Highly Flexible Synthetic Routes to Functionalized Phospholanes from Carbohydrates

Article abstract of DOI:10.1021/jo991762j

Highly functionalized phospholanes 15, 17, and 26 and the corresponding diastereomers in which the configurations of the phospholane carbon-2 and carbon-5 are inverted can be readily prepared from D-mannitol by displacement of the appropriate dimesylate or cyclic sulfate with dilithium-phosphide reagents. The diols from which these ligands are prepared can also be converted into diarylphosphinite ligands. A route to related monophosphines bearing hemilabile tert-butylthio groups is also described. Complexes of these ligands and of related deprotected derivatives are potentially useful for enantioselective catalysis in organic and aqueous media.

Full text of DOI:10.1021/jo991762j

900
J . Org. Chem. 2000, 65, 900-906
High ly F lexible Syn th etic Rou tes to F u n ction a lized P h osp h ola n es
fr om Ca r boh yd r a tes
Yuan-Yong Yan and T. V. RajanBabu*
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210
Received November 11, 1999
Highly functionalized phospholanes 15, 17, and 26 and the corresponding diastereomers in which
the configurations of the phospholane carbon-2 and carbon-5 are inverted can be readily prepared
from D-mannitol by displacement of the appropriate dimesylate or cyclic sulfate with dilithium-
phosphide reagents. The diols from which these ligands are prepared can also be converted into
diarylphosphinite ligands. A route to related monophosphines bearing hemilabile tert-butylthio
groups is also described. Complexes of these ligands and of related deprotected derivatives are
potentially useful for enantioselective catalysis in organic and aqueous media.
In tr od u ction
not been fully exploited is the polyhydroxylic nature of
their deprotected derivatives, which should make them
water-soluble.3 Such complexes can now be used as
catalysts for organic reactions in water, which can serve
as an environmentally friendly solvent if certain strin-
gent criteria for solubility of the products and catalyst
can be met. Ideally, water-soluble contaminants and side
products should be avoided, and the product(s) should
be soluble in an organic medium, and the catalyst, in the
aqueous medium. Under these circumstances, the water-
soluble catalyst can be separated and reused in subse-
quent cycles.4 Yet another approach is the use of sup-
ported aqueous phase catalysts.5 In either of these cases,
a catalyst with a very high partition coefficient between
water and the appropriate organic solvent is one of the
most critical components if catalyst recovery is desired.
Pioneering studies by the Selke/Oehme groups6 have
shown that vicinal diarylphosphinite-Rh complexes de-
rived from glucose (1) can be used for the asymmetric
hydrogenation of acetamidoacrylic acid derivatives in
water. Very high enantioselectivities can be obtained,
especially in the presence of micelle-forming amphiphiles.
The high selectivities of these reactions notwithstanding,
anecdotal evidence suggests that the monosaccharide
diarylphosphinite ligands have only solubility in water,
and quantitative recovery/reuse of the catalyst could be
problematic. In an approach to circumvent this problem,
we7 and others8 have resorted to preparing the vicinal
diarylphosphinite complexes (e.g., 2) from a disaccharide,
Carbohydrates with their rich array of stereochemical
and functional group diversity have been a popular
source of starting materials in organic synthesis. Many
mono- and disaccharides are abundantly available in
100% enatiomeric purity, and there is a prolific history
of functional group manipulations that dates back to
more than a century of carbohydrate chemistry. It is
therefore surprising that they have attracted broad
attention as ligand precursors for asymmetric catalysis
only recently.1 In previous work from our laboratories,
we have shown that carbohydrate-derived diarylphos-
phinite complexes of transition metals catalyze a wide
variety of C-C and C-H bond forming reactions2 includ-
ing hydrogenation (Rh), hydroformylation (Rh), hydro-
cyanation (Ni), hydrovinylation (Ni), and allylation re-
actions (Ni and Pd). The modular construction of these
ligands renders them amenable to electronic and steric
tuning, and unprecedented enantioselectivity has been
achieved in hydrocyanation and hydrovinylation reac-
tions. One salient property of these complexes that has
(1) For some early representative examples, see: (a) Kawabata, Y.;
Tanaka, M.; Ogata, I. Chem. Lett. 1976, 1213. (b) J ackson, R.;
Thompson, D. J . J . Organomet. Chem. 1978, 159, C29. (c) Cullen, W.
R.; Sugi, Y. Tetrahedron Lett. 1978, 1635. (d) Selke, R. React. Kinetic.
Catal. Lett. 1979, 10, 135. (e) Nakamura, Y.; Saito, S.; Morita, Y. Chem.
Lett. 1980, 7. (f) J ohnson, T. H.; Rangarajan, G. J . Org. Chem. 1980,
45, 62. (g) Brunner, H.; Pieronczyk, W. J . Chem. Res., Synop. 1980,
76. (h) Yamada, M.; Yamashita, M.; Inokawa, S. Carbohydr. Res. 1981,
95, C9. (i) Habus, I.; Raza, Z.; Sunjic, V. J . Mol. Catal. 1987, 42, 173.
(j) Brown, J . M.; Cook, S. J . Tetrahedron 1986, 42, 5105. For recent
reviews, see: (k) Holz, J .; Quirmbach, M.; Bo¨rner, A. Synthesis 1997,
983. (l) RajanBabu, T. V.; Casalnuovo, A. L.; Ayers, T. A. Ligand Tuning
in Asymmetric Catalysis: Hydrocyanation and Hydrogenation Reac-
tions. In Advances in Catalytic Processes; Doyle, M., Ed.; J AI Press:
Greenwich, CT, 1998; pp 1-41.
(2) (a) Ni-catalyzed hydrocyanation: Casalnuovo, A. L.; RajanBabu,
T. V.; Ayers, T. A.; Warren, T. H. J . Am. Chem. Soc. 1994, 116, 9869.
(b) Rh-catalyzed hydrogenations: RajanBabu, T. V.; Ayers, T. A.;
Casalnuovo, A. L. J . Am. Chem. Soc. 1994, 116, 4101. RajanBabu, T.
V.; Ayers, T. A.; Halliday, G. A.; You, K. K.; Calabrese, J . C. J . Org.
Chem. 1997, 62, 6012. See also: Kumar, A.; Oehme, G.; Roque, J . P.;
Schwarze, M.; Selke, R. Angew. Chem., Int. Ed. Engl. 1994, 33, 2197
and references therein. (c) Hydroformylation: RajanBabu, T. V.; Ayers,
T. A. Tetrahedron Lett. 1994, 35, 4295. (d) Hydrovinylation: Park, H.;
RajanBabu, T. V. Unpublished results. (e) Pd-catalyzed allylation:
Nomura, N.; Mermet-Bouvier, Y. C.; RajanBabu, T. V. Synlett 1996,
745. Clyne, D.; Mermet-Bouvier, Y. C.; Nomura, N.; RajanBabu, T. V.
J . Org. Chem. 1999, 64, 7601. See also: Evans, D. A.; Campos, K. R.;
Tedrow, J . S.; Michael, F. E.; Gagne´, M. R. J . Org. Chem. 1999, 64,
2994.
