A general, practical, and versatile strategy for accessing ω- functional 1,2-diols of high enantiomeric excess

Full text of DOI:10.1021/jo980844p

8554
J . Org. Chem. 1998, 63, 8554-8557
Sch em e 1
A Gen er a l, P r a ctica l, a n d Ver sa tile
Str a tegy for Accessin g ω-F u n ction a l
1,2-Diols of High En a n tiom er ic Excess
Thomas R. Hoye,* Michael J . Mayer, Tricia J . Vos, and
Zhixiong Ye
University of Minnesota, Department of Chemistry
Minneapolis, Minnesota 55455
ω-Functional 1,2-diols (4) represent a subset of all 1,2-
diols that are particularly versatile subunits for con-
Received May 5, 1998
In tr od u ction
Enantiomerically pure 1,2-diols and 1,2-epoxides are
useful building blocks for synthesis. Methods for access-
ing these substrates include asymmetric dihydroxylation
(AD) and asymmetric epoxidation (AE) of terminal alk-
enes, but the levels of enantiomeric excess of the derived
products are often less than ideal. Considerable effort
has been directed toward improving the Sharpless AD
of 1-alkenes.1 Use of the commercially available ligands
[DHQ(D)]2-PHAL,2 [DHQ(D)]2-PYR,3 and [DHQ(D)]2-
AQN1 provides 1,2-diols such as 2 from simple alkenes 1
with enantiomeric excesses ranging from 76 to 92%. The
use of more exotic ligands does not lead to higher
enantioselectivities for dihydroxylations of this class of
substrate. For certain, more specialized classes of ter-
minal alkene substrates, such as allylic and homoallylic
ethers4 and esters, the % ee’s of the 1,2-diols range higher
using the AD-mix-â reagent (82-95%). In the best case,
allyl 4-methoxybenzoate gave a 98% ee of the glycerol
derivative 3 when a (noncommercially available) py-
ridazine-based DHQD ligand was used.5 Alternatively,
the effect of the bulk oxidant on the enantioselectivity of
the AD has been recently reported. Enantiomeric ex-
cesses of >99% were observed for the diols derived from
many types of alkenes, including monosubstituted, when
iodine (I2) was used as the stoichiometric oxidant in place
of the usual potassium ferricyanide in the AD-mix
system.6 We have reexamined this modification for
terminal alkene substrates (see below) but have not been
able to achieve improved enantiofacial selectivities [vis-
a`-vis the use of K3Fe(CN)6]. Finally, since 1,2-diols can
be easily converted by a variety of methods into 1,2-
epoxides,7-9 it is also relevant that there are no effective
methods for direct asymmetric epoxidation of alkenes
such as 1 to give 1,2-epoxy analogues of 2.10-14,15
structing skeletons of higher complexity. We have often
had need for a variety of such building blocks and have
directed attention toward developing a general and
practical method for the synthesis of a family of ω-func-
tional 1,2-diols of high enantiomeric excess. As now
described, this was achieved by coupling the AD reaction
with a reliable strategy for upgrading the optical purity
of the product 1,2-diols.
Since many of the desired targets 4 are not likely to
be crystalline, simple recrystallization of products of less
than 100% optical purity16 does not constitute a general
solution for obtaining 4 with high enantiomeric excess.
Thus, we looked for an appropriate derivatizing/protect-
ing group for the terminal functionality that would be
expected to render the 1,2-diol products crystalline in
most instances. To also capitalize on the anticipated
greater efficiency of separating diastereomeric (rather
than enantiomeric) impurities from the desired product,16
we first investigated the AD of dienes such as 5, in which
a linking group would render the tetrol products 6
crystalline (see Scheme 1). Fractional crystallization
should then, at least, allow for removal of the meso
diastereomer (6-R,S) and, at best, also enhance the
enantiopurity of the 6-R,R/6-S,S enantiomeric pair. A
related strategy for upgrading the % ee of a chiral,
nonracemic sample has been demonstrated.17,18 In each
(1) Cf. Becker, H.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl.
1996, 35, 448-451 and references therein.
(10) Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J .-R.; Shi, Y. J . Am.
Chem. Soc. 1997, 119, 11224-11235.
(2) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.;
Hartung, J .; J eong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.;
Xu, D.; Zhang, X.-L. J . Org. Chem. 1992, 57, 2768-2771.
