Dynamic Kinetic Resolution of Secondary Diols via Coupled Ruthenium and Enzyme Catalysis

Article abstract of DOI:10.1021/jo990447u

Enzymatic acylation of secondary symmetrical diols (as meso/dl mixtures) in combination with ruthenium-catalyzed isomerization of the diol led to efficient dynamic kinetic resolution. In this way, a meso/dl mixture of the diol was transformed to enantiomerically pure (R,R)-diacetate, making efficient use of all the diol material. For some of the flexible substrates, substantial amounts of meso-diacetates were formed as side products. The results indicate that the major part of the meso product is formed via an intramolecular acyl-transfer pathway.

Full text of DOI:10.1021/jo990447u

J . Org. Chem. 1999, 64, 5237-5240
5237
Dyn a m ic Kin etic Resolu tion of Secon d a r y Diols via Cou p led
Ru th en iu m a n d En zym e Ca ta lysis
B. Anders Persson,† Fernando F. Huerta,‡ and J an-E. Ba¨ckvall*,‡
Department of Organic Chemistry, Uppsala University, Box 531, SE-751 21 Uppsala, Sweden, and
Department of Organic Chemistry, Stockholm University, Arrhenius Laboratory,
SE-106 91 Stockholm, Sweden
Received March 11, 1999
Enzymatic acylation of secondary symmetrical diols (as meso/dl mixtures) in combination with
ruthenium-catalyzed isomerization of the diol led to efficient dynamic kinetic resolution. In this
way, a meso/dl mixture of the diol was transformed to enantiomerically pure (R,R)-diacetate, making
efficient use of all the diol material. For some of the flexible substrates, substantial amounts of
meso-diacetates were formed as side products. The results indicate that the major part of the meso
product is formed via an intramolecular acyl-transfer pathway.
Sch em e 1
In tr od u ction
We recently reported on an efficient dynamic kinetic
resolution of secondary alcohols employing an enzyme-
catalyzed acylation in combination with a ruthenium-
catalyzed racemization of the substrates (Scheme 1).1 The
reaction gave enantiomerically pure acetates in good
yields with a variety of substrates.
During this work, we found in preliminary experiments
that 2,5-hexanediol (2), as a 1:1 mixture of meso and dl,
also underwent a dynamic kinetic resolution to give
mainly one enantiomer. We have now studied this
reaction in more detail and report on the transformation
of meso/dl mixtures of symmetric diols to the C2-sym-
metric R,R product. This new procedure gives access to
synthetically important C2-symmetric diols in high opti-
cal purity. These diols are a source of chiral auxiliaries
and ligands2 and have been used in the preparation of
enantiomerically pure trans-2,5-disubstituted pyrro-
lidines,3 phospholanes,4 and thiolanes.5
as a 86:14 mixture of (R,R)-3 (>99% ee) and meso-3 (eq
1, entry 1, Table 1). It should be kept in mind that the
Resu lts a n d Discu ssion
Treatment of 2,5-hexanediol (2), with 4 mol % of
ruthenium catalyst 1,6 Novozym 435 (Candida antarctica
lipase B), and 3 equiv of the acyl donor, 4-chlorophenyl
acetate, in toluene at 70 °C gave diacetate 3 in 63% yield
† Uppsala University.
theoretical maximum yield in enzymatic kinetic resolu-
tion of these diols is ca. 25%, because of the meso and dl
forms normally being present in approximately equal
amounts in the starting material.7,8
To avoid the undesired formation of meso-3 in our
system, the effects of altering parameters such as solvent,
concentration, acyl donor, and stoichiometry of the
‡ Stockholm University.
(1) (a) Larsson, A. L. E.; Persson, B. A.; Ba¨ckvall, J . E. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1211. (b) Persson, B. A.; Larsson, A.
L. E.; Le Ray, M.; Ba¨ckvall, J . E. J . Am. Chem. Soc. 1999, 121, 1645.
(2) For the importance of C2-symmetric auxiliaries and ligands in
asymmetric synthesis, see: Whitesell, J . K. Chem. Rev. 1989, 89, 1581.
(3) (a) Short, R. P.; Kennedy, R. M.; Masamune, S. J . Org. Chem.
1989, 54, 1755. (b) Zwaagstra, M. E.; Meetsma, A.; Feringa, B. L.
Tetrahedron: Asymmetry 1993, 4, 2163. (c) Kim, M.-J .; Lee, I. S. Synlett
1993, 767.
(4) (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.
