 31P{1H} NMR (CDCl3, 162 MHz)
d
(ppm)¼47.7 (br m); IR
spectrum (neat)
n
(cmꢂ1)¼3050, 2975, 1385, 2317, 1591, 1457, 1371,
4.2. General procedure for the preparation of borane-
protected ligands (Ra)-2aeb.BH3
1246, 1113, 1057,þ934, 837, 819, 738; HRMS (ESI positive) calcd for
23
593.2775 [MꢂH] , found 593.2794; mp¼138e140 ꢀC; [
(c 1.0 in CH2Cl2).
a
]
þ2.96
D
In an oven-dry
5
mL Schlenk tube 20-bromo-2,6-
dialkoxybiphenyl (0.31 mmol, 1.0 equiv) was dissolved in 1.6 mL
of THF. The resulting solution was cooled to ꢂ78 ꢀC and nBuLi
(0.33 mmol, 1.05 equiv) was added dropwise. After 1 h at ꢂ78 ꢀC,
a solution of (Ra)-3 (0.33 mmol, 1.05 equiv) in 1.1 mL of dry and
degassed THF was added dropwise and the resulting mixture stir-
red at ꢂ78 ꢀC for additional 3 h. The reaction was quenched with
1.5 mL of degassed water and the aqueous phase was extracted
with toluene (3ꢃ1 mL) under nitrogen. The combined organic
layers were dried under vacuum and the resulting oil was dissolved
in 1 mL of dry and degassed THF. The solution was cooled to 0 ꢀC
and BH3eTHF 1.0 M in THF (1.1 mmol, 3.5 equiv) was added
dropwise. The resulting mixture was stirred at room temperature
for 16 h. The excess of BH3eTHF was quenched by careful addition
of few drops of methanol and all the volatiles were subsequently
evaporated. The crude mixture was then purified by flash chro-
matography (pentane/CH2Cl2) to afford the protected ligand as
a foamy solid.
4.3. Preparation of borane-protected ligands (Ra)-2c.BH3
In an oven-dry 25 mL Schlenk tube, 1-bromo-2,4,6-
triisopropylbenzene (1.8 mmol, 1.0 equiv), and magnesium
turnings (4.2 mmol, 2.4 equiv) were mixed in 2 mL of THF. One
drop of 1,2-dibromoethane was added and the mixture was
placed at 65 ꢀC for 1 h. 2-Bromochlorobenzene (1.9 mmol,
1.1 equiv) was added slowly over 10 min and the reaction was
stirred at 65 ꢀC for 1.5 h. After cooling to room temperature, CuCl
(0.089 mmol, 0.05 equiv) was added to the reaction followed by
a solution of (Ra)-3 (1.8 mmol, 1 equiv) in 2 mL of THF. The
resulting mixture was stirred at room temperature for 25 h. After
cooling to 0 ꢀC, few drops of methanol were added to quench the
remaining Grignard followed by the addition of BH3eTHF 1.0 M in
THF (8.88 mmol, 5.0 equiv). The resulting mixture was stirred at
room temperature for 16 h. The excess of BH3eTHF was quenched
by careful addition of few drops of methanol and all the volatiles
were evaporated. The crude mixture was then purified by flash
chromatography (eluent pentane/CH2Cl2¼2:1) to afford the pro-
tected ligand as a foamy solid (253 mg, 24% yield). 1H NMR
4.2.1. Protected ligand (Ra)-2a.BH3. The crude reaction mixture was
purified by flash chromatography (pentane/CH2Cl2¼2:1) to afford
the desired compound as a white foamy solid (31% yield). 1H NMR
(CDCl3, 400 MHz)
d
(ppm)¼ꢂ0.36 (d, 3JHH¼6.8 Hz, 3H), 0.51 (br q,
2
(CDCl3, 500 MHz)
d
(ppm)¼0.45 (br q, 3H), 2.43 (dd, JHP¼2.4 Hz,
3H), 0.73 (d, 3JHH¼6.8 Hz, 3H), 0.84 (d, 3JHH¼6.8 Hz, 3H), 1.17e1.20
2JHH¼12.9 Hz, 1H), 2.77e2.86 (m, 2H), 3.04 (s, 3H), 3.19 (dd,
(m, 6H), 1.41 (d, JHH¼6.8 Hz, 3H), 1.57 (hept, JHH¼6.8 Hz, 1H),
3
3
2
3
2 2 2
2JHP¼5.4 Hz, JHH¼14.4 Hz, 1H), 3.81 (s, 3H), 6.32 (d, JHH¼8.4 Hz,
1.82 (dd, JHP¼2.5 Hz, JHH¼13.4 Hz, 1H), 2.50 (dd, JHH¼13.4 Hz,
3
3
3
1H), 6.60 (d, JHH¼8.4 Hz, 1H), 7.04 (d, JHH¼8.3 Hz, 1H), 7.11e7.14
(m, 2H), 7.18e7.25 (m, 4H), 7.37 (br t, 1H), 7.40e7.43 (m, 2H),
2JHP¼18.7 Hz, 1H), 2.64 (hept, JHH¼6.8 Hz, 1H), 2.80 (hept,
3JHH¼6.8 Hz, 1H), 2.95 (dd, JHP¼6.8 Hz, JHH¼14.7 Hz, 1H), 3.40