(3) For recent reports dealing with the use of carbohydrates for
solubilizing organometallic complexes, see: (a) Mitchell, T. N.; Heesche-
Wagner, K. J . Organomet. Chem. 1992, 436, 43. (b) Sawamura, M.;
Kitayama, K.; Ito, Y. Tetrahedron: Asymmetry 1993, 4, 1829. (c) Beller,
M.; Krauter, J . G. E.; Zapf, A. Angew. Chem., Int. Ed. Engl. 1997, 36,
772.
(4) (a) Sinou, D. Bull. Soc. Chim. Fr. 1986, 480. (b) Herrmann, W.
A.; Kohlpaintner, W. Angew. Chem., Int. Ed. Engl. 1993, 32, 1524. (b)
Horva´th, I. T.; J oo´, F. Aqueous Organometallic Chemistry and Cataly-
sis; Horva´th, I. T., J oo´, F., Eds.; Kluwer: Dodrecht, 1995.
(5) (a) Wan, K. T.; Davis, M. E. Nature 1994, 370, 449. (b) Choplin,
A.; Santos, S. D.; Quignard, F.; Sigismondi, S.; Sinou, D. Catal. Today
1998, 42, 471.
(6) (a) Graseert, I.; Paetzold, E.; Oehme, G. Tetrahedron 1993, 49,
6605. (b) Kumar, A.; Oehme, G.; Roque, J . P.; Schwarze, M.; Selke, R.
Angew. Chem., Int. Ed. Engl. 1994, 33, 2197. (c) Selke, R.; Ohff, M.;
Riepe, A. Tetrahedron 1996, 52, 15079.
(7) Shin, S.; RajanBabu, T. V. Org. Lett. 1999, 1, 1229.
(8) Yonehara, K.; Hashizume, T.; Ohe, K.; Uemura, S. J . Org. Chem.
1999, 64, 5593.
10.1021/jo991762j CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/07/2000

Routes to Phospholanes from Carbohydrates
J . Org. Chem., Vol. 65, No. 3, 2000 901
Sch em e 1. Syn th esis of Diol P r ecu r sor s fr om
D-Ma n n itol13,14
trehalose, with the expectation that the increased num-
ber of hydroxyl groups would improve the water solubil-
ity. While these studies8 have shown that with the right
glycoside (in this case, the â,â-isomer of trehalose)
outstanding enantioselectivity can be achieved, the dis-
tribution coefficient for the cationic rhodium complexes
between water and organic solvents (determined by the
ion-coupled plasma method) is too low to be of practical
value.7 Yet another potential problem with phosphinites
could be their long-term hydrolytic instability due to the
presence of the P-O bond. As a solution to these
problems, we envisioned the design of polyhydroxy phos-
phine ligands (viz., with only P-C bonds) with less
hydrophobic P-substituents compared to the commonly
encountered P-aryl groups. The P-C bonds in these
ligands should be considerably more stable in an aqueous
medium.9 For our initial studies, we chose the C2-
symmetric phospholane system (3), which forms the
backbone of the enormously successful DuPHOS and
bisphospholanoethane (BPE) series of ligands discovered
by Burk and co-workers.10,11 In view of the flurry of
activity in this area, most notably from the groups of
Bo¨rner, Brown, and Zhang, in this paper we report our
preliminary findings on a highly versatile route for the
synthesis of two classes of appropriately protected C2-
symmetric phospholanes from D-mannitol.12
epoxides 6 and 10 can be prepared. These can be further
elaborated into diols 7 and 11, respectively, via known
chemistry.13 The epoxides 6 and 10 could also serve in
the future as electrophiles for copper-mediated ring-
opening14 from which a variety of 1,4-diols can be
prepared, allowing sufficient flexibility in steric tuning
of the final phospholane ligands (vide infra). In the event,
the epoxides were reduced with superhydride in THF to
the diols 7 and 11.
Each of the diols was separately transformed into a
number of ligands via the intermediate dimesylates or
the cyclic sulfates (Scheme 2). Reaction of 11 with
methanesulfonyl chloride in pyridine gave in 97% yield
the mesylate 12, which is a key intermediate for the
synthesis of a number of phosphine ligands (Scheme 3).
Alternatively, the diol can be transformed into a cyclic
sulfate 14, which can also be used for phospholane
synthesis. Two other ligands that are readily prepared
from the diol and the respective diarylchlorophosphines
are the 1,4-diarylphosphinites 13a and 13b.
Resu lts a n d Discu ssion
We considered the diol 4 as a key intermediate in our
synthetic planning (Scheme 1). Depending on the specific
sequence of reactions that follow, two diastereomeric bis-
(9) An outstanding example of this is the sulfonated triphenylphos-
phine, BINAP, and their analogues. See refs 4 and 5. See also: (a)
Nagel, U.; Kinzel, E. Chem. Ber. 1986, 119, 1731. (b) To´th, I.; Hanson,
B. E. Tetrahedron Asymmetry 1990, 1, 895. (c) Uozumi, Y.; Danjo, H.;
Hayashi, T. Tetrahedron Lett. 1998, 39, 8303.
(10) (a) Burk, M. J .; Feaster, J . E.; Harlow, R. L. Tetrahedron:
Asymmetry 1991, 2, 569. (b) Burk, M. J .; Feaster, J . E.; Nugent, W.
A.; Harlow, R. L. J . Am. Chem. Soc. 1993, 115, 10125. (c) Burk, M. J .;
Harper, T. G. P.; Kalberg, C. S. J . Am. Chem. Soc. 1995, 117, 4423.
(d) Burk, M. J .; Kalberg, C. S.; Pizzano, A. J . Am. Chem. Soc. 1998,
120, 4345. (e) Burk, M.; Gross, M. F.; Harper, T. G. P.; Kalberg, C. S.;
Lee, J . R.; Martinez, J . P. Pure Appl. Chem. 1996, 68, 37 and references
therein.
(11) For other modifications of the bisphospholane scaffolding, see:
(a) Zhu, G.; Chen, Z.; J iang, Q.; Xiao, D.; Cao, P.; Zhang, X. J . Am.
Chem. Soc. 1997, 119, 3836. (b) Vedejs, E.; Daugulis, O. J . Am. Chem.
Soc. 1999, 121, 5813.
(12) While our studies were in progress, a number of reports dealing
with the synthesis of functionalized bisphospholanes have appeared.
(a) Holz, J .; Quirmbach, M.; Schmidt, U.; Heller, D.; Stu¨rmer, R.;
Bo¨rner, A. J . Org. Chem. 1998, 63, 8031. (b) Carmichael, D.; Doucet,
H.; Brown, J . M. J . Chem. Soc., Chem. Commun. 1999, 261. (c) Li, W.;
Zhang, Z.; Xiao, D.; Zhang, X. Tetrahedron Lett. 1999, 40, 6701. (d)
Holz, J .; Heller, D.; Stu¨rmer, R.; Bo¨rner, A. Tetrahedron Lett. 1999,
40, 7059. The earliest report in this area, which appeared in 1992,
has received no mention in subsequent papers: Hitchcock, P. B.;
Lappert, M. F. Yin, P. J . Chem. Soc., Chem. Commun. 1992, 1598.