(5) (a) J ulienne, K.; Metzner, P.; Henryon, V.; Greiner, A. J . Org.
Chem. 1998, 63, 4532. (b) Otten, S.; Fro¨hlich, R.; Haufe, G. Tetrahe-
dron: Asymmetry 1998, 9, 189.
(6) This catalyst is readily prepared from Ru3(CO)12 and tetraphenyl
cyclopentadienone: Shvo, Y.; Menashe, N. Organometallics 1991, 10,
3885. For a modified procedure, see ref 1b.
(7) For studies on enzymatic kinetic resolutions of diols, see: (a)
Mattson, A.; O¨ hrner, N.; Hult, K.; Norin, T. Tetrahedron: Asymmetry
1993, 4, 925. (b) Kim, M.-J .; Lee, I. S. J . Org. Chem. 1993, 58, 6483.
(c) Nagai, H.; Moromoto, T.; Achiwa, K. Synlett 1994, 289. (d) Caron,
G.; Kazlauskas, R. J . Tetrahedron: Asymmetry 1994, 5, 657. (e)
Wallace, J . S.; Baldwin, B. W.; Morrow, C. J . J . Org. Chem. 1992, 57,
5231.
(8) Removal of the meso isomer before enzymatic resolution, which
increases the theoretical yield to 50%, has been reported; see ref 7d.
10.1021/jo990447u CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/17/1999

5238 J . Org. Chem., Vol. 64, No. 14, 1999
Persson et al.
Sch em e 2a
Ta ble 1. En zym a tic Acyla tion of Secon d a r y Diols
Cou p led w ith Ru th en iu m -Ca ta lyzed Isom er iza tion
Em p loyin g Ca ta lyst 1a
aKey: (A) K2CO3, MeOH-H2O, rt, 16 h, 82%; (B) MsCl, NEt3,
CH2Cl2, -15 °C, 1 h; (C) BnNH2, rt, 96 h, 53% (two steps).
resulted in problems with solubility of the diol, and
changing to more polar solvents led to no improvements.
For all other substrates the reaction was carried out
under the same conditions as the initial experiment
although at a slightly higher concentration (0.5 M, entries
4-10, Table 1).
Thus, treatment of 2,4-pentanediol (4) under these
reaction conditions afforded diacetate 5 in 90% yield. In
this case, the meso form was the major isomer, giving
the desired (R,R)-5 in a total yield of 34% (entry 4, Table
1), i.e., not much better than a traditional kinetic
resolution would accomplish.10 However, a poor diaste-
reoselectivity for this substrate has previously been
reported in enzymatic kinetic resolution using C. ant-
arctica lipase.7a
Reaction of 2,6-heptanediol (6), prepared by NaBH4
reduction of the corresponding diketone,11 under the same
reaction conditions as above gave the diacetate 7 in 63%
yield (entry 5, Table 1). Neither the enantiomeric excess
nor the R,R/meso ratio could be determined directly on
7,12 and therefore, 7 was transformed to the known 2,6-
dimethylpiperidine 8.13 NMR analysis of 8, as its chiral
salt with (R)-MTPA (PhC(OMe)(CF3)COOH), showed that
the enantiomeric excess was >97% and the ratio (S,S)-
trans-8/cis-8 was 90:10 (Scheme 2). It is not clear at
present whether the small amount of meso compound is
formed in the resolution process or in the transformation
to 8. Cyclization of a 2,5-dimesylate to the corresponding
pyrrolidine has been reported to be stereospecific and to
proceed with complete inversion,3a but in one case a lower
degree of stereospecificity was observed.3b,14 Separation
of cis- and trans-piperidine 8 by chromatographic meth-
ods gave a pure sample of (S,S)-trans-8, of which the
a
The reactions were carried out on a 0.5 mmol scale using 4
mol % of catalyst 1, 3 equiv of 4-chlorophenyl acetate (except in
entries 2 and 3, see text), and 30 mg of enzyme in 1.0 mL of toluene
under argon atmosphere. Isolated yield. c The diastereomeric
b
ratio and ee were determined on the diacetate by using chiral GC
on a J W Cyclodex B column. Enantiomeric excess determined
d
by 1H NMR (acetone-d6) on the diastereomeric salt with (R)-MTPA
after derivatization to 8 (see text). e The diastereomeric ratio and
ee were determined on the bis-2-chlorobenzoic acid ester of the
diol corresponding to the diacetate formed by using chiral HPLC
on a Chirasil OD-H column. f The diasteromeric ratio and ee were
determined on the diol corresponding to the diacetate formed, by
optical rotation was measured; [R]25 +77.0°, c ) 0.64 in
g
using chiral HPLC on a Chirasil OD-H column. Enantiomeric
D
excess determined by 1H NMR (acetone-d6) on the diastereomeric
CHCl3 (lit.12 -72.2°, c ) 3.18 in CHCl3, temperature not
specified).