(dd, 2JHP¼5.5 Hz, 2JHH¼14.7 Hz, 1H), 6.59 (d, 4JHH¼1.6 Hz, 1H), 7.08
(d, 4JHH¼1.6 Hz, 1H), 7.08e7.11 (m, 1H), 7.11e7.22 (m, 5H), 7.27 (dd
2
2
7.47e7.55 (m, 3H), 7.72 (d, 3JHH¼8.3 Hz, 1H), 7.86e7.91 (m, 3H); 13
C
{1H} NMR (CDCl3,125 MHz)
d
(ppm)¼28.9 (d, 1JCP¼32.6 Hz), 32.6 (d,
1JCP¼30.6 Hz), 55.3, 55.9, 103.6, 203.9, 118.2 (d, 3JCP¼2.8 Hz), 125.7,
partially overlapped with the signal of the solvent, JHP¼1.2 Hz);
4
3
3
125.8, 126.3, 126.4, 126.9, 127.1, 127.1 (d, JCP¼8.9 Hz), 127.8 (d,
7.39e7.47 (m, 3H), 7.55 (tt, J¼1.5 Hz, JHH¼7.9 Hz, 1H), 7.75 (d,
3JCP¼2.4 Hz), 128.4, 128.5, 128.6, 128.7, 129.8 (d, 3JCP¼3.6 Hz), 130.3,
130.8 (d, 4JCP¼2.3 Hz), 131.3 (d, 2JCP¼6.3 Hz), 132.1 (d, 2JCP¼8.0 Hz),
132.2e132.3 (m), 133.0 (d, 5JCP¼1.6 Hz), 133.1 (d, 3JCP¼7.9 Hz), 133.4
(d, 5JCP¼2.6 Hz), 133.9 (d, 3JCP¼2.7 Hz), 133.9 (d, 3JCP¼4.2 Hz), 139.6
3JHH¼8.4 Hz, 1H), 7.83e7.85 (m, 2H), 7.88 (d, JHH¼8.2 Hz, 1H),
3
3
3
7.96 (dd, JHH¼7.9 Hz, JHP¼11.6 Hz, 1H); 13C{1H} NMR (CDCl3,
100 MHz)
d
(ppm)¼21.1, 23.2, 24.2, 24.6, 25.9, 26.0, 28.5 (d,
1JCP¼30.3 Hz), 30.5, 30.8, 67.5 (d, 1JCP¼32.7 Hz), 34.5, 120.8, 120.9,
(d, JCP¼7.6 Hz), 158.2, 158.4; 31P{1H} NMR (CDCl3, 162 MHz)
125.9, 126.4, 126.6, 127.1, 127.3, 127.5 (d, JCP¼10.1 Hz), 128.5,
2
3
3
d
(ppm)¼49.3 (br m); IR spectrum (neat)
n
(cmꢂ1)¼2931, 2381,
128.7, 128.8 (d, 1JCP¼45.4 Hz), 128.9, 129.4 (d, JCP¼3.5 Hz), 129.8
4
2
2
1590, 1470, 1430, 1248, 1108, 1054, 840, 820, 731; HRMS (ESI posi-
(d, JCP¼30.3 Hz), 131.0 (d, JCP¼6.8 Hz), 131.8 (d, JCP¼10.0 Hz),
4 2
tive) calcd for 537.2149 [MꢂH]þ, found 537.2153; mp¼150e152 ꢀC;
132.2 (d, JCP¼2.2 Hz), 132.5 (d, JCP¼11.5 Hz), 132.7, 133.4e133.5
23 þ7.82 (c 1.0 in CH2Cl2).
(m), 133.7 (d, JCP¼4.5 Hz), 133.9 (d, JCP¼2.5 Hz), 135.3 (d,
3
3
[a]
D
3JCP¼2.0 Hz), 143.8 (d, JCP¼4.6 Hz), 146.3, 147.5, 149.9; 31P{1H}
2
4.2.2. Protected ligand (Ra)-2b.BH3. The crude reaction mixture
was purified by flash chromatography (pentane/CH2Cl2¼2:1) to
NMR (CDCl3, 162 MHz)
d
(ppm)¼51.6 (br m); IR spectrum (neat)
n
(cmꢂ1)¼3052, 2961, 2869, 2382, 1605, 1509, 1461, 1361, 1265,

I. Franzoni et al. / Tetrahedron 70 (2014) 4181e4190
4187
23
1137, 1055, 935, 838, 820, 761, 735; HRMS (ESI positive) calcd for
469.2250 [Mꢂ3H]þ, found 469.2342; mp¼215e217 ꢀC;
[
a
]
D
23
603.3347 [MꢂH]þ, found 603.3342; mp¼232e234 ꢀC;
ꢂ38.96 (c 1.0 in CH2Cl2).
[
a
]
ꢂ658.4 (c 1.0 in CH2Cl2).
D
4.4.3. Protected ligand (Ra,R,RP)-2f.BH3. 8 equiv of a-chloroisodur-
4.4. General procedure for the preparation of borane-
protected ligands (Ra,R,RP)-2dej.BH3
ene were employed. The crude reaction mixture was purified by
flash chromatography (pentane/CH2Cl2¼2:1) to afford the desired
compound as a white foamy solid (78% yield). 1H NMR (CDCl3,
In a 10 mL Schlenk tube (Ra)-4.BH3 (0.35 mmol, 1.0 equiv) was
400 MHz)
d
(ppm)¼0.73 (br q, 3H), 1.13 and 1.16 (2s, 9H), 1.80 (s,
2
dissolved in
5
mL of THF. After cooling to ꢂ78 ꢀC, tBuLi
6H), 2.15e2.21 (m and s, 1Hþ3H), 2.87 (dd, JHP¼3.1 Hz,
(0.87 mmol, 2.5 equiv) was added dropwise and the reaction was
slowly warmed to ꢂ40 ꢀC over 2 h. After cooling again to ꢂ78 ꢀC
the appropriate electrophile (7e10 equiv) was added in one
portion and the mixture was stirred at room temperature for 16 h.
The reaction was quenched with 5 mL of water and the aqueous
phase was extracted with CH2Cl2 (3ꢃ3 mL). The combined or-
ganic layers were dried over Na2SO4, the solvent was evaporated,
and the resulting crude mixture was purified by flash chroma-
tography (pentane/CH2Cl2) to afford the desired product as
a foamy solid.
