A general and efficient method for the preparation of unsymmetrical bidentate P,N and P,S ligands

Article abstract of DOI:10.1016/j.tetlet.2005.12.041

A general and efficient preparation of chiral and achiral P,N and P,S ligands is described where ligands are prepared by reacting a variety of 2- or α-lithio N- or S-heterocycles and a lithiated phosphine with 1,2-cyclic sulfates.

Full text of DOI:10.1016/j.tetlet.2005.12.041

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1473–1475
A general and efficient method for the preparation
of unsymmetrical bidentate P,N and P,S ligands
M. Abdul Jalil* and Ee Bee Hui
New Synthesis Techniques and Applications Group, Institute of Chemical and Engineering Sciences (ICES),
1, Pesek Road, Jurong Island, Singapore 627833, Singapore
Received 21 October 2005; revised 30 November 2005; accepted 7 December 2005
Abstract—A general and efficient preparation of chiral and achiral P,N and P,S ligands is described where ligands are prepared by
reacting a variety of 2- or a-lithio N- or S-heterocycles and a lithiated phosphine with 1,2-cyclic sulfates.
Ó 2006 Elsevier Ltd. All rights reserved.
The search for new ligands for homogeneous catalysis is
a field of continuing interest. A huge effort has been
devoted to the development of highly efficient transition
metal catalyzed reactions using ligands based on P–P,
P–N, or N–N coordination modes.1 Of special interest
are the P,N ligands due to their unsymmetrical nature.2
The ligand imparts bonding versatility and enables tun-
ing of the electronic and steric properties of the donor
atoms. This heterofunctional system can display unique
dynamic features, such as hemilability, which represents
an efficient way to control the selectivity of catalytic pro-
cesses.3 These features of P,N ligands are useful in
homogeneous transition metal catalysis for C–C bond
forming reactions such as oligomerization, polymeriza-
tion, and copolymerization of olefins.4 In addition to
this, chiral P,N ligands are useful in asymmetric cataly-
sis.5 For example, oxazole based chiral P,N ligands are
now widely used in various asymmetric reactions and
these can be considered as privileged ligands.5,6 Due to
the importance and growing demand of P,N ligands,
their easy accessibility is highly desirable. We report
here a simple, and generic one-pot reaction that affords
a variety of chiral/achiral P,N and P,S ligands contain-
ing various N- and S-heterocycles.
protocol in which diols are treated with SOCl2 to form
cyclic sulfites, which are then oxidized to cyclic sulfates
with NaIO4 in the presence of a catalytic amount of
RuCl3.7 Cyclic sulfates readily undergo mono substitu-
tion reactions at the ring carbon with a range of nitro-
gen, oxygen, sulfur, and carbon based nucleophiles.8,9
Double substitution reactions with dianions leading to
the loss of sulfate have also been reported.10 Inspired
by this, we envisaged that it would be possible to attach
an appropriate heterocyclic ring and a phosphine moiety
to the two different ring carbons of a 1,2-cyclic sulfate to
afford a hetero bidentate phosphine ligand.11 To initiate
our studies, we first chose a simple symmetric cyclic sul-
fate 1 to produce imidazole-based P,N ligands 2a and 2b
according to Scheme 1.
First, the cyclic sulfate 1 was treated with an equimolar
amount of the 2-lithio N-heterocycle in THF at À78 °C
resulting in quantitative ring opening of the five-mem-
bered ring. Addition of the second nucleophile, LiPPh2,
led to the displacement of the sulfate group by the PPh2
moiety. Subsequent hydrolysis and work-up afforded the
crude ligand 2a as a viscous liquid and 2b as white pow-
der. The hydrobromide salt of 2b (oxide) was obtained
when 2b was treated with an equimolar amount of
47% HBr in ethanol for 2 h. A good quality crystal suit-
able for X-ray analyses was obtained from its ethanol-
diethyl ether solution. The molecular structure of 2b
(oxide)ÆHBrÆC2H5OH is depicted in Figure 1.12
In this route we used 1,2-cyclic sulfates as starting mate-
rials, since these are easily accessible by the Sharpless
Keywords: P,N Ligands; P,S Ligands; Cyclic sulfates; Imidazole;
Asymmetric synthesis.
The satisfactory result obtained from the successive
addition of two different nucleophiles led us to investi-
gate the reactions of non-symmetrical 1,2-cyclic sulfates.
*
Corresponding author. Tel.: +65 6796 3931; fax: +65 6316 6184;
e-mail: md_jalil@ices.a-star.edu.sg
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.12.041