h
salt with (R)-MTPA. The reaction was carried out at a lower
concentration (0.33 M). The reaction was carried out with 160
mg enzyme/mmol substrate.
i
When the allylic diol 9 was subjected to the same
reaction conditions, a competing reaction deteriorated the
yield of the diacetate (entry 6, Table 1). A considerable
amount (ca. 40% isolated) of the γ-keto acetate was
formed as a result of ruthenium-catalyzed isomerization
of the double bond.15
reagents were investigated. It was found that by increas-
ing the amount of enzyme the reaction time could be
shortened considerably (entries 2 and 3, Table 1). An
improvement of the diastereoselectivity was made using
4-chlorophenyl propionate as the acyl donor, giving the
(R,R)- and meso-diacetate in a 96/4 ratio, although in a
lower yield (entry 2, Table 1).9 Running the reaction with
an even larger acyl donor, the 2-methylpropionate ester,
gave a mixture of (R,R)-3 and meso-3 in an 86/14 ratio
in 61% yield (entry 3, Table 1). Thus, a yield and
selectivity comparable with the initial experiment (entry
1, Table 1) were obtained in only 2 h. Further increasing
the size of the acyl group to the 2,2-dimethylpropionate
gave no reaction, probably because of steric interactions
in the active site of the enzyme. Carrying out the
reactions at higher concentration (>0.5 M on substrate)
The aromatic diols 117e and 137e (entries 7 and 8, Table
1) afforded enantiomerically pure diesters 12 and 14 in
(10) It was possible to separate the two diastereomers, (R,R)-5 and
meso-5, by flash chromatography.
(11) Micheli, R. A.; Hajos, Z. G.; Cohen, N.; Parrish, D. R.; Portland,
L. A.; Sciamanna, W.; Scott, M. A.; Wehrli, P. A. J . Org. Chem. 1975,
40, 675
(12) It was not possible to separate the enantiomers of diacetate 7
or diol 6 by HPLC or GC using the chiral columns specified in the
general Experimental Section. Derivatization to the bis-2-chlorobenzoic
acid ester or mono- or bis-benzyl ether prior to chromatographic
analysis did not improve the separation.
(13) (a) Najdi, S.; Kurth, M. J . Tetrahedron Lett. 1990, 31, 3279. (b)
Boga, C.; Manescalchi, F.; Savoia, D. Tetrahedron 1994, 50, 4709.
(14) In this case, the cyclization was carried out at
temperature (65 °C); see ref 3b.
a higher
(9) Using 4-chlorophenyl acetate as acyl donor under these condi-
tions (160 mg enzyme/mmol substrate) gave (R,R)-3/meso-3 (80/20) in
55% yield after 1.5 h.
(15) Ba¨ckvall, J . E.; Andreasson, U. Tetrahedron Lett. 1993, 34,
5459. See also: Trost, B. M.; Kulawiec, R. J . Tetrahedron Lett. 1991,
32, 3039.

Dynamic Kinetic Resolution of Secondary Diols
J . Org. Chem., Vol. 64, No. 14, 1999 5239
Sch em e 3. F or m a tion of Meso Com p ou n d by
ruthenium catalyst in combination with enzymatic acy-
lation resulted in full transformation of the diol to
enantiomerically pure diacetate. The yields and selectivi-
ties were consistently high, and in most cases ee’s were
>99%.
In tr a m olecu la r Acyl Tr a n sfer
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. 1H and 13C NMR
spectra were recorded in CDCl3 at 400 and 100 MHz, respec-
tively. Solvents for extraction and chromatography were
technical grade and distilled. Column chromatography was
performed with Merck 60 silica gel. Analytical high-pressure
liquid chromatography (HPLC) was performed employing a
Daicel, Chiralcel OD-H column. Solvents for HPLC use were
spectrometricgrade. Flow parameters were isocratic at the
stated conditions: method (hexane/iPrOH, 0.5 mL/min). GLC
analyses were performed with the following columns: Rescom
SE54 and J W Cyclodex B.