2JHH¼12.5 Hz, 1H), 3.04e3.23 (m, 3H), 6.64 (s, 2H), 7.05 (d,
3JHH¼8.4 Hz, 1H), 7.12 (br d, JHH¼8.5 Hz, 1H), 7.15e7.19 (m, 1H),
3
7.24e7.27 (m, 2H), 7.42 (br t, 3JHH¼7.1 Hz,1H), 7.47 (ddd, JHH¼2.1 Hz,
3
4
3
JHH¼5.9 Hz, JHH¼8.2 Hz, 1H), 7.68 (dd, JHP¼1.2 Hz, JHH¼8.4 Hz,
3
3
1H), 7.76 (d, JHH¼8.4 Hz, 1H), 7.90 (d, JHH¼8.2 Hz, 1H), 7.93 (d,
3JHH¼8.2 Hz, 1H), 7.99 (d, JHH¼8.4 Hz, 1H); 13C{1H} NMR (CDCl3,
3
400 MHz)
d
(ppm)¼21.1, 22.0, 26.7, 27.5 (d, 1JCP¼29.0 Hz), 31.7 (d,
1JCP¼25.0 Hz), 32.7 (d, JCP¼4.7 Hz), 41.5 (d, JCP¼19.2 Hz), 125.8,
125.9, 126.3, 126.4, 127.6, 127.9, 128.4, 128.5, 128.9, 129.0, 129.2,
129.9 (d, 3JCP¼3.3 Hz), 130.3 (d, 2JCP¼6.5 Hz), 131.4 (d, 3JCP¼4.0 Hz),
2
1
4
3
132.3 (d, JCP¼2.1 Hz), 133.0 (d, JCP¼4.9 Hz), 133.1, 133.4, 133.6 (d,
3
4.4.1. Protected ligand (Ra,R,RP)-2d.BH3. 10 equiv of bromome-
thylcylcohexane were employed. The crude reaction mixture was
purified by flash chromatography (pentane/CH2Cl2¼2:1) to afford
the desired compound as a white foamy solid (63% yield). 1H NMR
5JCP¼1.8 Hz), 134.5, 135.5, 136.5 (d, JCP¼10.9 Hz), 136.9, 138.8 (d,
2JCP¼7.1 Hz); 31P{1H} NMR (CDCl3, 162 MHz)
d
(ppm)¼70.1 (br m);
IR spectrum (neat)
n
(cmꢂ1)¼2946, 2865, 2382, 1596, 1505, 1462,
1365, 1062, 846, 819, 748, 691, 659, 626; HRMS (ESI positive) calcd
23
(CDCl3, 400 MHz)
d
(ppm)¼0.11e0.15 and 0.28e0.37 (2m, 2ꢃ1H),
for 513.2877 [MꢂH]þ, found 513.2873; mp¼222e224 ꢀC; [
ꢂ460.07 (c 1.0 in CH2Cl2).
a]
D
0.31 (br q, 3H), 0.41e0.52 (m,1H), 0.65e0.71 (m, 3H), 0.83e0.93 (m,
2H), 1.13 and 1.16 (2s, 9H), 1.23e1.30 (m, 2H), 1.41 (m, 1H), 1.57 (m,
1H), 1.84 (m, 1H), 2.80 (dd, 1JHP¼2.8 Hz, 1JHH¼12.7 Hz, 1H), 3.14 (dd,
4.4.4. Protected ligand (Ra,R,RP)-2g.BH3. 7 equiv of 2,4,6-
triisopropylbenzyl chloride were employed. The crude reaction
mixture was purified by flash chromatography (pentane/
CH2Cl2¼2:1) to afford the desired compound as a white foamy solid
1
1JHH¼12.7 Hz, JHP¼16.2 Hz, 1H), 3.32 (ddd, J¼4.5 Hz, J¼9.5 Hz,
J¼13.5 Hz, 1H), 6.94 (br d, 3JHH¼8.2 Hz, 1H), 7.15 (ddd, 4JHH¼1.2 Hz,
3JHH¼6.8 Hz, 3JHH¼8.2 Hz, 1H), 7.21e7.25 (m, 2H), 7.37e7.41 (m, 1H),
7.43e7.48 (m, 3JHH¼8.4 Hz, 2H), 7.57 (dd, 4JHP¼1.1 Hz, 3JHH¼8.4 Hz,
(59% yield). 1H NMR (CDCl3, 400 MHz)
d
(ppm)¼0.74 (br s, 9H),
1H), 7.89e7.94 (m, 4H); 13C{1H} NMR (CDCl3, 400 MHz)
d
(ppm)¼
1.11e1.14 (2s, 9H), 1.19 (d, 3JHH¼6.9 Hz, 6H), 2.14e2.20 (m, 1H), 2.67
26.2, 26.3, 26.6 (d, 1JCP¼28.4 Hz), 26.7, 26.7, 30.7 (d, 1JCP¼25.3 Hz),
(br s, 2H), 2.79 (hept, JHH¼6.9 Hz, 1H), 2.88 (dd, JHP¼3.1 Hz,
2JHH¼12.5 Hz, 1H), 3.01e3.20 (m, 3H), 6.81 (br s, 2H), 7.02 (d,
3
2
31.2, 33.6, 35.8, 35.9 (d, 1JCP¼13.9 Hz), 38.5 (d, JCP¼2.5 Hz), 125.7,
3
3
126.2, 126.6, 126.7, 127.1, 128.3, 128.4, 128.6e128.7 (m), 129.5 (d,
2JCP¼6.8 Hz), 129.7 (d, 3JCP¼3.4 Hz), 131.1 (d, 3JCP¼3.9 Hz), 132.7 (d,
3JHH¼8.4 Hz, 1H), 7.12 (d, JHH¼8.5 Hz, 1H), 7.22e7.26 (m, 3H),
3
3
7.41e7.48 (m, 2H), 7.68 (dd, JHP¼1.2 Hz, 1H), 7.73 (d, JHH¼8.4 Hz,
5JCP¼2.3 Hz), 133.0, 133.2 (d, JCP¼2.1 Hz), 133.2, 133.8 (d,
1H), 7.88 (d, JHH¼8.2 Hz, 1H), 7.94 (d, JHH¼7.9 Hz, 1H), 7.99 (d,
4
3
3
3JCP¼4.6 Hz), 134.3 (d, JCP¼1.6 Hz), 136.8 (d, JCP¼7.5 Hz); 31P{1H}
3JHH¼8.4 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz)
d
(ppm)¼24.2,
3
2
NMR (CDCl3, 162 MHz)
d
(ppm)¼64.0 (br m); IR spectrum (neat)
n
24.4, 26.6, 27.5 (d, 1JCP¼29.1 Hz), 29.5, 29.8 (d, 2JCP¼4.8 Hz), 31.4 (d,
(cmꢂ1)¼2921, 2849, 2391, 2374, 1507, 1447, 1365, 1061, 1018, 844,
1JCP¼24.8 Hz), 34.2, 43.1 (d, 1JCP¼18.7 Hz), 121.2, 125.5, 126.2, 126.3,
3
818, 745, 693, 624, 565; HRMS (ESI positive) calcd for 475.2721
127.1, 127.5, 128.3, 128.4, 129.0e129.1 (m), 129.8 (d, JCP¼3.4 Hz),
[Mꢂ3H]þ, found 475.2705; mp¼155e157 ꢀC; [
a
]
23 ꢂ215.73 (c 1.0 in
130.3 (d, 2JCP¼6.7 Hz), 132.0 (d, 3JCP¼4.3 Hz), 132.3 (d, 4JCP¼2.3 Hz),
D
3
CH2Cl2).
