Asymmetric oxidation of enol phosphates to α-hydroxy ketones by?(salen)manganese(III) complex. Effects of the substitution pattern of enol phosphates on the stereochemistry of oxygen?transfer

Article abstract of DOI:10.1016/j.tet.2006.09.100

This paper presents a study of enantioselective catalytic oxidation of a variety of differently substituted, cyclic (E) and acyclic (Z)-enol phosphates. The asymmetric oxidation of acyclic (Z)-enol phosphates containing alkoxy substituents in the phosphate group 2a, c, e-g, i, and j and Z-configured enol phosphates containing aryloxy substituents in the phosphate group 2b, d, and h afforded optically active α-hydroxy ketones 4a-j of opposite configuration with good to high enantioselectivity. The influence of electronic and steric effects of the enol phosphate substituents on the stereoselectivity of oxidation was studied.

Full text of DOI:10.1016/j.tet.2006.09.100

Tetrahedron 62 (2006) 12363–12374
Asymmetric oxidation of enol phosphates to a-hydroxy ketones
by (salen)manganese(III) complex. Effects of the substitution
pattern of enol phosphates on the stereochemistry of
oxygen transfer
*
Marek Koprowski, Jerzy quczak and Ewa Krawczyk
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Heteroorganic Chemistry,
Sienkiewicza 112, 90-363 Łoꢀdꢀz, Poland
Received 30 June 2006; revised 11 September 2006; accepted 28 September 2006
Available online 27 October 2006
Abstract—This paper presents a study of enantioselective catalytic oxidation of a variety of differently substituted, cyclic (E) and acyclic
(Z)-enol phosphates. The asymmetric oxidation of acyclic (Z)-enol phosphates containing alkoxy substituents in the phosphate group 2a,
c, e–g, i, and j and Z-configured enol phosphates containing aryloxy substituents in the phosphate group 2b, d, and h afforded optically active
a-hydroxy ketones 4a–j of opposite configuration with good to high enantioselectivity. The influence of electronic and steric effects of the
enol phosphate substituents on the stereoselectivity of oxidation was studied.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Enol phosphates constitute a class of important organic com-
pounds exhibiting biological activity.9 They are very easy to
prepare.10 However, the utility of enol phosphates in organic
synthesis is still limited.11
The a-hydroxy carbonyl unit is found in many biologically
active natural products such as sugars and antibiotics.1 Enan-
tiomerically pure a-hydroxy carbonyl compounds are also
important synthons for the asymmetric synthesis of natural
products.1a,2 Consequently, efficient methods for the con-
struction of enantiomerically pure, or at least enriched,
a-hydroxy carbonyl derivatives are in demand.3 This class of
compounds has been prepared by both nonoxidative4 and
oxidative methods.3a,b,5 Among the latter, the asymmetric
oxidation of enolate or enol ethers using chiral N-sulfonyl-
oxaziridine3a or a Sharpless dihydroxylation catalyst3b has
been applied with success. Epoxidation is among the most
useful oxidation reactions, since the epoxides may be trans-
formed by stereoselective ring opening into highly function-
alized products.6 A recent major advance in catalytic
enantioselectiveepoxidation is oxidation of prochiral unsatu-
rated compounds with readily accessible (salen) Mn(III)
complexes. It has been demonstrated that these complexes
are highly enantioselective catalysts for the epoxidation of
various conjugated substituted olefins,7 enol ethers,5a,8 and
esters.5a,8a These epoxy derivatives were easily converted
into optically active a-hydroxy carbonyl compounds.
We have previously described the application of cyclic enol
phosphates in the stereoselective synthesis of newly func-
tionalized polycyclic compounds including functionalized
enol phosphates with an allyl hydroxy group. We also found
that epoxidation of these compounds led to a-hydroxy
ketones.12 We then elaborated methodology, based on
epoxy phosphate intermediates,12,13 for an alternative gen-
eral synthesis of acyclic and cyclic a-hydroxy carbonyl com-
pounds.14
In a recent paper15 we showed that readily available enol
phosphates can be stereoselectively oxidized to a-hydroxy
ketones with high enantioselectivity using (salen) Mn(III)
Jacobsen’s catalyst 116 (Fig. 1). We observed that reactions
H
H
1
N
N
Mn
O
O
Cl
Keywords: Enol phosphates; Asymmetric oxidation; a-Hydroxy ketones;
Jacobsen’s catalyst.
* Corresponding author. Tel.: +48 42 680 32 16; fax: +48 42 684 71 26;
e-mail: ewakrsoj@bilbo.cbmm.lodz.pl
Figure 1. (R,R)-(ꢀ)-N,N0-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclo-hex-
anediamino manganese(III) chloride.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.100

12364
M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
of asymmetric epoxidation of enol phosphates bearing
phenoxy instead of ethoxy substituents at phosphorus led to
a-hydroxy ketones of opposite configuration to that of other
a-hydroxy carbonyl compounds obtained. We decided to
develop these studies, which could provide an insight into
factors controlling stereoinduction in the epoxidation of
enol phosphates.
Catalytic oxidation of phosphates 2a–j was carried out with
NaOCl in phosphate buffer (pHw11) as oxygen source,
4-phenylpyridine N-oxide (PPNO) as additive and 7% of
(salen) Mn(III) complex 1 as catalyst.7b,19 The best conver-
sion of enol phosphates to a-hydroxy ketones was achieved
in the oxidation performed at 0 ꢁC for 24 h. Opening of
the intermediate epoxides 3 was carried out with 25%
CF3COOH at 5 ꢁC (Scheme 1) and pure a-hydroxy ketones 4
were obtained by flash chromatography. All the results of
epoxidation of enol phosphates 2 are summarized in Table 2.
2. Results and discussion
We first prepared a set of enol phosphates 2 (Table 1),
substituted with phenyl in the a-position and alkyl or phenyl
in the b-position, which would afford the more persistent
a-hydroxy ketones. Besides the phosphates containing
ethoxy groups at phosphorus atom, the phosphorus com-
pounds with bulky alkoxy and phenoxy groups at phospho-
rus were also chosen for oxidation. This allowed us to test
the influence of steric and electronic aspects of the substrates
on the stereochemistry of their asymmetric epoxidation. All
compounds 2a–j were obtained by the reaction of dialkyl
(R¼Et, i-Pr, and t-BuCH2) and diaryl (R¼Ph and p-MeO–
Ph) phosphorochloridates with enolate anions. The latter
were generated from the appropriate ketones by action of
LDA.10d
(Z)-Configured enol phosphates 2a, c, f, g, and j with an
alkyl substituent b to the phosphate group afforded S enan-
tiomers of the corresponding a-hydroxy ketones 4a, c, f,
and j with high ee (83–96%) (entries 1, 3, 6, 7, and 10).
Catalytic oxidation of enol phosphate 2i containing a phenyl
group in both a- and b-positions gave the benzoin 4i with
89% ee (entry 9), whereas oxidation of diphenyl substituted
silyl enol ether by chiral complex 1 led to the formation of
benzoin with only 12% ee.5a
To test the steric influence of the phosphoryloxy group on
asymmetric induction and enantioselectivity, enol phos-
phates with bulkier isopropoxy (R¼i-Pr, R1¼Pr) 2g and
neopentoxy substituents (R¼t-BuCH2, R1¼Et) 2e were
selected. Compound 2g afforded (S)-configured a-hydroxy
ketone 4g with 88% ee, which is only a slightly better value
than for 2f (R¼Et, R1¼Pr), ee¼83% (entries 6 and 7). For
compound 2e enantioselectivity is very low (13% estimated
Table 1. Acyclic Z-enol phosphates 2
2
R1
Ar
R
a
b
c
d
ea
f
g
h
ia
j
Me
Me
Et
Et
Et
Pr
Pr
Pr
Ph
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Et
Ph
Et
Ph
t-BuCH2
Et
i-Pr
4-MeOC6H4
Et
Et
Table 2. Enantioselective synthesis of a-hydroxy ketones 4a, 4c, 4f, 4i, and
4j by catalyst (R,R)-(ꢀ) salen Mn(III) 1 with NaOCl
Entry Substrate Product Yielda(%) eeb(%) Config.c of 4
O
R1
H
OP(OR)2
Ar
2a-j
1
2
3
4
5
6
7
8
9
10
2a
2b
2c
2d
2e
2f
2g
2h
2i
4a
4a
4c
4c
4c
4f
4f
4f
4i
57
47
50
58
50
58
70
50
56
60
96
68
93
81
13d
83
88
68
89
87
S-(ꢀ)
R-(+)
S-(ꢀ)
R-(+)
S-(ꢀ)
S-(ꢀ)
S-(ꢀ)
R-(+)
S-(+)
S-(ꢀ)
Ph
4-MeOC6H4
a
Mixture of E and Z isomers.
Most enol phosphates 2 were formed as single isomers. All
compounds had Z-configuration, assigned on the basis of 1H
NMR spectral analysis and in particular for compound 2g on
the observation of a positive nuclear Overhauser effect
(NOE)—a 3% increase in area for the vinyl proton cis to
phenyl.17 Z-Configuration of the other enol phosphates was
determined by comparison of the chemical shift of vinyl pro-
tons and the coupling constant (4JPH) observed for 2g and
2a–d, f, and h–j18 and additionaly by a NOESY experiment
carried out on compound 2d.
2j
4j
a
Yield of pure, isolated compounds 4 (not optimized) based on enol phos-
phates 2.
Determined by HPLC analysis (Chiracel OD, for details see Section 4)
using racemic compounds as references.
Configurations were assessed by comparison of sign of the optical rotation
with literature data, for 4f in analogy to the elution order of the enantio-
mers of 4a and 4c (see Section 4).
Enantiomeric excess was estimated by comparison of values of optical
rotation of S-(ꢀ)-a-hydroxy ketones 4f.
b
c
d
O
R1
H
OP(OR)2
O
R1
H
OP(OR)2
O
O
NaOCl
O
Ar
R1
H3O
R1
0°C
or
or
Ar
Ar
O
Ar
(R, R)-salen 1
R1
OH
(R)-4a, c, f
OH
(S)-4a, c, f, i, j
OP(OR)2
2a-j
PPNO
H O Ar
3a-j
Scheme 1. Asymmetric oxidation of enol phosphates 2 by (R,R)-(ꢀ) salen Mn(III) catalyst 1.

M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
12365
Table 3. Enantioselective synthesis of a-hydroxy ketones 7a and 7c–e by
catalyst (R,R)-(ꢀ) (salen) Mn(III) 1 with NaOCl
Entry Substrate Product Yielda(%) eeb(%) Config. of 6c
on optical rotation of 4c compared to reported data), but the
starting enol phosphate 2e is a mixture of Z and E isomers.
Enol phosphates 2b, d, and h, bearing phenoxy groups at
phosphorus, afforded R enantiomers of a-hydroxy ketones
4a, c, and f with enantiomeric excess of 68–81% (Table 2,
entries 2, 4, and 8). Comparing the absolute configuration
of these products with the S configuration of 4a, c, and f ob-
tained from enol phosphates 2a, c, f, and g (entries 1, 3, 6,
and 7) reveals that the change of R substituent in phosphate
group from Alk (2a, c, f, and g) to Ar (2b, d, and h) leads to
the opposite absolute configuration of a-hydroxy ketones
formed, and has influence on the enantioselectivity of the
oxidation. Decrease in enantioselectivity was observed for
2b—68% ee compared to 96% ee for 2a; 81% ee for 2d ver-
sus 93% ee for 2c and 68% ee for 2h compared to 83–88% ee
for 2f and g (entries 1–4 and 6–8). Oxidation of the enol
phosphate with electronically modified phenoxy groups
(R¼4-MeOC6H4) 2h afforded the corresponding a-hydroxy
ketone 4f of R configuration (entry 8). This stereochemical
result confirms that the phenoxy substituents in enol phos-
phates are responsible for the opposite sense of asymmetric
induction in these oxidations.