76 and 77% yield, respectively, and, importantly, with
high diastereoselectivities (<2% meso). The pyridine
derivative 157e behaved similarly, and diacetate 16 was
isolated in 78% yield as a single enantiomer with no
detectable amount of the meso isomer (entry 9, Table 1).
The corresponding diol is a useful precursor for enantio-
merically pure tridentate diphosphine ligands.16 Amino-
diol 1717 gave a result comparable to that of heptanediol
6 in terms of both yield and diastereoselectivity, produc-
ing diacetate 18 in 64% yield with an R,R/meso ratio of
89:11 (entry 10, Table 1). We were not able to separate
these diastereomers, but an estimate of the enantiomeric
All reactions were carried out under dry argon atmosphere
in oven-dried (140 °C) glassware except for those reactions
utilizing water as a solvent, which were run in air. Novozym
435 (C. antarctica lipase B; 8200 U/g) was a generous gift from
Novo Nordisk A/S, Denmark. Substrate 4 was commercially
available and used without further purification. 2,5-Hexanediol
2 and 2,6-heptanediol 6 were prepared by NaBH4 reduction
of commercially available 2,5-hexanedione and 2,6-heptanedi-
one11 using standard techniques. Compounds 1,6 9,21 11,7e 13,7e
15,7e and 1717a were prepared following literature procedures.
Gen er a l P r oced u r e for th e Ru th en iu m - a n d En zym e-
Cou p led Resolu tion of Secon d a r y Diols. Catalyst [Ru2-
(CO)4(µ-H)(C4Ph4COHOCC4Ph4] (1) (22 mg, 0.02 mmol) and
Novozym 435 (30 mg) were placed in a long Schlenk flask, and
the atmosphere was changed to argon. Argon was bubbled
through a solution of R,R′-dihydroxy-1,3-diethylbenzene (11)
(83 mg, 0.5 mmol; dl/meso ∼50/50) and 4-chlorophenyl acetate
(0.26 g, 1.5 mmol) in toluene (1.0 mL), followed by transfer to
the ruthenium catalyst and enzyme. The reaction was stirred
under argon for 24 h at 70 °C. The reaction mixture was
filtered and separated on silica (pentane/Et2O 9:1) to yield R,R′-
diacetoxy-1,3-diethylbenzene (12) (95 mg, 76%). The NMR-
spectra were in agreement with the data previously reported
in the literature.7e Diacetate 12 (85 mg, 0.51 mmol) was
hydrolyzed by treatment with K2CO3 (207 mg, 1.5 mmol) in
methanol/water (4:1) for 16 h at room temperature. The
methanol was evaporated, and the aqueous phase was ex-
tracted with Et2O (4 × 20 mL). The combined organic phases
were washed with brine, dried over Na2SO4, and reduced in
vacuo. The residue was filtered through a short plug of Celite
(Et2O) to give diol 11 (56 mg, 99%).The ee and diastereomeric
ratio were determined by chiral HPLC analysis (hexane/iPrOH
9:1): ee >99%, R,R/meso 98/2, racemic/meso 11 was used as
reference.
1
excess was obtained by H NMR analysis of the diaster-
eomeric salt formed upon addition of (R)-MTPA.
In a previous report on the enzymatic resolution of
diols using C. antarctica lipase, it was shown that
considerable amounts of the meso-diacetate were formed
when diol 4 was employed as the substrate.7a The authors
proposed two possible reasons for its formation: (i) an
intramolecular acyl transfer from the (R)-acetate to the
(S)-alcohol in the monoacylated (R,S)-diol with subse-
quent enzyme-catalyzed acylation of the (R)-alcohol func-
tion released would give the meso-diacetate (Scheme 3);18
(ii) the selectivity of the enzyme may differ for the diol
and the monoacetylated product. Thus, if the acylation
of the (S)-alcohol group in the (R)-acetoxy monoacetate
of the (R,S)-diol is comparable in rate to the acylation of
the (R,R)-diol, this would lead to formation of the meso
compound.19,20
Our results support the first explanation since a clear
trend in diastereoselectivity can be seen on going from
pentanediol 2 to heptanediol 6. A highly favored six-
membered transition state for the pentanediol leads to
a large amount of meso compound, which decreases with
increased chain length. Further evidence in favor of the
intramolecular acyl-transfer mechanism is given by the
nonflexible aromatic substrates 11, 13, and 15, which all
give significantly lower amounts of the corresponding
meso-diacetates.