133.0 (d, JCP¼4.9 Hz), 133.1, 133.4e133.5 (m), 133.7 (d,
3JCP¼11.3 Hz), 134.9 (d, JCP¼0.9 Hz), 137.8 (d, JCP¼7.1 Hz), 146.7,
3
2
4.4.2. Protected ligand (Ra,R,RP)-2e.BH3. 10 equiv of benzyl bromide
were employed. The crude reaction mixture was purified by flash
chromatography (pentane/CH2Cl2¼2:1) to afford the desired com-
147.2; 31P{1H} NMR (CDCl3, 162 MHz)
d
(ppm)¼69.8 (br m); IR
spectrum (neat)
n
(cmꢂ1)¼2958, 2381, 1461, 1362, 1061, 816, 747;
HRMS (ESI positive) calcd for 597.3816 [MꢂH]þ, found 597.3838;
23
pound as a white foamy solid (72% yield). 1H NMR (CDCl3, 400 MHz)
mp¼155e157 ꢀC; [
a
]
ꢂ476.70 (c 0.51 in CH2Cl2).
D
3
d
(ppm)¼0.51 (br, 3H), 1.17 (d, JHH¼13.2 Hz, 9H), 1.83 (t,
3JHH¼12.4 Hz, 1H), 2.88 (d, 3JHH¼12.6 Hz, 1H), 3.04 (t, 3JHH¼12.4 Hz,
1H), 3.37 (dd, 2JHP¼15.9 Hz, 3JHH¼12.6 Hz,1H), 3.37 (t, 3JHH¼12.6 Hz,
4.4.5. Protected ligand (Ra,R,RP)-2h.BH3. 10 equiv of 2-(bromo-
methyl)naphthalene were employed. The crude reaction mixture
was purified by flash chromatography (pentane/CH2Cl2¼2:1) to
afford the desired compound as a white foamy solid (75% yield). 1H
3
1H), 6.66 (m, 2H), 6.96 (d, JHH¼8.3 Hz, 1H), 7.03 (m, 4H), 7.20 (m,
2H), 7.26 (t, 3JHH¼7.7 Hz,1H), 7.44 (m, 2H), 7.65 (d, 3JHH¼8.3 Hz, 1H),
3
3
7.67 (d, JHH¼8.3 Hz, 1H), 7.84 (d, JHH¼8.1 Hz, 1H), 7.95 (d,
NMR (CDCl3, 400 MHz)
d
(ppm)¼0.79 (br q, 3H), 1.20 (2s, 9H),
3JHH¼8.1 Hz, 1H), 7.99 (d, JHH¼8.3 Hz, 1H); 13C{1H} NMR (CDCl3,
1.94e2.01 (m, J¼2.4 Hz, 1H), 2.91 (dd, JHP¼2.8 Hz, JHH¼12.9 Hz,
1H), 3.17e3.27 (m, 2H), 3.52e3.58 (ddd, J¼3.2 Hz, J¼10.1 Hz,
J¼13.0 Hz, 1H), 6.83 (br s, 1H), 6.97e7.01 (m, 2H), 7.06 (d,
3JHH¼8.5 Hz, 1H), 7.20e7.21 (m, 2H), 7.31e7.35 (m, 3H), 7.39e7.42
(m, 1H), 7.45e7.47 (m, 1H), 7.51e7.54 (m, 1H), 7.57e7.60 (m, 2H),
3
1 1
1
400 MHz)
d
(ppm)¼26.2, 26.3 (d, JCP¼28.6 Hz), 30.7 (d,
1JCP¼25.8 Hz), 37.8 (d, JCP¼4.6 Hz), 41.5 (d, JCP¼22.1 Hz), 125.7,
126.0, 126.2, 126.3, 127.0, 128.0, 128.0, 128.1, 128.6, 128.7, 128.8,
129.6 (d, 3JCP¼6.5 Hz), 129.7 (d, 3JCP¼3.7 Hz), 131.3 (d, 3JCP¼3.7 Hz),
2
1
2
2
132.4 (d, JCP¼1.8 Hz), 132.8, 133.0, 133.1 (d, JCP¼1.8 Hz), 133.2 (d,
7.68e7.70 (m, 2H), 7.79 (d, 3JHH¼8.2 Hz, 1H), 8.00e8.05 (m, 2H); 13
C
2JCP¼4.6 Hz), 134.0, 136.0 (d, JCP¼7.4 Hz), 140.6 (d, JCP¼13.8 Hz);
{1H} NMR (CDCl3, 100 MHz)
d
(ppm)¼26.5, 26.6 (d, 1JCP¼28.4 Hz),
3
3
31P{1H} NMR (CDCl3, 162 MHz)
d
(ppm)¼65.2 (br m); IR spectrum
31.0 (d, 1JCP¼25.4 Hz), 38.1 (d, JCP¼4.4 Hz), 41.2 (d, 1JCP¼22.5 Hz),
2
(neat)
n
(cmꢂ1)¼3048, 2957, 2864, 2388, 2316, 2260, 1945, 1906,
125.5, 125.9, 126.0, 126.2, 126.4, 127.1, 127.1, 127.5, 127.7, 127.8, 127.9,
4
2
1595, 1503, 1460, 1397, 1365, 1261, 1244, 1189, 1143, 1062, 1019, 956,
931, 845, 819, 750, 702, 657, 627; HRMS (ESI positive) calcd for
128.3, 128.3, 128.9 (d, JCP¼2.0 Hz), 129.0, 129.8 (d, JCP¼6.8 Hz),
3 3
129.9 (d, JCP¼3.4 Hz), 131.5 (d, JCP¼3.7 Hz), 132.2, 132.6 (d,

4188
I. Franzoni et al. / Tetrahedron 70 (2014) 4181e4190
4JCP¼2.4 Hz), 132.9, 133.1, 133.5, 133.6 (d, 3JCP¼4.7 Hz), 134.2, 136.0
evaporated under vacuum to afford the pure deprotected ligand as
a foamy solid. As all deprotected ligands disclosed in this study are
relatively air-sensitive, characterizations requiring long measuring
time or exposure to air could not be performed without partial or
complete oxidation of the free ligands. Hence, in the
Supplementary data, only the 1H NMR and 31P NMR of all depro-
tected ligands are reported.
