Tetrathiaheterohelicene phosphanes as helical-shaped chiral ligands for catalysis

Article abstract of DOI:10.1002/ejoc.201100726

Tetrathia[7]helicene-based phosphanes thiaheliphos (2a), nPr-thiaheliphos (2b) and di-nPr-thiaheliphos (2c) have been prepared from the 2,13-dilithio derivatives of thiahelicenes 1a-c by reaction with an excess of Ph ₂PCl. Protection of the air

Full text of DOI:10.1002/ejoc.201100726

FULL PAPER
DOI: 10.1002/ejoc.201100726
Tetrathiaheterohelicene Phosphanes as Helical-Shaped Chiral Ligands for
Catalysis
Marco Monteforte,[a] Silvia Cauteruccio,[b] Stefano Maiorana,[b] Tiziana Benincori,[c]
Alessandra Forni,*[d] Laura Raimondi,[b] Claudia Graiff,[e] Antonio Tiripicchio,[e]
G. Richard Stephenson,[f] and Emanuela Licandro*[b]
Dedicated to Professor Gianfranco Scorrano on the occasion of his 72nd birthday
Keywords: Helical structures / Heterohelicenes / Sulfur heterocycles / Phosphanes / Thiaheliphos / Rhodium / Asymmetric
catalysis / Hydrogenation
Tetrathia[7]helicene-based phosphanes thiaheliphos (2a),
nPr-thiaheliphos (2b) and di-nPr-thiaheliphos (2c) have been
prepared from the 2,13-dilithio derivatives of thiahelicenes
1a–c by reaction with an excess of Ph2PCl. Protection of the
air-sensitive products as BH3 adducts, from which the phos-
phanes 2a–c are easily regenerated on heating with ethanol,
reaction of the dilithio species with ClP(O)(OEt)2 gave the
diphosphonate 17, which was characterized by X-ray crystal-
lography. Comparison of data from DFT calculations (B3LYP/
SVP) on 2c, 8 and 10 and X-ray data for 17 reveals a strong
tension within the thiaheliphos ligands that is partially re-
laxed by increasing the Rh–P distances and the bite angle
is described. New rhodium(I) complexes 8 and 9 were ob- of the chelating ligand. Compound (P)-(+)-1c, obtained by
tained by reaction of 2c with [Rh(COD)2]+[BF4]– and [BARF]–, chromatographic resolution, was transformed into optically
respectively, which were converted by oxidation into the
chelating phosphane–phosphane oxide RhI complexes 10
and 11. The monophosphane 5 was similarly prepared, and
pure (P)-(+)-2c, which was used in the asymmetric hydrogen-
ation of itaconic acid ester and methyl 2-acetamidoacrylate
(product ees up to 40%).
whereas heterohelicenes have one or more heterocycles. The
reason for our interest in the area of tetrathiaheterohelic-
enes is the possibility of combining the electronic properties
of oligothiophenes with the unique chiroptical properties
of helical shaped molecules. Tetrathiaheterohelicenes are a
particular type of heterohelicene, in which thiophene rings
are fused to alternating arene rings to form the helical skel-
eton, such as in 1a (Scheme 1). This structure represents
the parent compound of a class of derivatives that we have
considered of interest as molecules with specific functions.
In these systems, chirality is important in view of potential
applications, for example in the field of materials with non-
linear optical properties[1] and in catalysis.[2a] Tetrathiahet-
erohelicene (7-TH) 1a has an extended conjugated π system,
and a configurationally stable helix with intrinsic asym-
metry, which can be separated into M and P enantiomers.
Furthermore, we have established that the 7-TH system can
be easily functionalized at the alpha positions of the two
terminal thiophene rings,[3] allowing the modulation of the
chemical and physical properties by varying the substitu-
ents. In addition, the presence of substituents with different
steric demands can tune the distance between the two ter-
minal thiophene rings resulting in remarkable variations in
the dihedral angle of the molecule, which can accommodate
Introduction
Helicenes are polyconjugated π systems which, when they
contain at least four aromatic rings, have overlapping ends.
Because of their nonplanarity, the structures are chiral and
with sufficient fused rings, can be separated into configura-
tionally stable P and M enantiomers. Carbohelicenes only
include carbocyclic aromatic rings in their structures,
[a] Biolife Italiana S.r.l.,
Viale Monza, 272, 20128 Milan, Italy
[b] Dipartimento di Chimica Organica e Industriale,
Via Venezian 21, 20133 Milan, Italy
Fax: +39-02-50314139
E-mail: emanuela.licandro@unimi.it
[c] Dipartimento di Scienze Chimiche e Ambientali, Università
dell’Insubria,
Via Valleggio 11, 22100 Como, Italy
[d] CNR-ISTM, Institute of Molecular Science and Technology –
University of Milan,
Via Golgi 19, 20133 Milan, Italy
E-mail: alessandra.forni@istm.cnr.it
[e] Dipartimento di Chimica Generale e Inorganica, Chimica
Analitica, Chimica Fisica dell’Università di Parma,
Viale delle Scienze 17/A, 43100 Parma, Italy
[f] School of Chemistry, University of East Anglia,
Norwich, NR4 7TJ, UK
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100726.
Eur. J. Org. Chem. 2011, 5649–5658
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5649

A. Forni, E. Licandro, et al.
FULL PAPER
a variety of bulky groups at C2 and C13.[4] Although a
plethora of chiral phosphane ligands characterized by dif-
ferent stereogenic elements have been reported, and biden-
Results and Discussion
The introduction of a range of substituents in one or
tate ligands based on four consecutive fused aromatic rings both the 2- and 13-positions of the 7-TH system, important
have been known for many years,[5] only a limited number for further synthetic elaborations and for the modulation of
of hexa- and heptacarbohelicene-based monodentate[6] and chemical and physical properties, can be easily ac-
bidentate[7] phosphane derivatives have been described. To complished by deprotonation of the alpha positions of ter-
the best of our knowledge, only 2,15-bis(diphenylphos- minal thiophene rings by nBuLi at –78 °C and reaction with
phanyl)hexahelicenes have been employed by Reetz[8,9] as electrophiles.[3,12] We have also reported that, by using the
ligands for transition metals in enantioselective homogen- appropriate number of equivalents (2 or 4 equiv.) of nBuLi
eous catalysis. In particular, a Rh complex with the M en- and electrophile, selective mono- or difunctionalization can
antiomer has been used as catalyst in the asymmetric hydro- be achieved. Following this general procedure, and using
genation of itaconic ester (ee 39%).[8] However, the organo- 4 equiv. of nBuLi and 4 equiv. of the electrophile, we syn-
metallic catalyst was not characterized. The P enantiomer thesized the diphosphane derivatives 2a (thiaheliphos) from
of the same helical phosphane has been employed as a chi- 1a, 2b (nPr-thiaheliphos) from 1b and 2c (di-nPr-thiaheli-
ral ligand to form a structurally undefined Pd allyl complex phos) from 1c in good yields (Scheme 1). All of the reac-
(probably not chelated) employed in Pd-catalyzed allylic tions reported in Scheme 1 were completed in five hours.
substitution (ee 99%).[9] In contrast to carbohelicenes, het- The new helical phosphanes 2a–c were isolated as yellow
erohelicenes have been much less considered as potential solids and completely characterized by analytical and spec-
chiral ligands in catalysis. Only recently, Soai, in collabora- troscopic methods. Alkyl chains in the 7- and 8-positions
tion with some of us, has used simply substituted enantio- of the helical system improve the solubility of helicenes in
merically pure 1a and 1c as chiral inducers in the autocata- organic solvents, but also render the phosphorus atoms of
lytic “Soai reaction”,[2a] and so far, no tetrathiahelicene- substituted thiaheliphos more electron rich and therefore
based phosphanes have been reported as potential ligands more prone to air oxidation. As a consequence, the trans-
for catalysis or other applications, despite the fact that achi- formation of phosphanes 2b and 2c into the corresponding
ral monodentate ligands based on the first three rings of phosphane oxide derivatives by air was easy and, in the case
chelating tetrathiahelicene-based phosphanes have been of 2c, it occurred during the purification procedure.
shown to have interesting properties.[10]
For these reasons, we decided to examine the possibility
of temporary protection of the phosphorus atoms, by the
formation of a phosphane–borane adduct. This is a well
known methodology to protect phosphanes from oxi-
dation,[13] which can be easily carried out by reacting the
commercially available toluene solution of BH3/dimethyl
sulfide or the tetrahydrofuran (THF) solution of the
BH3·THF adduct with the free phosphane. In principle,
BH3 adducts can be kept for long time. A further advantage
of this procedure is the easy deprotection to restore the free
phosphane, which is generally accomplished by the use of
protic acids[14] or, more conveniently, by reaction with etha-
nol with heating to reflux.[15] In practice, when 1c (1 equiv.)