2,5-Dia cetoxyh exa n e (3). Following the general procedure,
but using 1.5 mL of toluene and running the reaction 48 h,
diol 2 gave diacetate 3 in 63% yield. The ee and diastereomeric
ratio were determined on 3 by chiral GC; ee >99%, R,R/meso
86/14. The NMR spectra were in agreement with the data
previously reported in the literature.1b
2,4-Dia cetoxyp en ta n e (5). Following the general proce-
dure, diol 4 gave diacetate 5 in 90% yield. The ee and
diastereomeric ratio were determined on 5 by chiral GC; ee
>99%, R,R/meso 38/62. The NMR spectra were in agreement
with the data previously reported in the literature.22
Con clu sion
We have demonstrated that an in situ isomerization
of a substrate diol, as a mixture of dl/meso, by a
2,6-Dia cetoxyh ep ta n e (7). Following the general proce-
dure, diol 6 gave diacetate 7 in 63% yield. H NMR, δ: 4.87
(m, 2H), 2.01 (s, 6H), 1.64-1.20 (m, 6H), 1.91 (d, J ) 6.2 Hz,
1
(16) Sablong, R.; Newton, C.; Dierkes, P.; Osborn, J . A. Tetrahedron
Lett. 1996, 37, 4933.
(17) (a) Dubois, L.; Fiaud, J .-C.; Kagan, H. B. Tetrahedron 1995,
51, 3803. (b) Zhang, H.-C.; Harris, B. D.; Costanzo, M. J .; Lawson, E.
C.; Maryanoff, C. A.; Maryanoff, B. E. J . Org. Chem. 1998, 63, 7964.
(18) Liu, K. K.-C.; Nozaki, K.; Wong, C.-H. Biocatalysis 1990, 3, 169.
(19) An observation where the rate of the first acylation of the slow
reacting S,S isomer of diol 4 is of the same magnitude as the second
acylation of the fast reacting R,R isomer in a lipase catalyzed kinetic
resolution has been reported: Guo, Z.-W.; Wu, S.-H.; Chen, C.-S.;
Girdaukas, G.; Sih, C. J . J . Am. Chem. Soc. 1990, 112, 4942.
(20) The (S,S)-4 isomer has been shown to be almost totally
unreactive toward acylation using lipase from C. antarctica; see ref
7a.
(21) Ba¨ckvall, J . E.; Bystro¨m, S. E.; Nordberg, R. E. J . Org. Chem.
1984, 49, 4619.
(22) Itoh, O.; Ichikawa, Y.; Katano, H.; Ichikawa, K. Bull. Chem.
Soc. J pn. 1976, 49, 1353.

5240 J . Org. Chem., Vol. 64, No. 14, 1999
Persson et al.
6H). 13C NMR δ: 170.6, 70.7, 35.6, 21.32, 21.27, 19.9. The ee
and diastereomeric ratio were determined after derivatization
to the known piperidine 8,13 which was obtained as a 90:10
mixture of (S,S)-trans-8 and cis-8 with >97% ee of the S,S
enantiomer (see below).
Cl2 (3 mL) was added 2-chlorobenzoic acid (97 mg, 0.62 mmol),
and the reaction was stirred at room temperature until judged
complete by TLC. The mixture was filtered through a short
plug of Celite (Et2O), and the organic phase was washed with
1.2 M HCl and 2 M NaOH and subsequently dried over Na2-
SO4. After evaporation of the solvents, the residue was
chromatographed (pentane/Et2O 9:1) to give 2,5-bis(2-ch lo-
r oben zoyloxy)-3-h exen e in quantitative yield. 1H NMR
(mixture R,R/meso), δ: 7.80 (m, 2H), 7.46-7.37 (m, 4H), 7.31
(m, 2H), 5.94 (m, 2H), 5.65 (m, 2H), 1.47 (d, J ) 6.4 Hz, 6H).
13C NMR (mixture R,R/meso), δ: 164.9, 133.5, 132.3, 131.5,
131.3, 131.2, 131.0, 130.6, 126.5, 71.5, 71.4, 20.19, 20.16. The
ee and diastereomeric ratio were determined by HPLC analysis
(hexane/iPrOH 96:4); R,R/ meso 74:26; ee >99%.
r,r′-Dia cetoxy-1,4-d ieth ylben zen e (14). Following the
general procedure, diol 13 gave diacetate 14 in 77% yield. The
NMR spectra were in agreement with the data previously
reported in the literature.7e The ee and diastereomeric ratio
were determined by HPLC analysis after hydrolysis of the
diacetate as described above for diacetate 12 (hexane/iPrOH
9:1); R,R/meso 98:2; ee >99%.
r,r′-Dia cetoxy-1,3-d ieth ylp yr id in e (16). Following the
general procedure, diol 15 gave diacetate 16 in 78% yield. The
NMR spectra were in agreement with the data previously
reported in the literature.7e The ee and diastereomeric ratio
were determined by HPLC analysis after hydrolysis of the
diacetate as described above for diacetate 12 (hexane/iPrOH
9:1); R,R/meso 100:0; ee >99%.