2
3
(d, JCP¼7.0 Hz), 137.9 (d, JCP¼13.2 Hz); 31P{1H} NMR (CDCl3,
162 MHz)
d
(ppm)¼65.1 (br m); IR spectrum (neat)
n
(cmꢂ1)¼3052,
2958, 2384, 1597, 1507, 1463, 1365, 1246, 1062, 1019, 818, 804, 743,
691; HRMS (ESI positive) calcd for 545.2540 [MþNa]þ, found
23
545.2545; mp¼125e127 ꢀC; [
a]
ꢂ638.28 (c 1.0 in CH2Cl2).
D
4.4.6. Protected ligand (Ra,R,RP)-2i.BH3. 8 equiv of 3,5-
dimethylbenzyl bromide were employed. The crude reaction
mixture was purified by flash chromatography (pentane/
CH2Cl2¼2:1) to afford the desired compound as a white foamy
4.6. General procedure for the intramolecular
aldehydes
a-arylation of
solid (69% yield). 1H NMR (CDCl3, 500 MHz)
d
(ppm)¼0.10e0.70
Inside a glove box a 2 mL Schlenk tube was charged with
Pd(OAc)2 (1.1 mg, 0.005 mmol, 0.05 equiv), the appropriate ligand
(0.012 mmol, 0.12 equiv), and Cs2CO3 (39.1 mg, 0.12 mmol,
1.2 equiv). The tube was sealed and taken out from the glove box
and connected to a Schlenk line. After conditioning, 0.30 mL of DMF
was added followed by the substrate (0.1 mmol, 1.0 equiv). The tube
was placed in an oil bath preheated at 80 ꢀC for 48 h. The reaction
was diluted with 0.5 mL of Et2O and washed with 0.5 mL of water.
The aqueous phase was extracted with Et2O (4ꢃ0.5 mL), the com-
bined organic layers dried over Na2SO4, filtered, and the solvent
evaporated. The crude mixture was purified by flash chromatog-
raphy (pentane/CH2Cl2 or pentane/Et2O). For all products spectro-
metric and spectroscopic analyses were consistent with the data
reported in literature.
(br q, 3H), 1.18 (d, 9H), 1.69e1.75 (m, J¼12.75 Hz, J¼2.5 Hz, 1H),
2
2
2.08 (s, 6H), 2.86 (dd, JHH¼12.7 Hz, JHP¼2.8 Hz, 1H), 2.85 (ddd,
4JHH¼14.1 Hz, JHP¼8.4 Hz, JHH¼3.1 Hz, 1H), 3.18 (dd,
3
3
2JHH¼12.7 Hz, JHP¼16.4 Hz, 1H), 3.41 (ddd, JHH¼13.0 Hz,
2
3
2JHP¼10.0 Hz, 3JHH¼13.0 Hz, 1H), 6.21 (s, 2H), 6.62 (s, 1H), 6.99 (d,
3JHH¼8.6 Hz, 1H), 7.03 (d, JHH¼8.4 Hz, 1H), 7.17e7.24 (m, 3H),
3
7.41e7.47 (m, 2H), 7.64 (dd, 3JHH¼8.4 Hz, 4JHP¼1.9 Hz, 1H), 7.68 (d,
3JHH¼8.4 Hz, 1H), 7.68 (d, JHH¼8.4 Hz, 1H), 7.84 (d, JHH¼8.2 Hz,
3
3
1H), 7.95 (d, JHH¼8.1 Hz, 1H), 7.99 (d, JHH¼8.4 Hz, 1H); 13C{1H}
3
3
NMR (CDCl3, 125 MHz)
d
(ppm)¼21.5, 25.4 (d, 1JCP¼25.4 Hz), 26.6,
26.7 (d, 1JCP¼28.3 Hz), 37.7 (d, 2JCP¼4.2 Hz), 41.2 (d, 1JCP¼22.4 Hz),
125.9, 126.1, 126.3, 126.4, 126.9, 127.2, 127.5, 127.8, 128.1, 128.2,
4
2
128.8 (d, JCP¼1.7 Hz), 128.9, 129.8 (d, JCP¼6.7 Hz), 129.9
3
3
4
(d, JCP¼3.3 Hz), 131.8 (d, JCP¼3.7 Hz), 132.6 (d, JCP¼2.2 Hz),
5
3
132.9, 133.2, 133.4 (d, JCP¼1.8 Hz), 133.7 (d, JCP¼4.6 Hz), 134.2,
4.7. General procedure for the intermolecular
aldehydes
g-arylation of
136.4 (d, 2JCP¼7.1 Hz), 137.5, 140.3 (d, 3JCP¼13.1 Hz); 31P{1H} NMR
(CDCl3, 162 MHz)
d
(ppm)¼64.8 (br m); IR spectrum (neat)
n
(cmꢂ1)¼3056, 2961, 2865, 2383, 1605, 1509, 1461, 1362, 1057,
Inside a glove box a 5 mL Schlenk tube was charged with
Pd(OAc)2 (1.1 mg, 0.005 mmol, 0.05 equiv), the appropriate ligand
(0.012 mmol, 0.12 equiv), and Cs2CO3 (39.1 mg, 0.12 mmol,
1.2 equiv). The tube was sealed and taken out from the glove box
and connected to a Schlenk line. After conditioning, 0.30 mL of
DMF, followed by the bromoarene (0.1 mmol, 1.0 equiv) and next
the aldehyde (0.1 mmol, 1.0 equiv). The tube was placed an oil bath
preheated at 110 ꢀC for 14 h. The reaction was diluted with 0.5 mL of
Et2O and washed with 0.5 mL of water. The aqueous phase was
extracted with Et2O (4ꢃ0.5 mL), the combined organic layers dried
over Na2SO4, filtered, and the solvent evaporated. The crude mix-
ture was purified by flash chromatography (pentane/CH2Cl2 or
pentane/Et2O).
935, 840, 820, 739; HRMS (ESI positive) calcd for 497.2564
23
[Mꢂ3H]þ, found 497.2552; mp¼132e134 ꢀC; [
a
]
ꢂ483.27 (c 1.0
D
in CH2Cl2).