The mesylate 12 is a versatile intermediate that reacts
with various phosphide reagents to give the phospholanes
15 and 17 (Scheme 3). In these reactions, it is important
to keep the temperatures low, and to carefully monitor
the reaction, to obtain reasonable yields of the product.15
The ligands were purified by careful column chromatog-
raphy in an inert atmosphere, and in most cases analyti-
(13) Le Merrer, Y.; Dure´ault, A.; Greck, C.; Micas-Languin, D.;
Gravier, C.; Depezay, J .-C. Heterocycles 1987, 25, 541.
(14) Allevi, P.; Ciuffreda, P.; Sanvito, A. M. Tetrahedron: Asymmetry
1994, 5, 927.
(15) See Experimental Section for details.

902 J . Org. Chem., Vol. 65, No. 3, 2000
Yan and RajanBabu
Sch em e 3. Utility of a Dim esyla te a n d a
1,4-Cyclic Su lfa te for th e Syn th esis of Mon o- a n d
Dip h osp h in e Liga n d s
Sch em e 2. Su lfon a te, P h osp h in ite, a n d Su lfa te
P r ecu r sor s fr om a 1,4-Diol
cally pure ligands could be obtained. The mesylate reacts
with 2 equiv of lithium diphenylphosphide to give 16, an
analogue of the well-known DIOP (2,2-dimethyl-1,3-
dioxalane-4,5-diylbismethylene)bisdiphenylphosphine)
ligand.16 The monophosphine 15 and the diphosphine 17
can also be prepared by the recipe originally prescribed
by Burk using the cyclic sulfate 14.
The diastereomeric diol 7 readily forms the mesylate
12′, which is useful for the synthesis of a new set of
ligands 19, 20, and 21. Dimethyl DIOP analogue 20 has
been described in the literature.17 1,4-Bis-diarylphos-
phinites 18a and 18b are also readily prepared from 7.
generally applicable for the synthesis of phospholane
ligands bearing other hemilabile atoms. Dimesylate
derived from alcohol 7 likewise yielded the ligand 27.
In summary, we have discovered a versatile route for
the synthesis of various functionalized mono and bis-
phospholane ligands. The starting materials are readily
available, and the transformations highly diastereo-
selective, ensuring enantiomeric purity of the final
products. The synthetic scheme is characterized by
sufficient flexibility to allow fine tuning of the final
phospholane ligands. Utility of these ligands in asym-
metric catalysis and also for the synthesis of water-
soluble transition-metal catalysts will be reported in due
course.20
Exp er iem en ta l Section
Gen er a l. All anaerobic reactions were carried out an inert
atmosphere of nitrogen in a Vacuum Atmospheres drybox, or
(18) (a) Slone, C. S.; Weinberger, D. A.; Mirkin, C. A. The Transition
Metal Coordination Chemistry of Hemilabile Ligands. In Progress in
Inorganic Chemistry; Karlin, K. D., Ed.; J ohn Wiley: New York, 1999;
p 233. (b) Bader, A.; Lindner, E. Coord. Chem. Rev. 1991, 108, 27. (c)
J effrey, J . C.; Rauchfuss, T. B. Inorg. Chem. 1979, 18, 2658. (d)
Britovsek, G. J . P.; Keim, W.; Mecking, S.; Sainz, D.; Wagner, T. J .
Chem. Soc., Chem. Commun. 1993, 1632. (e) Britovsek, G. J . P.; Cavell,
K. J .; Keim, W. J . Mol. Catal. A, Chemical 1996, 110, 77. (f) Meking,
S.; Keim, W. Organometallics 1996, 15, 2650. (g) Nomura, N.; J in, J .;
Park, H.; RajanBabu, T. V. J . Am. Chem. Soc. 1998, 120, 459. (h)
Nandi, M.; J in, J .; RajanBabu, T. V. J . Am. Chem. Soc. 1999, 120,
9899.
(19) For typical examples, see: (a) von Matt, P.; Pfaltz, A. Angew.
Chem., Int. Ed. Engl. 1993, 32, 566. (b) Sprinz, J .; Kiefer, M.;
Helmchen, G.; Reggelin, M.; Huttner, G.; Walter, O.; Zsolnai, L.
Tetrahedron Lett. 1994, 35, 1523. (c) Williams, J . M. J . Synlett 1996,
705. (d) Pregosin, P. S.; Salzmann, R. Coord. Chem. Rev. 1996, 155,
35. (e) Schnyder, A.; Hintermann, L.; Togni, A. Angew. Chem., Int.
Ed. Engl. 1995, 34, 931. For recent examples, see: (f) Old, D. W.; Wolfe,
J . P.; Buchwald, S. L. J . Am. Chem. Soc. 1998, 120, 9722. (g) Evans,
D. A.; Campos, K. R.; Tedrow, J . S.; Michael, F. E.; Gagne´, M. R. J .
Org. Chem. 1999, 64, 2994.
Yet another application of this chemistry is in the
synthesis of “hemilabile” ligands containing the phos-
pholano moiety. It has been known for some time that
the use of hemilabile ligands can improve the efficiency
and selectivity of certain transition-metal-catalyzed reac-
tions.18 Selectivities of many allylation and Heck-type
reactions catalyzed by Pd(0) complexes are also improved
by judicious choice of unsymmetrical ligands carrying
P/N, N/S, or P/S chelating atoms.19 Synthesis of a
phospholane ligand 26 carrying a potentially hemilabile
tert-butylthioether functionality at the γ-position is
shown in Scheme 4. The anticipated problem with the
benzylic sulfur in the Pd-catalyzed P-C bond formation
did not materialize, and we expect this scheme to be
(16) Dang, T. P.; Poulin, J . C.; Kagan, H. B. J . Organomet. Chem.
1975, 91, 105.
(17) Kagan, H. B.; Fiaud, J . C.; Hoornaert, C.; Meyer, D.; Poulin, J .
C. Bull. Soc. Chim. Belg. 1979, 88, 923.
(20) Note a d d ed in p r oof: Applications of these ligands for a
prototypical Pd(0)-catalyzed allylation (yields up to 99% and ee’s >99%
in selected cases) have been reported. Yan, Y.; RajanBabu, T. V. Org.
Lett. 2000, 2, 199.

Routes to Phospholanes from Carbohydrates
J . Org. Chem., Vol. 65, No. 3, 2000 903
was stirred at 0 °C for 2 h and was kept in the refrigerator
overnight. The mixture was poured into 30 mL of ice-cold water
and extracted with CH2Cl2 (3 × 20 mL). The combined extracts
were successively washed with 20 mL each of 3 N HCl and
saturated NaCl solution and dried with anhydrous MgSO4.
Removal of the solvent on the evaporator gave the crude
product, which was purified by chromatography eluting with
ethyl acetate/hexane (3:7), to give 0.779 g (97%) of the
Sch em e 4. Syn th esis of a P h osp h ola n e w ith a
Hem ila bile Th ioeth er
1
dimesylate (12). H NMR (CDCl3): δ 1.38 (s, 6 H), 1.46 (d, J
) 10.0 Hz, 6 H), 3.04 (s, 6 H), 4.00 (m, 2H), 4.81 (m, 2H). 13C
NMR (CDCl3): δ 17.69, 26.79, 38.60, 76.19, 78.14, 110.19.