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M. A. Jalil, E. B. Hui / Tetrahedron Letters 47 (2006) 1473–1475
N
N
N
Li
O
Ph2P
O
O
O
O
N
N
PPh2Li
THF
N
S
O
S
OLi
THF
O
1
2a = Im (73%)
2b = BzIm (64%)
Scheme 1. Synthesis of ligands 2a and 2b using the symmetric cyclic sulfate 1.
as was evidenced by the coupling of the methyl protons
with the phosphorus atom. The methyl protons of 4
appeared at d = 1.04, as a doublet of doublets, with a
3
coupling constant JPH = 15.0 Hz.
Encouraged by this result, we decided to attach an opti-
cally active heterocyclic moiety to this ligand system and
to this end, successfully constructed the ligand 5 con-
taining an oxazole ring according to Scheme 3.
The chiral oxazole used in this reaction was readily pre-
pared from L-valinol by reacting with ethyl iminoacetate
hydrochloride.13 Several convenient routes are available
for the construction of similar types of chiral oxazoles
with different substituents at the 5-position, and this
broadens the scope for the preparation of a series of
chiral oxazoline ligands.14 Recently Gilbertson et al.
synthesized a series of similar ligands by multi-step
reactions where the oxazole and phosphine moieties
were connected by two carbon atoms and these ligands
were successfully utilized in palladium-catalyzed allylic
alkylations reactions.15 Very high ee (90–97%) and
conversions were achieved, in some cases, for the alkyl-
ation of 1,3-diphenyl-2-propenyl acetate with dimethyl
malonate.
Figure 1. Molecular structure of 2b (oxide)ÆHBrÆC2H5OH. Selected
bond lengths [A] and bond angles [°]: P–C1 1.808(4), P–C11 1.812(4),
P–Cl7 1.808(4), P–O 1.396(5); C1–P–C11 101.81(17), C1–P–Cl7
105.27(17), C11–P–C17 103.66(17), P–C1–C2 109.5(2), Cl–C2–C3
114.1(3). All hydrogen atoms, the bromide ion, and the solvent
molecule are omitted for clarity.
˚
We conducted reactions using the cyclic sulfate 3 in its
racemic and non-racemic forms. Successive addition of
2-lithio N-methylimidazole and LiPPh2 to 3 in an ana-
logous way to that described for 2 led to the formation
of the ligand 4 in 68% yield (Scheme 2).
To explore the wider application of this methodology,
we also prepared a representative P,S ligand 6 by attach-
ing the sulfur-containing heterocycle, thiophene, accord-
ing to Scheme 4. Recently P,S ligands have been shown
to be very effective in asymmetric catalytic reactions.16
Therefore, the scope of this protocol is wide as various
heterocycles can be attached to this system.
Starting from the S enantiomer 3, (R)-4 was obtained
stereoselectively through inversion of the configuration
at the stereogenic center. The reaction was highly regio-
selective with the first C-nucleophile attacking the less
hindered carbon atom of the cyclic sulfate exclusively,
N
N
Li
O
O
O
O
O
N
N
PPh2Li
THF
N
Ph2P
O
S
S
N
OLi
THF
O
(R)-4 (68%)
(S)-3
Scheme 2. Synthesis of ligand 4 using the unsymmetric cyclic sulfate 3.
O
O
N
THF
O
O
O
Li
O
O
O
PPh2Li
THF
Ph2P
N
O
N
S
S
OLi
O
1
(S)-5 (58%)
Scheme 3. Synthesis of ligand (S)-5 having a chiral center in the heterocyclic ring.