1
2
3
4
5
6
5a
5b
5c
5d
5e
5f
7a
7a
7c
7d
7e
7e
37
35
54
22
57
49
89
88
94
81
69
60
S-(ꢀ)
S-(ꢀ)
S-(+)d
R-(+)d
R-(+)
R-(+)
a
b
c
d
Yield of isolated pure compounds 7 (not optimized) based on enol phos-
phates 5 (see text).
Determined by HPLC analysis (Chiracel OD, for details see Section 4)
using racemic compounds as references.
Configurations were assessed by comparison of the sign of optical rotation
with literature data (see Section 4).
Absolute configurations were assigned by comparing circular dichroism
(CD) spectra of the purified a-hydroxy ketones 7c and 7d to the CD spec-
trum of (S)-2-hydroxy tetralone 7a (see Supplementary information).
The degree of conversion of cyclic enol phosphates 5a, b,
and d to a-hydroxylated products 7a and d is not as good
as for phosphates 5c, e, and f (Table 3). Low yields of 7a
and d are due in part to the participation of an aromatization
pathway leading to the corresponding naphthalene and phen-
anthrene derivatives.7c
In order to determine the usefulness of enol phosphates as
prochiral substrates for metal-catalyzed oxidation by a chiral
oxygen complex, and to test the influence of the substitution
pattern of the enol phosphate substrates on the stereo-
chemistry, further studies with cyclic compounds were
undertaken. We chose bi- and tricyclic systems containing
enol phosphate and aromatic moieties. Similar a-hydroxy
ketones simulate functionalities in natural products.20
Oxidation of enol phosphates 5a, b, and c afforded (S)-(ꢀ)-
2-hydroxy tetralone 7a and (S)-(+)-2-hydroxy benzosuber-
one 7c in high enantioselectivity 88–94% (Table 3, entries
1–3). High enantioselectivity 81% was also observed for
the oxidation of the enol phosphate 5d but for 7d the R con-
figuration prevailed (Table 3, entry 4).
Stereoselectivity of the oxidation of tetrasubstituted enol
phosphates 5e and f leading to (R)-(+)-2-hydroxy-2-methyl-
1-indanone 7e is substantially lower at 69–60% ee (Table 3,
entries 5 and 6).
The corresponding enol phosphates 5a–f (Fig. 2) were pre-
pared according to the procedure described above. Pure
5a–f were the subject of asymmetric epoxidation, performed
as before and after hydrolysis of the intermediate epoxides 6
the a-hydroxy ketones 7 were obtained and isolated by flash
chromatography (Fig. 3). Their enantiomeric purity was
determined by chiral HPLC (Table 3).
The change of substituents RO in the phosphate group from
EtO (5a and e) to PhO (5b and f) had no influence on the abso-
lute configuration of products 7 (Table 3 entries 1, 2 and 5, 6).
The results presented in Tables 2 and 3 demonstrate that the
degree of enantioselectivity and absolute configuration of
a-hydroxy ketones in the catalytic oxidation of enol phos-
phates 2 and 5 by Jacobsen’s chiral oxo complex is con-
trolled by the substitution pattern of these phosphates, and
particularly by the steric and electronic factors of the phos-
phate group in enol compounds. In order to rationalize the
stereochemical results we have analyzed the mechanistic
models proposed for metal-catalyzed asymmetric oxidation
of trisubstituted olefins. Generally two proposals for the
mechanism of oxygen-atom transfer from metal oxo com-
plexes have been considered. One invokes substrate attack
at both the metal and oxo centers to form an oxametallacycle
intermediate.21 The other widely accepted mechanism
involves direct substrate attack at the oxo ligand with
concerted or stepwise C–O bond formation.19b,22 Two ap-
proaches of the olefin to the metal–oxygen bond have been
proposed (Fig. 4): side-on along the direction of the chiral
diamine bridge b (Jacobsen model)23 and a skewed side-on
attack c or c0 along the metal C]N ligand of the diamine
bridge (Katsuki model),7e,g,h which is more adequate for
oxofunctionalization of trisubstituted olefins.
O
O
O
OP(OR)2 (EtO)2PO
OP(OR)2
n
5a R = Et, n = 1
5b R = Ph, n = 1
5c R = Et, n = 2
5e R = Et
5d
5f R = Ph
Figure 2. Cyclic E-enol phosphates 5.
O
O
OH
OH
7a
7c
OH
O
O
OH
7d
7e
Figure 3. Cyclic a-hydroxy ketones 7.

12366
M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
metal–oxo bond, shown in Scheme 3. In this approach the
b
electronic interactions between salen benzene ring and arene
substituents, including phenoxy groups in compound 5b,
orients these unsaturated substituents away from the salen
benzene ring.
H
H
c
c'
H
O
O
N
N
Mn
from 5a
O
OP(O)(OEt)2
H
H
H
O
H
Figure 4. The view of the olefin approaches to the metal–oxygen bond.
N
N
Mn
Oxidation of (Z) acyclic enol phosphates, containing alkoxy
substituents at the phosphorus atom 2a, c, e–g, i, and j led to
the formation of S-configured a-hydroxy ketones. This
means that one of the two possible enantiofacial orientations
of these enol phosphates is favored. Following the sugges-
tion by Adam5a we considered a skewed side-on approach
of the enol phosphate to the oxo ligand of the catalyst, which
would avoid steric and electronic interaction between the
substrate’s substituents and its salen framework. This enan-
tiofacial approach, illustrated in Scheme 2, should lead to
S-configured a-hydroxy ketones, in accord with our experi-
mental data.
O
t-Bu
t-Bu
O
t-Bu
t-Bu
S-(-)-7a
Scheme 3. Mechanistic proposal for the oxidation of the phosphate 5a by
the oxo-metal complex of catalyst 1.
The a-hydroxy ketones of opposite configuration (R) 7d–e
were formed from catalytic epoxidation of the enol phos-
phate derivatives of 2,3-dihydro-phenanthren-4-one 5d and
of 2-methyl indanone 5e and f. Such stereochemical results
can be analyzed in terms of electronic as well as steric
interactions of bulkier aromatic substituent with the salen
framework. The lower enantiomeric excesses of 2-hydroxy-
2-methyl indanone 7e correlate with the poorer stereoselec-
tivity of manganese-assisted oxidation of tetrasubstituted
olefins.7c Thus, we have considered the top-on approach
(the olefin and salen-ligand planes parallel)7c of enol phos-
phates 5d–f to the oxo-metal catalyst.
O
OP(OEt)2
Ph
2b
Me
c'
H
H
from 2a
H
O
O
H
N
N
Mn
O
t-Bu
t-Bu
O
t-Bu
t-Bu
via c'
Likely transition states were proposed for oxygen transfer
from oxo Mn–salen complex to olefin to form the possible
radical22 or metallaoxetane intermediates.21b Adam et al.
considered a metallaoxetane mechanism as more adequate
for the oxofunctionalization of silyl enol ethers and ketene
acetals to the corresponding a-hydroxy ketones and a-hy-
droxy acetals.5a It seems reasonable to assume on the basis
of presented data for salen Mn-catalyzed epoxidation of
enol phosphates, that direct attack of enol phosphate on an
(oxo) manganese species generates a radical intermediate,
which collapses to the epoxide, which then transposes to
an a-hydroxy ketone.
Me
OH
Ph
R-(-)-4a
S-(-)-4a
H
Scheme 2. Mechanistic proposal for the oxidation of enol phosphates 2a and
2b by the oxo-metal complex of catalyst 1.
Enol phosphates with PhO groups at the phosphorus atom
2b, d, and h display the opposite facial selectivity in the re-
sulting a-hydroxy ketones. Again we considered the privi-
leged enantiofacial orientation of enol phosphates, which
means that the phosphate groups should avoid the arene
rings of the salen ligand. The opposite configuration of a-hy-
droxy ketones 4a, c, and f obtained from 2b, d, and h, and the
lower enantioselectivity in the oxidation of these substrates
compared with the enantioselectivity of a-hydroxy ketones
4a, c, and f derived from 2a, c, f, and g can suggest that ap-
proach along trajectory c0 is also possible (Scheme 2). A
similar proposal explaining the stereoselectivity of catalytic
oxidation of some aromatic derivatives has been reported in
the literature.7f
3. Conclusion
We have shown that a variety of readily available (Z) and
(E)-enol phosphates 2 and 5 are good synthons in the stereo-
selective syntheses of the corresponding a-hydroxy ketones
4 and 7. Asymmetric epoxidation of these phosphates using
Jacobsen’s (salen) Mn(III) complex afforded a-hydroxy
ketones 4 and 7 in high enantioselectivity up to 96%.
The stereochemistry of epoxides obtained from the Mn–salen
catalyzed oxidation of 1- or 2-methyl-3,4-dihydronaphtha-
lene has been rationalized by taking the electronic effects
of the aromatic moiety into consideration.7e So we proposed
the approach of enol phosphate tetralone derivatives 5a and b
and enol phosphate benzosuberone derivative 5c to the
Our results demonstrate that absolute configuration of these
target compounds is controlled by steric bulk and electronic
aspects of the phosphate group in enol phosphates. By
choosing the right substituents in the remote phosphate
group of acyclic (Z)-enol phosphate 2 ArO or AlkO, both
enantiomers of a-hydroxy ketones 4 may be obtained with

M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
12367
the same chiral catalyst. In contrast bulky aromatic groups
display an influence on the enantioselectivity as well as on
the sense of stereoselectivity of catalytic oxidation of cyclic
(E)-enol phosphates 5.
petroleum ether–EtOAc); nmax/cmꢀ1 3061, 1667, 1591,
1490, 1294, 1216, 1189, 1024, 954, 764, 689; dH
(200 MHz, CDCl3) 7.51–7.45 (2H, m, Ph), 7.33–7.26 (7H,
m, Ph, PhO), 7.19–7.11 (6H, m, PhO), 5.74 (1H, dq,
J¼7.0, 2.0 Hz, C]CH), 1.85 (3H, dd, J¼7.0, 3.1 Hz,
C]CCH3); dC (50.3 MHz, CDCl3) 150.3 (d, J¼7.2 Hz,
ipso-PhO), 146.8 (d, J¼9.6 Hz, POC]CH), 134.8 (ipso-
Ph), 129.5, 128.1, 125.1 (Ph, PhO), 119.8 (d, J¼4.9 Hz,
POPh), 112.6 (d, J¼6.8 Hz, POC]CH), 11.5 (CH3); dP
(81.0 MHz, CDCl3) ꢀ16.98; MS (CI-isobutane): m/z (%)
367 (36) [M+H]+, 251 (100), 95 (10).
4. Experimental
4.1. General
1H, 13C, and 31P NMR spectra were recorded on a Bruker AC
200 Spectrometer at 200.13, 50.32, and 81.02 MHz, respec-
tively (using deuterochloroform as solvent) unless otherwise
noted. IR spectra were measured on an Ati Mattson Infinity
FT IR 60. GC spectra were performed on a Hewlett–Packard
5890. MS spectra (EI, CI, and HRMS) were recorded on a
Finnigan MAT 95 spectrometer. Microanalyses were carried
out on EA1108 apparatus. Melting points were measured
with PHMK Boetius (VEB Analytik Dresden) apparatus.