1,6-Did eoxy-3,4-O-isop r op ylid en e-D-m a n n itol Dim eth -
a n esu lfon a te (12′). To a solution of 0.76 g (4.0 mmol) of diol
7 in 10 mL of pyridine was added 1.5 mL (5 equiv) of
methanesulfonyl chloride. The mixture was stirred at 0 °C for
2 h and kept in the refrigerator overnight. The mixture was
poured into 30 mL of ice-cold water and extracted with CH2-
Cl2 (3 × 20 mL). The combined extracts were successively
washed with 20 mL of 3 N HCl and saturated NaCl solution
and dried with anhydrous MgSO4. Removal of the solvent on
the evaporator gave the crude product, which was purified by
column chromatography on silica gel (elution with ethyl
acetate/hexane 3:7) to give 1.29 g (93%) of the dimesylate 12′.
1H NMR (CDCl3): δ 1.41 (s, 6 H), 1.49 (d, J ) 6.4 Hz, 6 H),
3.07 (s, 6 H), 4.03 (m, 2 H), 4.81 (m, 2 H). 13C NMR (CDCl3):
δ 17.28, 27.01, 38.77, 78.02, 80.01, 111.20.
using Schlenk techniques. Methylene chloride was distilled
from calcium hydride under nitrogen and stored over molecular
sieves. Tetrahydrofuran (THF) and diethyl ether were distilled
under nitrogen from sodium/benzophenone ketyl. All chemicals
were purchased from Aldrich Chemical Co. unless otherwise
noted. Analytical TLC was done on E. Merck precoated (0.25
mm) silica gel 60 F254 plates. Column chromatography was
conducted by using silica gel 40 (Scientific Adsorbents Incor-
porated, Microns Flash). 1H NMR spectra were recorded in
CDCl3 unless otherwise mentioned. Gas chromatographic
analyses were performed using HP-ultra-1 cross-linked methyl
silicone capillary column (25 m length × 0.2 mm i.d.).
1,6-Did eoxy-3,4-O-isop r op ylid en e-L-id itol Bis(d ip h en -
ylp h osp h in ite) (13a ). In a drybox, to a stirring solution of
0.285 g (1.498 mmol) of 11 and 18 mg of DMAP in 5 mL of
pyridine was added 0.727 g (2.2 equiv) of chlorodiphenylphos-
phine in 5 mL of CH2Cl2. After stirring overnight, the mixture
was filtered and concentrated. The residue was purified by
flash chromatography eluting with ether/hexane (1:9), to
obtain 0.553 g (66%) of (13a ). 1H NMR (CDCl3): δ 1.26 (d, J )
6.4 Hz, 6 H), 1.39 (s, 6 H), 3.96 (m, 2 H), 4.03 (m, 2 H); 7.34
(m, 12 H); 7.50 (m, 8 H). 13C NMR (CDCl3): δ 18.68 (d, J )
5.1 Hz), 27.37, 75.67 (d, J ) 19.5 Hz), 80.08 (d, J ) 6.5 Hz)
109.43, 128.12, 128.18, 128.25, 128.99, 129.36, 130.01, 130.22,
130.81, 131,03, 142.08 (d, J ) 17.5 Hz), 142.76 (d, J ) 16.2
Hz). 31P NMR (CDCl3): δ 112.54. Elemental analysis for
1,6-Did eoxy-3,4-O-isop r op ylid en e-D-m a n n itol (7). To an
oven-dried 250 mL flask was introduced 68 mL of a 1.0 M
solution in THF of LiEt3BH, followed by 4.22 g (22.66 mmol)
of the diepoxide 6 in 40 mL of THF at 0 °C (ice bath). After
the mixture was stirred at room temperature for 2 h, the excess
hydride was decomposed with water and the organoborane was
oxidized with H2O2 (15 mL of 30% aqueous solution) and
NaOH (15 mL of 3 N aqueous solution) at 0 °C for 1 h. Then
the THF layer was separated, and the aqueous layer was
extracted with diethyl ether-hexane (1:1, v/v). The combined
organic extract was washed with sodium bicarbonate solution,
dried (MgSO4), and evaporated. Column chromatography
(silica gel; 1:3 of ethyl acetate:hexanes) gave 3.66 g (85%) of
7.14 1H NMR (CDCl3): δ 1.28 (d, J ) 6.1 Hz, 6 H), 1.35 (s, 6
H), 3.56 (m, 2 H), 3.72 (m, 2 H), 4.21 (s, 2 H). 13C NMR (CD3-
OD): δ 20.41, 26.81, 69.19, 84.20, 108.73.
1,6-Did eoxy-3,4-O-isop r op ylid en e-L-id itol (11). The title
compound was prepared by a route similar to the previous
experiment. To an oven-dried 250 mL flask was introduced
53 mL of a 1.0 M solution in THF of LiEt3BH, followed by 3.275
g (17.58 mmol) of diepoxide (10)13 in 40 mL of THF at 0 °C
(ice bath). After the mixture was stirred at room temperature
for 2 h, the excess hydride was decomposed with water and
the organoborane was oxidized with H2O2 (10 mL of 30%
aqueous solution) and NaOH (10 mL of 3 N aqueous solution)
at 0 °C for 1 h. Then the THF layer was separated, and the
aqueous layer was extracted with diethyl ether-hexane (1:1,
v/v). The combined organic extracts were washed with sodium
bicarbonate solution, dried (MgSO4), and evaporated. Column
chromatography (silica gel; 1:3 of ethyl acetate:hexanes) gave
2.847 g (85%) of the expected product. 1H NMR (CDCl3): δ
1.21 (d, J ) 6.4 Hz, 6 H), 1.40 (s, 6 H), 2.39 (m, 2 H), 3.72 (m,
2 H), 3.77 (m, 2 H). 13C NMR (CDCl3): δ 20.01, 27.36, 66.97,
81.25, 109.33.
C
33H36O4P2. Calcd: C, 70.96; H, 6.50. Found: C, 71.22; H, 6.68.
1,6-Did eoxy-3,4-O-isop r op ylid en e-L-id it ol Bis(3,5-d i-
m eth ylp h en yl)p h osp h in ite (13b). In a drybox, to a stirring
solution of 0.197 g (1.035 mmol) of (11) and 12 mg of DMAP
in 4 mL of pyridine was added 0.633 g (2.2 equiv) of bis(3,5-
dimethylphenyl)chlorophosphine in 4 mL of CH2Cl2. After
stirring overnight, the mixture was filtered and concentrated.
The residue was purified by flash chromatography eluting with
ether/hexane (1:9) to give 0.295 g (42%) of (13b). 1H NMR
(CDCl3): δ 1.29 (d, J ) 6.3 Hz, 6 H), 1.48 (s, 6 H); 2.31 (s, 12
H), 2.33 (s, 12 H); 4.03 (m, 4 H), 7.05 (m, 4 H); 7.19 (s, 4 H),
7.21 (m, 4 H). 13C NMR (CDCl3): δ 18.76 (d, J ) 5.0 Hz), 21.25,
21.29, 27.34, 75.11 (d, J ) 19.8 Hz), 80.19 (d J ) 6.5 Hz),
109.17, 127.62, 127.84, 128.42, 128.64, 130.70, 131.05, 137.40,
137.44, 137.46, 137.52, 141.81 (d, J ) 17.1 Hz), 142.47 (d, J )
15.9). 31P NMR (CDCl3): δ 114.12 (s). Elemental analysis for
C
41H52O4P2. Calcd: C, 73.41; H, 7.81. Found: C, 72.66; H, 7.97.
