Synthesis of some C2-symmetric bidentate ligands and their complexes derived from Feist's acid

Article abstract of DOI:10.1002/hlca.201100305

Various new C₂-symmetric bidentate ligands, bearing phosphorus, nitrogen, and sulfur, were obtained in an efficient manner, starting from (±)-trans-3-methylidenecyclopropane-1,2-dicarboxylic acid (Feist's acid; (±)-trans-3). The structures of the new bidentate ligands, di(tert-butyl) (±)-[(trans-3-methylidenecyclopropane-1,2-diyl)dimethanediyl] biscarbamate ((±)-9), (±)-(trans-3-methyldienecyclopropane-1,2- diyl)dimethanaminium dichloride ((±)-10), (±)-S,S′-[(trans- 3-methylidenecyclopropane-1,2-diyl)dimethanediyl] diethanethioate ((±)-11), and (±)-[(trans-3-methylidenecyclopropane-1,2-diyl) dimethanediyl]bis(diphenylphosphane) ((±)-12), were fully characterized by standard spectroscopic techniques. These new classes of C₂- symmetric bidentate ligands have the potential to be used in asymmetric catalysis. Copyright

Full text of DOI:10.1002/hlca.201100305

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Helvetica Chimica Acta – Vol. 95 (2012)
Synthesis of Some C2-Symmetric Bidentate Ligands and Their Complexes
Derived from Feistꢀs Acid
by Abdullah M. A. Al-Majid*, Zeid A. Al-Othman, and Mohammad Shahidul Islam
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451,
Kingdom of Saudi Arabia
(phone: þ 9661-4675889; fax: þ 9661-4675992; e-mail: amajid@ksu.edu.sa)
Various new C2-symmetric bidentate ligands, bearing phosphorus, nitrogen, and sulfur, were
obtained in an efficient manner, starting from (ꢀ)-trans-3-methylidenecyclopropane-1,2-dicarboxylic
acid (Feistꢀs acid; (ꢀ)-trans-3). The structures of the new bidentate ligands, di(tert-butyl) (ꢀ)-[(trans-3-
methylidenecyclopropane-1,2-diyl)dimethanediyl]biscarbamate ((ꢀ)-9), (ꢀ)-(trans-3-methyldienecyclo-
propane-1,2-diyl)dimethanaminium dichloride ((ꢀ)-10), (ꢀ)-S,S’-[(trans-3-methylidenecyclopropane-
1,2-diyl)dimethanediyl] diethanethioate ((ꢀ)-11), and (ꢀ)-[(trans-3-methylidenecyclopropane-1,2-diyl)-
dimethanediyl]bis(diphenylphosphane) ((ꢀ)-12), were fully characterized by standard spectroscopic
techniques. These new classes of C2-symmetric bidentate ligands have the potential to be used in
asymmetric catalysis.
Introduction. – The development of novel and efficient C2-symmetric ligands for
the synthesis of various catalysts is one of the most challenging goals in modern organic
chemistry [1]. As the use of ligandꢁmetal catalysts is incrementally increasing in
organic synthesis [2 – 4], it is important to synthesize appropriate ligands with metal-
binding capacity to form metal catalysts. In this search, diamine, diphosphine, and
dithiol derivatives have attracted specific attention due to their wide range of
applications [3 – 6]. These C2 symmetric ligands are highly capable of binding with
various transition metals, such as Ti, Cu, Ni, Zr, Ru, Rh, and Pd, to form metal catalysts
of varying potentials and properties [5][7 – 16]. These ligandꢁmetal components have
been widely used in many asymmetric catalyses, such as alkylation, DielsꢁAlder
reactions, hydrogenation reactions, etc. [4 – 6][8][10][15][17]. Furthermore, these
asymmetric ligands are also useful as catalysts in the addition of organozinc reagents to
carbonyl compounds [8][18]. The Ti, Zr, and Hf complexes of these bidentate ligands
were also found to be quite useful for the polymerization of alkenes [19 – 24]. In
addition, these bidentate ligands can be used for the formation of metallocene
complexes, which have been employed to catalyze a wide range of enantioselective
reactions, including epoxidation, aziridination, sulfoxidation, as well as the Michael
addition reaction [25 – 29]. In brief, both the P- and N-based ligands have broadened
the scope of the new ligand architecture in transition metal catalysis [30].
During this study, we focussed on the synthesis and characterization of new classes
of C2 symmetric bidentate ligands, containing N-, S- and P- donor atoms, and some Ti-
based metal complexes which can be used as catalysts for co-polymerization and
polymerization of ethenes [31]. Basically, the heteroatoms are responsible of the strong
ꢁ 2012 Verlag Helvetica Chimica Acta AG, Zꢂrich

Helvetica Chimica Acta – Vol. 95 (2012)
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chelation with transition metals. Interestingly, these ligands can be derived directly
from the well-known (ꢀ)-trans-3-methylidenecyclopropane-1,2-dicarboxylic acid
(Feistꢀs acid; 3). The synthesis of 3 is shown in Scheme 1.
Scheme 1
i) Dry HCl (g), 16 d, in a dark place. ii) Br2, CHCl3, 24 h, r.t. iii) 7m KOH, 1058, 1 h.