Scheme 1. (a) nBuLi (4 equiv.), Ph2PCl (4 equiv.), dry THF, –78 °C
to room temp., 5 h; yield of 2a: 78%; yield of 2b: 84%; yield of 2c:
96%.
As already mentioned, the tetrathiahelicene backbone ex- was treated with nBuLi (2 equiv.) and chlorodiphenylphos-
hibits several points of interest such as chiroptical proper- phane (2 equiv.) at –78 °C followed by the addition of the
ties, easy and regioselective functionalization of terminal BH3·THF complex (10 equiv.), a mixture of di- and mono-
thiophene rings, which can be controlled and driven to af- borane adducts 3 and 4 arose from diphosphane 2c, and
ford mono- or disubstituted derivatives, and the possibility monophosphane 5 was observed in the crude reaction mix-
of modulating the electron density at the phosphorus atom ture. Chromatographic purification furnished the diborane
through appropriate substitutions in the 7- and 8-positions adduct 3 in 49% yield and the monoborane adduct 4 in
of the central benzene ring. Last but not least, the phospho- 39%, together with some unreacted helicene 1c (about 10%,
rus atom can be the core of a wide variety of other phos- Scheme 2).
phorus-based ligands, extending the scope of this chemistry
Two general methods have been reported for the recovery
from phosphanes to, for example, phosphane oxides and of free phosphanes from the corresponding borane adducts.
phosphonic acids,[11] potentially useful for organic and or- The first method requires the treatment of the adduct with
ganometallic catalysis. In this paper, we describe the synthe- strong acids,[14] such as MeSO3H, CF3SO3H or
sis and characterization of phosphanes 2a–c derived from HBF4·Me2O, followed by neutralization with NaHCO3 or
1a–c, as well as an initial study demonstrating the use of 2c K2CO3. The second method uses amines to displace the
as a chiral ligand for organometallic catalysis. In addition, boron atom, and is based on the equilibrium established
we also report the synthesis and X-ray characterization of between phosphane–borane and amine–borane adducts.[16]
the new 7-TH-based diphosphonate 17.
More recently, the use of alcohols with heating to deprotect
5650
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 5649–5658

Helical Chiral Ligands for Catalysis
(CF3)2C6H3]4.The ligand exchange reaction between equi-
molar amounts of 2c and 6 or 7 was carried out in dichloro-
methane at room temperature under an argon atmosphere
for two hours (Scheme 4).
Scheme 2. (a) nBuLi (2 equiv.), Ph2PCl (2 equiv.), dry THF, –78 °C
to room temp., 5 h; (b) BH3·THF (1 m in THF, 10 equiv.), 0 °C,
overnight; yield of 3: 49%; yield of 4: 39%; (c) EtOH, THF, reflux,
3 h.
Scheme 4. (a) Compound 6 (1 equiv.), dry CH2Cl2, room temp.,
2 h, yield of 8: Ͼ 99%; (b) Compound 7 (1 equiv.), dry CH2Cl2,
room temp., 2 h, yield of 9: Ͼ 99%.
Evaporation of the solvent afforded orange solids 8 and
9 in quantitative yields, and the complexes were completely
characterized analytically and spectroscopically. In particu-
lar, 31P NMR spectra of 8 and 9 show only one resonance
signal in each case, split into a clearly resolved doublet at
22.8 ppm, resulting from the coupling of phosphorus with
103Rh. As expected,[17] 31P NMR signals of the complexed
phosphanes 8 and 9 occur at significantly lower fields
(22.8 ppm) than that of ligand 2c (–15 ppm). The shift to
lower field of both phosphorus resonances, and the pres-
borane–phosphorus adducts under neutral conditions has
been described.[15] This is a very convenient and mild pro-
cedure and was examined with the borane–monophosphane
4, which was easily and quantitatively deprotected by treat-
ment with a mixture of EtOH and THF with heating to
reflux for 3 h affording the free monophosphane 5 in quan-
titative yield (Scheme 2).
Based on these encouraging results, an efficient one-pot
procedure was developed to obtain the borane complex 3
directly from 1c, thus avoiding the isolation of the free
phosphane 2c. This was performed by reaction of 1c with
nBuLi (4 equiv.) at –78 °C followed by the addition of
Ph2PCl (4 equiv.), and then, after 5 h, quenching the reac-
tion mixture containing 2c with an excess of BH3·THF
(10 equiv.) at 0 °C (Scheme 3).
1
ence of a JP,Rh coupling (144 Hz), suggest that coordina-
tion of 2c to the rhodium centre occurs through the two
phosphanyl phosphorus groups, affording the symmetrical
structures shown in Scheme 4. The presence of the chelated
di-nPr-thiaheliphos-(1,5-cyclooctadiene)rhodium(I) cation
in 8 and 9 was also confirmed by HRMS (ESI).
We also observed that the NMR sample of 8 in CDCl3,
after exposure to air for 24 h, underwent a complete trans-
formation into an oxidized species. Analytical and spectro-
scopic data are in agreement with the formation of the
phosphane–phosphane oxide RhI complex 10 (Figure 1).
Scheme 3. (a) nBuLi (4 equiv.), Ph2PCl (4 equiv.), dry THF, –78 °C
to room temp., 5 h; (b) BH3·THF (1 m in THF, 10 equiv.), 0 °C,
overnight; yield: 73%.
In this manner, the borane adduct 3 was isolated, with-
out any particular precautions, as a yellow, air-stable solid
in 73% yield. Using the same mild deprotection procedure,
we easily converted 3, in quantitative yield, to the corre-
sponding free-phosphane 2c, by heating to reflux in a mix-
ture of EtOH and THF for 3 h under a nitrogen atmo-
sphere.
Figure 1. Phosphane–phosphane oxide RhI complexes 10 and 11.
In fact, the 31P NMR spectrum of 10 shows a broad sing-
let at 23.3 ppm, due to the phosphoryl group, and a sharp
These results provide a general and reliable synthetic pro- doublet at 20.9 ppm (1JP,Rh = 145 Hz), due to 103Rh cou-
cedure to prepare the new 7-TH phosphanes 2a–c, allowing pling with the phosphanyl phosphorus atom. In this case,
us to address the next step, which was to explore the pos- the chelating coordination to the rhodium centre may occur
sibility of using them as new phosphorus-based ligands for through the oxygen donor of the phosphoryl group and the
transition metals, with a view to their application in asym- phosphanyl phosphorus atom. It should also be noted that
metric catalysis. We first made two rhodium complexes. For the absence of coupling between rhodium and the phos-
this purpose, we selected 2c, which is very soluble in most phoryl phosphorus, is in agreement with a previous obser-
organic solvents, and two commercially available rhodium vation reported for Rh–BINAPO complexes.[18] The HRMS
complexes [Rh(COD)2]BF4 (6) and [Rh(COD)2]BARF (7), (ESI) confirms the presence of the cationic species of 10.
where COD is cycloocta-1,5-diene and BARF is B[3,5- Complex 9 appears somewhat more stable than 8 as it
Eur. J. Org. Chem. 2011, 5649–5658
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5651

A. Forni, E. Licandro, et al.
FULL PAPER
shows only traces of the monooxidation product 11 (Fig- Table 1. Geometrical parameters [Å and °] of 2c, 8 and 10 from
B3LYP/SVP calculations in the gas phase.[a]
ure 1) after 24 h when exposed to air in an NMR tube un-
der the same conditions described for 8, and the complete
conversion of 9 into 11 was observed after three weeks. It
is noteworthy that the oxidation of 8 and 9 is faster if air is
2c
8
10
C2–C13
Dihedral A/AЈ
4.435
50.2
3.784
37.3
3.948
41.8
bubbled into the CDCl3 solution of Rh complexes. In fact, Dihedral A/B(AЈ/BЈ) 9.0 (9.0)
2.0 (3.8)
7.3 (7.4)
11.5 (11.2)
2.194
5.6 (4.3)
8.3 (7.8)
11.0(11.2)
2.126
Dihedral B/C(BЈ/CЈ) 9.7 (9.7)
in the case of more stable 9, the bubbling of air resulted in
a 1:1 ratio of 9 and 11 after 3 h. Analytical and spectro-
Dihedral C/D(CЈ/DЈ) 11.5 (11.5)
[b]
Rh–CCOD
–
scopic data for 11 are consistent with a phosphane–phos-
phane oxide RhI complex, as the 31P NMR spectrum of 11
is very similar to that of 10 and the HRMS confirms the
molecular weight. This type of phosphane–phosphane ox-
ide RhI complex has been reported and behaves as a hemil-
abile ligand, where the two phosphorus atoms exhibit dif-
ferent donor properties toward the central metal.[19] In con-
clusion, the behaviour of 8 and 9 seems to indicate an in-
trinsic low stability to air, leading to a new, stable phos-
phane–phosphane oxide RhI complex with a defined struc-
ture.