Optical rotation values were measured in 100 mm cell on
Perkin Elmer 241 MC under Na lamp radiation. The enantio-
meric ratios were determined by HPLC analysis on the com-
mercially available column Chiracel OD under conditions
specified.
4.1.3. Phosphoric acid diethyl ester 1-phenyl-but-1-enyl
ester 2c. Single isomer, colorless oil (90%); Rf 0.25 (1:1 pe-
troleum ether–EtOAc); nmax/cmꢀ1 2980, 2934, 2874, 1660,
1494, 1446, 1273, 1165, 1099, 980, 767; dH (200 MHz,
CDCl3) 7.53–7.49 (2H, m, Ph), 7.35–7.26 (3H, m, Ph),
5.56 (1H, dt, J¼7.3, 2.0 Hz, C]CH), 4.06 (4H, q,
J¼7.2 Hz, OCH2CH3), 2.38 (2H, dquint, J¼7.5, 2.5 Hz,
C]CCH2), 1.23 (6H, t, J¼7.1 Hz, OCH2CH3), 1.08
(3H, t, J¼7.5 Hz, C]CCH2CH3); dC (50.3 MHz, CDCl3)
145.2 (d, J¼9 Hz, POC]CH), 135.5 (ipso-Ph), 127.9,
127.8, 125.1 (Ph), 119.4 (d, J¼6.4 Hz, POC]CH),
64.0 (d, J¼5.9 Hz, POCH2CH3), 19.4 (CH2), 15.7 (d,
J¼6.9 Hz, POCH2CH3), 13.4 (CH3); dP (81.0 MHz,
CDCl3) ꢀ5.64; MS (EI, 15 eV): m/z (%) 284 (38) [M]+,
155 (100), 130 (42). Anal. calcd for C14H21O4P (284.29):
C, 59.15; H, 7.44; P, 10.89. Found: C, 58.59; H, 7.71;
P, 10.53%.
Chromatographic purification was performed on silica gel
columns (Merck, Kieselgel 70–230 mesh) with an indicated
eluent. Chemicals and solvents were obtained from commer-
cial sources and distilled or dried according to standard
methods. The products were characterized by comparison
of their data with those of known samples or by their spectral
data.
4.1.4. Phosphoric acid diphenyl ester 1-phenyl-but-1-
enyl ester 2d. Single isomer, yellow oil (72%); Rf 0.42
(1:1 petroleum ether–EtOAc); nmax/cmꢀ1 3062, 2968,
1590, 1489, 1299, 1216, 1189, 1042, 1011, 959, 765; dH
(200 MHz, CDCl3) 7.51–7.46 (2H, m, Ph), 7.40–7.32 (7H,
m, Ph, PhO), 7.22–7.10 (6H, m, PhO), 5.64 (1H, dt,
J¼7.4, 1.8 Hz, C]CH), 2.33 (2H, dquint, J¼7.5, 2.5 Hz,
C]CCH2), 1.04 (3H, t, J¼7.5 Hz, C]CCH2CH3); NOESY
(1H–1H): cross peak [5.64 (C]CH) and 7.51–7.46 (o-Ph)];
dC (50.3 MHz, CDCl3) 150.3 (d, J¼7.2 Hz, ipso-PhO),
145.4 (d, J¼9.5 Hz, POC]CH), 132.7 (ipso-Ph), 129.6,
129.5, 129.3, 128.3, 128.1 (Ph, PhO), 125.3 (d, J¼6.3 Hz,
POPh), 119.8 (d, J¼4.7 Hz, POC]CH), 19.4 (CH2), 14.2
(CH3); dP (81.0 MHz, CDCl3) ꢀ17.0; MS (CI-isobutane):
m/z (%) 381 (56) [M+H]+, 251 (100); calcd for C22H21O4P
[M]+: 380.1177; found [M]+: 380.1179.
4.1.1. Phosphoric acid diethyl ester 1-phenyl-propenyl
ester 2a.10d General procedure. To a solution of freshly
prepared LDA (21 mmol) in THF (50 mL) at ꢀ78 ꢁC was
added propiophenone (2.68 g, 20 mmol) in THF solution
(10 mL) and the mixture was stirred under an Ar atmosphere
for 1 h, then the solution of diethylphosphorochloridate
(5.1 g, 30 mmol) in THF (5 mL) was dropped at the same
temperature. The mixture was stirred and allowed to warm
slowly to room temperature. After 1 h of stirring at ambient
temperature the solvent was evaporated, the residue was
dissolved in ether, washed with saturated NH4Cl and water
and dried (MgSO4). Evaporation of solvent afforded the
1
crude reaction mixture, which was analyzed by H and 31P
NMR spectroscopy. Pure enol phosphate was obtained
from column chromatography with petroleum ether–EtOAc
(5:1 v/v) as single isomer, yellow oil (4.9 g, 91%); Rf 0.34
(1:1 petroleum ether–EtOAc); nmax/cmꢀ1 2984, 2911, 2866,
1665, 1445, 1392, 1269, 1165, 1027, 979; dH (200 MHz,
CDCl3) 7.51–7.45 (2H, m, Ph), 7.35–7.24 (3H, m, Ph), 5.65
(1H, dq, J¼7.0, 2.2 Hz, C]CH), 4.06 (4H, q, J¼7.3 Hz,
OCH2CH3), 1.87 (3H, dd, J¼7.0, 3.0 Hz, C]CCH3), 1.22
(6H, t, J¼7.1 Hz, OCH2CH3); dC (50.3 MHz, CDCl3) 146.6
(d, J¼9.1 Hz, POC]CH), 135.5 (ipso-Ph), 127.9, 127.8,
125.0 (Ph), 111.9 (d, J¼5.9 Hz, POC]CH), 64.0 (d,
J¼5.9 Hz, POCH2CH3), 15.7 (d, J¼6.8 Hz, POCH2CH3),
11.5 (CH3); dP (81.0 MHz, CDCl3) ꢀ5.6; MS (CI-isobutane):
m/z (%) 271 (80) [M+H]+, 155 (100).
4.1.5. Phosphoric acid 2,2-dimethyl-propyl ester 1-phen-
yl-but-1-enyl ester 2e. Prepared as the mixture E/Z (1:1.5),
a dark yellow oil (30%); Rf 0.6 (1:1 petroleum ether–
EtOAc); nmax/cmꢀ1 2980, 2870, 1671, 1668, 1495, 1440,
1394, 1360, 1275, 1268, 1200, 1165, 1020, 890, 880; dH
(200 MHz, CDCl3) 7.54–7.46 (2H, m, Ph), 7.45–7.40 (2H,
m, Ph), 7.39–7.28 (6H, m, Ph), 5.68 (1H, dt, J¼7.8,
2.6 Hz, C]CH, ‘E’), 5.57 (1H, dt, J¼7.2, 2.1 Hz, C]CH,
‘Z’), 3.86–3.59 (8H, m, OCH2C), 2.40 (2H, dquint, J¼7.5,
2.5 Hz, C]CCH2, ‘Z’), 2.17 (2H, dquint, J¼7.6, 2.3 Hz,
C]CCH2, ‘E’), 1.08 (3H, t, J¼7.5 Hz, C]CCH2CH3),
1.03 (3H, t, J¼7.5 Hz, C]CCH2CH3), 0.89 (9H, m,
CCH3), 0.86 (9H, m, CCH3); dC (50.3 MHz, CDCl3) 146.9
(d, J¼9.1 Hz, POC]CH, ‘E’), 145.5 (d, J¼8.9 Hz,
POC]CH, ‘Z’), 134.7 (ipso-Ph), 128.1, 127.8, 127.5,
125.5 (Ph), 118.2 (d, J¼6.2 Hz, POC]CH, ‘E’), 116.9
4.1.2. Phosphoric acid diphenyl ester 1-phenyl-propenyl
ester 2b.23 Single isomer, yellow oil (85%); Rf 0.51 (1:1

12368
M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
(d, J¼7.0 Hz, POC]CH, ‘Z’), 78.0, 77.8 (d, J¼7.1 Hz,
POCH2), 32.1 (d, J¼8.8 Hz, C(CH3)3), 26.8 (C(CH3)3),
20.5 (CH2, ‘Z’), 19.8 (CH2, ‘E’), 15.1 (CH3); dP
(81.0 MHz, CDCl3) ꢀ5.55 (Z), ꢀ5.46 (E); MS (EI, 15 eV):
m/z (%) 368 (35) [M]+, 239 (100), 117 (25); calcd for
C20H33O4P [M]+: 368.2116; found [M]+: 368.2109.
4.1.9. Phosphoric acid 1,2-diphenyl-vinyl ester diethyl
ester 2i.17a,24 The mixture E/Z isomers (1/10), yellowish oil
(75%); Rf 0.33 (1:1 petroleum ether–EtOAc); nmax/cmꢀ1
2988, 2845, 1667, 1495, 1410, 1370, 1270, 1020, 980; dH
(200 MHz, CDCl3) 7.69–7.62 (4H, m, Ph), 7.45–7.09 (6H,
m, Ph), 6.72 (1H, d, J¼2.7 Hz, C]CH, ‘E’), 6.41 (1H, d,
J¼1.2 Hz, C]CH, ‘Z’), 4.22–4.06 (4H, m, OCH2CH3,
‘E’), 4.05–3.78 (4H, m, OCH2CH3, ‘Z’), 1.30 (6H, dt,
J¼7.0, 1.1 Hz, OCH2CH3, ‘E’), 1.11 (6H, dt, J¼7.1,
1.2 Hz, OCH2CH3, ‘Z’); dC (50.3 MHz, CDCl3) 145.2 (d,
J¼9.0 Hz, POC]CH), 136.3 (ipso-Ph), 134.5 (d, J¼6 Hz,
ipso-Ph), 129.0, 128.3, 127.5, 127.0, 126.3 (Ph), 117.2 (d,
J¼8.4 Hz, POC]CH, ‘E’), 116.0 (d, J¼7.0 Hz, POC]CH,
‘Z’), 64.3 (d, J¼6.1 Hz, POCH2CH3), 15.9 (d, J¼7.6 Hz,
POCH2CH3); dP (81.0 MHz, CDCl3) ꢀ6.08 (Z), ꢀ5.5 (E);
MS (CI-isobutane): m/z (%) 333 (100) [M+H]+, 105 (18).
4.1.6. Phosphoric acid diethyl ester 1-phenyl-pent-1-enyl
ester 2f. Single isomer, yellowish oil (76%); Rf 0.20 (2:1 pe-
troleum ether–EtOAc); nmax/cmꢀ1 2981, 2934, 2900, 1670,
1471, 1369, 1280, 1028, 1013, 980, 801; dH (200 MHz,
CDCl3) 7.53–7.42 (2H, m, Ph), 7.36–7.26 (3H, m, Ph),
5.58 (1H, dt, J¼7.3, 2.0 Hz, C]CH), 4.07, 4.06 (4H, 2q,
J¼7.2 Hz, OCH2CH3), 2.34 (2H, dq, J¼7.4, 2.5 Hz,
C]CCH2), 1.49 (2H, q, J¼7.5 Hz, C]CCH2CH2), 1.23
(6H, t, J¼7.1 Hz, OCH2CH3), 0.97 (3H, t, J¼7.3 Hz,
C]CCH2CH2CH3); dC (50.3 MHz, CDCl3) 145.7 (d,
J¼9 Hz, POC]CH), 135.5 (ipso-Ph), 127.9, 127.5, 125.2
(Ph), 117.4 (d, J¼6.1 Hz, POC]CH), 63.6 (d, J¼6.0 Hz,
POCH2CH3), 28.7, 22.3 (CH2), 15.7 (d, J¼6.5 Hz,
POCH2CH3), 13.7 (CH3); dP (81.0 MHz, CDCl3) ꢀ5.3;
MS (CI-isobutane): m/z (%) 299 (100) [M+H]+, 155 (12);
calcd for C15H23O4P [M]+: 298.1334; found [M]+:
298.1331.