Results and Discussion. – (ꢀ)-trans-3-Methylidenecyclopropane-1,2-dicarboxylic
acid ((ꢀ)-3) is the precursor of newly synthesized C2 symmetric bidentate ligands in our
work. Feistꢀs acid is commercially available, but expensive. We therefore prepared this
acid in house, starting from cheap and readily available ethyl acetoacetate by using a
procedure described by Goss, Ingold, and Thorpe [32]. The original method has been
slightly modified, as described in the experimental section. Pyrone 1 was obtained as a
slightly yellow colored liquid in 65% yield by purging freshly prepared dry HCl through
neat ethyl acetoacetate for 16 d. Pyrone 1 was then treated with Br2 in CHCl3 to form
the colorless and crystalline bromopyrone 2 in 85% yield. Feistꢀs acid ((ꢀ)-3) was
obtained by the reaction of bromopyrone 2 with concentrated aqueous KOH in a good
yield (68%), as crystalline product (Scheme 1). All analytical data of compounds 1 – 3
were in agreement with those previously reported in the literature [32]. Racemic Feistꢀs
acid is the key precursor in our synthesis of new diphosphine, diamine, and dithiolate
ligands, and their complexes. Thus, (ꢀ)-trans-(3-methylidenecyclopropane-1,2-diyl)di-
methanol ((ꢀ)-5) was readily prepared according to the method of Al-Majid et al. [33]
in two steps, as depicted in Scheme 2. The new ligands, i.e., the dicarbamate (ꢀ)-9 and
the diammonium salt (ꢀ)-10, were synthesized in good yields in six and seven steps,
respectively, starting from (ꢀ)-3, as shown in Scheme 2.
The dithiolate and diphosphine ligands 11 and 12, respectively, were obtained in
good yields from intermediate (ꢀ)-6 in a single step, as shown in Scheme 3.
The titanium complexes (ꢀ)-13 and (ꢀ)-14 were synthesized by treating ligands
(ꢀ)-5 and (ꢀ)-10, respectively, with TiCl4 solution in CH2Cl2 in rather good yields, as
shown in Scheme 4.
Esterification of (ꢀ)-3 gave dimethyl ester (ꢀ)-4 in 88% yield (1H-NMR (CDCl3):
d(H) 3.68 (2 Me)). Compound 4 was then reduced by LiAlH4 at 08 in dry THF under an
1
inert atmosphere to afford diol (ꢀ)-5 in 93% yield, which showed, in the H-NMR
spectrum, a characteristic multiplet at d(H) 3.30 – 3.38 for the two CH2 groups. Another
characteristic triplet signal at d(H) 4.61 was assigned to the two OH H-atoms.
The diol (ꢀ)-5 was protected with methanesulfonyl chloride in the presence of Et3N
in CH2Cl2 under dry conditions to obtain the corresponding bis[methanesulfonate] (ꢀ)-
6 in excellent yield (92%). The formation of (ꢀ)-6 was confirmed by means of
1
1H-NMR and IR spectroscopy. In the H-NMR spectrum, a new singlet could be
observed at d(H) 3.02 for the two mesylate groups, and the OH signal of (ꢀ)-5 at d(H)

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 2
i) MeOH, H2SO4 (cat.), 408, 24 h. ii) THF, LiAlH4 (2.0 equiv.), 08 to r.t., 4 h. iii) MesCl (3.0 equiv.),
Et3N (3.0 equiv.), CH2Cl2, 08, 1.5 h. iv) DMF, NaN3 (9.2 equiv.), 608, 4 h. v) 5% Pd on CaCO3 (10 wt-%),
EtOH, H2 pressure, r.t., 24 h. vi) DIPA (2.5 equiv.), (Boc)2O (3.0 equiv.), EtOH, r.t., 2 h. vii) Dioxane/
HCl, r.t., 3 h.
Scheme 3
i) AcSK (2.5 equiv.), MeCN, reflux, 3 h. ii) Dry THF, ꢁ 158, Ph2PLi (0.5m in THF; 6 equiv.), 2 d.
4.61 disappeared. In the IR spectrum, two sharp bands were observed at 1344 and
1173 cmꢁ1 due to the asymmetric and symmetric stretching of the SO2 groups. Having
the bismesylate (ꢀ)-6 in hand prompted us to study its utility for the synthesis of novel
C2-symmetric bidentate ligands. Therefore, it was used as the key intermediate for the
synthesis of several ligands such as 9 – 12, as described in Schemes 2 and 3, respectively.
For synthesis of the diazido compound (ꢀ)-7, (ꢀ)-6 was treated with an excess
amount of NaN3 (9.2 equiv.) due to the low nucleophility of Nꢁ3 at 608 in dry DMF for
4 h. The product was isolated in a yield of 73%. The formation of (ꢀ)-7 was confirmed
by the 1H-NMR and IR spectra. The 1H-NMR spectrum showed the absence of the Me
groups of (ꢀ)-6. Furthermore, the IR spectrum showed a sharp band at 2091 cmꢁ1,
representing the asymmetric stretching vibration of the N¼N¼N group.

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Scheme 4
i) TiCl4 (1m in CH2Cl2; 0.5 equiv.), 24 h. ii) CH2Cl2, NaHCO3. iii) TiCl4 (1m in CH2Cl2; 0.5 equiv.), 24 h.