(3) Crispino, G. A.; J eong, K.-S.; Kolb, H. C.; Wang, Z.-M.; Xu, D.;
Sharpless, K. B. J . Org. Chem. 1993, 58, 3785-3786.
(4) Wang, Z.-M.; Zhang, X.-L.; Sharpless, K. B. Tetrahedron Lett.
1993, 34, 2267-2270.
(11) Berkessel, A.; Frauenkron, M. J . Chem. Soc., Perkin Trans. 1
1997, 2265-2266.
(12) Barry, J . F.; Campbell, L.; Smith, D. W.; Kodadek, T. Tetrahe-
dron 1997, 53, 7753-7776.
(13) Barf, G. A.; van den Hoek, D.; Sheldon, R. A. Tetrahedron 1996,
52, 12971-12978.
(14) Rasmussen, K. G.; Thomsen, D. S.; J ørgensen, K. A. J . Chem.
Soc., Perkin Trans. 1 1995, 2009-2017.
(5) Corey, E. J .; Noe, M. C.; Guzman-Perez, A. J . Am. Chem. Soc.
1995, 117, 10817-10824.
(15) Tokunaga, M.; Larrow, J . F.; Kakiuchi, F.; J acobsen, E. N.
Science 1997, 277, 936-938.
(6) Torii, S.; Liu, P.; Bhuvaneswari, N.; Amatore, C.; J utand, A. J .
Org. Chem. 1996, 61, 3055-3060.
(16) Wilen, S. H.; Collet, A.; J acques, J . Tetrahedron 1977, 33, 2725-
(7) Kolb, H. C.; Sharpless, K. B. Tetrahedron 1992, 48, 10515-
2736.
10539.
(17) D’Arrigo, P.; Feliciotti, L.; Pedrocchi-Fantoni, G.; Servi, S. J .
Org. Chem. 1997, 62, 6394-6396.
(18) Fleming, I.; Ghosh, S. K. J . Chem. Soc., Chem. Commun. 1994,
99-100.
(8) Murthy, V. S.; Gaitonde, A. S.; Rao, S. P. Synth. Commun. 1993,
23, 285-289.
(9) Hicks, D. R.; Fraser-Reid, B. Synthesis 1974, 203.
10.1021/jo980844p CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/16/1998

Notes
J . Org. Chem., Vol. 63, No. 23, 1998 8555
Ta ble 1. En a n tiofa cia l Selectivity (R vs S) in th e Asym m etr ic Dih yd r oxyla tion of Ter m in a l Alk en e Su bstr a tes w ith
Va r iou s AD Liga n d s a n d Differ en t Oxid a n ts
Sch em e 2
case, a tether was used to covalently link two chiral
molecules. The resulting meso- and d,l-diastereomers
were then separated, and the starting compound, now
of higher % ee, was retrieved following tether removal.
The approach outlined in Scheme 1 is unique in that the
linker (a) is installed prior to the establishment of the
stereogenic centers and (b) can also play a subsequent
beneficial role as a protecting group.
Resu lts a n d Discu ssion
We envisioned that an ideal linker would be readily
Although we planned to eventually elevate the optical
purity of tetrols 10, we first surveyed various AD reaction
conditions to identify those that gave the highest initial
stereoselectivity. We examined the three different com-
mercially available ligands for the Sharpless asymmetric
dihydroxylation: (DHQD)2-PHAL (the ligand contained
in the commercial AD-mix-â reagent),2 (DHQD)2-PYR,3
and (DHQD)2-AQN.1 Additionally, we investigated the
use of iodine (I2) as an alternative oxidant to K3Fe(CN)6.6
The results of these studies are shown in Table 1. In
every case, we used the DHQD version of the ligand
(which tends to give slightly higher enantioselectivity
available, rigid and symmetrical (to promote crystallin-
ity), easy to incorporate, stable to handling and a
manifold of other reaction conditions, and easily and
efficiently removed. Our first choice proved to be a good
one. Hydroquinone (7) was converted to a series of
alkenyl ethers 9 by alkylation with various alkenyl
halides, tosylates, or alcohols (Mitsunobu) 8 (Scheme 2).