4.1.10. Phosphoric acid diethyl ester 1-(4-methoxy-phen-
yl)-propenyl ester 2j.25 Single isomer, yellow oil (85%); Rf
0.25 (1:1 petroleum ether–EtOAc); nmax/cmꢀ1 2980, 2961,
1667, 1505, 1260, 1022, 1007, 814; dH (200 MHz, CDCl3)
7.44–7.41 (2H, 5 lines, Ar), 6.86–6.81 (2H, 6 lines, Ar),
5.52 (1H, dq, J¼7.0, 2.0 Hz, C]CH), 4.06 (4H, dsext,
J¼7.1, 1.8 Hz, OCH2CH3), 3.80 (3H, s, OCH3), 1.86 (3H,
dd, J¼7.0, 3.0 Hz, C]CCH3), 1.25 (6H, t, J¼7.0 Hz,
OCH2CH3); dC (50.3 MHz, CDCl3) 144.3 (d, J¼9.0 Hz,
POC]CH), 140.5 (ipso-Ar), 127.8, 125.2 (Ar), 112.9 (d,
J¼6.0 Hz, POC]CH), 114.7 (Ar), 64.4 (d, J¼5.5 Hz,
POCH2CH3), 52.8 (CH3O), 14.9 (d, J¼6.6 Hz, POCH2CH3),
11.8 (CH3); dP (81.0 MHz, CDCl3) ꢀ4.37; MS (EI, 15 eV):
m/z (%) 300 (50) [M]+, 155 (22), 146 (100).
4.1.7. Phosphoric acid diisopropyl ester 1-phenyl-pent-1-
enyl ester 2g. Single isomer, yellowish oil (90%); Rf 0.44
(2:1 petroleum ether–EtOAc); nmax/cmꢀ1 2980, 2934,
2873, 1649, 1450, 1386, 1267, 1179, 1010; dH (200 MHz,
CDCl3) 7.53–7.49 (2H, m, Ph), 7.37–7.26 (3H, m, Ph),
5.57 (1H, dt, J¼7.4, 2.0 Hz, C]CH), 4.65 (2H, octet,
J¼6.3 Hz, OCHCH3), 2.37 (2H, dq, J¼7.3, 2.5 Hz,
C]CCH2), 1.51 (2H, sext, J¼7.4 Hz, C]CCH2CH2CH3),
1.31 (6H, t, J¼6.1 Hz, OCHCH3), 1.19 (6H, t, J¼6.1 Hz,
OCHCH3), 0.99 (3H, t, J¼7.3 Hz, C]CCH2CH2CH3); dC
(50.3 MHz, CDCl3) 145.9 (d, J¼9.2 Hz, POC]CH),
135.8 (ipso-Ph), 127.9, 127.8, 125.4 (Ph), 117.5 (d, J¼
6.0 Hz, POC]CH), 72.8, 72.7 (d, J¼6.0 Hz, CH(CH3)2),
28.1 (CH2), 23.6, 23.5, 23.3, 23.2 (CH(CH3)2), 22.2 (CH2),
13.7 (CH3); dP (81.0 MHz, CDCl3) ꢀ7.3; MS (CI-iso-
butane): m/z (%) 327 (100) [M+H]+, 183 (20). Anal. calcd
for C17H27O4P (326.37): C, 62.56; H, 8.34; P, 9.49. Found:
C, 61.90; H, 8.48; P, 10.05%.
4.1.11. Phosphoric acid 3,4-dihydro-naphthalen-1-yl ester
diethyl ester 5a.26 Yellow oil (85%); Rf 0.37 (1:1 petroleum
ether–EtOAc); nmax/cmꢀ1 2949, 2888, 2835, 1650, 1470,
1270, 1162, 1038, 952, 737; dH (200 MHz, CDCl3) 7.42–
7.38 (1H, m, Ph), 7.23–7.07 (3H, m, Ph), 5.87 (1H, dt,
J¼4.6, 1.7 Hz, C]CH), 4.19 (4H, 2q, J¼7.4 Hz,
OCH2CH3), 2.78 (2H, t, J¼7.4 Hz, CH2), 2.33–2.42 (2H,
m, CH2), 1.33 (6H, t, J¼7.1 Hz, OCH2CH3); dC
(50.3 MHz, CDCl3) 144.8 (d, J¼7.7 Hz, POC]CH),
136.2 (C4a–Ar), 130.1 (d, J¼6.5 Hz, C8a–Ar), 127.8, 127.0,
126.1, 121.0 (Ar), 110.3 (d, J¼3.7 Hz, POC]CH), 64.1 (d,
J¼5.9 Hz, POCH2CH3), 27.0, 21.6 (CH2), 15.8 (d,
J¼6.5 Hz, POCH2CH3); dP (81.0 MHz, CDCl3) ꢀ5.7; MS
(CI-isobutane): m/z (%) 283 (10) [M+H]+, 157 (100); calcd
for C14H19O4P [M]+: 282.1020; found [M]+: 282.1016.
4.1.8. Phosphoric acid bis-(4-methoxy-phenyl) ester 1-
phenyl-pent-1-enyl ester 2h. Single isomer, yellowish oil
(78%); Rf 0.70 (1:1 petroleum ether–EtOAc); nmax/cmꢀ1
3060, 3028, 2983, 2909, 1660, 1495, 1275, 1130, 1052,
1031, 979; dH (200 MHz, CDCl3) 7.50–7.46 (2H, m, Ph),
7.29–7.26 (3H, m, Ph), 7.02 (4H, d, J¼9.0 Hz, 4-MeO–
C6H4O), 6.78 (4H, d, J¼9.1 Hz, 4-MeO–C6H4O), 5.63
(1H, dt, J¼7.4, 1.8 Hz, C]CH), 3.76 (6H, s, OCH3),
2.23 (2H, dq, J¼7.4, 2.6 Hz, C]CCH2), 1.44 (2H, sext,
J¼7.3 Hz, CH2CH2CH3), 0.89 (3H, t, J¼7.3 Hz,
C]CCH2CH2CH3); dC (50.3 MHz, CDCl3) 156.9 (ipso-
Ph), 152.5 (d, J¼9.0 Hz, ipso-4-MeO–C6H4O), 144.4
(d, J¼9.0 Hz, POC]CH), 128.2, 125.6 (Ph, 4-MeO–
C6H4O) 121.0 (d, J¼4.7 Hz, POC6H4–MeO), 118.3 (d,
J¼6.2 Hz, POC]CH), 114.6 (4-MeO–C6H4O), 55.6
(CH3O), 28.1, 22.3 (CH2), 13.8 (CH3); dP (81.0 MHz,
CDCl3) ꢀ15.99; MS (CI-isobutane): m/z (%) 455 (100)
[M+H]+; calcd for C25H27O6P [M]+: 454.1545; found
[M]+: 454.1542.
4.1.12. Phosphoric acid 3,4-dihydro-naphthalen-1-yl ester
diphenyl ester 5b. Yellowish oil (86%); Rf 0.70 (1:1 petro-
leum ether–EtOAc); nmax/cmꢀ1 3068, 2939, 1649, 1590,
1488, 1299, 1187, 1083, 956, 765; dH (200 MHz, CDCl3)
7.41–7.12 (14H, m, PhO, Ar), 6.01 (1H, dt, J¼4.6, 2.0 Hz,
C]CH), 2.83 (2H, t, J¼8.0 Hz, CH2), 2.37–2.49 (2H, m,
CH2); dC (50.3 MHz, CDCl3) 150.4 (d, J¼7.5 Hz, ipso-
PhO), 145.1 (d, J¼8.2 Hz, POC]CH), 136.3 (C4a–Ar),
129.8 (C8a–Ar), 129.6, 128.1, 127.6, 126.3, 125.3, 121.3
(PhO, Ar), 120.0 (d, J¼4.9 Hz, POPh), 111.4 (d,
J¼4.0 Hz, POC]CH), 27.0, 21.8 (CH2); dP (81.0 MHz,
CDCl3) ꢀ17.0; MS (CI-isobutane): m/z (%) 379 (40)
[M+H]+, 251 (100). Anal. calcd for C22H19O4P (378.36):
C, 69.84; H, 5.06; P, 8.18. Found: C, 69.40; H, 5.01; P,
8.04%.

M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
12369
4.1.13. Phosphoric acid 8,9-dihydro-7H-benzocyclo-
hepten-5-yl ester diethyl ester 5c. Yellowish oil (79%);
Rf 0.32 (1:1 petroleum ether–EtOAc); nmax/cmꢀ1 3060,
2983, 2932, 2861, 1648, 1449, 1272, 1119, 1030, 972,
903, 771; dH (200 MHz, CDCl3) 7.57–7.52 (1H, m, Ph),
7.29–7.14 (3H, m, Ph), 6.08 (1H, dt, J¼6.4, 2.5 Hz,
C]CH), 4.19 (4H, dquint, J¼7.5, 3.0 Hz, OCH2CH3),
2.72 (2H, t, J¼6.2 Hz, CH2), 2.08–2.02 (4H, m, CH2),
1.29 (6H, t, J¼7.1 Hz, OCH2CH3); dC (50.3 MHz, CDCl3)
146.4 (d, J¼8.8 Hz, POC]CH), 142.3 (C9a–Ar), 135.4 (d,
J¼4.7 Hz, C4a–Ar), 129.8, 129.2, 127.6, 126.9 (Ar), 117.1
(d, J¼4.7 Hz, POC]CH), 65.1 (d, J¼6.0 Hz, POCH2CH3),
34.3, 32.6, 25.5 (CH2), 16.9 (d, J¼6.8 Hz, POCH2CH3); dP
(81.0 MHz, CDCl3) ꢀ5.4; MS (CI-isobutane): m/z (%) 297
(100) [M+H]+, 155 (8). Anal. calcd for C15H21O4P
(296.30): C, 60.80; H, 7.14; P, 10.45. Found: C, 60.55; H,
7.33; P, 10.34%.
120.0 (d, J¼4.8 Hz, POPh), 117.6 (Ar), 38.8 (CH2), 12.0
(CH3); dP (81.0 MHz, CDCl3) ꢀ16.8; MS (CI-isobutane):
m/z (%) 379 (100) [M+H], 95 (8). Anal. calcd for
C22H19O4P (378.36): C, 69.84; H, 5.06; P, 8.18. Found: C,
69.92; H, 5.12; P, 7.97%.