2.251
2.237
2.280
2.425
2.492
97.5
2.155
2.200
2.258
2.426
2.187
94.2
Rh–P/O[c]
–
–
P–Rh–P/O[d]
[a] Compounds 8 and 10 without counterions. Least-squares planes
through the heavy atoms of the tetrathiahelicene rings were used
to compute the dihedral angles. [b] Rh–C distances between the
metal and the four-coordinated carbon atoms of COD. [c] Rh–P
distances for 8 and Rh–P and Rh–O distances for 10. [d] P–Rh–P
angle for 8 and P–Rh–O angle for 10.
The knowledge of the molecular parameters of the thia-
heliphos derivatives described above and/or their Rh com-
plexes would be interesting. However, until now, we have
been unable to obtain single crystals suitable for X-ray
analysis, even using the bulky BARF counterion in the case
of 9.
Consequently, we decided to perform theoretical calcula-
tions on 2c and its Rh complexes 8 and 10 (without coun-
terions) in order to predict their geometrical features, as
Figure 2. Nomenclature of fused rings.
well as to assess the stability of the complexes. Preliminary in the crystal structure of the racemic tetrathiahelicene[23]
work in the gas phase at a semiempirical level was per- [8.6(1)–11.3(1)° and 48.6(1)°, respectively]. The computed
formed because of the reliable results found in the literature C2–C13 distance for 2c (4.435 Å) is only slightly greater
for simulations on fused oligothiophenes.[20] The method than that observed in racemic tetrathiahelicene
was validated by comparison with PM6[21] calculated struc- (4.171 Å),[23] indicating a minor influence of the phenyl-
tures for diethylphosphonate hexahelicene 15 (vide infra) phosphane groups on the distortion of the 7-TH skeleton.
and [Rh(COD)(THP)2]+ with known X-ray data[22] and was As expected, both the C2–C13 distance and all the dihedral
applied successfully to 2a–c. However, when we moved on angles (except those between the inner rings C/D and CЈ/
to the structure of 8, we were unable to locate a stable mini- DЈ) decrease significantly on going from 2c to 8 (see
mum.
Table 1), as a consequence of the constraint imposed by co-
We significantly enhanced the level of theory of our cal- ordination to the metal atom.[24] Such constraint is partially
culations by resorting to DFT methods. Geometry optimi- released in 10, which may contribute to the observed ease
zations of 2c, 8 and 10 were carried out in the gas phase of transformation of 8 into the oxidized species.
at the B3LYP/SVP level, using the relativistic effective core
In 8 and 10, the Rh–C distances range from 2.125–
potential for Rh. In all cases, geometry optimizations led 2.280 Å and are on average shorter in 10 than 8 thanks to
to energy minima, which were verified by frequency calcula- the greater electron-donor capability of the phosphane ox-
tions at the B3LYP/3-21G level. Table 1 lists selected geo- ide than the phosphane group. The Rh–P bond lengths
metrical parameters of 2c and its Rh complexes. A plot of (2.425–2.492 Å), the P–Rh–P bite angle (97.5° in 8) and
the optimized structures is reported in Figure 3. A relevant that of P–Rh–O (94.2° in 10) are comparable. Owing to
geometrical feature of the 7-TH derivatives is the significant the lack of X-ray structures of analogous thiaheliphos Rh
deviation of the π-conjugated system from planarity. Such complexes in the literature, the coordination geometry of
a deviation can be quantified by the distance between the the metal atom has been compared with that of structures
carbon atoms in the 2- and 13-positions, which should containing the Rh(PPh2)2(COD) fragment by a survey of
nearly overlap in a hypothetical all-planar structure, or by the Cambridge Structural Database (Version 5.31, Novem-
the dihedral angles between adjacent fused rings and be- ber 2009).[25] Only complexes where the P atoms are part of
tween the terminal thiophene rings (see Figure 2 for no- a common cyclic structure were included in the search. For
menclature of fused rings).
the 56 retrieved fragments, the Rh–C and Rh–P distances
The values of such dihedral angles computed for 2c range were found in the range 2.11–2.35 and 2.24–2.36 Å, respec-
from 9.0–11.5° for the adjacent rings and is equal to 50.2° tively (average values are 2.25 and 2.30 Å, respectively), and
for the terminal thiophene rings, resembling those observed the P–Rh–P bite angle was found in the range 74–95°
5652
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 5649–5658

Helical Chiral Ligands for Catalysis
(average value of 89°). Although all the computed Rh–C two transitions in the simulated spectrum. Both transitions
distances fall into the corresponding experimental range, undergo a further redshift, which is more pronounced for
the Rh–P distances are significantly larger than the experi- the HOMOǞLUMO transition (from 402 in 2c to 425 nm
mental values, and the computed bite angles are in the up- in 8). Also in this case the computed trend reproduces that
per limit of the experimental range. However, these appar- seen experimentally in CH2Cl2, where a redshift of the low-
ent discrepancies are perfectly justified in view of the fact energy band is observed (from 405 in 2c to 413 nm in 8, see
that, in all cases, the retrieved structures contained much Supporting Information).
less constrained cyclic structures connecting the phospho-
rus atoms compared with the ligand considered here. The
strong tension that such a ligand undergoes within the com-
plex can be partially relaxed by increasing the Rh–P dis-
Hydrogenation Reactions
Rhodium complexes are typically active in the hydrogen-
ation of C=C double bonds. These reactions have repre-
sented the bench test for a vast number of phosphane-based
catalysts, many of which have been successful. It was of
interest to us to check if the new tetrathiahelicene-based Rh
complexes described above had catalytic activity in hydro-
genation reactions. In particular, it is valuable to compare
the catalytic activity of 8, containing the enantiomerically
pure ligand 2c, with that of other Rh complexes based on
the carbohelicene phosphane reported by Reetz.[8] In order
to obtain enantiomerically pure 2c, and owing to the low
stability of 2c, we first resolved 1c into its enantiomers
using HPLC with a chiral stationary phase (Chiralpak IA)
and hexane/dichloromethane (19:1, v/v) as the mobile
phase. The enantiomer with right-handed helicity (P config-
uration), [α]D = +685 (c = 0.187, 20 °C, CHCl3, 98.9% ee),
has a shorter retention time, and the enantiomer with left-
handed (M configuration), [α]D = –678 (c = 0.180, 20 °C,
CHCl3, 94.9% ee), has a longer retention time.[2a] It is com-
monly accepted from theoretical and experimental evidence,
that (+)-helicenes and (+)-heterohelicenes correspond to the
tances and the bite angle.
The optimized geometries of 2c and 8 have been used to
compute the UV spectra in CH2Cl2 by the time dependent
(TD)-DFT approach at the B3LYP/SVP level of theory. The
properties of the more significant transitions are reported
in Table 2 and Figure 3. The computed spectrum of 2c re-
sembles that previously reported for 1c obtained in CHCl3
at the TD-DFT/B3LYP/6-311G* level,[26] which differs
from 2c by lacking both the phosphane groups and, less
importantly, the n-propyl substituents. The two almost de-
generate transitions of 1c (389 and 385 nm)[26] undergo a
slight redshift in 2c (403 and 402 nm), which can be as-
cribed to the introduction of the two PPh2 groups in the
tetrathiahelicene moiety. These correspond to HOMO-
1ǞLUMO transitions. This trend nicely reproduces the ex-
perimentally observed redshift of the low-energy excitation
in CH2Cl2 on going from 1c (387 nm) to 2c (405 nm, see
Supporting Information). In 8, the presence of the metal
atom determines the breaking of the quasidegeneracy of the
Table 2. Computed vertical excitation energies, λ [nm], correspond-
ing oscillator strengths, f, and major contributions to the transition absolute configuration of a right-handed helix (P configu-
ration).[2b]
(weight in parenthesis) of 2c and 8 in CH2Cl2 at the B3LYP/SVP
level of theory.
Next, using the standard procedure shown in Scheme 1,
λ
f
Major contribution[a]
(P)-(+)-1c was transformed into the optically pure diphos-
phane (P)-(+)-2c, [α]D = +2344, (c 0.058, 20 °C, CH2Cl2),
which exhibited the CD spectrum shown in Figure 4.