A new dicarbamate derivative, di(tert-butyl) (ꢀ)-[(trans-3-methylidenecyclopro-
pane-1,2-diyl)dimethanediyl]dicarbamate ((ꢀ)-9) was synthesized in good yield (66%).
Thus, the diamine 8 was obtained by reduction of 7 using 10 wt-% of 5% Pd on CaCO3
poisoned with lead (Lindlar catalyst) in EtOH. The free amine is unstable to air,
therefore it was immediately protected with di-tert-butyl dicarbonate to obtain the Boc-
1
protected amine (ꢀ)-9. The overall yield in two steps was 65%. In the H-NMR
spectrum, a broad signal at d(H) 4.8 and a sharp signal at d(H) 1.45 appeared, which
were assigned to H-atoms of the NH and t-Bu groups, respectively. The IR spectrum
showed bands at 3331 and 1688 cmꢁ1, assigned to NꢁH and ꢁHNꢁC¼O stretching
vibrations, respectively. The bisammonium salt (ꢀ)-10 was then obtained in 85% yield
as a white solid by treating (ꢀ)-9 with a HCl/dioxane mixture. The formation of (ꢀ)-10
1
was inferred from the H-NMR spectrum, where the signal of the H-atoms of the
aminium groups appeared at d(H) 8.36. In the IR spectrum, bands at 3424 and
3029 cmꢁ1 were observed due to the stretching vibrations of the NHþ3 group. It is
important to note that also the dithiolate ligand (ꢀ)-11 could be prepared in excellent
yield (94%) from (ꢀ)-6 and AcSK under reflux conditions in MeCN, as shown in
1
Scheme 3. In the H-NMR spectra of compound (ꢀ)-11, a new singlet at d(H) 2.33
appeared due to the thioacetate group. The IR spectra showed a band at 1691 cmꢁ1
assigned to the C¼O stretching vibration of thioester group (SꢁC¼O). Consequently,
the diphosphine ligand (ꢀ)-12 was obtained in the same manner by the reaction of (ꢀ)-
6 with 3 equiv. of lithium diphenylphosphanide (Ph2PLi) using dry THF as solvent at
low temperature (ꢁ208), as depicted in Scheme 3. Even after 24 h, the reaction remained
incomplete, probably due to decomposition of the Li reactant. This decomposition may
be attributed to the highly hygroscopic nature of Ph2PLi. To improve the yield of the
reaction, 3 equiv. of Ph2PLi were further added, under dry conditions and the reaction
was continued for additional 24 h. The desired product (ꢀ)-12 was then obtained as
viscous liquid in good yield (87%). The formation of the product was confirmed by
1H-NMR spectroscopy, where the H-atoms of the two Ph groups appeared as a
multiplet at d(H) 7.34 – 7.37. The up-field shift of the signal of the CH2 H-atoms (PCH2)
at d(H) 1.36 – 1.55 can be attributed to the decreased electronegativity of the P-atom
compared to S, while further splitting of the signal of the CH2 H-atoms is due to

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coupling with 31P. The formation of ligand (ꢀ)-12 was further confirmed by the 31P-
NMR spectrum, which showed a signal at d(P) ꢁ 16.72, which was assigned to the 31
P
isotope of phosphorous.
The Ti complex (ꢀ)-13 was prepared in moderate yield by treating one equiv. of the
ligand (ꢀ)-5 with 0.5 equiv. of TiCl4 under dry conditions with CH2Cl2 as a solvent
(Scheme 4). The proposed composition for the Ti-complex (ꢀ)-13 is based on
1
1
microanalysis, H- and 13C-NMR studies, and MS data. The H-NMR spectrum of
complex (ꢀ)-13 showed absence of the OH signal at d(H) 4.61, indicating that the
complex (ꢀ)-13 was really formed. Furthermore, complex (ꢀ)-13 was also confirmed
by elemental analysis. Crystallization of complex (ꢀ)-13 was not succesful due to its
highly moisture sensitivity.
Complex (ꢀ)-14 was synthesized by the reaction of ligand (ꢀ)-10 with 0.5 equiv. of
TiCl4 solution in dry CH2Cl2. Since the free amine is not stable in air, the reaction has
been carried out under dry conditions in Ar atmosphere. The HCl salt of ligand (ꢀ)-10
was neutralized with saturated NaHCO3 solution, and the free amine was then
extracted with CH2Cl2. The free amine solution was immediately added to the TiCl4
solution at 08. Complex (ꢀ)-14 was obtained as a brown solid and confirmed by
1
1H-NMR and IR spectra, as well as elemental analysis. In the H-NMR spectrum, the
intergral of the signal of the amino-H-atoms was counted only for four H-atoms,
compared to eight in the free ligand (ꢀ)-10. In the IR spectrum, only one NH band was
observed at 3332 cmꢁ1 as a strong, broad stretching vibration.
Conclusions. – In conclusion, a series of new N-, S-, and P-bearing C2 symmetrical
ligands were synthesized. All these ligands were derived from (ꢀ)-trans-3-methylidene-
cyclopropane-1,2-dicarboxylic acid (Feistꢀs acid; 3) which served as the key precursor.