4.2. Syntheses of racemic a-hydroxy ketones 4 and 7
4.2.1. Epoxidation procedure.27
4.2.1.1. Phosphoric acid diethyl ester 2-phenyl-3-
methyl-oxiranyl ester 3a. To a solution of enol phosphate
2a (810 mg, 3 mmol) in methylene chloride (30 mL) was
added a solution of m-chloroperbenzoic acid (1 g, 6 mmol)
in CH2Cl2 (30 mL) at ꢀ20 ꢁC, with stirring. The reaction
mixture was stirred at this temperature until enol phosphate
disappeared (monitored by TLC). Then the reaction mixture
was washed with sodium thiosulfate (10%, 2ꢂ10 mL), satu-
rated NaHCO3 (2ꢂ5 mL), and water (10 mL) and dried
(MgSO4). Evaporation of solvent afforded the crude epoxide
3a. Colorless oil (755 mg, 88%); Rf 0.54 (1:1 petroleum
ether–EtOAc); nmax/cmꢀ1 2987, 2885, 2807, 1450, 1274,
1167, 1064, 1028, 699; dH (200 MHz, CDCl3) 7.52–7.47
(2H, m, Ph), 7.40–7.33 (3H, m, Ph), 4.07, 4.06 (4H,
2q, J¼7.3 Hz, OCH2CH3), 3.04 (1H, dq, J¼5.3, 1.9 Hz,
POCOC(H)CH3), 1.56 (3H, d, J¼5.3 Hz, POCOC(H)CH3),
1.26 (3H, dt, J¼7.1, 1.1 Hz, OCH2CH3), 1.16 (3H, dt,
J¼7.1, 1.1 Hz, OCH2CH3); dC (50.3 MHz, CDCl3) 136.1
(ipso-Ph), 128.9, 127.9, 125.3 (Ph), 88.6 (d, J¼9.0 Hz,
POCOC(H)CH3), 68.8 (d, J¼6.7 Hz, POCOC(H)CH3), 64.0
(d, J¼5.9 Hz, POCH2CH3), 15.8 (t, J¼6.5 Hz, POCH2CH3),
10.0 (CH3); dP (81.0 MHz, CDCl3) ꢀ3.97; MS (CI-isobu-
tane): m/z (%) 287 (100) [M+H]+, 211 (38), 151 (34), 135
(16); calcd for C13H19O5P [M]+: 286.0970; found [M]+:
286.0962.
4.1.14. Phosphoric acid 1,2-dihydro-phenanthren-4-yl
ester diethyl ester 5d. Yellowish oil (85%); Rf 0.20 (1:1
petroleum ether–EtOAc); nmax/cmꢀ1 2957, 2924, 2869,
1688, 1460, 1279, 1260, 1090, 799; dH (200 MHz, CDCl3)
8.63 (1H, dt, J¼8.5, 1.2 Hz, Ar), 7.79–7.67 (2H, m, Ar),
7.49–7.27 (3H, m, Ar), 6.14 (1H, dt, J¼5.6, 2.4 Hz,
C]CH), 4.10 (4H, dquint, J¼7.1, 1.7 Hz, OCH2CH3),
2.92–2.84 (2H, m, CH2), 2.38–2.26 (2H, m, CH2), 1.23
(6H, dt, J¼7.1, 1.1 Hz, OCH2CH3); dC (50.3 MHz, CDCl3)
147.4 (d, J¼8.0 Hz, POC]CH), 137.3 (CIV–Ar), 133.4
(CIV–Ar), 129.8 (CIV–Ar), 128.8, 128.5, 126.0, 124.8 (Ar),
119.2 (CIV–Ar), 113.4 (d, J¼4.7 Hz, POC]CH), 64.4 (d,
J¼5.9 Hz, POCH2CH3), 29.8, 22.6 (CH2), 16.1 (d,
J¼6.5 Hz, POCH2CH3); dP (81.0 MHz, CDCl3) ꢀ5.96;
MS (CI-isobutane): m/z (%) 333 (100) [M+H]+, 155 (8).
Anal. calcd for C18H21O4P (332.33): C, 65.05; H, 6.37; P,
9.32. Found: C, 65.56; H, 6.12; P, 9.02%.
4.2.1.2. Phosphoric acid diphenyl ester 2-phenyl-3-
methyl-oxiranyl ester 3b. Yellow oil (74%); Rf 0.61 (1:1
petroleum ether–EtOAc); nmax/cmꢀ1 3068, 2910, 1588,
1491, 1395, 1312, 1214, 1128, 1092, 959, 773; dH
(200 MHz, CDCl3) 7.53–7.05 (15H, m, Ph, OPh), 3.11 (1H,
dq, J¼5.3, 1.9 Hz, POCOC(H)CH3), 1.54 (3H, d, J¼5.3 Hz,
POCOC(H)CH3); dC (50.3 MHz, CDCl3) 156.7 (d,
J¼7.0 Hz, ipso-PhO), 135.3 (ipso-Ph), 129.6, 128.3, 125.4
(Ph, PhO), 120.1 (d, J¼4.4 Hz, POPh), 87.8 (d, J¼9.0 Hz,
POCOC(H)CH3), 72.2 (d, J¼6.7 Hz, POCOC(H)CH3), 17.1
(CH3); dP (81.0 MHz, CDCl3) ꢀ15.3; MS (CI-isobutane):
m/z (%) 383 (100) [M+H]+, 289 (4); calcd for C21H19O5P
[M]+: 382.0970; found [M]+: 382.0965.
4.1.15. Phosphoric acid diethyl ester 2-methyl-3H-inden-
1-yl ester 5e. Yellow oil (87%); Rf 0.5 (1:1 petroleum ether–
EtOAc); nmax/cmꢀ1 3047, 2983, 2911, 1647, 1463, 1395,
1300, 1136, 1051, 983, 911, 763; dH (200 MHz, CDCl3)
7.43–7.13 (4H, m, Ar), 4.26 (4H, dquint, J¼7.2, 1.4 Hz,
OCH2CH3), 3.29 (2H, d, J¼4.4 Hz, CH2), 2.14 (3H, d,
J¼2.9 Hz, CH3), 1.37 (6H, t, J¼7.1 Hz, OCH2CH3); dC
(50.3 MHz, CDCl3) 143.2 (d, J¼7.7 Hz, POC]CCH3),
139.8 (d, J¼3.6 Hz, C7a–Ar), 139.7 (C3a–Ar), 126.5 (d,
J¼6.3 Hz, POC]CCH3), 126.1, 124.5, 123.7, 117.6 (Ar),
64.4 (d, J¼6.0 Hz, POCH2CH3), 38.7 (CH2), 15.9 (d,
J¼6.7 Hz, POCH2CH3), 12.1 (CH3); dP (81.0 MHz,
CDCl3) ꢀ5.19; MS (CI-isobutane): m/z (%) 283 (100)
[M+H]+, 256 (16). Anal. calcd for C14H19O4P (282.27): C,
59.57; H, 6.78; P, 10.97. Found: C, 59.51; H, 7.02; P,
10.78%.
4.2.1.3. Phosphoric acid diethyl ester 2-phenyl-3-eth-
yl-oxiranyl ester 3c. Colorless oil (85%); Rf 0.5 (1:1
petroleum ether–EtOAc); nmax/cmꢀ1 2967, 1449, 1259,
1031, 816, 699; dH (200 MHz, CDCl3) 7.50–7.45 (2H, m,
Ph), 7.40–7.33 (3H, m, Ph), 4.07, 4.06 (4H, 2q, J¼7.3 Hz,
OCH2CH3), 2.85 (1H, dt, J¼6.2, 1.9 Hz, POCOC(H)CH2),
1.87 (2H, quint, J¼7.2 Hz, POCOC(H)CH2), 1.24 (3H,
t, J¼7.1 Hz, OCH2CH3), 1.14 (3H, t, J¼7.1 Hz, OCH2CH3),
1.09 (3H, t, J¼7.3 Hz, POCOC(H)CH2CH3); dC (50.3 MHz,
CDCl3) 136.1 (ipso-Ph), 128.8, 128.1, 125.7 (Ph), 86.3
(d, J¼8.8 Hz, POCOC(H)CH2), 67.3 (d, J¼6.9 Hz,
POCOC(H)CH2), 63.9 (d, J¼5.7 Hz, POCH2CH3), 20.8
(CH2), 15.7 (t, J¼6.6 Hz, POCH2CH3), 9.8 (CH3); dP
(81.0 MHz, CDCl3) ꢀ4.29; MS (CI-isobutane): m/z (%)
4.1.16. Phosphoric acid diphenyl ester 2-methyl-3H-
inden-1-yl ester 5f. White solid, mp 67 ꢁC (68%); Rf 0.66
(1:1 petroleum ether–EtOAc); nmax/cmꢀ1 3050, 2932,
1657, 1441, 1353, 1274, 1167, 1031, 967, 898, 721; dH
(200 MHz, CDCl3) 7.42–7.13 (14H, m, Ar, PhO), 3.31
(2H, d, J¼4.5 Hz, CH2), 2.07 (3H, d, J¼3.0 Hz, CH3); dC
(50.3 MHz, CDCl3) 150.5 (d, J¼7.5 Hz, POPh), 143.2 (d,
J¼9.9 Hz, POC]CCH3), 139.7 (C3a–Ar), 139.2 (d,
J¼2.1 Hz, C7a–Ar), 129.6 (PhO), 127.2 (d, J¼6.7 Hz,
POC]CCH3), 126.3 (Ar), 125.4 (PhO), 124.8, 123.4 (Ar),

12370
M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
301 (100) [M+H]+, 155 (12), 149 (8); calcd for C14H21O5P
[M]+: 300.1126; found [M]+: 300.1119.
(ipso-Ph), 128.8, 128.3, 127.8, 125.4 (Ph), 87.3 (d,
J¼8.5 Hz, POCOC(H)CH2), 72.8 (d, J¼6.0 Hz,
POCH(CH3)2), 64.4 (d, J¼7.2 Hz, POCOC(H)CH2), 29.3
(CH2), 23.5, 23.4, 23.25, 23.2 (CH(CH3)2), 20.1 (CH2),
13.8 (CH3); dP (81.0 MHz, CDCl3) ꢀ6.09; MS (CI-iso-
butane): m/z (%) 343 (100) [M+H]+, 183 (16); calcd for
C17H27O5P [M]+: 342.1596; found [M]+: 342.1593.
4.2.1.4. Phosphoric acid diphenyl ester 2-phenyl-3-
ethyl-oxiranyl ester 3d. Yellow oil (80%); Rf 0.7 (1:1
petroleum ether–EtOAc); nmax/cmꢀ1 3032, 2990, 1595,
1460, 1297, 1187, 946, 790; dH (200 MHz, CDCl3) 7.51–
7.04 (2H, m, Ph), 7.36–7.09 (13H, Ph, OPh), 2.93 (1H, dt,
J¼6.2, 2.1 Hz, POCOC(H)CH2), 1.83 (2H, quint,
J¼7.5 Hz, POCOC(H)CH2), 1.04 (3H, t, J¼7.5 Hz, CH3);
dC (50.3 MHz, CDCl3) 156.7 (d, J¼7.0 Hz, ipso-PhO),
134.4 (ipso-Ph), 129.7, 129.1, 128.3, 127.9, 125.8 (Ph,
PhO), 125.0 (d, J¼4.8 Hz, POPh), 86.8 (d, J¼8.5 Hz, PO-
COC(H)CH2), 68.2 (d, J¼6.7 Hz, POCOC(H)CH2), 20.2
(CH2), 13.5 (CH3); dP (81.0 MHz, CDCl3) ꢀ15.48; MS
(CI-isobutane): m/z (%) 397 (100) [M+H]+, 155 (12), 149
(10), 95 (15); calcd for C22H21O5P [M]+: 396.1126; found
[M]+: 396.1119.