2c
403
402
357
335
0.209
0.241
0.137
0.296
HOMO-1ǞLUMO (0.68)
HOMOǞLUMO (0.67)
HOMO-2ǞLUMO (0.68)
HOMO-4ǞLUMO (0.36)
HOMO-1ǞLUMO+1 (0.50)
HOMOǞLUMO (0.68)
HOMO-1ǞLUMO (0.67)
8
425
409
0.158
0.243
[a] Compound 2c: HOMO and HOMO-1 are localized on 7-TH
and the P atoms, HOMO-2 and HOMO-4 extend over 7-TH and
the phosphane groups, the LUMO is localized almost exclusively
on 7-TH and LUMO+1 extends over 7-TH and the phosphane
groups; Compound 8: HOMO and HOMO-1 are localized on 7-
TH and Rh and the LUMO is localized almost exclusively on 7-
TH.
Figure 4. CD spectrum of (P)-(+)-2c in CH2Cl2 (4.52ϫ10–5 m).
To check the enantiopurity of (P)-(+)-2c, it was trans-
formed into the corresponding phosphane oxide 12 by oxi-
dation with 35% hydrogen peroxide in dichloromethane
solution (Scheme 5).
Figure 3. Optimized B3LYP/SVP structures of 2c (left), 8 (centre)
and 10 (right). Hydrogen atoms are omitted for clarity. An enlarged
version of this image is presented in the Supporting Information.
Eur. J. Org. Chem. 2011, 5649–5658
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5653

A. Forni, E. Licandro, et al.
FULL PAPER
–78 °C. After 5.5 h of reaction, we isolated the diphos-
phonate 17 in 77% yield (Scheme 7).
Scheme 5. (a) H2O2 35%, CH2Cl2, 0 °C, 1.5 h, then room temp.,
1.5 h, yield: Ͼ98%.
Scheme 7. Synthesis of 17.
Comparison of the HPLC trace of 12, obtained from (P)-
(+)-2c, with that of a racemic sample, confirmed that the
enantiopurity was at a level similar to that of the starting
helicene (+)-1c [Chiralpack IA column (10ϫ 250 mm), elu-
ent: iPrOH/CH2Cl2/MeOH, 52.5:30:17.5].
The optically active phosphane (P)-(+)-2c was then used
for the preparation of the corresponding optically active Rh
catalyst, by reacting (P)-(+)-2c with 6 in dichloromethane
at room temperature as reported in Scheme 4. In this way
we obtained catalyst (P)-8 in quantitative yield.
The structure of 17 was fully elucidated by X-ray diffrac-
tion methods, using crystals obtained from a CH2Cl2/pent-
ane solution. An ORTEP view of the molecule is reported
in Figure 5 together with the atomic labelling scheme. Se-
lected bond lengths and angles are collected in the caption.
Compound 17 crystallizes in a centrosymmetric space
group, and both enantiomers are present in the crystals.
The C–C outer core bond lengths of 17 are shorter and
those of the C–C inner core are longer than the normal
value of 1.39 Å, in common with similar compounds,[4,27]
implying a lower π character for the inner core C–C bonds
and a higher π character for those of the outer core (i.e.
there is higher π electron density along the periphery of the
molecule). All seven of the fused rings show distortion from
planarity, and the dihedral angles between adjacent rings
increase passing from the “external” thiophene rings to the
“central” benzene ring of the helicene. These features are
in full agreement with those typically observed in similar
helicene compounds.
We then carried out a small series of catalytic hydrogena-
tions of dimethyl 2-methylenesuccinate (13, Scheme 6) and
methyl 2-acetamidoacrylate (14, Table 3).
Scheme 6. Asymmetric hydrogenation reaction of 13.
Table 3. Asymmetric hydrogenation reactions of 14.
Substrate concentration [m] Time [h] Conversion [%][a] ee [%][b]
0.29
0.57
5
24
67
32
quantitative
40[c]
[a] Determined by 1H NMR spectroscopy. [b] Determined by chiral
GC (MEGADEX DACTBSβ column). [c] In a separate experiment
with a shorter reaction time (9 h), a lower ee (22%) was observed,
indicating that the efficiency of asymmetric induction improves as
the reaction progresses.
Both reactions were performed using a substrate/catalyst
ratio of 500:1 in CH2Cl2 at room temperature in an auto-
clave with a back pressure of 5 bar of H2. Scheme 6 and
Table 3 report the conditions and the results of the hydro-
genation tests. Using (P)-8 as the catalyst, the hydrogena-
tion of 13 and 14 preferentially gave the S enantiomer of
the reduced product.
Figure 5. ORTEP view of 17 with the atomic numbering scheme
ellipsoids are drawn at 30% probability. Selected bond lengths [Å]:
C1–C2 1.365(3), C1–P1 1.775(3), C3–C4 1.425(3), C4–C5 1.457(3),
C5–C6 1.420(3), C6–C7 1.463(3), C7–C8 1.427(3), C8–C9 1.423(3),
C10–P2 1.776(2), C12–C13 1.360(4), C16–C17 1.361(5), C20–C21
1.365(4).
The functionalization of the tetrathiahelicenes described
here offers an important general procedure. To illustrate
this point, we used the same methodology described above
for the synthesis of 2a–c to obtain the diphosphonate 17,
Conclusions
In this paper we have shown that the tetrathiahelicenes
by reacting the dianion, generated from 1a with nBuLi 1a–c can easily and regioselectively be functionalized with
(4 equiv.), with chlorodiethylphosphonate (4 equiv.) at phosphane and phosphonate groups in the alpha positions
5654
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 5649–5658

Helical Chiral Ligands for Catalysis
1H NMR (200 MHz, CDCl3): δ = 6.90 (d, JH,P = 3.0 Hz, 2 H), 7.17
(m, 20 H), 7.80 (d, J = 8.7 Hz, 2 H), 7.84 (d, J = 8.7 Hz, 2 H), 7.93
(s, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 119.0 (CH), 120.2
(CH), 121.3 (CH), 128.3 (CH), 128.4 (CH), 128.5 (CH), 128.9
(CH), 129.9 (Cq), 130.4 (Cq), 132.9 (CH), 133.1 (CH), 133.2 (CH),
133.4 (CH), 136.1 (Cq), 136.3 (Cq), 136.4 (CH), 136.5 (Cq), 136.7
(Cq), 136.9 (Cq), 137.0 (Cq), 137.6 (Cq) ppm. 31P NMR (121 MHz,
CDCl3): δ = –15.5 (s) ppm. UV/Vis (CH2Cl2): λ = 230, 304, 321,
402 nm. MS (EI): m/z = 770 [M]+, 429, 400, 242, 215, 199, 183, 108.
HRMS (EI): calcd. for C46H28P2S4 [M]+ 770.0549; found 770.0582.
of the terminal thiophene rings. The phosphane derivatives
2a–c have been completely characterized and 2c was used
to obtain the rhodium(I) complexes 8 and 9, which have
been isolated and characterized. The efficiency of such cata-
lysts in the asymmetric hydrogenation of itaconic acid and
N-acyl-dehydroalanine is comparable with that achieved by
Reetz with carbohelicene phosphanes. The thiaheliphos-
based ligands described here are members of a much larger
class of structures in which the phosphorus atom can be the
core of many alternative phosphorus-based ligands, dif-
ferent from phosphanes, such as phosphane oxides and
phosphonic acids. These can easily be prepared by the syn-
thetic procedures described here, and are potentially useful
for organic and organometallic catalysis.
nPr-Thiaheliphos 2b: A solution of nBuLi (1.57 m in hexane,
0.32 mL, 0.504 mmol, 4 equiv.) was added dropwise to a stirring
solution of 1b (56.0 mg, 0.126 mmol) in dry THF (6 mL) at –78 °C
under an argon atmosphere. The solution was stirred for 30 min at
–78 °C. The resulting yellow suspension was treated with Ph2PCl
(0.090 mL, 0.504 mmol, 4 equiv.), at –78 °C and the progress of the
reaction was monitored by TLC (hexane/toluene, 7:3). After 3 h at
–78 °C, the yellow solution was warmed to room temperature and
quenched by addition of silica gel (300 mg). THF was removed
under reduced pressure and the crude material was purified by flash
chromatography on silica gel (hexane/toluene, 7:3) to give 2b as a
yellow solid (86.2 mg, 84%). 1H NMR (200 MHz, CDCl3): δ = 1.12
(t, J = 7.3 Hz, 3 H), 1.96 (m, 2 H), 3.06 (t, J = 7.5 Hz, 2 H), 6.98
(d, JH,P = 3.0 Hz, 2 H), 7.21 (m, 20 H), 7.80 (s, 2 H), 7.85 (m, 2
H), 7.87 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.6
(CH3), 23.0 (CH2), 37.4 (CH2), 119.5 (CH), 121.4 (CH), 121.7
(CH), 125.7 (CH), 128.9 (CH), 129.3 (CH), 130.2 (Cq), 131.0 (Cq),
131.4 (Cq), 133.6 (CH), 133.9 (CH), 135.0 (Cq), 136.6 (Cq), 137.5
(Cq), 138.6 (Cq), 138.8 (CH), 139.3 (Cq), 139.7 (Cq), 139.9 (Cq),
141.6 (Cq) ppm. 31P NMR (121 MHz, CDCl3): δ = –15.5 (s) ppm.