1,6-Did eoxy-3,4-O-isop r op ylid en e-L-id itol Cyclic Su l-
fa te (14). The preparation of the cyclic sulfate is based upon
the method used by Burk et al. to prepare similar compounds.10b
The mixture that resulted by addition of 0.63 mL of thionyl
chloride to a solution of 1.32 g (6.93 mmol) of (2S,3R,4R,5S)-
diol 11 in 10 mL of CCl4 was stirred under reflux for 1.5 h.
After cooling, the solvent was evaporated to dryness in a rotary
evaporator. The cyclic sulfite, obtained as a brown oil, was
dissolved in 6 mL of CCl4, 6 mL of CH3CN, and 9 mL of H2O.
After cooling to 0 °C, 12.3 mg of RuCl3‚3H2O and 2.95 g (13.7
mmol) of NaIO4 were added with stirring. Two yellow layers
formed, which gradually became black. Later, a yellow pre-
cipitate appeared, and the solution became yellow again. After
the solution was stirred for 1 h, 40 mL of water and 20 mL of
diethyl ether were added. The two layers were separated, and
the aqueous phase was extracted with 3 × 20 mL of the ether.
The combined organic extracts were washed with 2 × 10 mL
of saturated aqueous solution of NaCl and dried over MgSO4.
(2S ,3S ,4S ,5S )-2,5-Di-O -m e t h a n e su lfo n y l-3,4-O -iso -
p r op ylid en eh exa n etetr a ol (1,6-Did eoxy-3,4-O-isop r op y-
lid en e-L-id itol Dim eth a n esu lfon a te) (12). To a solution of
0.44 g (2.3 mmol) of the diol 11 in 8 mL of pyridine was added
1.0 mL (5.5 equiv) of methanesulfonyl chloride. The mixture

904 J . Org. Chem., Vol. 65, No. 3, 2000
Yan and RajanBabu
The solution was filtered through silica gel, and the volume
was reduced to 3 mL. The addition of hexane (7 mL) and
cooling to -10 °C afforded 1.40 g (80%) of 14 as a colorless,
crystalline solid. 1H NMR (CDCl3): δ 1.35 (d, J ) 6.0 Hz, 3
H), 1.40 (s, 3 H), 1.43 (s, 3 H), 1.59 (d, J ) 6.2 Hz, 3 H), 3.63
(dd, J ) 1.6, 8.2 Hz, 1 H), 4.23 (m, 1 H), 4.48 (dd, J ) 1.6, 8.7
Hz, 1 H), 5.14 (m, 1 H). 13C NMR (CDCl3): δ 16.94, 17.33,
25.97, 27.28, 72.55, 78.19, 80.75, 84.51, 110.05.
was stirred for 2 h. Then 2.2 equiv of n-BuLi (2.2 mL) were
added dropwise at 0 °C, and the orange suspension was stirred
overnight. After 14 h, 8 mL of water was added to the
suspension, and the THF layer was separated. The water
phase was extracted with Et2O (2 × 15 mL). The combined
organic extracts were dried over Na2SO4, and the solvent was
distilled off under reduced pressure. The crude was purified
by flash chromatography on silica gel (elution with ether-
hexane, 5:95, v/v, in the drybox) to obtain 0.246 g (34%) of the
(3aS,4R,6R,6aS)-Tetr ah ydr o-2,2,4,6-tetr am eth yl-5-ph en -
yl-4H-p h osp h olo[3,4-d ]-1,3-d ioxole (15). To phenylphos-
phine (0.110 g, 1.0 mmol) in THF (10 mL) was added n-BuLi
(0.88 mL of 2.5 M solution in hexane, 2.2 equiv) via syringe at
-78 °C over 5 min. Then the orange solution was warmed to
room temperature, and stirring was continued for 1 h. To the
resulting yellow suspension was added a solution of dimesylate
12 (0.346 g, 1.0 mmol) in THF (5 mL) over 5 min, and the
mixture was stirred for an additional 3 h at room temperature.
A few drops of methanol were added to quench any excess
BuLi. The solvent was distilled off. The residue was purified
by flash chromatography on silica gel (elution with ether-
hexane, 1:9, v/v, in the drybox) to obtain 0.150 g (57%) of
1
diphosphine 17 as a white powder. H NMR (CDCl3): δ 0.87
(m, 6 H), 1.35 (m, 6 H), 1.50 (s, 6 H), 1.51 (s, 6 H), 2.44 (m, 2
H), 2.71 (m, 2H), 3.83 (m, 4 H), 7.44 (m 2 H), 7.71 (m, 2 H).
13C NMR (CDCl3): δ 15.23, 17.11 (t, J ) 17.0 Hz), 27.52, 27.60,
28.98, 29.40 (t, J ) 11.0 Hz), 86.74 (t, J ) 7.0 Hz), 89.09,
118.39, 129.39, 132.70, 140.29. 31P NMR (CDCl3): δ 33.71 (s).
Elemental analysis for C24H36O4P2. Calcd: C, 63.99; H, 8.05.
Found: C, 62.76; H, 8.03.
(3a S,3′a S,4S,4′S,6S,6′S,6a S,6′a S)-5,5′-o-P h en ylen e-bis-
[tetr a h yd r o-2,2,4,6-tetr a m eth yl-4H-p h osp h olo[3,4-d ]1,3-
d ioxole] (21). To a solution of 1,2-bis-phosphinobenzene (0.085
g, 0.6 mmol) in 5 mL of THF was added n-BuLi (0.8 mL of 1.6
M solution in hexane) via syringe at -78 °C. Then the solution
was warmed to room temperature and was stirred for an
additional 1 h. After the solution was cooled to 0 °C, a solution
of (2R,3S,4S,5R)-3,4-O-isopropylidene-2,5-di-O-methanesulfo-
nyloxyhexanediol (12′, 0.416 g, 1.2 mmol) in 4 mL of THF was
added, and the mixture was stirred for 2 h. Then 2.2 equiv of
n-BuLi (0.8 mL) were added dropwise at 0 °C, and the orange
suspension was stirred overnight. After 14 h, 8 mL of water
was added to the suspension, and the THF layer was sepa-
rated. The water phase was extracted with Et2O (2 × 15 mL).
The combined organic extracts were dried over Na2SO4, and
the solvent was distilled off under reduced pressure. The crude
was purified by flash chromatography on silica gel (elution
with ether-hexane, 5:95, v/v, in the drybox) to obtain 0.081 g
(30%) of the diphosphine 21 as a white powder. 1H NMR
(CDCl3): δ 0.70 (m, 6 H), 1.31.(m, 6 H), 1.46 (s, 6 H), 1.49 (s,
6 H), 2.53 (m, 2 H), 2.86 (m, 2 H), 4.40 (m, 4 H), 7.35 (m, 4 H).
13C NMR (CDCl3): δ 12.14, 13.72 (t, J ) 16.4 Hz), 24.16, 24.99
(t, J ) 8.7 Hz), 27.28, 27.31, 80.47 (t, J ) 5.5 Hz), 81.37, 117.41,
128.98, 130.56, 140.49 (t, J ) 4.7 Hz). 31P NMR (CDCl3): δ
45.92 (s). Elemental analysis for C24H36O4P2. Calcd: C, 63.99;
H, 8.05. Found: C, 62.00; H, 7.79.