The complexation of these ligands in their optical active form with different metals can
lead to potential catalysts for various asymmetric inductions such as alkylation,
hydrogenation, DielsꢁAlder reaction, polymerization, isomerization, etc. This will be
investigated in near future. Our current studies were focused on the development of
novel classes of chiral C2 symmetrical bidentate, or tetradentate ligands, based on
Feistꢀs acid with bulky environment. The activity of these ligands in the asymmetric
induction will be studied, and we plan to report these results in due course.
Experimental Part
General. All the moisture- and air- sensitive reactions were carried out under an inert atmosphere
using an Ar filled glove box and standard Schlenk-line techniques. All the chemicals were purchased from
Aldrich, SigmaꢁAldrich, and Fluka, etc., and were used without further purification, unless otherwise
stated. Pyridine, Et3N, and DIPA were distilled over NaOH. Et2O and THF were distilled over Na/
benzophenone. Hexane, heptanes, and pentane were distilled over Na/triglyme/benzophenone. CHCl3,
CH2Cl2, benzene, toluene, and DMF were dried over CaH2. Deuterated solvents were dried over CaH2
and deoxygenated prior to use. Flash column chromatography (FC): silica gel (SiO2; 100 – 200 mesh). IR
1
Spectra: in KBr; FT-IR-800 spectrophotometer; n in cmꢁ1. H-, 13C-, and 31P-NMR spectra: Geol 400
spectrometer at 400 MHz (1H), 100.6 MHz (13C), and 121.5 MHz (31P); in CDCl3 or (D6)DMSO; d in
ppm rel. to Me4Si as internal standard, J in Hz; d in ppm (for 31P-NMR rel. to an 85% H3PO4 external
reference); the NMR spectra of all the intermediates, ligands, and complexes were recorded at ambient
temp. unless otherwise stated. HR-ESI-MS: Mass-ESI-POS (AGILENT Technologies 6410ꢁtriple quad

Helvetica Chimica Acta – Vol. 95 (2012)
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LC/MS instrument) spectrometer; in m/z. Elemental analyses: Perkin-Elmer 2400 Elemental Analyzer;
CHN mode.
Ethyl 4,6-Dimethyl-2-oxo-2H-pyran-5-carboxylate (1). In a threeneck 2 l round bottom flask, ethyl
acetoacetate (¼ethyl 3-oxobutanoate; 486.4 g, 3.74 mol) was treated with dry HCl gas for a period of 8 h
at ꢁ 158 to 08 using an ice salt bath (HCl gas was freshly prepared by dropwise addition of 35% HCl to
conc. H2SO4). The mixture was tightly closed and kept in a dark place for 8 d. The color turned into dark
reddish. The above procedure was repeated again, and the mixture was kept in a dark place for another
8 d. Finally, the mixture was diluted with Et2O and washed with cold H2O. The aq. layers were extracted
again with Et2O. The combined org. phases were washed with 1m aq. Na2CO3 soln. and brine, dried with
anh. Na2SO4, filtered, and concentrated in vacuum. The dark red residue was purified by fractional
distillation at 1608 to 1908 under high vacuum to afford pure product 1 (240 g, 65%). Light yellowish
liquid. IR: 2984s, 1725w, 1553s, 1399s, 1084s, 756s. 1H-NMR (CDCl3): 1.32 (t, J ¼ 7.4, MeCH2O); 2.15 (s,
MeꢁC(4)); 2.32 (s, MeꢁC(6)); 4.28 (q, J ¼ 7.3, MeCH2O); 5.94 (s, HꢁC(3)). 13C-NMR (CDCl3): 14.2
(MeCH2O); 19.6 (MeꢁC(6)); 21.2 (MeꢁC(4)); 61.7 (MeCH2O); 111.9 (C(5)); 113.2 (C(3)); 154.4
(C(4)); 160.7 (C(2)); 164.6, 165.5 (COOEt, C(6)). LC/MS (ESI): 196.1 (Mþ, C10H12O4þ ). Anal. calc. for
C10H12O4 (196.20): C 61.22, H 6.16; found: C 60.81, H 7.09.
Ethyl 3-Bromo-4,6-dimethyl-2-oxo-2H-pyran-5-carboxylate (2). To a soln. of 1 (430 g, 2.19 mol) in
dry CHCl3 (870 ml) was added a soln. of Br2 (430.26 g, 2.52 mol) in dry CHCl3 at 08. The mixture was
allowed to warm up to r.t., and then stirred for 24 h until complete consumption of 1 was observed by
TLC (Rf ¼ 0.6, 50% AcOEt in hexane). The mixture was poured into crushed ice and extracted with
AcOEt. The combined org. phases were washed with 10% Na2CO3 and brine, dried (MgSO4), filtered,
and concentrated in vacuum. The crude residue was purified by crystallization from cold MeOH to give 2
(515 g, 85%). White crystals. M.p. 838. IR: 3426s (br.), 2976m, 2942m, 1724w, 1630s, 1529s, 1371s, 1096s,
748s, 516s. 1H-NMR (CDCl3): 1.30 (t, J ¼ 7.4, MeCH2O); 2.26 (s, 2 Me); 4.28 (q, J ¼ 7.3, MeCH2O).