UV/Vis (CH2Cl2): λ = 232, 294, 326, 346, 384, 404 nm. MS (EI):
m/z = 812 [M]+, 783, 506, 471, 442, 413. HRMS (EI): calcd. for
C49H34P2S4 [M]+ 812.1018; found 812.0995.
Experimental Section
General: Reagents obtained from commercial sources were used
without further purification. Rh(COD)2BF4 (6) and Rh(COD)2-
BARF (7) were purchased from Aldrich and used without further
purification. Before use, butyllithium solutions were titrated. Anhy-
drous THF and CH2Cl2 were purchased from Aldrich and purged
with argon or nitrogen prior to use. Tetrathia[7]helicenes 1a,[27]
1b[28] and 1c[29] were prepared according to the literature. To moni-
tor the progress of the reactions, TLC was performed with Merck
silica gel 60 F254 precoated plates. Flash chromatography was per-
formed with Merck silica gel 60, 230–400 mesh. Melting points
were determined with a Büchi 510 apparatus. 1H NMR and 13C
NMR were recorded with Bruker AC200, Bruker AC300 or Bruker
AMX-300 spectrometers with chemical shifts reported relative to
residual deuterated solvent peaks. 31P NMR were recorded with
Bruker AC300 or Bruker AMX-300 spectrometers and the experi-
ments were referenced to 85% H3PO4. The IR spectra were re-
corded with a Perkin–Elmer FT-IR 1725X. UV spectra were re-
corded with a Perkin–Elmer Lambda E2 210 spectrophotometer.
HRMS were recorded with a Vg Analytical 7070 EQ spectrometer.
An Agilent 1100 series HPLC, equipped with DAD analyzer and
a chiral stationary phase (Chiralpack IA), was used to resolve (Ϯ)-
1c and (Ϯ)-12. The conversions and the ees reported in Scheme 6
and Table 3 were determined with a DANI GC1000, equipped with
a flame ionization detector, using hydrogen as the carrier and two
types of chiral capillary column: a GAMMA DEX 225 (diameter:
0.25 mm; length: 30 m) and a MEGADEX DACTBSβ (diameter:
0.25 mm; length: 30 m). Unless otherwise stated, all of the opera-
tions were performed under an argon or nitrogen atmosphere in
flame-dried glassware.
Di-nPr-thiaheliphos 2c: A solution of nBuLi (1.40 m in hexane,
0.59 mL, 0.825 mmol, 4 equiv.) was added dropwise to a stirring
solution of 1c (100.4 mg, 0.206 mmol) in dry THF (10 mL) at
–78 °C under an argon atmosphere. The solution was stirred for
30 min at –78 °C. The resulting yellow suspension was treated with
Ph2PCl (0.150 mL, 0.825 mmol, 4 equiv.) at –78 °C, and the pro-
gress of the reaction was monitored by TLC (hexane/CH2Cl2, 7:3).
After 3 h at –78 °C, the yellow solution was warmed to room tem-
perature and THF was removed under reduced pressure. The crude
material was purified by flash chromatography on silica gel under
a nitrogen atmosphere using a degassed mixture of hexane/CH2Cl2
(7:3) as eluent to give 2c as a yellow solid (168.6 mg, 96%). 1H
NMR (300 MHz, CDCl3): δ = 1.14 (t, J = 7.3 Hz, 6 H), 1.85 (m,
4 H), 3.10 (m, 4 H), 6.89 (d, JH,P = 5.7 Hz, 2 H), 7.17 (m, 20 H),
7.81 (d, J = 8.5 Hz, 2 H), 7.85 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.7 (CH3), 23.2 (CH2), 34.3 (CH2), 119.0
(CH), 120.8 (CH), 128.1 (Cq), 128.4 (CH), 128.5 (CH), 128.8 (CH),
129.0 (CH), 131.1 (Cq), 132.2 (Cq), 133.1 (CH), 133.4 (CH), 135.9
(Cq), 136.2 (Cq), 137.1 (Cq), 139.7 (Cq), 140.5 (Cq), 141.2 (Cq) ppm.
31P NMR (121 MHz, CDCl3): δ = –15.6 (s) ppm. HRMS (EI):
calcd. for C52H40P2S4 [M]+ 854.1488; found 854.1478.
Thiaheliphos 2a: A solution of nBuLi (1.48 m in hexane, 0.23 mL,
0.345 mmol, 4 equiv.) was added dropwise to a stirring solution of
1a (34.7 mg, 0.0862 mmol) in dry THF (6 mL) at –78 °C under an
argon atmosphere. The solution was stirred for 30 min at –78 °C.
The resulting yellow suspension was treated with Ph2PCl
(0.061 mL, 0.345 mmol, 4 equiv.) at –78 °C, and the progress of the
reaction was monitored by TLC (hexane/toluene, 7:3). After 1.5 h
at –78 °C, the yellow solution was warmed to room temperature
and quenched by addition of silica gel (300 mg). THF was removed
under reduced pressure and the crude material was purified by flash
chromatography on silica gel (hexane/toluene, 7:3) to give 2a as a
yellow solid (51.8 mg, 78%); m.p. 151–155 °C (CH2Cl2/pentane).
Diborane Adduct 3 of Di-nPr-thiaheliphos: A solution of nBuLi
(1.6 m in hexane, 1.54 mL, 2.464 mmol, 4 equiv.) was added drop-
wise to a stirring solution of 1c (300 mg, 0.616 mmol) in dry THF
(15 mL) at –78 °C under an argon atmosphere. The solution was
stirred for 30 min at –78 °C. The resulting yellow suspension was
treated with Ph2PCl (0.442 mL, 2.464 mmol, 4 equiv.) at –78 °C,
and the progress of the reaction was monitored by TLC (hexane/
CH2Cl2, 5:5). After 5 h at –78 °C, the yellow solution was warmed
Eur. J. Org. Chem. 2011, 5649–5658
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5655

A. Forni, E. Licandro, et al.
FULL PAPER
to 0 °C and treated with a solution of BH3·THF (1 m in THF,
6 mL, 6 mmol, 10 equiv.) under an argon atmosphere. The yellow
suspension was stirred for 30 min at 0 °C then warmed to room
temperature. After 16 h at room temperature, the suspension was
diluted with THF and slowly added to a saturated aqueous solu-
tion of NH4Cl (30 mL) at 0 °C. THF was removed under reduced
pressure, the crude material was taken up with CH2Cl2 (10 mL)
and the aqueous phase was extracted into CH2Cl2 (3ϫ 10 mL).
The organic phase was dried with Na2SO4, concentrated under re-
duced pressure and the residue was purified by flash chromatog-
raphy on silica gel (hexane/CH2Cl2, 5:5) to give 3 as a pale yellow
solid (396 mg, 73%); m.p. 177–179 °C. 1H NMR (300 MHz,
CDCl3): δ = 1.14 (t, J = 7.2 Hz, 6 H), 1.83 (m, 4 H), 3.05 (m, 4
H), 7.29 (m, 22 H), 7.87 (d, J = 8.4 Hz, 2 H), 7.94 (d, J = 8.4 Hz,
2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.7 (CH3), 23.2
(CH2), 34.3 (CH2), 120.6 (CH), 121.2 (CH), 127.7 (Cq), 128.6 (CH),
128.8 (CH), 129.0 (Cq), 129.2 (Cq), 129.4 (Cq), 129.8 (Cq), 131.2 (2
C, CH), 131.5 (Cq), 132.5 (CH), 132.7 (CH), 135.3 (CH), 136.6
(Cq), 140.2 (Cq), 142.4 (Cq) ppm. 31P NMR (121 MHz, CDCl3): δ
3 h, the yellow solution was cooled to room temperature and the
solvents and the byproduct triethyl borate were removed under re-
duced pressure at 50 °C to afford, without further purification, 2c
(48 mg, 0.057 mmol, 99%) as a yellow solid. The spectral properties
of this compound were in agreement with those of a sample of 2c
prepared according to the reaction illustrated in Scheme 1.