Dienes 9 were then subjected to AD under various
conditions. The crude mixture of tetrol products 10 for
each of the 1,4-bis(2-propenyl-, 5-hexenyl-, and 7-octe-
nyloxy)benzenes (9a , 9b, and 9c) was a solid material,
and the d,l-diastereomer was crystalline in every case.

8556 J . Org. Chem., Vol. 63, No. 23, 1998
Notes
Ta ble 2. Ster eoisom er En r ich m en t th r ou gh Rep ea ted
Recr ysta lliza tion
catalyzed carbonylation) and was easily cleaved under
mild, oxidative conditions (CAN, MeCN, H2O, 0 °C).
In conclusion, we have developed a practical and
general route to enantiomerically pure ω-functional 1,2-
diols. Sharpless asymmetric dihydroxylation was used
to install the desired stereogenic center(s); subsequent
recrystallization was used to enhance the optical purity
of the sample. This method should be both convenient
and cost effective for the preparation of a wide variety of
compounds belonging to this class of useful building
blocks.
compd
no. of recrystallizations
R:Sa
yieldb (%)
10a
10a
10b
10b
10b
10b
10b
0
1
0
1
2
3
4
1:49.0
1:>99
19.0:1
24.0:1
32.3:1
40.8:1
46.8:1
93
68
99
72
64
51
43
a
b
See note a in Table 1. Total mass recovery of all isomeric
tetrols.
than the corresponding DHQ-based ligand). There is no
single ligand that shows superior facial selectivity for the
entire set of substrates. In our hands, the use of iodine
rather than K3Fe(CN)6 never gave better stereoselectiv-
ity. For comparison, 5-hexen-1-ol was studied. The
stereoselectivity of the AD of this “parent” ω-hydroxy-1-
alkene was found to be lower than for the analogous 9b,
and since the product (1,2,6-hexanetriol) is a viscous oil,
its optical purity could not be easily enhanced.
Exp er im en ta l Section
P r ep a r a tion of 1,4-bis(5-Hexen yloxy)ben zen e (9b) by
Th r ee Differ en t Meth od s. Meth od A. To a suspension of
potassium carbonate (3.98 g, 28.8 mmol) in DMF (60 mL) were
added hydroquinone (1.05 g, 9.54 mmol) and 6-iodo-1-hexene
(6.01 g, 28.6 mmol) at room temperature. The reaction mixture
was warmed to 100 °C and stirred for 10 h. After being cooled
to room temperature, the mixture was quenched with 10%
aqueous sodium hydroxide (60 mL) and extracted with diethyl
ether (3 × 50 mL). The combined organic solutions were washed
with aqueous saturated sodium chloride, dried over anhydrous
magnesium sulfate, and concentrated. The crude product was
purified by MPLC (80:1 hexane/ethyl acetate) to give the diene
9b (1.86 g, 71%) as a white solid: mp 29.0-30.0 °C; Rf 0.48 (9:1
hexane/ethyl acetate); 1H NMR (500 MHz, CDCl3) δ 6.86 (s, 4H),
5.87 (ddt, J ) 16.8, 10.1, 6.7 Hz, 2H), 5.08 (ddt, J ) 17.1, 1.8,
1.5 Hz, 2H), 5.02 (ddt, J ) 10.1, 1.4, 0.9 Hz, 2H), 3.94 (t, J ) 6.4
Hz, 4H), 2.16 (dt, J ) 7.3, 7.0 Hz, 4H), 1.81 (tt, J ) 6.7, 6.5 Hz,
4H), 1.61 (tt, J ) 7.6, 7.3 Hz, 4H); 13C NMR (125 MHz, CDCl3)
δ 153.2, 138.6, 115.4, 114.7, 68.3, 33.6, 28.9, 25.4; IR (thin film)
3077, 1642, 1511, 1477, 1461 cm-1. Anal. Calcd for C18H26O2:
C, 78.79; H, 9.55. Found: C, 78.69; H, 9.37. Diene 9c was
prepared as a white solid by a similar procedure in 76% yield:
1H NMR (300 MHz, CDCl3) δ 6.83 (s, 4H), 5.90 (ddt, J ) 17.4,
10.4, 6.7 Hz, 2H), 5.14 (ddt, J ) 17.1, 1.5, 1.5 Hz, 2H), 5.07 (ddt,
J ) 10.4, 1.5, 1.5 Hz, 2H), 3.92 (t, J ) 7.0 Hz, 4H), 2.04 (dt, J )
7.3, 7.0 Hz, 4H), 1.7-1.60 (m, 4H), 1.51 (tt, J ) 7.2, 7.3 Hz, 4H),
1.32 (tt, J ) 7.1, 7.1 Hz, 4H); 13C NMR (125 MHz, CDCl3) δ 162.6,
138.1, 116.1, 115.5, 76.2, 69.6, 68.6, 60.5, 33.7, 29.5, 27.0, 26.1,