13C-NMR (CDCl3): 14.2 (Me); 19.0 (Me); 21.9 (Me); 62.2 (MeCH2O); 110.1 (C(3)); 114.2 (C(5)); 152.0
(C(4)); 157.4 (C(2)); 161.1, 165.0 (COOEt, C(6)). LC/ESI-MS: 275 (Mþ, C10H1179BrO4þ ), 277 (Mþ,
C10H1181BrOþ4 ). Anal. calc. for C10H11BrO4 (275.10): C 43.66, H 4.03; found: C 43.48, H 4.61.
(ꢀ)-trans-3-Methylidenecyclopropane-1,2-dicarboxylic Acid (¼ Feistꢀs Acid; (ꢀ)-trans-3). To a soln.
of KOH (7m, 514 ml) at 1058 was added a soln. of compound 2 (100 g, 0.36 mol) in dioxane (200 ml) over
a period of 20 min. The mixture was then further heated at 1058 until complete consumption of 2
(determined by TLC, Rf ¼ 0.2 in pure AcOEt; 30 min), and cooled to 08. The mixture was then acidified
with 50% H2SO4 (200 ml), a solid precipitate was formed, filtered off through a sintered funnel and
washed with Et2O. The aq. layers were also extracted with Et2O, and the combined org. phases were
washed with brine, dried (MgSO4), filtered, and concentrated in vacuum. The crude residue was purified
by crystallization from cold Et2O to give (ꢀ)-3 (35 g, 68%). Off-white crystal. M.p. 201 – 2048. IR: 3500 –
2500s (br., OH stretching), 1700s (br., CO stretching), 1470s, 1320s, 1300s, 1210s, 1100s, 980s, 920s, 790s,
1
660m. H-NMR ((D6)DMSO): 2.85 (s, 2 HꢁC); 5.9 (s, CH2¼C); 12.9 – 13.2 (br. s, 2 COOH). 13C-NMR
((D6)DMSO): 29.5 (2 CH); 110 (C¼CH2); 133.5 (C¼CH2); 174.0 (2 COOH). LC/ESI-MS: 141.02 ([M ꢁ
H]þ, C6H6Oþ4 ). Anal. calc. for C6H6O4 (142.11): C 50.71, H 4.26; found: C 50.52, H 4.33.
Dimethyl trans-3-Methylidenecyclopropane-1,2-dicarboxylate ((ꢀ)-4). In a 100 ml single-neck
round-bottom flask equipped with condenser, compound 3 (10 g, 70.4 mmol) was dissolved in MeOH
(150 ml). A cat. amount of H2SO4 was added, and the mixture was held at 35 – 408 for 24 h. The progress
of the reaction was monitored by TLC (Rf (20% AcOEt/hexane) 0.6). The solvent was then removed
under reduced pressure and diluted with H2O. The aq. layers were extracted with AcOEt. The org. phase
was washed with 10% NaHCO3 soln. and brine, and dried (MgSO4). The combined org. extracts were
concentrated in vacuum. The residue was purified by SiO2 chromatography, eluted with 5 – 10% AcOEt
in hexane, to provide (ꢀ)-4 (10.5 g, 88%). Colorless liquid. IR: 2955s, 1733s (CO stretching), 1437s,
1309s, 1165s, 790s, 1000m, 917s (CH2), 661s. 1H-NMR (CDCl3): 2.85 (s, 2 HꢁC); 3.68 (s, 2 COOMe); 5.64
(s, CH2¼C). 13C-NMR (CDCl3): 25.6 (2 CH); 52.5 (2 COOMe); 106.7 (C¼CH2); 128.9 (C¼CH2); 169.7 (2
COOMe). LC/ESI-MS: 170.05 (Mþ, C8H10O4þ ). Anal. calc. for C8H10O4 (170.16): C 56.47, H 5.92; found:
C 56.51, H 6.01.
(ꢀ)-(trans-3-Methylidenecyclopropane-1,2-diyl)dimethanol ((ꢀ)-5). To a suspension of LiAlH4
(2.6 g, 67.85 mmol) in dry THF (40 ml) was added dropwise a soln. of compound (ꢀ)-4 (5.7 g,

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Helvetica Chimica Acta – Vol. 95 (2012)
33.9 mmol) in THF (40 ml) at ꢁ 108 during 20 min under Ar. The mixture was warmed to r.t., and stirred
for 4 h until complete consumption of (ꢀ)-4 (determined by TLC, Rf (pure AcOEt) 0.3). The mixture
was cooled to ꢁ 108, and the reaction was quenched with 10% HCl. The precipitate (a white solid) was
filtered off through a pad of Celite and washed with Et2O. The org. phases were separated, and the aq.
layers were further extracted with AcOEt. The combined org. extracts were washed with brine, dried
(MgSO4), and concentrated in vacuum to give (ꢀ)-5 (3.6 g, 93%). Colorless liquid. IR: 3348s (br., OH
stretching), 1760s (br.), 1422w, 1135s, 1033s, 896s, 695m, 594s. 1H-NMR ((D6)DMSO): 1.44 (t, J ¼ 5.2, 2
HꢁC); 3.30 – 3.38 (m, 2 CH2OH); 4.6 (t, J ¼ 5.8, 2 CH2OH); 5.37 (s, CH2¼C). 13C-NMR ((D6)DMSO):
24.0 (2 CH); 63.3 (2 CH2OH); 104.2 (C¼CH2); 137.9 (C¼CH2). LC/MS (ESI): 140.1 (Mþ, C6H10O2þ ).