Deprotection of Phosphane–Borane Adduct 4: A suspension of 4
(30 mg, 0.043 mmol) in a mixture of EtOH/THF (7:4) (15 mL) was
stirred and heated to reflux (the suspension became a yellow solu-
tion when hot) under an argon atmosphere, and the progress of the
reaction was monitored by 31P NMR analysis. After 3 h, the yellow
solution was cooled to room temperature and the solvents and the
byproduct triethyl borate were removed under reduced pressure at
50 °C to afford, without further purification, 5 (29 mg, 0.043 mmol,
99%) as a pale yellow solid. 1H NMR (300 MHz, CDCl3): δ = 1.15
(t, J = 7.3 Hz, 6 H), 1.85 (m, 4 H), 3.12 (m, 4 H), 6.81 (d, J =
5.7 Hz, 1 H), 6.97 (d, J = 5.7 Hz, 1 H), 7.22 (m, 12 H), 7.94 (m, 4
H) ppm. 31P NMR (121 MHz, CDCl3): δ = –15.9 (br. s) ppm.
HRMS (EI): calcd. for C40H31PS4 [M]+ 670.10463; found
670.10419.
= 15.1 (br. s) ppm. IR (neat): ν = 2957, 2927, 2858, 2374 (BH ),
˜
3
2331 (BH3), 1740, 1464, 1435, 1158 cm–1. MS (FAB+): m/z (%) =
882 (93) [M]+, 867 (52) [M – BH3]+, 854 (100) [M – 2 BH3]+.
HRMS (ESI): calcd. for C52H46P2S4B2Na [M + Na]+ 903.21005;
found 903.20980.
Rh Complex 8: To a solution of 2c (11.7 mg, 0.0133 mmol, 1 equiv.)
in dry, degassed CH2Cl2 (1.5 mL) was added
6 (5.4 mg,
0.0133 mmol, 1 equiv.) under an argon atmosphere. The resulting
orange solution was stirred at room temperature for 2 h before the
solvent was removed under reduced pressure to afford, without fur-
ther purification, 8 (15.0 mg, 0.0133 mmol, 99%) as an orange so-
lid. 31P NMR (121 MHz, CDCl3): δ = 21.9 (d, JRh,P = 145 Hz)
ppm. HRMS (ESI): calcd. for C60H52P2S4Rh [M]+ (monoisotopic)
1065.14766; found 1065.14644.
Monoborane Adduct 4 of Di-nPr-thiaheliphos: A solution of nBuLi
(1.5 m in hexane, 0.885 mL, 1.327 mmol, 2 equiv.) was added drop-
wise to a stirring solution of 1c (323 mg, 0.664 mmol) in dry THF
(10 mL) at –78 °C under an argon atmosphere. The solution was
stirred for 30 min at –78 °C. The resulting yellow suspension was
treated with Ph2PCl (0.238 mL, 1.327 mmol, 2 equiv.) at –78 °C,
and the progress of the reaction was monitored by TLC (hexane/
CH2Cl2, 7:3). After 5 h at –78 °C, the yellow solution was warmed
to 0 °C and treated with a solution of BH3·THF (1 m in THF,
6.7 mL, 6.7 mmol, 10 equiv.) under an argon atmosphere. The yel-
low suspension was stirred for 30 min at 0 °C then warmed to room
temperature. After 16 h at room temperature, the suspension was
diluted with THF and slowly added to a saturated aqueous NH4Cl
solution (20 mL) at 0 °C. THF was removed under reduced pres-
sure, the crude material was taken up with CH2Cl2 (10 mL) and
the aqueous phase was extracted into CH2Cl2 (3 ϫ 10 mL). The
organic phase was dried with Na2SO4 and concentrated under re-
duced pressure. The crude product was purified by flash
chromatography on silica gel (with a gradient from hexane/CH2Cl2,
7:3 to 5:5) to give 4 as a pale yellow solid (180 mg, 39%) and 3 as
a yellow solid (286 mg, 49%); m.p. 250 (dec.). 1H NMR (300 MHz,
CDCl3): δ = 1.14 (t, J = 7.2 Hz, 6 H), 1.83 (m, 4 H), 3.05 (m, 4
H), 6.79 (d, J = 5.5 Hz, 1 H), 6.99 (d, J = 5.5 Hz, 1 H), 7.19 (d,
JH,P = 7.8 Hz, 1 H), 7.34 (m, 10 H), 7.90 (m, 2 H), 7.94 (d, J =
8.5 Hz, 1 H), 8.01 (d, J = 8.5 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.7 (CH3), 23.2 (CH2), 34.3 (CH2), 119.4 (CH), 120.9
(CH), 121.2 (CH), 121.9 (CH), 125.1 (CH), 125.7 (CH), 128.2 (Cq),
129.1 (CH), 129.2 (CH), 129.5 (Cq), 130.1 (Cq), 131.8 (2 C, CH),
132.6 (Cq), 133.2 (CH), 133.4 (CH), 133.5 (Cq), 135.8 (Cq), 136.2
(CH), 136.4 (Cq), 136.8 (Cq), 137.0 (Cq), 137.8 (Cq), 140.0 (Cq),
142.3 (Cq) ppm. 31P NMR (121 MHz, CDCl3): δ = 15.3 (br. s) ppm.
Rh Complex 9: To a solution of 2c (54.6 mg, 0.064 mmol, 1 equiv.)
in dry, degassed CH2Cl2 (10 mL) was added 7 (75 mg, 0.064 mmol,
1 equiv.) under an argon atmosphere. The resulting orange solution
was stirred at room temperature for 2 h before the solvent was re-
moved under reduced pressure to afford, without further purifica-
tion, 9 (123 mg, 0.064 mmol, 99%) as an orange solid. 1H NMR
(300 MHz, CDCl3): δ = 1.19 (t, J = 7.2 Hz, 6 H), 1.86 (m, 4 H),
2.09 (m, 2 H), 2.38 (m, 4 H), 2.75 (m, 2 H), 3.17 (m, 4 H), 4.45
(m, 2 H), 4.72 (m, 2 H), 7.26 (m, 2 H), 7.53 (m, 22 H), 7.80 (m, 12
H), 7.96 (d, J = 8.5 Hz, 2 H) ppm. 31P NMR (121 MHz, CDCl3):
δ = 22.8 (d, JRh,P = 145 Hz) ppm. IR (neat): ν = 1610, 1436, 1353,
˜
1270, 1105 cm–1. HRMS (ESI): calcd. for C60H52P2S4Rh [M]+
(monoisotopic) 1065.14766; found 1065.14524.
Racemic Phosphane Oxide 12: A solution of H2O2 (0.5 mL, 35%)
was added dropwise to a solution of (Ϯ)-2c (50.0 mg, 0.058 mmol)
in CH2Cl2 (2 mL) at 0 °C. The mixture was stirred for 1 h at 0 °C,
1 h at room temperature and added to water (4 mL). The aqueous
phase was extracted into CH2Cl2 (2ϫ 4 mL) and the organic phase
was dried with Na2SO4 and concentrated under reduced pressure
to afford, without further purification, 12 (49.7 mg, 0.056 mmol,
96%) as a yellow solid; m.p. 140–143 °C. 1H NMR (300 MHz,
CDCl3): δ = 1.14 (t, J = 6.0 Hz, 6 H), 1.83 (m, 4 H), 3.07 (m, 4
H), 6.98 (d, JP,H = 9.0 Hz, 2 H), 7.37 (m, 20 H), 7.86 (m, 4 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 14.7 (CH3), 23.2 (CH2),
34.3 (CH2), 120.9 (CH), 121.3 (CH), 127.5 (Cq), 128.4 (CH), 128.9
(CH), 131.2 (CH), 131.5 (Cq), 131.7 (CH), 132.3 (CH), 132.7 (Cq),
133.7 (CH), 133.9 (CH), 135.2 (Cq), 136.6 (Cq), 136.7 (Cq), 140.2
(Cq), 140.3 (Cq), 141.7 (Cq) ppm. 31P NMR (121 MHz, CDCl3): δ
= 24.0 (s) ppm. UV/Vis (CH2Cl2): λ = 230, 251, 293, 323, 335, 387,
IR (neat): ν = 2957, 2925, 2866, 2390 (BH ), 2336 (BH ), 2307
˜
3
3
(BH3), 1738, 1435, 1159 cm–1. MS (FAB+): m/z (%) = 684 (62)
[M]+, 670 (100) [M
–
BH3]+. HRMS (ESI): calcd. for
C40H34PS4BNa [M + Na]+ 706.13025; found 706.13039.