4.4.7. Protected ligand (Ra,R,RP)-2j.BH3. 8 equiv of 3,5-
ditertbutylbenzyl bromide were employed. The crude reaction
mixture was purified by flash chromatography (pentane/
CH2Cl2¼2:1) to afford the desired compound as a white foamy
solid (70% yield). 1H NMR (CDCl3, 400 MHz)
d
(ppm)¼0.50 (br q,
3H), 1.13 (s, 18H), 1.16 (2s, 9H), 1.84 (t, J¼13.1 Hz, 1H), 2.88 (dd,
2
2JHP¼2.8 Hz, JHH¼12.6 Hz, 1H), 2.93e2.99 (m, 1H), 3.18e3.28 (m,
2H), 6.48 (d, 4JHH¼1.75 Hz, 2H), 6.92 (d, 3JHH¼8.4 Hz, 1H), 7.07e7.11
(m, 2H), 7.18e7.25 (m, 3H), 7.40e7.47 (m, 2H), 7.65 (dd,
3
3
4JHP¼1.1 Hz, JHH¼8.4 Hz, 1H), 7.68 (d, JHH¼8.4 Hz, 1H), 7.86 (d,
4.7.1. (E)-4-(2-Methoxyphenyl)-2,4-dimethyl-5-phenylpent-2-enal
9aa. Prepared from 7a and 2-bromoanisole 8a using the general
procedure. The E/Z ratio was determined to be >50:1 by 1H NMR
analysis of the crude reaction mixture. The crude residue was pu-
rified by flash chromatography (pentane/Et2O¼16:1). The enan-
tiomeric excess was determined by chiral HPLC analysis (OJ-H,
3JHH¼8.2 Hz, 1H), 7.94 (d, JHH¼8.1 Hz, 1H), 7.98 (d, JHH¼8.4 Hz,
3
3
1H); 13C{1H} NMR (CDCl3,1 100 MHz)
d
(ppm)¼26.5, 26.6 (d,
1JCP¼28.5 Hz), 30.9 (d, JCP¼25.4 Hz), 31.7, 34.9, 38.4 (d,
2JCP¼4.1 Hz), 41.9 (d, 1JCP¼22.0 Hz), 119.9, 123.4, 125.8, 126.2, 126.4,
4
126.6, 127.0, 127.2, 128.1, 128.2, 128.9 (d, JCP¼2.0 Hz), 129.0, 129.9
(d, 3JCP¼3.4 Hz), 129.9 (d, 2JCP¼6.6 Hz), 131.9 (d, 3JCP¼3.8 Hz), 132.7
hexanes/iPrOH 99:1,
1
mL/min,
l
¼278 nm): t1¼11.38 and
4
5
(d, JCP¼2.4 Hz), 132.9, 133.3, 133.4 (d, JCP¼2.2 Hz), 133.5 (d,
t2¼12.44 min. 1H NMR (CDCl3, 500 MHz)
d
(ppm)¼1.24 (d,
3JCP¼4.8 Hz), 134.1, 136.8 (d, JCP¼7.0 Hz), 140.1 (d, JCP¼12.8 Hz),
4JHH¼1.3 Hz, 3H), 1.44 (s, 3H), 3.00 (d, JHH¼12.9 Hz, 1H), 3.57 (d,
2JHH¼12.9 Hz, 1H), 3.77 (s, 3H), 6.76e6.78 (m, 2H), 6.85 (td,
2
3
2
150.4; 31P{1H} NMR (CDCl3, 162 MHz)
d
(ppm)¼65.4 (br m); IR
4
spectrum (neat)
n
(cmꢂ1)¼2957, 2370, 1597, 1463, 1363, 1247, 1203,
3JHH¼7.6 Hz, JHH¼1.0 Hz, 1H), 6.89e6.91 (m, 2H), 6.98 (dd,
4
1062, 1017, 819, 736, 715; HRMS (ESI positive) calcd for 583.3660
3JHH¼7.7 Hz, JHH¼1.6 Hz, 1H), 7.11e7.14 (m, 3H), 7.23e7.27 (m,
[MꢂH]þ, found 583.3658; mp¼122e124 ꢀC; [
a
]
23 ꢂ426.60 (c 1.0 in
4JHH¼1.7 Hz, 1H), 9.40 (s, 1H); 13C NMR (CDCl3, 125 MHz)
(ppm)¼
d
D
CH2Cl2).
9.8, 23.3, 43.7, 47.1, 55.7, 111.8, 120.9, 126.6, 127.7, 127.8, 128.5, 131.1,
133.7, 136.7, 137.9, 157.5, 165.4, 196.8; IR spectrum (neat)
n
(cmꢂ1)¼
4.5. General procedure for deprotection of ligands 2aej.BH3
3024, 2964, 2843, 2730, 1676, 1634, 1599, 1491, 1467, 1452, 1435,
1374, 1288, 1243, 1221, 1180, 1124, 1080, 1020, 848, 746, 695; HRMS
(ESI positive) calcd for 295.1692 [MþH]þ, found 295.1705;
mp¼84e86 ꢀC.
In a 2 mL Schlenk tube the protected ligand (0.10 mmol) was
dissolved in 0.25 mL of Et2NH. The tube was sealed and placed at
80 ꢀC for 4 days. The excess of amine was eliminated under vacuum
and the residual was taken up in 0.5 mL of toluene. The Schlenk was
brought back inside the glove box and the reaction mixture was
4.7.2. (E)-4-(4-Methoxyphenyl)-2,4-dimethyl-5-phenylpent-2-enal
9ab. Prepared from 7a and 4-bromoanisole 8b using the general
procedure. The E/Z ratio was determined to be 21:1 by 1H NMR
filtered through
a
small pad of CeliteÓ. The volatiles were

I. Franzoni et al. / Tetrahedron 70 (2014) 4181e4190
4189
analysis of the crude reaction mixture. The crude residue was
purified by flash chromatography (pentane/Et2O¼16:1). The en-
antiomeric excess was determined by chiral HPLC analysis (OJ-H,
1488, 1452, 1238, 1020, 750; LRMS (ESI positive) calcd for 287.2
[MþH]þ, found 287.5.