M. A. Jalil, E. B. Hui / Tetrahedron Letters 47 (2006) 1473–1475
1475
Li
O
PPh2Li
THF
O
O
O
O
S
S
Ph2P
O
S
S
S
THF
OLi
O
6 (72%)
1
Scheme 4. Synthesis of ligand 6 containing a S-heterocycle.
Chem. Rev. 2000, 100, 1169; (d) Mecking, S. Coord. Chem.
Rev. 2000, 203, 325; (e) Braunstein, P.; Fryzuk, M. D.;
Dall, M. L.; Naud, F.; Rettig, S. J.; Speiser, F. Dalton
2000, 1067.
In conclusion, we have reported a simple reaction for the
preparation of a variety of P,N and P,S ligands contain-
ing various N- and S-heterocycles. The synthetic strat-
egy can be extended to other heterocyclic-phosphine
ligands. The procedure allows the steric and electronic
properties of ligands to be fine tuned by choosing differ-
ent cyclic sulfates and by changing the substituents on
the phosphorus or the heterocyclic ring.
5. For recent reviews on chiral P,N-ligands; see: (a) Chelucci,
`
G.; Orru, G.; Pinna, G. A. Tetrahedron 2003, 59, 9471;
(b) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33,
336.
6. McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151.
7. Gao, Y.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110,
7538.
8. (a) Byun, H.-S.; He, L.; Bittman, R. Tetrahedron 2000, 56,
7051; (b) Lohray, B. B. Synthesis 1992, 1035; (c) Lohray,
B. B.; Bhushan, V. Adv. Heterocycl. Chem. 1997, 68, 89.
9. (a) Lohray, B. B.; Bhushan, V. Adv. Heterocycl. Chem.
1997, 68, 89; (b) Vanhessche, K. P. M.; Sharpless, K. B.
Chem. Eur. J. 1997, 3, 517.
10. (a) Leurquin, F.; Ozturk, T.; Pilkington, M.; Wallis, J. D.
J. Chem. Soc., Perkin Trans. 1 1997, 3173; (b) Calvo-
Flores, F.; Garcia-Mendoza, P.; Hernandez-Mateo, F.;
Isac-Garcia, J.; Santoyo-Gonzalez, F. J. Org. Chem. 1997,
62, 3944; (c) Oi, R.; Sharpless, K. B. Tetrahedron Lett.
1991, 32, 999.
11. Werner’s group reported several 1,2-bis(phospha-
nyl)ethanes and 1,2-arsanyl(phosphanyl)ethanes by using
similar cyclic sulfate: (a) Fries, G.; Wolf, J.; Pfeiffer, M.;
Stalke, D.; Werner, H. Angew. Chem., Int. Ed. 2000, 39,
564; (b) Fries, G.; Wolf, J.; Ilg, K.; Walfort, B.; Stalke, D.;
Werner, H. Dalton Trans. 2004, 1873.
Acknowledgments
We gratefully thank Dr. Christina Chai of ICES for her
support. We thank the Agency for Science, Technology
and Research (A STAR) of Singapore under the project
*
code ICES 03-141005 for financial support.
Supplementary data
Supplementary data (synthetic and spectroscopic data
for the compounds 2a–b, 4, 5, and 6) associated with this
article can be found, in the online version, at doi:10.1016/
j.tetlet.2005.12.041.
References and notes
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[C24H27BrN2O2P] have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary
publication no. CCDC-284831. This data can be obtained
free of charge via the internet www.ccdc.cam.ac.uk/conts/
retrieving.html or by sending an email to deposit@ccdc.
cam.ac.uk.
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