Deprotection of Phosphane–Borane Adduct 3: A solution of 3
(50 mg, 0.057 mmol) in a mixture of EtOH/THF (2:1) (5 mL) was
stirred and heated to reflux under an argon atmosphere, and the
progress of the reaction was monitored by 31P NMR analysis. After
406 nm. IR (CHCl ): ν = 1214 cm–1 (P=O) cm–1. MS (ESI): m/z
˜
3
887 [M + 1]. HRMS (ESI): calcd. for C52H46P2S4B2Na [M +
Na]+ 909.12786; found 909.12637.
5656
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 5649–5658

Helical Chiral Ligands for Catalysis
(P)-(+)-Phosphane Oxide (12): Compound (P)-(+)-12 was obtained
in 98% yield by oxidation of phosphane (P)-(+)-2c by the same
procedure described to prepare racemic phosphane oxide 12. The
spectral properties of this compound were in agreement with those
of racemic 12.
Table 4. Crystal data for 17.
Formula
FW
Crystal system
Space group
C30H30O7P2S4
692.72
triclinic
¯
P1
a [Å]
b [Å]
c [Å]
α [°]
15.262(5)
11.819(4)
10.608(4)
62.502(3)
85.197(5)
74.320(4)
1632.3(10)
2
1.409
720
0.11ϫ0.10ϫ0.08
4.34
General Procedure for Hydrogenation of Dimethyl 2-Methylenesuc-
cinate (13): A Parr multireactor was employed, allowing up to six
reactions in parallel under hydrogen. To a solution of 13 (181.9 mg,
1.15 mmol) in CH2Cl2 (7 mL) was added a solution of (P)-8
(2.6 mg, 0.0023 mmol) in CH2Cl2 (1 mL) under an argon atmo-
sphere. The vessels were placed in the respective autoclaves and
purged three times with hydrogen at 5 bar. The reaction was stirred
for 24 h at room temperature under hydrogen and then analysed
by chiral GC for conversion and ee determination (see Scheme 6).
β [°]
γ [°]
V [Å3]
Z
Dcalcd. [gcm–3]
F(000)
Crystal size [mm]
μ [cm–1]
General Procedure for Hydrogenation of Methyl 2-Acetamido-
acrylate (14): A Parr multireactor was employed. To a solution of
14 (326.4 mg, 2.28 mmol) in CH2Cl2 (3 mL) was added a solution
of (P)-8 (5.2 mg, 0.0046 mmol) in CH2Cl2 (1 mL) under an argon
atmosphere. The vessels were placed in the respective autoclaves
and purged three times with hydrogen at 5 bar pressure. The reac-
tions were stirred for the time indicated in Table 3 at room tempera-
Reflections collected
Reflections unique
Reflections observed [IϾ2σ(I)]
Parameters
R indices [IϾ2σ(I)]
R indices (all data)
9521
9503 (Rint = 0.0076)
6590
418
R1 = 0.0553, wR2 = 0.1513[a]
R1 = 0.0825, wR2 = 0.1675[a]
[a] R1 = Σ||Fo| – |Fc||/Σ|Fo|; wR2 = (Σ[w(Fo – Fc ) ]/Σ[w(Fo2)2])1/2
.
2
2 2
1
ture under hydrogen and then analysed by H NMR spectroscopy
for conversion and by chiral GC for ee determination.
Diphosphonate 17: A solution of nBuLi (1.27 m in hexane, 0.39 mL,
0.500 mmol, 4 equiv.) was added dropwise to a stirring solution of
1a (49.7 mg, 0.124 mmol) in dry THF (3.5 mL) at –78 °C under a
nitrogen atmosphere. The solution was stirred for 45 min at –78 °C.
The resulting yellow suspension was treated with ClOP(OEt)2
(0.075 mL, 0.500 mmol, 4 equiv.) at –78 °C, and the progress of the
reaction was monitored by TLC (hexane/AcOEt, 1:4). After 3.5 h
at –78 °C, the yellow solution was warmed to room temperature,
quenched with saturated aqueous NH4Cl solution (3 mL) and di-
luted with water (5 mL). The aqueous phase was extracted into
CH2Cl2 (3ϫ 5 mL) and the organic phase was washed with H2O
(2ϫ 15 mL), dried with Na2SO4 and concentrated under reduced
pressure. The crude product was purified by flash chromatography
on silica gel (with a gradient from hexane/CH2Cl2, 7:3 to hexane/
AcOEt 1:4) to give 17 as a yellow solid (64.7 mg, 78%); m.p. 151–
CCDC-815740 (for 17) contain 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.
Computational Details: Preliminary calculations were performed at
PM6 semiempirical level (MOPAC2009 package)[21,31] on 2a and
2c, as well as on the cationic moiety of 8. The structures of 2a
and 2c were easily optimized with the EF routine and were fully
characterized as minima.
More accurate calculations were performed at the DFT level on 2c,
8 and 10, considering for the latter cases only the cationic moieties.
Geometries were optimized in the gas phase using the Becke three
parameter hybrid functional[32] with the nonlocal correlation given
by the Lee–Yang–Parr[33] expression (B3LYP), and the SVP split
valence basis set with polarization functions on all atoms.[34] Rh
was treated as a 17-electron system, with relativistic effective core
potentials taken from the literature.[35] The energy minimum was
verified by harmonic vibrational frequency calculations, using a
smaller basis set (3-21G) owing to the dimensions of the investi-
gated systems.
1
161 °C (CH2Cl2/pentane). H NMR (300 MHz, CDCl3): δ = 1.19
(t, J = 7.0 Hz, 6 H), 1.20 (t, J = 7.0 Hz, 6 H), 3.80 (m, 8 H), 7.31
(d, JH,P = 9.3 Hz, 2 H), 8.05 (s, 2 H), 8.05 (d, J = 8.7 Hz, 2 H),
8.08 (d, J = 8.7 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
16.1 (m, CH3), 62.6 (m, CH2), 120.7 (s, CH), 121.1 (s, CH), 121.4
(s, CH), 127.0 (d, 1JC,P = 206.4 Hz, Cq), 129.4 (s, Cq), 131.1 (s, Cq),
134.1 (d, 2JC,P = 12.0 Hz, CH), 135.1 (d, 3JC,P = 18.7 Hz, Cq), 137.6
3
(s, Cq), 138.1 (s, Cq), 141.0 (d, JC,P = 7.5 Hz, Cq) ppm. 31P NMR
(121 MHz, CDCl3): δ = 11.6 (s) ppm. MS (ESI): m/z = 697 [M +
Na]+. HRMS (EI): calcd. for C30H28O6P2S4 [M]+ 674.024403;
found 674.024110.
The UV/Vis spectra of 2c and 8 were computed with the TD-DFT
approach[36] at the B3LYP/SVP level of theory. Such calculations
were performed by taking into account the solvent effects through
the conductor-like polarizable continuum model[37] using the struc-
ture optimized in the gas phase. CH2Cl2 was considered as the sol-
vent. Only transitions covering the spectral region up to 330 nm
with non-negligible oscillator strengths, f, i.e. transitions with
f Ͼ 0.1, are reported.
X-ray Data Collection, Structure Solution and Refinement for 17:
The intensity data were collected at room temperature with a
PHILIPS PW 1100 single crystal diffractometer using a graphite
monochromated Mo-Kα radiation, λ = 0.71073 Å. Crystallographic
and experimental details are summarized in Table 4. The structure
was solved by direct methods and refined by full-matrix least-
squares procedures (based on Fo2) (SHELX-97)[30] first with iso-
tropic thermal parameters and then with anisotropic thermal pa-
rameters in the last cycles of refinement for all the non-hydrogen
atoms. Disorder was found in one of the two ethyl chains of the
two phosphonate moieties. The hydrogen atoms were introduced
into the geometrically calculated positions and refined riding on
the corresponding parent atoms.
All DFT and TD-DFT calculations were performed with the
Gaussian 09 code.[38]
Supporting Information (see footnote on the first page of this arti-
cle): UV/Vis absorption spectra of compounds 2c and 8 in CH2Cl2;
enlargement of details of Figure 3 (optimized B3LYP/SVP struc-
tures of compounds 2c, 8 and 10).
Eur. J. Org. Chem. 2011, 5649–5658
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5657

A. Forni, E. Licandro, et al.
FULL PAPER
[16]
[17]
[18]
F. Langer, P. Knochel, Tetrahedron Lett. 1995, 36, 4591–4594.
D. G. Dick, D. W. Stephan, Can. J. Chem. 1986, 64, 1870–1875.
V. V. Grushin, Chem. Rev. 2004, 104, 1629–1662, and references
cited therein.