1
monophosphine 15 as an oil. H NMR (CDCl3): δ 0.75 (dd, J
) 6.9, 10.1 Hz, 3 H), 1.40 (dd, J ) 6.8, 18.7 Hz, 3 H), 1.50 (s,
3 H), 1.52 (s, 3 H), 2.32 (m, 1 H), 2.66 (m, 1 H), 3.85 (m, 1 H),
3.98 (m, 1 H), 7.37 (m, 3 H), 7.58 (m, 2 H). 13C NMR (CDCl3):
δ 12.81, 17.12 (d, J ) 31.5 Hz), 27.46, 27.50, 29.15 (d J ) 18.3
Hz), 30.15 (d, J ) 12.9 Hz), 87.50 (d, J ) 10.6 Hz), 88.83,
118.48, 128.17, 128.24, 129.38, 133.21 (d, J ) 27.5 Hz), 134.51,
134.72. 31P NMR (CDCl3): δ 44.24 (s). Elemental analysis for
C
15H21O2P. Calcd: C, 68.17; H, 8.01. Found: C, 67.92; H, 7.99.
(3aS,4S,6S,6aS)-Tetr ah ydr o-2,2,4,6-tetr am eth yl-5-ph en -
yl-4H-p h osp h olo[3,4-d ]-1,3-d ioxole (19). To phenylphos-
phine (180 mg, 1.63 mmol) in THF (10 mL) was added n-BuLi
(1.43 mL of 2.5 M solution in hexane, 2.2 equiv) via syringe at
-78 °C over 5 min. Then the orange solution was warmed to
room temperature, and stirring was continued for 1 h. To the
resulting yellow suspension was added a solution of dimesylate
12′ (566.3 mg, 1.63 mmol) in THF (5 mL) over 5 min, and the
mixture was stirred for 3 h at room temperature. A few drops
of methanol were added to quench any excess BuLi. The
solvent was distilled off. The residue was purified by flash
chromatography on silica gel (elution with ether-hexane, 1:9,
v/v, in the drybox) to give 0.217 g (50%) of monophosphine 19
1
as an oil. H NMR (CDCl3): δ 0.62 (t, J ) 7.2 Hz, 3 H), 1.34
Bisp h osp h ola n e (17) fr om Cyclic Su lfa te 14. To a
solution of 1,2-bisphosphanobenzene (64 mg, 0.45 mmol) in 5
mL of THF was added n-BuLi (0.6 mL of 1.6 M solution in
hexane, 2.0 equiv) via syringe at -78 °C. Then the solution
was warmed to room temperature and stirred for an additional
1 h. After the mixture was cooled to 0 °C, the cyclic sulfate 14
(0.229 g, 0.9 mmol) was added, and the mixture was stirred
for 2 h. Then 2.2 equiv of n-BuLi (0.7 mL) were added dropwise
at 0 °C, and the orange suspension was stirred overnight. After
14 h, 8 mL of water was added to the suspension, and the THF
layer was separated. The water phase was extracted with Et2O
(2 × 15 mL). The combined organic extracts were dried over
Na2SO4, and the solvent was distilled off under reduced
pressure. The crude product was purified by flash chromatog-
raphy eluting with ether-hexane (5:95, v/v, in the drybox) to
obtain the diphosphine 17 as a white powder, identical in all
respects to the sample prepared in the previous experiment.
[[(4S,5S)-2,2-Dim eth yl-1,3-d ioxola n e-4,5-d iyl]d i(R)-eth -
ylid en e]bis[d ip h en ylp h osp h in e] (16). In 100 mL of Schlenk
tube was charged 105 mg of lithium strips, 20 mL of anhydrous
THF, and 1.433 g (6.49 mmol) of chlorodiphenylphosphine. The
mixture was stirred at room temperature for 1 h. The excess
of lithium strips was fetched out by a spatula. The resultant
deep red solution was added to a solution of the dimesylate
(12) (0.75 g, 2.16 mmol) in 10 mL of the same solvent over a
period of 15 min at 0 °C. The mixture was stirred for 6 h at
room temperature. The solvent was distilled off, and the
residue was partitioned between 30 mL of CH2Cl2 and 20 mL
of saturated and degassed NaCl solution. The organic phase
was separated, and the water layer was extracted with CH2-
Cl2 (2 × 10 mL). The combined organic extracts were worked-
up to afford crude, which was purified by flash chromatography
(dd, J ) 7.5, 20.0 Hz, 3 H), 1.48 (s, 3 H), 1.50 (s, 3 H), 2.49 (m,
1 H), 2.62 (m, 1 H), 4.20 (m, 1 H), 4.52 (m, 1 H), 7.39 (m, 5 H).
13C NMR (CDCl3): δ 10.96 (d, J ) 4.3 Hz), 13.54 (d, J ) 30.4
Hz), 24.42 (d, J ) 14.2 Hz), 25.44 (d, J ) 20.2 Hz), 27.21, 27.25,
81.24 (d, J ) 10 Hz), 81.55, 117.71, 128.22, 128.33, 128.70,
133.02, 133.34, 134.32 (d, J ) 26.1 Hz). 31P NMR (CDCl3): δ
50.95 (s). Elemental analysis for C15H21O2P. Calcd: C, 68.17;
H, 8.01. Found: C, 67.87; H, 7.98.
P r ep a r a tion of 15 via th e Cyclic Su lfa te 14. To phen-
ylphosphine (0.083 g, 0.75 mmol) in THF (5 mL) was added
n-BuLi (0.5 mL of 1.6 M solution in hexane) via syringe at
-78 °C. Then the orange solution was warmed to room
temperature, and stirring was continued for 1 h. To the
resulting yellow suspension was added a solution of cyclic
sulfate 14 (0.190 g, 0.75 mmol) in THF (5 mL), and the mixture
was stirred for 2 h at room temperature. Then 1 equiv of
n-BuLi (0.5 mL) was added dropwise at 0 °C, and the orange
suspension was stirred for 3 h. A few drops of methanol were
added to quench any excess BuLi. The solvent was distilled
off. The residue was purified by flash chromatography on silica
gel (elution with ether-hexane, 1:9, v/v, in the drybox) to
obtain the monophosphine 15 as an oil, identical to the sample
prepared earlier from the corresponding dimesylate 12.