Anal. calc. for C6H10O2 (114.14): C 63.14, H 8.83; found: C 59.51, H 8.91.
(ꢀ)-(trans-3-Methylidenecyclopropane-1,2-diyl)dimethanediyl Dimethanesulfonate ((ꢀ)-6). To a
soln. of (ꢀ)-5 (3.6 g, 31.6 mmol) in CH2Cl2 (105 ml) at 08 was added Et3N (13 ml, 9.6 g, 94.7 mmol)
under Ar and stirred for 5 min. MsCl (7.36 ml, 10.85 g, 94.73 mmol) was then added dropwise over 15 min
and the mixture was then stirred for 1.5 h until complete consumption of (ꢀ)-5 (determined by TLC, Rf
(pure AcOEt) 0.5). The reaction was quenched with 10% soln. of Na2CO3, and the product was
extracted with CH2Cl2. The combined org. layers were washed with 10% soln. of Na2CO3, dried
(Mg2SO4), filtered through a pad of Celite, and concentrated in vacuum. The residue was purified by FC
(70% AcOEt in hexane) to give (ꢀ)-6 (7.8 g, 92%). White viscous liquid. IR: 1344s (SO2 asym.
stretching), 1173s (sym. stretching), 1053s, 975m, 831s, 528s. 1H-NMR (CDCl3): 1.96 (t, J ¼ 5.9, 2 HꢁC);
3.02 (s, 2 SO2Me); 4.02 – 4.05 (m, CH2O); 4.28 – 4.31 (m, CH2O); 5.64 (s, CH2¼C). 13C-NMR
((D6)DMSO): 21.10 (2 SO2Me); 38.0 (2 CH); 70.8 (2 CH2); 106.8 (C¼CH2); 130.9 (C¼CH2). LC/ESI-
MS: 270.03 (Mþ, C8H14O6S2þ ). Anal. calc. for C8H14O6S2 (270.32): C 35.54, H 5.22; found: C 35.39, H 5.43.
(ꢀ)-trans-1,2-Bis(azidomethyl)-3-methylidenecyclopropane ((ꢀ)-7). To a soln. of (ꢀ)-6 (1.8 g,
6.67 mmol) in dry DMF (40 ml) under Ar was added NaN3 (4 g, 61.5 mmol) portionwise and heated
to 608 for 4 h until complete consumption of (ꢀ)-6 (confirmed by TLC, Rf (50% AcOEt/hexane) 0.8).
The mixture was cooled to r.t., and poured into H2O. The product was extracted with Et2O, and the
combined org. phases were washed with H2O, brine, dried (Mg2SO4), filtered, and concentrated in
vacuum. The residue was purified by FC (SiO2, 100 – 200 mesh; 5 – 10% AcOEt in hexane) to provide
(ꢀ)-7 (0.80 g, 73%). Yellow liquid. IR (neat): 3077w (HC¼C stretching), 2991w, 2927w, 2872s (CH
alkene stretching), 2091s (N3 stretching), 1724s (CHꢁCH2 stretching), 1451s, 1258s, 903s. 1H-NMR
(CDCl3): 1.69 (m, 2 HꢁC); 3.2 (s, 2 CH2); 5.61 (s, CH2¼C). 13C-NMR (CDCl3): 21.3 (2 CH); 53.0 (2 CH2);
108.2 (C¼CH2); 133.2 (C¼CH2). LC/ESI-MS: 164.1 (Mþ, C6H8N6þ ). Anal. calc. for C6H8N6 (164.17): C
43.90, H 4.91, N 51.19; found: C 44.36, H 5.13, N 49.58.
(ꢀ)-(trans-3-Methylidenecyclopropane-1,2-diyl)dimethanamine ((ꢀ)-8). To a soln. of diazide (ꢀ)-7
(0.5 g, 3.05 mmol) in abs. EtOH (15 ml) was added Pd on CaCO3 poisoned with lead (10 wt-%, 5%
Lindlar catalyst) under an inert atmosphere of Ar. The mixture was degassed by purging dry Ar through
the suspension for 10 min, and was then hydrogenated under atmospheric H2 pressure (H2 balloon) for
24 h at r.t., until complete consumption of (ꢀ)-7 (determined by TLC, Rf ¼ 0.05 in pure AcOEt). The
mixture was filtered through a pad of Celite and washed with EtOH (2 ꢂ 5 ml) to afford (ꢀ)-8 (0.334 g,
98% yield, crude) as a colorless crude product. This amine product is very unstable, so without isolating
the crude mixture was immediately taken for next step.