4.2.1.8. Phosphoric acid bis-(4-methoxy-phenyl) ester
2-phenyl-3-propyl-oxiranyl ester 3h. Yellow oil (55%);
Rf 0.57 (1:1 petroleum ether–EtOAc); nmax/cmꢀ1 2961,
1503, 1253, 1185, 1035, 967, 833; dH (200 MHz, CDCl3)
7.51–7.43 (2H, m, Ph), 7.35–7.26 (3H, Ph), 7.09–6.95
(4H, m, 4-MeOC6H4O), 6.82–6.75 (4H, m, 4-MeOC6H4O),
3.77 (6H, s, OCH3), 2.94 (1H, dt, J¼6.0, 1.9 Hz,
POCOC(H)CH2), 1.77 (2H, q, J¼7.0 Hz, POCOC(H)CH2),
1.49 (2H, sext, J¼7.4 Hz, CH2CH2CH3), 0.96 (3H, t,
J¼7.4 Hz, CH3); dC (50.3 MHz, CDCl3) 156.8 (ipso-4-MeO-
C6H4O), 135.7 (ipso-Ph), 129.1, 128.6, 128.3, 126.0 (Ph,
4-MeOC6H4O), 120.9 (d, J¼4.8 Hz, POC6H4–OMe), 114.5
(4-MeOC6H4O), 87.5 (d, J¼8.3 Hz, POCOC(H)CH2), 66.3
(d, J¼7.0 Hz, POCOC(H)CH2), 55.5 (CH3O), 29.3, 19.2
(CH2), 13.7 (CH3); dP (81.0 MHz, CDCl3) ꢀ14.78; MS
(CI-isobutane): m/z (%) 471 (100) [M+H]+, 311 (12); calcd
for C25H27O7P [M]+: 470.1494; found [M]+: 470.1487.
4.2.1.5. Phosphoric acid 2,2-dimethyl-propyl ester 2-
phenyl-3-ethyl-oxiranyl ester 3e. Colorless oil (30%); Rf
0.55 (1:1 petroleum ether–EtOAc); nmax/cmꢀ1 2952, 2901,
1460, 1310, 1225, 1165, 885; dH (200 MHz, CDCl3) 7.58–
7.41 (2H, m, Ph), 7.39–7.27 (3H, m, Ph), 3.68 (4H, d,
J¼4.6 Hz, OCH2C(CH3)3), 2.87 (1H, dt, J¼5.0, 2.0 Hz,
POCOC(H)CH2), 1.92 (2H, q, J¼7.6 Hz, POCOC(H)CH2),
1.11 (3H, t, J¼7.5 Hz, CH2CH3), 0.93, 0.86 (18H, 2ꢂs,
C(CH3)3); dC (50.3 MHz, CDCl3) 133.2 (ipso-Ph), 128.5,
128.1, 127.5, 126.1 (Ph), 83.1 (d, J¼8.0 Hz, POCOC(H)CH2),
78.4 (t, J¼7.0 Hz, POCH2), 67.1 (t, J¼7.0 Hz, POCOC(H)-
CH2), 32.3 (d, J¼6.7 Hz, C(CH3)3), 25.9 (C(CH3)3), 21.2
(CH2), 15.5 (CH3); dP (81.0 MHz, CDCl3) ꢀ4.06; MS (CI-
isobutane): m/z (%) 385 (100) [M+H]+, 239 (40); calcd for
C20H33O5P [M]+: 384.2065; found [M]+: 384.2057.
4.2.1.9. Phosphoric acid diethyl ester 2-phenyl-3-
phenyl-oxiranyl ester 3i. Colorless oil (55%); Rf 0.55 (1:1
petroleum ether–EtOAc); nmax/cmꢀ1 2983, 2870, 1456,
1394, 1271, 1165, 1035; dH (200 MHz, CDCl3) 7.64–7.60
(2H, m, Ph), 7.58–7.52 (2H, m, Ph), 7.51–7.29 (6H, m, Ph),
3.97 (1H, s, POCOC(H)Ph), 3.88 (4H, dq, J¼7.1, 2.9 Hz,
OCH2CH3), 1.14, 1.13 (6H, dt, J¼7.1, 0.6 Hz, OCH2CH3);
dC (50.3 MHz, CDCl3) 133.5 (ipso-Ph), 129.3, 129.1, 128.7,
128.6 (Ph), 81.1 (d, J¼8.0 Hz, POCOC(H)Ph), 80.2 (d,
J¼7.6 Hz, POCOC(H)Ph), 64.2 (d, J¼5.4 Hz, POCH2CH3),
15.9 (t, J¼6.6 Hz, POCH2CH3); dP (81.0 MHz, CDCl3)
ꢀ4.04; MS (CI-isobutane): m/z (%) 349 (100) [M+H]+, 333
(10), 243 (16), 195 (40), 155 (74); calcd for C18H21O5P
[M]+: 348.1126; found [M]+: 348.1121.
4.2.1.6. Phosphoric acid diethyl ester 2-phenyl-3-pro-
pyl-oxiranyl ester 3f. Colorless oil (90%); Rf 0.3 (1:1 petro-
leum ether–EtOAc); nmax/cmꢀ1 2970, 2860, 1498, 1244,
1052, 997, 756; dH (200 MHz, CDCl3) 7.52–7.45 (2H, m,
Ph), 7.42–7.28 (3H, m, Ph), 4.07, 4.06 (4H, 2q, J¼7.3 Hz,
OCH2CH3), 2.90 (1H, dt, J¼6.0, 2.0 Hz, POCOC(H)CH2),
1.91–1.80 (2H, m, POCOC(H)CH2), 1.56 (2H, sext, J¼
7.3 Hz, CH2CH2), 1.26 (3H, dt, J¼7.1, 1.1 Hz, OCH2CH3),
1.16 (3H, dt, J¼7.0, 1.1 Hz, OCH2CH3), 1.01 (3H, t,
J¼7.3 Hz, CH2CH2CH3); dC (50.3 MHz, CDCl3) 136.1
(ipso-Ph), 128.9, 128.3, 125.8 (Ph), 85.2 (d, J¼8.8 Hz,
POCOC(H)CH2), 66.4 (d, J¼7.0 Hz, POCOC(H)CH2),
63.9 (d, J¼5.4 Hz, POCH2CH3), 29.3, 19.1 (CH2), 15.9 (t,
J¼6.6 Hz, POCH2CH3), 13.8 (CH3); dP (81.0 MHz,
CDCl3) ꢀ3.93; MS (CI-isobutane): m/z (%) 315 (100)
[M+H]+, 155 (10); calcd for C15H23O5P [M]+: 314.1283;
found [M]+: 314.1281.
4.2.1.10. Phosphoric acid 2,3-dihydro-1aH-1-oxa-
cyclopropa[a]naphthalen-7b-yl ester diethyl ester 6a.
Yellowish oil (88%); Rf 0.25 (1:1 petroleum ether–EtOAc);
nmax/cmꢀ1 2970, 2870, 1450, 1410, 1285, 1150, 1070,
1053, 980; dH (200 MHz, CDCl3) 7.30–7.27 (3H, m,
Ar), 7.14–7.09 (1H, m, Ar), 4.40 (1H, d, J¼3.0 Hz,
POCOC(H)CH2), 4.20 (4H, dquint, J¼7.1, 0.6 Hz, OCH2CH3),
2.80–2.52 (2H, m, CH2), 2.43–2.30 (1H, m, CH2), 1.87 (1H,
ddd, J¼14.8, 12.9, 6.1 Hz, CH2), 1.36, 1.35, 1.34, 1.33
(6H, 4t, J¼7.1 Hz, OCH2CH3); dC (50.3 MHz, CDCl3)
131.7 (CIV–Ar), 130.3 (CIV–Ar), 129.8, 129.4, 127.8, 127.3
(Ar), 79.1 (d, J¼6.0 Hz, POCOCH), 64.4 (d, J¼6.0 Hz,
POCH2CH3), 63.4 (d, J¼5.0 Hz, POCOCH), 30.9, 27.4
(CH2), 15.9 (d, J¼6.6 Hz, POCH2CH3); dP (81.0 MHz,
CDCl3) ꢀ6.09; MS (CI-isobutane): m/z (%) 299 (100)
[M+H]+, 283 (20), 155 (36); calcd for C14H19O5P [M]+:
298.0970; found [M]+: 298.0964.
4.2.1.7. Phosphoric acid diisopropyl ester 2-phenyl-3-
propyl-oxiranyl ester 3g. Colorless oil (83%); Rf 0.5 (1:1
petroleum ether–EtOAc); nmax/cmꢀ1 2975, 2901, 2877,
1460, 1305, 1270, 1035, 983, 701; dH (200 MHz, CDCl3)
7.52–7.48 (2H, m, Ph), 7.46–7.34 (3H, m, Ph), 4.60 (2H,
septet, J¼6.3 Hz, OCHCH3), 2.88 (1H, dt, J¼6.0, 1.8 Hz,
POCOC(H)CH2), 1.93–1.81 (2H, m, POCOC(H)CH2),
1.57 (2H, sext, J¼7.1 Hz, CH2CH2), 1.27 (3H, dd, J¼6.1,
4.0 Hz, OCHCH3), 1.12 (3H, d, J¼6.0 Hz, OCHCH3),
1.00 (3H, t, J¼7.3 Hz, CH3); dC (50.3 MHz, CDCl3) 136.1
4.2.1.11. Phosphoric acid 2,3-dihydro-1aH-1-oxa-
cyclopropa[a]naphthalen-7b-yl ester diphenyl ester 6b.
Orange oil (52%); Rf 0.66 (1:1 petroleum ether–EtOAc);
nmax/cmꢀ1 3030, 2896, 1591, 1456, 1217, 1128, 1042, 908,

M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
12371
735; dH (200 MHz, CDCl3) 8.07–8.02 (1H, m, Ar), 7.55–
7.47 (1H, m, Ar), 7.39–7.09 (12H, m, Ar, Ph), 4.39 (1H, d,
J¼2.8 Hz, POCOC(H)CH2), 2.85–2.55 (2H, m, CH2),
2.48–2.36 (1H, m, CH2), 1.87 (1H, ddd J¼14.1, 13.1,
6.1 Hz, CH2); dC (50.3 MHz, CDCl3) 150.4 (d, J¼7.0 Hz,
ipso-OPh), 136.5 (CIV–Ar), 129.7 (CIV–Ar), 129.6 (OPh),
128.2, 128.0, 127.3, 127.0 (Ar), 125.4 (OPh), 120.4 (OPh),
82.8 (d, J¼6.4 Hz, POCOCH), 66.5 (d, J¼4.0 Hz,
POCOCH), 30.8, 27.3 (CH2); dP (81.0 MHz, CDCl3) ꢀ17.3;
MS (EI): m/z (%) 394 (4) [M]+, 300 (44), 250 (66), 144 (46),
94 (100); calcd for C22H19O5P [M]+: 394.0970; found [M]+:
394.0969.
5.9 Hz, CH2), 1.60–1.34 (3H, m, HCH–CH2), 0.89 (3H, t,
J¼7.0 Hz, CH3); dC (50.3 MHz, CDCl3) 202.1 (C]O),
133.6 (ipso-Ph), 133.8, 128.7, 128.4 (Ph), 72.8 (CH(OH),
37.8, 18.1 (CH2), 13.7 (CH3); MS (CI-isobutane): m/z (%)
179 (100) [M+H]+, 163 (16), 105 (10).
4.2.2.4. 2-Hydroxy-1,2-diphenyl-ethanone 4i.29 White
solid, mp 135 ꢁC; yield 73%; Rf 0.62 (1:1 petroleum
ether–EtOAc); dH (200 MHz, CD3OD) 7.98–7.93 (2H, m,
Ph), 7.56–7.26 (8H, m, Ph), 6.11 (1H, s, CH (OH)), 4.87
(1H, br s, OH); MS (CI-isobutane): m/z (%) 213 (100)
[M+H]+, 195 (74).