(3a S,3′a S,4R,4′R,6R,6′R,6a S,6′a S)-5,5′-o-P h en ylen e-bis-
[tetr a h yd r o-2,2,4,6-tetr a m eth yl-4H-p h osp h olo[3,4-d ]1,3-
d ioxole] (17). To a solution of 1,2-bis-phosphinobenzene (0.226
g, 1.59 mmol) in 10 mL of THF was added via syringe n-BuLi
(2 mL of 1.6 M solution in hexane, 2.0 equiv) at -78 °C. The
solution was warmed to room temperature and stirred for an
additional 1 h. After the mixture was cooled to 0 °C, the
dimesylate 12 (1.101 g, 3.18 mmol) was added, and the mixture

Routes to Phospholanes from Carbohydrates
J . Org. Chem., Vol. 65, No. 3, 2000 905
on silica gel (elution with ether-hexane, 5:95, v/v, in the
drybox) to give 0.561 g (49%) of the diphosphine 16 as a white
powder. 1H NMR (CDCl3): δ 0.88 (d, J ) 6.9 Hz, 3 H), 0.92 (d,
J ) 6.9 Hz, 3H), 1.36 (s, 6 H), 2.48 (m, 2 H), 3.78 (m, 2 H),
7.35 (m, 12 H), 7.54 (m, 8 H). 13C NMR (CDCl3): δ 10.51 (d, J
) 17.2 Hz), 26.86, 31.07 (d, J ) 13.9 Hz), 76.80 (t J ) 6.1 Hz),
108.00, 128.26, 128.33, 128.85, 128.87, 133.49, 133.58, 133.69,
133.78, 136.20 (d, J ) 15.0 Hz), 136.73 (d, J ) 15.2 Hz). 31P
NMR (CDCl3): δ -5.42 (s). Elemental analysis for C33H36O2P2.
Calcd: C, 75.27; H, 6.89. Found: C, 75.36; H, 6.90.
[[(4S,5S)-2,2-Dim eth yl-1,3-d ioxola n e-4,5-d iyl]d i(S)-eth -
ylid en e]bis[d ip h en ylp h osp h in e] (20). To a solution of
diphenylphosphine (0.409 g, 2.2 mmol) in 10 mL of THF at 0
°C was added 0.9 mL of n-BuLi (2.5 M in hexane) dropwise.
The mixture was stirred for 1 h at room temperature. To the
resulting deep red solution was added a solution of (2R,3S,-
4S,5R)-3,4-O-isopropylidene-2,5-di-O-methanesulfonyloxy-
hexanediol (12′, 0.416 g, 1.2 mmol) in 5 mL of THF. The
mixture was stirred overnight at room temperature. After 14
h, 5 mL of water was added to the suspension, and the THF
layer was separated. The water phase was extracted with Et2O
(2 × 10 mL). The combined organic extracts were dried over
Na2SO4, and the solvent was distilled off under reduced
pressure. The crude was purified by flash chromatography
eluting with ether-hexane (5:95, v/v, in the drybox) to obtain
0.332 g (63%) of the diphosphine 20 as a white powder. 1H
NMR (CDCl3): δ 1.16 (m, 6 H), 1.51 (s, 6 H), 2.95 (m, 2 H),
4.37 (m, 2 H), 7.31 (m, 12 H), 7.48 (m, 8 H). 13C NMR (CDCl3):
δ 14.71 (d, J ) 7.6 Hz), 27.37, 32.35 (dd, J ) 5.8, 15.7 Hz),
80.84, 108.13, 127.81, 127.87, 127.93, 128.25, 128.36, 128.42,
133.00, 133.32, 133.97, 134.29, 136.63 (d, J ) 3.4 Hz), 136.86
(d, J ) 8.5 Hz). 31P NMR (CDCl3): δ -10.75 (s). Elemental
analysis for C33H36O2P2. Calcd: C, 75.27; H, 6.89. Found: C,
75.13; H, 6.98.
was quenched by careful addition of 10 mL of H2O (degassed).
The organic layer was separated, and the aqueous phase was
extracted with three 10 mL portions of Et2O. The combined
organic extracts were washed with saturated NaCl solution
and dried over Na2SO4. Removal of the solvent afforded the
crude, which was purified by flash chromatography on silica
gel. Elution with hexane afforded 0.179 g (64%) of 25. 1H NMR
(CDCl3): δ 1.42 (s, 9 H), 3.62 (b s, 1 H), 3.97 (s, 2 H), 4.44 (b
s, 1 H), 7.14 (t, J ) 7.3 Hz, 1 H), 7.25 (ddd, J ) 1.1, 7.4, 14.8
Hz, 1 H), 7.35 (dd, J ) 1.5, 7.5 Hz, 1 H), 7.50 (t, J ) 7.1 Hz,
1 H). 13C NMR (CDCl3): δ 30.71, 33.44 (d, J ) 11.7 Hz), 43.18,
126.95 (d, J ) 4.1 Hz), 128.74, 129.18 (d, J ) 10.0 Hz), 130.00
(d, J ) 2.8 Hz), 136.26 (d, J ) 9.6 Hz), 141.07 (d, J ) 12.5
Hz). 31PNMR (CDCl3): δ -129.64 (s).
(3a S,4R,6R,6a S)-5-[r-(ter t-Bu tylth io)-o-tolyl]-tetr a h y-
d r o-2,2,4,6-t e t r a m e t h yl-4H -p h osp h olo[3,4-d ]-1,3-d iox-
ole (26). To a solution of 25 (0.145 g, 0.68 mmol) in THF (5
mL) was added n-BuLi (0.9 mL of 1.6 M solution in hexane,
2.1 equiv) via syringe at -78 °C. Then the solution was
warmed to room temperature and continued stirring for 1 h.
To the resulting brownish solution was added a solution of
dimesylate 12 (0.236 g, 0.68 mmol) in THF (3 mL), and the
mixture was stirred for 3 h at room temperature. A few drops
of methanol were added to quench any excess BuLi. The
solvent was distilled off. The residue was purified by flash
chromatography on silica gel (elution with ether-hexane, 1:9,
v/v, in the drybox) to give 53 mg (21%) of 26 as an oil. 1H NMR
(CDCl3): δ 0.85 (m, 3 H), 1.35 (m, 3 H), 1.37 (s, 9 H), 1.52 (s,
3 H), 1.55 (s, 3 H), 2.51 (m, 2 H), 3.88 (m, 1 H), 4.08 (m, 3 H),
7.28 (m, 2 H), 7.39 (m, 1 H), 7.67 (m, 1 H). 31P NMR (CDCl3):
δ 28.17 (s).
(3aS,4S,6S,6aS)-5-[r-(ter t-Bu tylth io)-o-tolyl]-tetr ah ydr o-
2,2,4,6-tetr a m eth yl-4H-p h osp h olo[3,4-d ]-1,3-d ioxole (27).