25.8, 23.1, 21.2; IR (thin film) 3070, 2941, 1642, 1511, 1477, 1461
Each of the tetrols 10a -c is crystalline. Starting with
initial mixtures having total (R/S)(1 ratios (MTPA ester
analysis) typically between 13:1 and 19:1, we found that
recrystallization (∼100 mL of EtOAc per gram of tetrol)
returned material with improved total R/S ratios (Table
2). In every case, material having a ratio of >45:1 was
achievable. For the simplest tetrol, the glycerol deriva-
tive 10a derived from hydroquinone bisallyl ether 9a ,21
a single recrystallization gave material of >99% optical
purity; no minor isomers could be detected in the 1H NMR
spectra of the per-Mosher esters. The R/S ratio of the
higher alkyl tetrols improved by several percent with
each successive recrystallization, but repeated (two to
five) recrystallizations were required to achieve high
levels of isomeric purity. The progress of the upgrading
process for 10a and 10b can be seen from the data in
Table 2. Also, compound 10c having an ultimate R/S
ratio >45:1 could be achieved in two recrystallizations
and 55% yield. For each of 10b and 10c, the recovered
mother liquors (with an R/S ratio of approximately
13:1) could be combined and upgraded to augment the
yield. Changes in solvent for the recrystallization (to
ethyl acetate/ethanol or ethyl acetate/toluene) did not
render the recrystallization more effective at upgrading
product purity. On the basis of these results, our
recommendation is to choose the ligand that gives the
highest initial (R/S)(1 ratio in order to minimize the
number of operations that are required to elevate the
configurational purity to the desired level. This strategy
represents a significant improvement over what can be
achieved with simple R,ω-alkenols.
cm-1
. Anal. Calcd for C22H34O2: C, 79.95; H, 10.37. Found:
C, 80.08; H, 10.09.
Meth od B. To a solution of hydroquinone (551 mg, 5.00
mmol) in THF (10 mL) were added 5-hexen-1-ol (1.67 g, 16.7
mmol) and triphenylphosphine (3.30 g, 12.6 mmol) at room
temperature. Diethyl azodicarboxylate (2.21 g, 12.7 mmol) was
then added dropwise. The reaction mixture was stirred at room
temperature for 24 h. The solution was decanted, and the solids
were washed several times with hexanes. The organic solutions
were combined and concentrated. The residue was purified by
MPLC to give the diene 9b (1.18 g, 86%).
Meth od C. Potassium hydroxide (1.40 g, 25.0 mmol) was
dissolved in absolute ethanol (150 mL) at room temperature.
To this stirred solution were added hydroquinone (0.983 g, 8.94
mmol) and 6-iodo-1-hexene (5.63 g, 26.8 mmol). The solution
was heated to 80 °C and allowed to stir for 24 h. After being
cooled to room temperature, the mixture was diluted with water
and CH2Cl2, and the layers were separated. The aqueous phase
was further extracted with CH2Cl2, and the combined organic
layers were dried over MgSO4, filtered, and concentrated. The
residue was purified by MPLC to give the diene 9b (1.89 g, 77%).
Note: To prepare other 1,4-bis(ω-alkenyloxy)benzenes, method
A was preferred for the preparation of 9a (n ) 0) where a large
excess of the alkenyl halide (i.e., allyl bromide) could be used.
Method B was preferred for 9 (n ) 1; not specifically shown)
due to competing elimination reaction when 4-bromo-1-butene
was used with method A. Method C was preferred when the
alkenyl halide was precious (e.g., 5-iodo-1-hexene and 7-bromo-
or 7-iodo-1-octene).