hexanes/iPrOH 95:5,
1
mL/min,
l
¼279 nm): t1¼16.22 and
4.8. Procedure for the complexation of (Ra,R,RP)-2i with
palladium
t2¼18.13 min. 1H NMR (CDCl3, 400 MHz)
d
(ppm)¼1.30 (d,
4JHH¼1.3 Hz, 3H), 1.47 (s, 3H), 3.05 (d, JHH¼12.9 Hz, 1H), 3.19 (d,
2JHH¼12.9 Hz, 1H), 3.81 (s, 3H), 6.77e6.83 (m, 4H), 6.85 (d,
4JHH¼1.3 Hz, 1H), 7.04e7.07 (m, 2H), 7.14e7.19 (m, 3H), 9.42 (s,
2
Inside a glove box a 2 mL oven-dry vial was charged with
[(CH3CN)2PdCl2] (10 mg, 0.039 mmol, 1.0 equiv) and (Ra,R,RP)-2i
(37.5 mg, 0.077 mmol, 2.0 equiv). Next, 0.77 mL of CH2Cl2 was
added and the resulting solution was stirred at room temperature
for 2 h. After filtration through CeliteÓ and evaporation of the
solvent, the crude residue was purified by flash chromatography
(pentane/CH2Cl2 1:1) to afford a 2:1 mixture of the isomeric com-
plexes as crystalline yellow solids. 31P{1H} NMR (CDCl3, 162 MHz)
1H); 13C NMR (CDCl3, 100 MHz)
d
(ppm)¼10.7, 24.4, 44.8, 51.0,
55.4, 113.7, 126.7, 127.9, 128.3, 131.0, 137.1, 138.0, 140.3, 158.2,
163.3, 196.4; IR spectrum (neat)
n
(cmꢂ1)¼3333, 3054, 3036,
3001, 2941, 2917.3, 2840, 2739, 2053, 1674, 1637, 1607, 1580, 1510,
1494, 1454, 1414, 1374, 1360, 1291, 1252, 1218, 1181, 1102, 1023,
954, 852, 826, 801, 760, 730, 705, 669, 640, 630, 555; HRMS (ESI
positive) calcd for 295.1692 [MþH]þ, found 295.1692;
mp¼68e70 ꢀC.
d
(ppm)¼69.25 (s), 70.71 (s); IR spectrum (neat)
n
(cmꢂ1)¼2931,
1598, 1505, 1463, 1367, 1245, 1174, 1245, 1174, 1018, 863, 829, 744,
690, 532; mp¼220e222 ꢀC. HRMS (ESI positive) calcd for 1155.3525
[MþLi]þ, found 1155.3650.
4.7.3. 20-Methoxy-1-methyl-1,4,5,6-tetrahydro-[1,10-biphenyl]-3-
carbaldehyde 9ba. Prepared from 7b and 2-bromoanisole 8a us-
ing the general procedure. The crude residue was purified by
flash chromatography (pentane/Et2O¼10:1). The enantiomeric
excess was determined by chiral HPLC analysis (OD-H, hexanes/
Acknowledgements
The authors thank the University of Geneva, the Swiss National
Foundation (Project PP00P2_133482), and Roche for financial
support. Johnson Matthey and Solvias are also thanked for gener-
ous gifts of precious metal precursors and chiral ligands, re-
spectively. Prof. A. Alexakis (University of Geneva) is gratefully
acknowledged for giving us access to his analytical facilities and S.
Rosset for performing some GC measurements.
iPrOH 99:1, 1 mL/min,
NMR (CDCl3, 400 MHz)
l
¼233 nm): t1¼8.66 and t2¼10.80 min. 1H
d
(ppm)¼1.54 (s, 3H), 1.58e1.72 (m, 3H),
2.13e2.38 (m, 3H), 3.80 (s, 3H), 6.84 (br t, 1H), 6.89e6.94 (m, 2H),
7.19 (dd, 4JHH¼1.6 Hz, 3JHH¼7.7 Hz, 1H), 7.22e7.25 (m, 1H), 9.50 (s,
1H); 13C{1H} NMR (CDCl3, 100 MHz)
d
(ppm)¼19.2, 21.7,
26.6, 35.1, 40.8, 55.4, 112.2, 120.8, 128.2, 128.3, 134.9, 139.5, 158.1,
159.9, 195.5; IR spectrum (neat)
1679, 1638, 1488, 1459, 1434, 1289, 1237, 1183, 1123, 1024, 802,
750, 696; HRMS (ESI positive) calcd for 231.1380 [MþH]þ, found
231.1380.
n
(cmꢂ1)¼2932, 2866, 2836,
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.02.079.
4.7.4. (E)-4-Cyclohexyl-4-(4-methoxyphenyl)-2-methylpent-2-enal
9cb. Prepared from 7c and 4-bromoanisole 8b using the general
procedure. The E/Z ratio was determined to be 16:1 by 1H NMR
analysis of the crude reaction mixture. The crude residue was pu-
rified by flash chromatography (pentane/Et2O¼18:1). The enan-
tiomeric excess was determined by chiral HPLC analysis (OD-H,
References and notes
1. (a) Metal-catalyzed Cross-coupling Reactions; de Meijere, A., Diederich, F., Eds.;
Wiley-VCH: Weinheim, Germany, 2004; (b) Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., de Meijere, A., Eds.; Wiley: New
York, NY, 2002; (c) Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.;
Snieckus, V. Angew. Chem., Int. Ed. 2012, 51, 5062.
2. (a) Privileged Chiral Ligands and Catalysts; Zhou, Q.-L., Ed.; Wiley-VCH: Wein-
heim, Germany, 2011; (b) Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691.
3. Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J. Org. Chem. 1993, 58, 1945.
4. Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 12051.
5. (a) Bonnaventure, I.; Charette, A. J. Org. Chem. 2008, 73, 6330; (b) Saget, T.;
Lemouzy, S.; Cramer, N. Angew. Chem., Int. Ed. 2012, 51, 2238 For a related ap-
proach, see also: (c) Erre, G.; Enthaler, S.; Junge, K.; Gladiali, S.; Beller, M. J. Mol.