4.2.1.12. Phosphoric acid diethyl ester 1a,2,3,4-tetra-
hydro-1-oxa-benzo[a]cyclopropa[c]cyclohepten-8b-yl ester
6c. Yellow oil (60%); Rf 0.45 (1:1 petroleum ether–EtOAc);
nmax/cmꢀ1 2995, 2880, 1440, 1310, 1270, 1160, 1038, 980;
dH (200 MHz, CDCl3) 7.77–7.71 (1H, m, Ph), 7.31–7.25
(3H, m, Ph), 3.91 (4H, m, OCH2CH3), 3.31 (1H, ddd,
J¼13.9, 12.1, 6.3 Hz, POCOC(H)CH2), 2.73–2.67 (2H, m,
CH2), 2.08–1.90 (4H, m, CH2), 1.29, 1.28 (6H, 2t, J¼7.1 Hz,
OCH2CH3); dC (50.3 MHz, CDCl3) 137.8 (C4a–Ar), 132.6
(C8a–Ar), 129.6, 129.3, 128.7, 126.7 (Ar), 84.2 (d, J¼6.1 Hz,
POCOCH), 64.1 (d, J¼5.4 Hz, POCH2CH3), 60.6 (d,
J¼4.6 Hz, POCOCH), 30.7, 27.0, 22.6 (CH2), 15.7 (d,
J¼4.8 Hz, POCH2CH3); dP (81.0 MHz, CDCl3) ꢀ6.23; MS
(CI-isobutane): m/z (%) 313 (100) [M+H]+, 297 (18), 155
(16); calcd for C15H21O5P [M]+: 312.1126; found [M]+:
312.1128.
4.2.2.5. 2-Hydroxy-1-(4-methoxyphenyl)-propan-1-one
4j.30 Colorless liquid; yield 48%; Rf 0.5 (1:1 petroleum
ether–EtOAc); dH (200 MHz, CDCl3) 7.91 (2H, d,
J¼8.9 Hz, Ph), 6.96 (2H, d, J¼8.9 Hz, Ph), 5.10 (1H, q,
J¼7.0 Hz, CH (OH)), 3.88 (3H, s, OCH3), 3.25 (1H, br s,
OH), 1.43 (3H, d, J¼7.0 Hz, CH3); MS (CI-isobutane): m/z
(%) 181 (100) [M+H]+, 163 (16), 135 (20).
4.2.2.6. 2-Hydroxy-3,4-dihydro-2H-naphthalen-1-one
7a.29 Colorless liquid; yield 68%; Rf 0.49 (1.5:1 petroleum
ether–EtOAc); dH (200 MHz, CDCl3) 8.10–7.97 (1H, m,
Ph), 7.62–7.31 (3H, m, Ph), 4.40 (1H, dd, J¼13.4, 5.4 Hz,
CH (OH)), 3.99 (1H, br s, OH), 3.26–2.97 (2H, m, CH2),
2.60–2.48 (1H, m, CH2), 2.04 (1H, ddd, J¼17.4, 12.5,
5.3 Hz, CH2); MS (CI-isobutane): m/z (%) 163 (100)
[M+H]+, 157 (36), 145 (32).
4.2.2. Hydrolysis of epoxides 3 and 6.
4.2.2.7. 6,7,8,9-Tetrahydro-6-hydroxy-5H-benzocyclo-
hepten-5-one 7c.31 Colorless liquid; yield 60%; Rf 0.55
(1:1 petroleum ether–EtOAc); dH (200 MHz, CDCl3)
7.95–7.90 (1H, m, Ph), 7.50–7.22 (3H, m, Ph), 4.50
(1H, dd, J¼10.0, 5.4 Hz, CH(OH)), 4.00 (1H, br s, OH),
3.03–2.90 (2H, m, CH2), 2.53–2.33 (1H, m, CH2), 2.30–
2.09 (1H, m, CH2), 1.90–1.59 (2H, m, CH2); MS (CI-
isobutane): m/z (%) 177 (100) [M+H]+, 157 (36), 145 (32).
4.2.2.1. 2-Hydroxy-1-phenyl-1-propan-1-one 4a.5a To
a solution of 3a (755 mg, 2.64 mmol) in diethyl ether
(10 mL), trifluoroacetic acid (2 mL) in water (10 mL)
was added with stirring at 5 ꢁC. The reaction was stirred
and monitored by TLC. After 24–48 h the reaction mix-
ture was diluted with chloroform, washed with saturated
NaHCO3 and water and dried (MgSO4). After removal
of the solvent the crude product was purified by column
chromatography with petroleum ether/EtOAc as an elu-
ent (5:1 v/v) to give 309 mg (78% yield) of product as
colorless liquid; Rf 0.52 (2:1 petroleum ether–EtOAc);
dH (200 MHz, CDCl3) 7.95–7.91 (2H, m, Ph), 7.63–7.46
(3H, m, Ph), 5.16 (1H, q, J¼7.0 Hz, CH (OH)), 3.04
(1H, br s, OH), 1.45 (3H, d, J¼7.0 Hz, CH3); MS
(CI-isobutane): m/z (%) 151 (100) [M+H]+, 133 (16),
123 (32).
4.2.2.8. 2,3-Dihydro-3-hydroxy-1H-phenanthren-4-
one 7d. Dark yellow oil; yield 66%; Rf 0.58 (1:1 petro-
leum ether–EtOAc); nmax/cmꢀ1 3454, 2962, 1664, 1260,
1089, 1021, 800; dH (200 MHz, CDCl3) 9.35 (1H, d,
J¼8.6 Hz, Ar), 7.97 (1H, d, J¼8.4 Hz, Ar), 7.83 (1H, d,
J¼8.1 Hz, Ar), 7.66 (1H, dd, J¼7.4, 8.1 Hz, Ar), 7.53
(1H, t, J¼7.4 Hz, Ar), 7.31 (1H, d, J¼8.4 Hz, Ar), 4.48
(1H, dd, J¼5.0, 13.6 Hz, CH–OH), 4.31 (1H, br s, OH),
3.99 (1H, ddd, J¼4.3, 13.0, 17.3 Hz, CH2), 3.20 (1H, dd,
J¼4.0, 17.5 Hz, CH2), 2.61 (1H, dd, J¼5.8, 6.1 Hz, CH2),
2.16 (1H, ddd, J¼4.8, 12.8, 17.5 Hz, CH2); dC (50.3 MHz,
CDCl3) 201.6 (C]O), 146.5 (CIV–Ar), 135.0 (Ar), 132.5
(CIV–Ar), 131.2 (CIV–Ar), 129.1 (Ar), 128.4 (Ar), 126.7
(Ar), 126.2 (Ar), 125.8 (Ar), 124.8 (CIV–Ar), 73.8
(CHOH), 32.2 (CH2), 29.1 (CH2); MS (CI-isobutane): m/z
(%) 213 (100) [M+H]+; calcd for C14H13O2 [M+H]+:
213.0916; found [M+H]+: 213.0910.
4.2.2.2. 2-Hydroxy-1-phenyl-1-butan-1-one 4c.5a Col-
orless liquid; yield 76%; Rf 0.69 (2:1 petroleum ether–
EtOAc); dH (200 MHz, CDCl3) 7.93–7.88 (2H, m, Ph),
7.66–7.57 (1H, m, Ph), 7.53–7.45 (2H, m, Ph), 5.16
(1H, dd, J¼6.8, 3.8 Hz, CH (OH)), 3.70 (1H, br s,
OH), 1.85 (1H, qdd, J¼7.4, 7.0, 3.8 Hz, CH2), 1.61 (1H,
septet, J¼7.0 Hz, CH2), 0.93 (3H, t, J¼7.4 Hz, CH3);
MS (CI-isobutane): m/z (%) 165 (100) [M+H]+, 147 (10),
136 (18).
4.2.2.9. 2-Hydroxy-2-methyl 1-indanone 7e.32 White
solid, mp 49 ꢁC; yield 65%; Rf 0.54 (1:1 petroleum ether–
EtOAc); dH (200 MHz, CDCl3) 7.77 (1H, d, J¼7.6 Hz,
Ph), 7.67 (1H, m, Ph), 7.49–7.36 (2H, m, Ph), 3.27 (2H, s,
CH2), 2.48 (1H, br s, OH), 1.44 (3H, s, CH3); MS (CI-iso-
butane): m/z (%) 163 (100) [M+H]+, 145 (16).
4.2.2.3. 2-Hydroxy-1-phenyl-1-pentan-1-one 4f.28 Col-
orless liquid; yield 55%; Rf 0.75 (1:1 petroleum ether–
EtOAc); dH (200 MHz, CDCl3) 7.91–7.88 (2H, 2 lines,
Ph), 7.60–7.44 (3H, m, Ph), 5.07 (1H, dd, J¼6.7, 3.2 Hz,
CH (OH)), 3.66 (1H, br s, OH), 1.81 (1H, dq, J¼3.2,

12372
M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
4.3. General procedure for asymmetric oxidation
S-(+)-4i Entry 9: 5% i-PrOH in hexane, 0.4 mL/min; tR
[min] 38.5 (S), tR [min] 57.6 (R), [a]2D0 +138.4 (c 0.25,
CHCl3); lit. (S)-4i: [a]D20 +114.9 (c 1.5, acetone), ee¼95%.33
To a stirred solution of NaOCl (4 mL, 7 equiv) and phos-
phate buffer (4 mL, pH¼11) the mixture of appropriate
enol phosphate (1.1 mmol, 1 equiv), 4-phenylpyridine
N-oxide (PPNO) (30 mol %), and (salen) Mn(III) complex
1 (7 mol %) in 4 mL CH2Cl2 was added at ꢀ10 ꢁC. The
stirring of the reaction mixture was continued at 0 ꢁC
for 18 h (the reaction was monitored by TLC), n-hexane
(40 mL) was added, organic layer was separated, washed
with distilled water and dried (MgSO4). Evaporation of
solvent afforded crude epoxide, which was diluted with
Et2O and treated with CF3COOH in H2O (10 mL) at 0 ꢁC.
Stirring was continued until TLC analysis revealed the
complete consumption of epoxide. Then the mixture was
washed with NaHCO3, CHCl3 was added, the organic layer
was separated, washed with water and dried. After removal
of the solvent the residue was subjected to silica gel column
chromatography with hexane–ethyl acetate (3:1 v/v) as the
eluent, to afford pure, optically active a-hydroxy ketones 4
and 7. Spectral data of 4 and 7 as described.
S-(ꢀ)-4j Entry 10: 0.25% i-PrOH in hexane, 0.3 mL/min; tR
[min] 221.6 (S), tR [min] 215.5 (R), [a]2D0 ꢀ30.7 (c 0.87,
CHCl3); lit. (S)-4j: [a]2D0 ꢀ33.4 (c 1.05, MeOH).30
4.3.1.2. HPLC conditions for compounds 7 (Table 3 in
text). S-(ꢀ)-7a Entry 1: 0.5% i-PrOH in hexane, 0.5 mL/
min; tR [min] 31.9 (S), tR [min] 29.3 (R), [a]2D0 ꢀ16.6 (c
0.35, CHCl3); lit.4a (S)-7a: [a]D20 ꢀ8.6 (c 1.0, CH2Cl2),
ee¼99%, (kinetic resolution, HPLC-Chiralcel OB-H).
S-(ꢀ)-7a Entry 2: 0.5% i-PrOH in hexane, 0.5 mL/min;
tR [min] 31.9 (S), tR [min] 29.4 (R), [a]2D0 ꢀ12.0 (c 0.2,
CHCl3).