This ligand was prepared in 24% yield by a similar route from
the phosphine 25 and the dimesylate 12′. 1H NMR (CDCl3): δ
0.70 (t, J ) 7.1 Hz, 3 H), 1.32 (m, 3 H), 1.38 (s, 9 H), 1.50 (s,
6 H), 2.43 (m, 1 H), 2.68 (m, 1 H), 3.82 (dd, J ) 1.7, 11.2 Hz,
1 H), 4.19 (dd, J ) 4.2, 11.2 Hz, 1 H), 4.44 (dd, J ) 4.4, 6.4
Hz, 1 H), 4.54 (m, 1 H), 7.26 (m, 2 H), 7.38 (m, 2 H). 13C NMR
(CDCl3): δ 11.24 (d, J ) 4.0 Hz), 14.10 (d, J ) 33.3 Hz), 25.00
(d, J ) 15.2 Hz), 26.66 (d, J ) 19.4 Hz), 27.29, 27.33, 30.84,
32.44 (d, J ) 27.5 Hz), 43.46, 80.95 (d, J ) 12.3 Hz), 81.61,
117.42, 126.95, 129.13, 130.25 (d, J ) 4.5 Hz), 132.28 (d, J )
2.4 Hz). 31P NMR (CDCl3): δ 39.45 (s).
1,6-Did eoxy-3,4-O-isop r op ylid en e-D-m a n n it ol Bis(d i-
p h en ylp h osp h in ite) (18a ). In a drybox, to a stirring solution
of 0.120 g (0.63 mmol) of 7 and 15 mg of DMAP in 4 mL of
pyridine was added 0.306 g (2.2 equiv) of diphenylchlorophos-
phine in 3 mL of CH2Cl2. After stirring overnight, the mixture
was filtered and concentrated. The residue was purified by
flash chromatography on silica gel (elution with ether/hexane
1:9, v/v) to obtain 0.327 g (93%) of 18a as an oil. 1H NMR
(CDCl3): δ 1.32 (d, J ) 6.0 Hz, 6 H), 1.36 (s, 6 H), 4.12 (m, 4
H), 7.29 (m, 6 H), 7.36 (m, 6 H), 7.53 (m, 8 H). 13C NMR
(CDCl3): δ 18.40 (d, J ) 5.5 Hz), 27.82, 77.64 (d, J ) 19.7
Hz), 82.11 (d, J ) 7.5 Hz), 110.00, 128.10, 128.21, 129.09,
129.17, 130.21, 130.47, 130.57, 130.83, 141.84 (d, J ) 16.1 Hz),
142.69 (d, J ) 17.9 Hz). 31P NMR (CDCl3): δ 111.89 (s).
2-[2-(2-Meth ylp r op yl)th iom eth yl]br om oben zen e (23).
To a solution of 2-methyl-2-propanethiol (2.5 mL, 22.2 mmol)
in 100 mL of THF was slowly added KH (0.89 g, 1 equiv) at 0
°C, which was stirred for an additional 2 h. Then a solution of
2-bromobenzylbromide (5.0 g, 20 mmol) in 10 mL of THF was
added. The suspension solution was stirred overnight at room
temperature. After the solution was cooled to 0 °C, a saturated
NH4Cl solution (100 mL) was added, and the organic phase
was separated. The water phase was extracted with Et2O (3
× 30 mL). The combined organic extracts were dried over
anhydrous MgSO4, and the solvent was evaporated. The crude
product was purified by flash chromatography on silica gel
(elution with EtOAc/hexane, 4:96, v/v) to give 5.18 g (99+%) of
1
23 as an oil. H NMR (CDCl3): δ 1.39 (s, 9 H), 3.89 (s, 2 H),
7.08 (m, 1 H), 7.25 (m, 1 H), 7.44 (dd, J ) 1.6, 7.6 Hz, 1 H),
7.53 (d, J ) 7.9 Hz, 1H). 13C NMR (CDCl3): δ 30.79, 33.45,
43.16, 124.31, 127.49, 128.41, 130.98, 132.88, 137.83.
2-(ter t-Bu tylth iom eth yl)p h osp h in oben zen e (25). To a
mixture of 23 (3.00 g, 11.57 mmol), diethyl phosphite (3.19 g,
23.14 mmol), palladium diacetate (130 mg, 0.58 mmol), and
1,4-bis(diphenylphosphino)butane (247 mg, 0.58 mmol) were
added 50 mL of dimethyl sulfoxide and diisopropylethyl-
amine (5.98 g, 46.28 mmol), and the mixture was heated with
stirring at 100 °C for 12 h. After the mixture was cooled to
room temperature, the reaction mixture was concentrated
under reduced pressure to give a dark brown residue. The
residue was diluted with EtOAc, washed twice with water,
dried over MgSO4, and concentrated on the evaporator. The
residue was chromatographed on silica gel (elution with
EtOAc/hexane, 40:60, v/v) to give 2.34 g, 64%) of 24 as an oil.
1H NMR (CDCl3): δ 1.32 (t, J ) 7.1 Hz, 6 H), 1.35 (s, 9 H),
4.12 (m, 6 H), 7.28 (m, 1 H), 7.46 (m, 1 H), 7.60 (t, J ) 6.6 Hz,
1 H), 7. 86 (m, 1 H). 13CNMR (CDCl3): δ 16.26 (d, J ) 6.5 Hz),
30.79, 30.87 (d, J ) 3.8 Hz), 43.06, 62.07 (d, J ) 5.5 Hz), 126.30
(d, J ) 14.3 Hz), 126.51 (d, J ) 183.4 Hz), 131.10 (d J ) 14.1
Hz), 132.42 (d, J ) 2.9 Hz), 133.83 (d, J ) 9.6 Hz), 142.16 (d,
J ) 10. 1 Hz). 31P NMR (CDCl3): δ 20.03 (s).
1,6-Did eoxy-3,4-O-isop r op ylid en e-D-m a n n itol Bis(3,5-
d im eth ylp h en yl)p h osp h in ite (18b). In a drybox, to a stir-
ring solution of 0.120 g (0.63 mmol) of 7 and 15 mg of DMAP
in 4 mL of pyridine was added 0.383 g (2.2 equiv) of bis(3,5-
dimethylphenyl)chlorophosphine in 3 mL of CH2Cl2. After
stirring overnight, the mixture was filtered and concentrated.
The residue was purified by flash chromatography on silica
gel (elution with ether/hexane 1:9, v/v) to give 0.186 g (44%)
of 18b as a white powder. 1H NMR (CDCl3): δ 1.33 (d, J ) 5.5
Hz, 6 H), 1.37 (s, 6 H), 2.25 (s, 12 H), 2.27 (s, 12 H), 4.13 (m,
4 H), 6.93 (s, 2 H), 6.96 (s, 2 H), 7.16 (s, 4 H), 7.19 (s, 4 H). 13
C
NMR (CDCl3): δ 18.24 (d, J ) 5.7 Hz), 21.20, 27.75, 77.29,
82.03 (d, J ) 7.2 Hz), 109.75, 127.85, 128.02, 128.21, 128.38,
130.84, 130.92, 137.42, 137.54, 141.85 (d, J ) 16.4 Hz), 142.51
(d, J ) 17.0 Hz). 31P NMR (CDCl3): δ 112.75 (s).
A solution of 24 (0.418 g, 1.32 mmol) in 5 mL of Et2O was
added dropwise to an ice-cold suspension of LiAlH4 (0.15 g,
3.96 mmol) in 10 mL of the same solvent under nitrogen. The
mixture was stirred for 6 h at room temperature. The reaction

906 J . Org. Chem., Vol. 65, No. 3, 2000
Yan and RajanBabu
Ack n ow led gm en t. This work was supported by the
EPA/NSF Program for Environmentally Benign Syn-
thesis (R826120-01-0) and NSF (CHE-9706766). We
thank Dr. Kurt Loening for assistance with nomencla-
ture of the heterocycles. We are grateful to Digital
Specialty Chemicals for the gift of chemicals in support
of our research programs.
J O991762J