Di(tert-butyl) (ꢀ)-[(trans-3-Methylidenecyclopropane-1,2-diyl)dimethanediyl]biscarbamate ((ꢀ)-
9). Under Ar, DIPA (¼1,1’-iminodipropan-2-ol; 1.44 ml, 10.2 mmol) and di(tert-butyl) dicarbonate
(2 ml, 10.2 mmol) were added to a soln. of (ꢀ)-8 (crude 3.05 mmol in EtOH), and the mixture was stirred
at ambient temp. for 2 h, until complete consumption of (ꢀ)-8 was observed by TLC (Rf in (30% AcOEt/
hexane) 0.8). The solvent was then removed under reduced pressure to afford a crude product which was
purified by FC (SiO2, 100 – 200 mesh; 5 – 10% AcOEt in hexane) to provide (ꢀ)-9 (0.63 g, 66%). Low-
melting solid. IR: 3331s (br., NH stretching), 2982s (br.), 1688s (C¼O stretching), 1542s, 1365s, 1180s,
942s, 891s, 648s. 1H-NMR (CDCl3): 1.45 (s, 2 HꢁC); 1.45 (s, 2 Me3C); 2.94 – 2.98 (m, CH2N); 3.18 – 3.22
(m, CH2N); 4.81 (s, 2 CH2NH); 5.45 (s, CH2¼C). 13C-NMR (CDCl3): 21.9 (2 CH); 28.5 (2 Me3C); 42.8 (2
CH2N); 79 (2 Me3C); 105.3 (C¼CH2); 135.7 (C¼CH2); 156.1 (2 CONH). LC/ESI-MS : 313 ([M þ H]þ,
C16H29N2O4þ ), 213 ([M þ H ꢁ COOCMe3]þ), 113 ([M þ H ꢁ 2 COOCMe3]þ). Anal. calc. for C16H28N2O4
(313.40): C 61.51, H 9.03, N 8.97; found: C 61.07, H 9.18, N 9.23.

Helvetica Chimica Acta – Vol. 95 (2012)
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(ꢀ)-(trans-3-Methylidenecyclopropane-1,2-diyl)dimethanaminium Dichloride ((ꢀ)-10). A dioxane/
HCl mixture (5 ml) was added to a soln. of (ꢀ)-9 (600 mg, 1.92 mmol) in CH2Cl2 (5 ml), and the mixture
was then stirred for 3 h at ambient temp. Total consumption of (ꢀ)-9 was determined by TLC (Rf (pure
AcOEt) 0.05). A white precipitate was formed. The solvent was removed under reduced pressure, and
the residue was washed with Et2O to afford the HCl salt of (ꢀ)-10 (302 mg, 85%). White solid. IR: 3424s
1
(br., NH stretching), 3029s (br., NH stretching), 1594, 1557s, 1506s, 1160s, 906s, 852s, 576s. H-NMR
((D6)DMSO): 1.82 (s, 2 HꢁC); 2.63 (br. s, CH2N); 3.03 (br. s, CH2N); 5.64 (s, CH2¼C); 8.36 (br. s, 2
NHþ3 Clꢁ). 13C-NMR ((D6)DMSO): 19.9 (2 CH); 40.7 (2 CH2N); 108.0 (C¼CH2); 133.9 (C¼CH2). LC/
ESI-MS : 113 ([M ꢁ 2 HCl þ H]þ, C6H13N2þ ). Anal. calc. for C6H14Cl2N2 (185.09): C 38.93, H 7.62, N
15.13; found: C 39.17, H 7.90, N 15.29.
(ꢀ)-S,S’-[(trans-3-Methylidenecyclopropane-1,2-diyl)dimethanediyl] Diethanethioate ((ꢀ)-11). The
bismesylate (ꢀ)-6 (2 g, 7.4 mmol) and AcSK (2.12 g, 18.5 mmol) were charged into a double-neck round-
bottom flask and dissolved in MeCN (40 ml). The mixture was heated to reflux for 3 h, and it was then
left under stirring at ambient temp. overnight. Complete consumption of (ꢀ)-6 was confirmed by TLC
(Rf (20% AcOEt/hexane) 0.6). The solvent was then removed under reduced pressure to afford a crude
product which was dissolved in CHCl3 and washed with dist. H2O. The aq. layers were further extracted
with CHCl3. The combined org. phases were dried (MgSO4), filtered, and concentrated in vacuum. The
residue was purified by FC (SiO2, 100 – 200 mesh; 5 – 10% AcOEt in hexane) to give (ꢀ)-11 (1.6 g, 94%).
Low-melting solid. IR: 1691s (C¼O stretching), 1134s, 627s. 1H-NMR (CDCl3): 1.52 (t, J ¼ 6.24, 2 HꢁC);
2.33 (s, 2 Me); 2.78 – 2.97 (m, 2 CH2S); 5.45 (s, CH2¼C). 13C-NMR (CDCl3): 11.9 (2 CH); 22.6 (2 Me);
30.7 (2 CH2S); 105.2 (C¼CH2); 138.3 (C¼CH2); 195.72 (2 C¼O). LC/ESI-MS: 230.1 (Mþ, C10H14O2S2þ ).
Anal. calc. for C10H14O2S2 (230.35): C 52.14, H 6.13; found: C 49.29, H 6.08.
(ꢀ)-[(trans-3-Methylidenecyclopropane-1,2-diyl)dimethanediyl]bis(diphenylphosphane) ((ꢀ)-12).