N,N-Bis-(2-a cetoxyp r op yl)ben zyla m in e (18). Following
the general procedure, diol 17 gave diacetate 18 in 64% yield
as a 89:11 mixture of R,R/meso. 1H NMR, δ: 7.32-7.20 (m,
5H), 5.03 (m, 2H), 3.66 (s, 2H), 2.65 (dd, J ) 13.4, 6.8 Hz, 2H),
2.50 (dd, J ) 13.4, 5.6 Hz, 2H), 2.01 (2, 6H), 1.17 (d, J ) 6.3
Hz, 6H). 13C NMR δ: 170.5, 139.1, 128.8, 128.1, 127.0, 69.0,
59.8, 59.3, 21.3, 18.2. The ee was determined by 1H NMR
(acetone-d6) on the benzylic protons after treatment with 1
equiv of (R)-MTPA (PhC(OMe)(CF3)COOH); ee >97%.
2,6-Dim eth yl-N-ben zylp ip er id in e (8). Diacetate 7 (268
mg, 1.24 mmol) was hydrolyzed by treatment with K2CO3 as
described above for diacetate 12 to give 2,6-heptanediol 6 (134
mg, 82%). According to ref 3a, a solution of diol 6 (128 mg,
0.97 mmol) and NEt3 (0.35 mL, 2.52 mmol) in CH2Cl2 (4 mL)
was cooled to -15 °C. Methanesulfonyl chloride (0.18 mL, 2.32
mmol) was added dropwise while the temperature was main-
tained between -20 and -15 °C. After the addition was
complete, the mixture was allowed to warm to 0 °C and then
poured into cold 1 M HCl (10 mL). The phases were separated,
and the aqueous phase was extracted with CH2Cl2 (3 × 15 mL).
The combined organic phases were washed with saturated Na2-
CO3(aq) (10 mL) and dried over Na2SO4. Filtration and
evaporation of the solvent gave the bis(methanesulfonate) as
a colorless oil, which was used in the next step without further
purification. The dimesylate was dissolved in benzylamine and
stirred at ambient temperature for 96 h. The reaction mixture
was poured into cold 2 M NaOH (20 mL) and extracted with
pentane (3 × 20 mL). After drying over Na2SO4, filtration, and
evaporation of the solvent, 1H NMR analysis of the residue
showed a 90:10 mixture of trans- and cis-8. The excess
benzylamine was distilled off, and chromatography (pentane)
of the residue afforded the title compound as a colorless oil as
a 90:10 mixture of trans- and cis-8 (104 mg, 53%). The first
fraction contained pure trans-8: [R]25D +77° (c ) 0.64, CHCl3)
(lit.13 -72.2°, c ) 3.18 in CHCl3, temperature not specified).
The NMR spectra were in agreement with the data previously
reported in the literature.13b The ee was determined by 1H
NMR (acetone-d6) on the benzylic protons after treatment with
1 equiv of (R)-MTPA (PhC(OMe)(CF3)COOH); ee >97%.
2,5-Dia cetoxy-3-h exen e (10). Following the general pro-
cedure, diol 9 gave diacetate 10 in 43% yield. The NMR spectra
were in agreement with the data previously reported in the
literature.21 The diacetate was hydrolyzed and derivatized with
2-chlorobenzoic acid before determination of ee and de. Diac-
etate 10 (62 mg, 0.31 mmol) was hydrolyzed as described above
for diacetate 12 to give 2,5-hexenediol (9) (30 mg, 83%), which
was used without further purification in the next step. To a
magnetically stirred solution of diol 9 (30 mg, 0.26 mmol), DCC
(128 mg, 0.62 mmol), and DMAP (1.6 mg, 0.013 mmol) in CH2-
Ackn owledgm en t. Financial support from the Swed-
ish Natural Science Research Council, the Swedish
Research Council for Engineering Sciences, and the
Swedish Foundation for Strategic Research is gratefully
acknowledged.
J O990447U