An additional advantage of this methodology is that
the hydroquinone ether serves as a versatile protecting
group for a primary alcohol that is compatible with many
synthetic transformations. For example, in our recent
synthesis of the annonaceous acetogenin (+)-parviflorin,22
the hydroquinone moiety protected the primary alcohol
during a variety of transformations (diol to epoxide; BF3‚
OEt2-mediated acetylide opening of the epoxide; TBDPS
protection/deprotection; Red-Al® alkyne reduction; Pd0-
(19) Rautenstrauch, V. Bull. Soc. Chim. Fr. 1994, 131, 515-524.
(20) Cf. Takahata, H.; Takahashi, S.; Kouno, S.; Momose, T. J . Org.
Chem. 1998, 63, 2224-2231.
(21) Wang, Z.-M.; Shen, M. J . Org. Chem. 1998, 63, 1414-1418.
(22) Hoye, T. R.; Ye, Z. J . Am. Chem. Soc. 1996, 118, 1801-1802.
[R-(R*,R*)]-6,6′-[1,4-P h en ylen eb is(oxy)]b is-1,2-h exa n e-
d iol (10b). Asym m etr ic Dih yd r oxyla tion w ith K3F e(CN)6.
To a mixture of tert-butyl alcohol (160 mL) and water (175 mL)

Notes
J . Org. Chem., Vol. 63, No. 23, 1998 8557
were added sequentially potassium ferricyanide (33.2 g, 100.8
mmol), potassium carbonate (13.9 g, 100.8 mmol), (DHQD)2-
PYR (0.285 g, 0.32 mmol), and K2OsO4‚(H2O)2 (0.023 g, 0.070
mmol) at room temperature with stirring. Once the solids had
dissolved, the solution was cooled to 0 °C, and a solution of 9b
(4.76 g, 17.4 mmol) in t-BuOH (15 mL) was added. The slurry
was vigorously stirred at 0 °C for 12 h and quenched with Na2-
SO3 (14 g). The mixture was allowed to warm to room temper-
ature with stirring overnight and extracted with ethyl acetate
(3 × 300 mL) and ethyl acetate/ethanol (4:1 v/v, 3 × 300 mL).
The combined organic layers were dried over Na2SO4, filtered,
and concentrated to give the crude tetrol 10b (5.7 g, 97%). The
tetrol was recrystallized as described in the text (∼1 g of tetrol/
100 mL of ethyl acetate): mp 105.0-105.5 °C; Rf 0.45 (4:1 ethyl
(4:1 v/v, 3 × 3 mL). The combined organic layers were dried
over Na2SO4, filtered, and concentrated to give the crude tetrol
(∼100%).
Tetr a -Mosh er Ester of Tetr ol 10b. The tetrol 10b (11
µmol, 3.7 mg) was added to a stirred solution of DMAP (11.1
µmol, 13.4 mg) and pyridine (20 µL) in CH2Cl2 (1 mL). (S)-
Mosher acid chloride (MTPA-Cl, 107 µmol, 20 µL) was added,
and the solution was stirred for 1 h at room temperature. Ether
(5 mL) and saturated aqueous Na2CO3 (5 mL) were added, and
the mixture was stirred for 30 min. The layers were separated,
and the organic layer was washed (1 M aqueous NaHSO4 and
saturated aqueous NaCl), dried over magnesium sulfate, and
concentrated to give the (R)-tetra-Mosher ester (8.1 mg, 61%)
as a clear colorless oil. The product could be purified by flash
chromatography (SiO2, 2:1 hexanes/ethyl acetate) but was often
sufficiently pure for direct analysis. The (S)-Mosher ester was
also prepared by this procedure starting from (R)-MTPA-Cl. For
in situ preparation and analysis of the Mosher ester, the tetrol
(2-5 mg) was stirred in CDCl3 (200 µL) with pyridine (4.8 equiv),
the appropriate MTPA-Cl (4.4 equiv), and DMAP. After 24-48
h at room temperature, the solution was diluted with 500 µL of
CDCl3 and the 1H NMR spectrum recorded.