It is known that transition metal complexes of phosphanes are
particularly stable with the BARF counterion: see B. Wüsten-
berg, A. Pfaltz, Adv. Synth. Catal. 2008, 350, 174–178.
K. Oyaizu, T. Iwasaki, Y. Tsukahara, R. Tsuchida, Macromole-
cules 2004, 37, 1257–1270.
Acknowledgments
This work was supported by the Ministero dell’Università e della
Ricerca (MIUR) and the University of Milan, PRIN 2007 (prot.
2007XFA27F_004), PUR 2008. A. F. acknowledges CASPUR for
computational resources within the project “Standard HPC Grant
2010”. G. R. S. acknowledges Engineering and Physical Sciences
Research Council (EPSRC) for support (grant number EH/
C009922).
[19]
[20]
[21]
[22]
J. P. P. Stewart, J. Mol. Model. 2007, 13, 1173–1213.
F. Lorenzini, B. O. Patrick, B. R. James, Dalton Trans. 2007,
3224–3226.
[23]
[24]
H. Nakagawa, A. Obata, K. Yamada, H. Kawazura, M.
Konno, H. Miyamae, J. Chem. Soc. Perkin Trans. 2 1985, 1899–
1903.
Interestingly, in the PM6-calculated structure of 2c the C2–C13
distance was 3.773 Å, which is significantly shorter than in the
B3LYP/SVP structure and extremely similar to that adopted by
the thiahelicene unit in 8. The fact that no minima for the
cationic moiety of 8 was located at PM3 level cannot be due
to the strain imposed by complexation with 2c.
F. H. Allen, Acta Crystallogr., Sect. B 2002, 58, 380–388.
A. Bossi, E. Licandro, S. Maiorana, C. Rigamonti, S. Righetto,
G. R. Stephenson, M. Spassova, E. Botek, B. Champagne, J.
Phys. Chem. C 2008, 112, 7900–7907.
a) H. Wynberg, Acc. Chem. Res. 1971, 4, 65–73; b) L.
Lehmann, H. Wynberg, Recueil Trav. Chim. Pays-Bas 1971, 90,
1113–1118; c) H. Wynberg, M. B. Groen, H. Shadenberg, J.
Org. Chem. 1971, 36, 2797–2809; see also ref.[3]
C. Baldoli, A. Bossi, C. Giannini, E. Licandro, S. Maiorana,
D. Perdicchia, Synlett 2005, 7, 1137–1141.
E. Licandro, C. Rigamonti, M. T. Ticozzelli, M. Monteforte,
C. Baldoli, C. Giannini, S. Maiorana, Synthesis 2006, 21, 3670–
3678.
M. Sheldrick, SHELXL-97, Program for crystal structure re-
finement, University of Göttingen, Germany, 1997.
J. P. P. Stewart, Stewart Computational Chemistry, Colorado
Springs, CO, USA, http://openmopac.net (2008).
A. D. Becke, J. Chem. Phys. 1993, 98, 5648–5652.
C. Lee, W. Yang, G. G. Parr, Phys. Rev. B: Condens. Matter
1988, 37, 785–789.
[1] a) L. M. Haupert, G. J. Simpson, Annu. Rev. Phys. Chem. 2009,
60, 345–65; b) L. D. Barron, Molecular Light Scattering and
Optical Activity, Cambridge Univ. Press, Cambridge (1982); c)
J. Zyss, D. S. Chemla, Nonlinear Optical Properties of Organic
Molecules and Crystals (Eds.: D. S. Chemla, J. Zyss), Academic
Press, Orlando, FL (1987); d) for chiral polymers, see: J. J.
Maki, M. Kauranen, A. Persoons, Phys. Rev. B 1995, 51, 1425–
1434; for chiral media, see: D. M. Walba, D. J. Dyer, X. H.
Chen, U. Muller, P. Cobben, R. F. Shao, N. A. Clark, Mol.
Cryst. Liq. Cryst. Sci. Technol. 1996, 288, 83–91; Y. Luo, M.
Lindgren, H. Agren, Opt. Mater. 1998, 9, 216–219.
[2] a) T. Kawasaki, K. Suzuki, E. Licandro, A. Bossi, S. Maiorana,
K. Soai, Tetrahedron: Asymmetry 2006, 17, 2050–2053; b)
M. B. Groen, H. Wynberg, J. Am. Chem. Soc. 1971, 93, 2968–
2974.
[3] S. Maiorana, A. Papagni, E. Licandro, R. Annunziata, P. Para-
vidino, D. Perdicchia, C. Giannini, M. Bencini, K. Clays, A.
Persoons, Tetrahedron 2003, 59, 6481–6488.
[25]
[26]
[27]
[28]
[29]
[4] A. Bossi, S. Maiorana, C. Graiff, A. Tiripicchio, E. Licandro,
Eur. J. Org. Chem. 2007, 4499–4509.
[5] a) N. J. De Stefano, D. K. Johnson, L. M. Venanzi, Angew.
Chem. 1974, 86, 133; b) N. J. De Stefano, D. K. Johnson, L. M.
Venanzi, Helv. Chim. Acta 1976, 59, 2683–2690.
[30]
[31]
ˇ
ˇ
[6] a) F. Teplý, I. G. Stará, I. Starý, A. Kollárovicˇ, D. Saman, S.
Vyskocˇil, P. Fiedler, J. Org. Chem. 2003, 68, 5193–5997; b) R.
El Abed, F. Aloui, J.-P. Genêt, B. Ben Hassine, A. Marinetti,
J. Organomet. Chem. 2007, 692, 1156–1160; c) F. Aloui, R.
El Abed, A. Marinetti, B. Ben Hassine, Tetrahedron Lett. 2007,
48, 2017–2020; d) F. Aloui, B. Ben Hassine, Tetrahedron Lett.
2009, 50, 4321–4323; e) F. Aloui, S. Moussa, B. Ben Hassine,
Tetrahedron Lett. 2011, 52, 572–575.
[32]
[33]
[34]
[35]
[36]
F. Weigend, R. Ahlrichs, Phys. Chem. Chem. Phys. 2005, 7,
3297–3305.
D. Andrae, U. Häussermann, M. Dolg, H. Stoll, H. Preuss,
Theor. Chim. Acta 1990, 77, 123–141.
M. E. Casida, C. Jamorski, K. C. Casida, D. R. Salahub, J.
Chem. Phys. 1998, 108, 4439–4449.
[7] a) A. Terfort, H. Görls, H. Brunner, Synthesis 1997, 79–86; b)
K. Paruch, L. Vyklický, D. Z. Wang, T. J. Katz, C. Incarvito,
L. Zakharov, A. L. Rheingold, J. Org. Chem. 2003, 68, 8539–
5844.
[8] M. T. Reetz, E. W. Beuttenmüller, R. Goddard, Tetrahedron
Lett. 1997, 38, 3211–3214.
[9] M. T. Reetz, S. Sostmann, J. Organomet. Chem. 2000, 603, 105–
109.
[10] M. H. Garcia, P. Florindo, M. Fátima, M. Piedade, M. T. Du-
arte, Polyhedron 2009, 28, 239–244.
[11] For examples of related chiral phosphites, see: a) D. J. Weix,
S. D. Dreher, T. J. Katz, J. Am. Chem. Soc. 2000, 122, 10027–
10032; b) D. Nakano, M. Yamaguchi, Tetrahedron Lett. 2003,
44, 4969–4971; c) D. Z. Wang, T. J. Katz, J. Org. Chem. 2005,
70, 8497–8502.
[12] C. Rigamonti, M. T. Ticozzelli, A. Bossi, E. Licandro, C. Gian-
nini, S. Maiorana, Heterocycles 2008, 76, 1439–1470.
[13] M. Ohff, J. Holz, M. Quirmbach, A. Börner, Synthesis 1998,
1391–1415.
[14] a) L. McKinstry, T. Livinghouse, Tetrahedron Lett. 1994, 35,
9319–9322; b) L. McKinstry, T. Livinghouse, Tetrahedron 1994,
50, 6145–6154.
[15] M. Van Overschelde, E. Vervecken, S. G. Modha, S. Cogen, E.
Van der Eycken, J. Van der Eycken, Tetrahedron 2009, 65,
6410–6415.
[37]
[38]
V. Barone, M. Cossi, J. Phys. Chem. A 1998, 102, 1995–2001.
M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B.
Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li,
H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Son-
nenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hase-
gawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai,
T. Vreven, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M.
Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Starov-
erov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell,
J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M.
Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Ad-
amo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev,
A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Mar-
tin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador,
J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B.
Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian 09,
revision A.2, Gaussian, Inc., Wallingford CT, 2000.
Received: May 24, 2011
Published Online: September 1, 2011
5658
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 5649–5658