A soln. of LiPPh2 (0.5m in THF; 24 ml, 3 equiv.) was added dropwise to a soln. of (ꢀ)-6 (1.1 g, 4 mmol)
in dry THF (15 ml) at ꢁ 158 under Ar atmosphere, and the mixture was slowly allowed to warm to r.t.
and stirred for 24 h. TLC showed that only 50% of the starting material was consumed. An extra amount
of LiPPh2 (3 equiv.) was then added at ꢁ 158 and the mixture was stirred at r.t. for further 24 h until total
consumption of (ꢀ)-6 was confirmed by TLC (Rf (10% AcOEt/hexane) 0.5). The reaction was then
quenched with NH4Cl soln., and the mixture was extracted with Et2O. The Et2O phase was washed with
brine, dried (MgSO4), filtered through a pad of Celite, and concentrated in vacuum to afford crude (ꢀ)-
12. The residue was purified by FC (SiO2, 100 – 200 mesh; 5% AcOEt in hexane) to afford pure (ꢀ)-12
(1.6 g, 87%). Oil. IR: 3366s (br.), 2932s, 1434s, 1068s, 695s. 1H-NMR (CDCl3): 1.36 – 1.55 (m, 2 CH2P);
2.06 (t, J ¼ 8.1, 2 HꢁC); 4.37 (t, J ¼ 5.1, CH2¼C); 7.34 – 7.37 (m, 20 arom. H). 13C-NMR (CDCl3): 22.8 (2
CH2P); 27.2 (2 HꢁC); 34.5 (C¼CH2); 60.9 (C¼CH2); 129.1 (each 4 C(3), C(4), C(5) of Ph); 132.9 (4 C(2)
and 4 C(6) of Ph); 139.2 (4 C(1) of Ph). 31P-NMR (CDCl3): ꢁ 16.72 (PPh2). LC/MS (ESI): 450.2 (Mþ,
C30H28Pþ2 ). Anal. calc. for C30H28P2 (450.49): C 79.98, H 6.26; found: C 79.65, H 6.02.
Preparation of the DiolꢁTitanium Complex (Bis[(trans-3-methylidenecyclopropane-1,2-diyl)dime-
thanolato-kO(2ꢁ)]titanium; (ꢀ)-13). A soln. of TiCl4 (1m in CH2Cl2; 0.875 ml, 0.875 mmol) was added
dropwise to the soln. of diol (ꢀ)-5 (200 mg, 1.75 mmol) at 58, and the resulting mixture was stirred for
14 h at r.t. A dark white solid precipitated. The solvent was removed under vacuum to give crude (ꢀ)-13.
This crude product was dissolved in anh. CH2Cl2 (40 ml), and the resulting mixture was stirred for 20 min,
and then filtered through a sintered funnel, followed by washing with CH2Cl2 (10 ml). The filtrate was
then concentrated in vacuum to afford a light yellow solid, which was further recrystalized from toluene
to afford desired (ꢀ)-13 (140 mg, 59%). IR: 3350s (br., OH str.), 1632s (br.), 1400w, 1135s, 1026s, 896s,
904m, 831s, 581s. 1H-NMR ((D6)DMSO): 1.43 (s, 4 HꢁC); 3.26 – 3.35 (m, 4 CH2O); 5.35 (s, 2 CH2¼C).
13C-NMR ((D6)DMSO): 24.1 (4 HꢁC); 63.3 (4 CH2O); 104.2 (2 C¼CH2); 137.96 (2 C¼CH2). Anal. calc.
for C12H16O4Ti (272.12): C 52.97, H 5.93; found: C 53.21, H 6.07.
Synthesis of DiamineꢁTitanium Complex (Bis[(trans-3-methylidenecyclopropane-1,2-diyl)dimethan-
aminato-kN(2ꢁ)]titanium; (ꢀ)-14). Compound (ꢀ)-10 (330 mg, 1.78 mmol) was dissolved in CH2Cl2
(10 ml) into a single-neck round-bottom flask (50 ml). Na2CO3 soln. (10%, 7.5 mmol) was added to the
mixture and stirred for 20 min. The CH2Cl2 layer containing free amine was separated out and dried
(MgSO4). The free amine soln. in CH2Cl2 was then taken into another single-neck round-bottom flask
under inert conditions and cooled to 58. A soln. of TiCl4 (1m soln. in CH2Cl2, 0.875 ml, 0.875 mmol) was

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Helvetica Chimica Acta – Vol. 95 (2012)
added dropwise to the mixture. The mixture was then stirred for 14 h at ambient temp., and a white solid
precipitated. The solvent was removed under vacuum to give a crude product. This crude product was
dissolved in anh. CH2Cl2 (40 ml), and the resulting mixture was stirred for 20 min and filtered through a
sintered funnel, followed by washing with CH2Cl2 (10 ml). The filtrate was then concentrated under
reduced pressure to afford a light yellow solid, which was further recrystalized from toluene to give (ꢀ)-
14 (165 mg, 70% yield). IR: 3332s (br., NH stretching), 2982 (CH stretching, alkene), 1542s, 1365s, 1180s,
942s, 891s, 648s. 1H-NMR ((D6)DMSO): 1.84 (s, 4 HꢁC); 2.60 – 2.61 (m, 2 CH2N); 3.00 – 3.02 (m, 2
CH2N); 5.64 (s, 3 CH2¼C); 8.48 (br. s, 4 NH2). 13C-NMR ((D6)DMSO): 20.0 (4 HꢁC); 40.7 (4 CH2N);
108.0 (2 C¼CH2); 134.0 (2 C¼CH2). Anal. calc. for C12H20N4Ti (268.18): C 53.74, H 7.52, N 20.89; found:
C 53.51, H 7.72, N 21.06.
The authors express their appreciation to the Deanship of Scientific Research, at King Saud
University for funding the work through the research group project No. RGP-VPP-044.
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Received August 1, 2011