1
acetate/ethanol); H NMR (500 MHz, DMSO-d6) δ 6.80 (s, 4H),
4.41 (dd, J ) 5.8, 5.5 Hz, 2H), 4.08 (d, J ) 5.2 Hz, 2H), 3.85 (t,
J ) 6.4 Hz, 4H), 3.38 (m, 2H), 3.24 (m, 4H), 1.65 (m, 4H), 1.51
(m, 4H), 1.37 (m, 2H), 1.24 (m, 2H); 13C NMR (125 MHz, DMSO-
d6) δ 153.1, 115.7, 71.5, 68.3, 66.4, 33.6, 29.5, 22.3; IR (KBr
pellet) 3351, 1515, 1473, 1462 cm-1; [R]rt ) +11.9° (c ) 5.44,
D
MeOH). Anal. Calcd for C18H30O6: C, 63.14; H, 8.78. Found:
C, 63.15; H, 8.83. [R-(R*,R*)]-8,8′-[1,4-Phenylenebis(oxy)]bis-
1,2-octanediol (10c) was prepared in similar fashion in 55% yield
of twice-recrystallized (EtOAc) material and 26% yield of
crystalline material recovered from the mother liquors: 1H NMR
(500 MHz, DMSO-d6) δ 6.82 (s, 4H), 4.47 (dd, J ) 5.8, 5.5 Hz,
2H), 4.38 (d, J ) 5.2 Hz, 2H), 3.87 (t, J ) 6.0 Hz, 4H), 3.37 (m,
2H), 3.30-3.22 (m, 4H), 1.69-1.63 (m, 4H), 1.50-1.24 (m, 16H);
13C NMR (125 MHz, DMSO-d6) δ 152.6, 114.7, 71.1, 67.8, 66.0,
33.3, 31.3, 28.8, 25.6, 25.1; IR (KBr pellet) 3351, 1515, 1473,
(R)-Mosh er ester fr om [R-(R*,R*)]-10b. 1H NMR (500
MHz, CDCl3) δ 7.49-7.26 (m, 20H), 6.77 (s, 4H), 5.36 (dddd, J
) 7.0, 7.0, 7.0, 3.0 Hz, 2H), 4.65 (dd, J ) 12.3, 3.0 Hz, 2H), 4.33
(dd, J ) 12.3, 7.0 Hz, 2H), 3.79 (dd, J ) 6.0, 6.0 Hz, 4H), 3.48
(s, 6H), 3.41 (s, 6H), 1.75-1.26 (m, 12H); 19F NMR (282 MHz,
CDCl3) δ -71.85, -72.09.
(S)-Mosh er ester fr om [R-(R*,R*)]-10b. 1H NMR (500
MHz, CDCl3) δ 7.49-7.26 (m, 20H), 6.77 (s, 4H), 5.36 (dddd, J
) 7.0, 7.0, 7.0, 3.0 Hz, 2H), 4.57 (dd, J ) 12.3, 3.0 Hz, 2H), 4.29
(dd, J ) 12.3, 7.0 Hz, 2H), 3.85 (dd, J ) 6.0, 6.0 Hz, 4H), 3.48
(s, 6H), 3.41 (s, 6H), 1.75-1.26 (m, 12H); 19F NMR (282 MHz,
CDCl3) δ -71.85, -72.06.
1462 cm-1
. Anal. Calcd for C22H38O6: C, 66.30; H, 9.61.
Found: C, 66.38; H, 9.75.
Asym m etr ic Dih yd r oxyla tion w ith I2. To a mixture of
tert-butyl alcohol (0.4 mL) and water (0.4 mL) were added
sequentially potassium carbonate (0.060 g, 0.44 mmol), iodine
(0.056 g, 0.22 mmol), (DHQD)2-PYR (0.002 g, 0.0015 mmol),
and K2OsO4‚(H2O)2 (0.004 g, 0.03 µmol) at room temperature
with stirring. Once the solids had dissolved, the solution was
cooled to 0 °C, and a solution of 9b (0.016 g, 0.058 mmol) in
t-BuOH (0.20 mL) was added. The slurry was vigorously stirred
at 0 °C for 18 h and quenched with Na2SO3. The mixture was
allowed to warm to room temperature while being stirred and
extracted with ethyl acetate (3 × 3 mL) and ethyl acetate/ethanol
Ackn owledgm en t. We thank Professor K. B. Sharp-
less for providing a sample of the (DHQD)2-PYR ligand
prior to its becoming commercially available. This work
was supported in part by a grant from the American
Cancer Society (DHP-140).
J O980844P