Catal. A Chem. 2008, 280, 148.
hexanes/iPrOH 99:1,
1
mL/min,
l
¼200 nm): t1¼7.35 and
t2¼8.01 min. 1H NMR (CDCl3, 400 MHz)
d
(ppm)¼0.88e0.96 (m,
2H), 1.03e1.25 (m, 4H), 1.62e1.79 (m, 5H), 1.35 (d, 4JHH¼1.3 Hz, 3H),
3
1.48 (s, 3H), 3.80 (s, 3H), 6.81 (d, JHH¼8.9 Hz, 2H), 6.92 (br s, 1H),
3
7.09 (d, JHH¼8.9 Hz, 2H), 9.45 (s, 1H); 13C{1H} NMR (CDCl3,
100 MHz)
d
(ppm)¼11.0, 21.3, 26.9, 27.3, 27.3, 28.3, 28.3, 50.6, 47.2,
55.5,113.6,128.7,137.4,140.5,158.0,163.9,196.8; IR spectrum (neat)
n
(cmꢂ1)¼2926, 2854, 1685, 1511, 1454, 1377, 1293, 1249, 1182, 1029,
830; HRMS (ESI positive) calcd for 287.2006 [MþH]þ, found
6. Donets, P.; Saget, T.; Cramer, N. Organometallics 2012, 31, 8040.
ꢀ
ꢀ
7. (a) Nareddy, P.; Mantilli, L.; Guenee, L.; Mazet, C. Angew. Chem., Int. Ed. 2012, 51,
287.1951.
3826; (b) Humbert, N.; Larionov, E.; Mantilli, L.; Nareddy, P.; Besnard, C.;
ꢀ
ꢀ
Guenee, L.; Mazet, C. Chem.dEur. J. 2014, 20, 745.
8. For a review on binepine ligands and their use in catalysis, see: Gladiali, S.;
4.7.5. (E)-4-Cyclohexyl-4-(2-methoxyphenyl)-2-methylpent-2-enal
9ca. Prepared from 7c and 2-bromoanisole 8a using the general
procedure. The E/Z ratio was determined to be 36:1 by 1H NMR
analysis of the crude reaction mixture. The crude residue was pu-
rified by flash chromatography (eluent pentane/CH2Cl2¼1:1). The
enantiomeric excess was determined by chiral HPLC analysis (OJ-H,
Alberico, E.; Junge, K.; Beller, M. Chem. Soc. Rev. 2011, 40, 3744.
ꢀ
9. (a) Kasak, P.; Mereiter, K.; Wildhalm, M. Tetrahedron: Asymmetry 2005, 16, 3416;
ꢀ
(b) Kasak, P.; Arion, V. B.; Wildhalm, M. Tetrahedron: Asymmetry 2006, 17, 3084;
(c) Dai, Q.; Li, W.; Zhang, X. Tetrahedron 2008, 64, 6943.
10. (a) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461; (b) Surry, D. S.;
Buchwald, S. L. Chem. Sci. 2010, 2, 27.
11. (a) Kaye, S.; Fox, J. M.; Hicks, F. A.; Buchwald, S. L. Adv. Synth. Catal. 2001, 343,
789; (b) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem.
hexanes/iPrOH 99:1,
1
mL/min,
l
¼225 nm): t1¼5.32 and
€
Soc. 2005, 127, 4685; (c) Holz, J.; Monsees, A.; Kadyrov, R.; Borner, A. Synlett
t2¼6.09 min. 1H NMR (CDCl3, 400 MHz)
d
(ppm)¼0.82e0.91 (m,
2007, 599.
1H), 0.97e1.00 (m, 1H), 1.08e1.18 (m, 3H), 1.25 (d, 4JHH¼1.2 Hz, 3H),
€
12. Enthaler, S.; Erre, G.; Junge, K.; Holz, J.; Borne, A.; Alberico, E.; Nieddu, I.;
Gladiali, S.; Beller, M. Org. Process Res. Dev. 2007, 11, 568.
1.25e1.33 (m, 1H), 1.43 (s, 3H), 1.64 (m, 2H), 1.82e1.86 (M, 1H),
3
3
13. (a) CCDC 978250 ((Ra,R,RP)-2j.BH3) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif. (b) The representation of (Ra,R,RP)-2j.BH3 was generated using CYLview:
1.93e1.96 (m, 1H), 2.18 (tt, JHH¼2.9 Hz, JHH¼11.8 Hz, 1H), 3.65 (s,
3H), 6.82 (dd, JHH¼1.0 Hz, JHH¼8.1 Hz, 1H), 6.94 (td, 4JHH¼1.2 Hz,
4
3
3JHH¼7.6 Hz, 1H), 7.11e7.12 (m, 1H), 7.19e7.26 (m, 2H), 9.42 (s, 1H);
ꢀ
13C{1H} NMR (CDCl3, 100 MHz)
d
(ppm)¼9.9, 18.6, 27.1, 27.4, 27.6,
Legault, C. Y. CYLview, Version 1.0.561b; Universite de Sherbrooke: Sherbrooke,
QC, 2009; http://www.cylview.org.
28.1, 29.1, 45.3, 46.1, 55.7, 112.4, 120.8, 127.9, 128.2, 134.7, 136.8,
14. For the first example of asymmetric intramolecular
a-arylation of aldehydes,
157.5, 166.2, 197.1; IR spectrum (neat)
n
(cmꢂ1)¼2926, 2852, 1679,
see: García-Fortanet, J.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 8108.

4190
I. Franzoni et al. / Tetrahedron 70 (2014) 4181e4190
15. For selected reviews on the asymmetric
a
-arylation of carbonyls, see: (a) Cul-
Luchhi, O.; Manassero, M. Tetrahedron: Asymmetry 1994, 5, 511; (b) Mereiter, K.;
Kasak, P.; Widhalm, M. Crystal Structure Deposited at CSD Database as a Private
Communication (Code: GOKVEI).
ꢀ
kin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234; (b) Johansson, C. C. C.;
Colacot, T. J. Angew. Chem., Int. Ed. 2010, 49, 676; (c) Bellina, F.; Rossi, R. Chem.
Rev. 2010, 110, 1082; (d) Mazet, C. Synlett 2012, 1999.
20. CDC 981313 (10i) contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge Crys-
tallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. The crystal
obtained for the diffraction study was twinned (non-merohedral twin) and the
structure contains two independent complexes 10i in the unit cell (one of
which is disordered). The non-disordered complex was used for representation
in Fig. 7.
ꢀ
ꢀ
16. Franzoni, I.; Guenee, L.; Mazet, C. Chem. Sci. 2013, 4, 2619.
17. Franzoni, I.; Mazet, C. Org. Biomol. Chem. 2014, 12, 233.
18. Martin, N.; Pierre, C.; Davi, M.; Jazzar, R.; Baudoin, O. Chem.dEur. J. 2012, 18,
4480.
19. For other examples of crystallographically characterized Pd complexes with
a monodentate binepine ligand, see: (a) Gladiali, S.; Dore, A.; Fabbri, D.; De