S-(+)-7c Entry 3: 2.25% i-PrOH in hexane, 0.3 mL/min; tR
[min] 32.6 (S), tR [min] 28.1 (R), absolute configuration of
product determined by comparing circular dichroism (CD)
spectrum of the purified a-hydroxy ketone 7c to the CD
spectrum of (S)-2-hydroxy tetralone 7a, [a]2D0 +44.2 (c 4.4,
CHCl3); lit.29 R-7c ([a]D20 +72.5 (c 1.0, EtOH)) at 94% ee,
[(CHIRALPAK AD (20% i-PrOH in hexane, 0.8 mL/
min)], tR [min] 20.9 (S), tR [min] 15.5 (R); lit.31 95% ee (Chi-
ral SFC AD, 10% MeOH/CO2, 1.5 mL/min, tR [min] 7.1 (S),
tR [min] 9.5 (R)).
4.3.1. Determination of the enantiomeric purity of com-
pounds 4 and 7. The enantiomeric ratios were determined
by HPLC analysis on Chiracel OD column. All runs were
carried out at room temperature.
4.3.1.1. HPLC conditions for compounds 4 (Table 2 in
text). S-(ꢀ)-4a Entry 1: 5% i-PrOH in hexane, 0.4 mL/min;
tR [min] 17.3 (S), tR [min] 19.8 (R), absolute configuration of
product determined by comparison of sign of optical rotation
to the literature value (S)-4a: [a]2D0 ꢀ82.7 (c 3.6, CHCl3); lit.
[a]2D0 ꢀ80.9 (c 2.0, CHCl3), ee¼95%;33a [a]2D0 ꢀ58.3 (c 2.0,
CHCl3), ee¼62%.33b
R-(+)-7d Entry 4: 5% i-PrOH in hexane, 0.4 mL/min, tR
[min] 34.3 (S), tR [min] 45.2 (R), absolute configuration of
product determined by comparing circular dichroism (CD)
spectrum of the purified a-hydroxy ketone 7d to the CD
spectrum of (S)-2-hydroxy tetralone 7a, [a]2D0 +17.5 (c 0.4,
CHCl3).
R-(+)-4a, Entry 2: 5% i-PrOH in hexane, 0.4 mL/min; tR
[min] 17.7 (S), tR [min] 20.1 (R), [a]2D0 +65.4 (c 0.75,
CHCl3); lit. (R)-4a: [a]2D0 +81.0 (c 1.5, CHCl3);30 [a]2D0
+82.2 (c 2.0, CHCl3), ee¼96%.34
R-(+)-7e Entry 5: hexane–EtOH–i-PrOH (98:1.6:0.4 v/v),
0.2 mL/min, tR [min] 65.9 (S), tR [min] 74.3 (R), absolute
configuration of product determined by comparison of sign
of optical rotation to the literature value [a]2D0 +19.8 (c 3.1,
CHCl3); lit.32a (R)-7e: [a]D20 +33.4 (c 1.4, CHCl3) at 78%
ee (chiral GC); lit32b (R)-7e: [a]2D5 +20.0 (c 2.0, MeOH) at
81% ee; (S)-7e: [a]2D5 ꢀ22.7 (c 1.62, MeOH) at 85% ee, (Dai-
cel Chiracel OB-H, 35% i-PrOH in hexane, 1.5 mL/min, tR
[min] 8.2 (S), tR [min] 4.2 (R)).
S-(ꢀ)-4c Entry 3: 4% i-PrOH in hexane, 0.4 mL/min; tR
[min] 14.7 (S), tR [min] 17.8 (R), [a]2D0 ꢀ29.3 (c 1.1,
CHCl3); lit. (S)-4c: [a]2D0 ꢀ30.78 (c 2.24, CHCl3),
ee¼95% was determined by Eu(hfc)3 NMR shift reagent
of acetate derivative.33a
R-(+)-4c Entry 4: 4% i-PrOH in hexane, 0.4 mL/min; tR
[min] 14.5 (S), tR [min] 19.0 (R), [a]2D0 +40.54 (c 0.3,
CHCl3).
R-(+)-7e Entry 6: hexane–EtOH–i-PrOH (98:1.6:0.4 v/v),
0.2 mL/min, tR [min] 63.5 (S), tR [min] 71.5 (R), [a]D20
+7.5 (c 0.48, CHCl3).
S-(ꢀ)-4c Entry 5: [a]2D0 ꢀ3.8 (c 0.5, CHCl3).
Acknowledgements
S-(ꢀ)-4f Entry 6: 3% i-PrOH in hexane, 0.3 mL/min; tR
[min] 16.1 (S), tR [min] 22.5 (R), [a]2D0 ꢀ14.0 (c 0.3,
CHCl3); lit.35 (S)-acetate derivative of 4f: [a]2D0 +1.9 (c 0.8,
acetone), (R)-acetate derivative of 4f: [a]2D0 ꢀ2.3 (c 0.5,
acetone), ee¼50%.
Financial support by the Ministry of Science and Higher
Education of Poland (Grant No 3 T09A 083 29; 2005–
2008) is gratefully acknowledged. The authors thank
ꢀ
Prof. A. Skowronska for her helpful discussion.
S-(ꢀ)-4f Entry 7: 3% i-PrOH in hexane, 0.3 mL/min; tR
[min] 18.8 (S), tR [min] 24.5 (R), [a]2D0 ꢀ19.9 (c 2.4, CHCl3).
Supplementary data
R-(+)-4f Entry 8: 3% i-PrOH in hexane, 0.3 mL/min; tR
[min] 19.7 (S), tR [min] 23.3 (R), [a]2D0 +17.3 (c 1.3, CHCl3).
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.09.100.

M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
12373
1981, 1001; (e) Ding, Y.; Huang, X. Heteroat. Chem. 1999,
10, 55; (f) Zhang, N.; Casida, J. E. Synthesis 2000, 1454.
11. (a) Nicolaou, K. C.; Shi, G.-Q.; Namoto, K.; Bernal, F. Chem.
Commun. 1998, 1757; (b) Nicolaou, K. C.; Shi, G.-Q.; Gartner,
G. P.; Yang, Z. J. Am. Chem. Soc. 1997, 119, 5467; (c) Jiang, J.;
De Vita, R. J.; Doss, G. A.; Goulet, M. T.; Wyvratt, M. J. J. Am.
Chem. Soc. 1999, 121, 593; (d) Lepifre, F.; Buon, C.; Rabot, R.;
Bouyssou, P.; Coudert, G. Tetrahedron Lett. 1999, 40, 6373; (e)
Lepifre, F.; Buon, C.; Bouyssou, P.; Coudert, G. Heterocycl.
Commun. 2000, 6, 397; (f) Buon, C.; Chacun-Lefevre, L.;
Rabot, R.; Bouyssou, P.; Coudert, G. Tetrahedron 2000,
56, 605.
References and notes
1. (a) Hanessian, S. Total Synthesis of Natural products: The
Chiron Approach; Pergamon: New York, NY, 1983; Chapter
2; (b) Whitesell, J. K.; Buchanan, C. M. J. Org. Chem. 1986,
51, 5443; (c) Du Bois, J.; Tomooka, C. S.; Hong, J.; Carreira,
E. M. Acc. Chem. Res. 1997, 30, 364.
2. Coppola, G. M.; Schuster, H. F. a-Hydroxy Acids in
Enantioselective Synthesis; Wiley-VCH: Weinheim, 1997.
3. (a) Davis, F. A.; Chen, B.-C. Chem. Rev. 1992, 92, 919; (b)
Hashiyama, T.; Morikawa, K.; Sharpless, K. B. J. Org. Chem.
1992, 57, 5067; (c) Knight, R. L.; Leeper, F. J. J. Chem. Soc.,
Perkin Trans. 1 1998, 1891; (d) Enders, D.; Breuer, K.; Teles,
J. Helv. Chim. Acta 1996, 79, 1217; (e) Enders, D.; Breuer,
K. Comprehensive Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol.
2, pp 1093–1102; (f) Koike, T.; Murata, K.; Ikariya, T. Org.
Lett. 2000, 2, 3833; (g) Lee, J. C.; Jin, Y. S.; Choi, J. H.
Chem. Commun. 2001, 956.
ꢀ
12. Koprowski, M.; Krawczyk, E.; Skowronska, A.; McPartlin, M.;
Choi, N.; Radojevic, S. Tetrahedron 2001, 57, 1105.
´
13. (a) Adam, W.; Hadjiarapoglou, L.; Klicic, J. Tetrahedron
Lett. 1990, 31, 6517; (b) Adam, W.; Hadjiarapoglou, L.;
€
´
Jager, V.; Klicic, J.; Seidel, B.; Wang, X. Chem. Ber. 1991,
124, 2361.
ꢀ
14. Skowronska, A.; Koprowski, M.; Krawczyk, E. Phosphorus,
Sulfur Silicon 2002, 177, 1877.
€
4. (a) Adam, W.; Diaz, M. T.; Fell, R. T.; Saha-Moller, C. R.
ꢀ
15. Krawczyk, E.; Koprowski, M.; Skowronska, A.; quczak, J.
Tetrahedron: Asymmetry 2004, 15, 2599.
Tetrahedron: Asymmetry 1996, 7, 2207; (b) Kawai, Y.; Hida,
K.; Tsujimoto, M.; Kondo, S.; Kitano, K.; Nakamura, K.;
Ohno, A. Bull. Chem. Soc. Jpn. 1999, 72, 99.
16. Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am.
Chem. Soc. 1990, 112, 2801.
€
5. (a) Adam, W.; Fell, R. T.; Stegmann, V. R.; Saha-Moller, C. R.
17. (a) Borowitz, I. J.; Kwok, Ch. Y.; Crouch, R. J. Org. Chem.
1973, 38, 1713; (b) Boyce, C. B. C.; Webb, S. B.; Phillips,
L.; Worthington, P. A. J. Chem. Soc., Perkin Trans. 1 1998,
2881.
J. Am. Chem. Soc. 1998, 120, 708; (b) Zhu, Y.; Tu, Y.; Yu, H.;
Shi, Y. Tetrahedron Lett. 1998, 39, 7819; (c) Adam, W.; Fell,
€
R. T.; Saha-Moller, C. R.; Zhao, C.-G. Tetrahedron:
Asymmetry 1998, 9, 4117.
18. Previously we incorrectly assigned the structures of 2a, b, d, f,
i, and j as E isomer. The attempts at observing an NOE effect in
2a–d had failed (Ref. 15).
19. (a) Pospisil, P. J.; Carsten, D. H.; Jacobsen, E. N. Chem.—Eur.
J. 1996, 2, 974; (b) Finney, N. S.; Pospisil, P. J.; Chang, S.;
Palucki, M.; Konsler, R. G.; Hansen, K. B.; Jacobsen, E. N.
Angew. Chem., Int. Ed. 1997, 36, 1720.
6. (a) Rao, A. S.; Paknokov, S. K.; Kirtane, J. G. Tetrahedron
1983, 39, 2323; (b) Smith, J. G. Synthesis 1984, 629; (c)
Paterson, I.; Berrisford, D. J. Angew. Chem., Int. Ed. Engl.
1992, 31, 1179; (d) Erden, I. Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V.,
Eds.; Elsevier: Oxford, 1996; Vol. 1A, pp 105–117; (e)
Hodgson, D. M.; Gibbs, A. R.; Lee, G. P. Tetrahedron 1996,
52, 14361; (f) Jacobsen, E. N. Acc. Chem. Res. 2000, 33,
421; (g) Schaus, S. E.; Brandes, B. D.; Larrow, J. F.;
Tokunago, M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.;
Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 1307 and refer-
ences cited therein; (h) Equey, O.; Alexakis, A. Tetrahedron:
Asymmetry 2004, 15, 1531; (i) Nielsen, L. P. C.; Stevenson,
Ch. P.; Blackmond, D. G.; Jacobsen, E. N. J. Am. Chem. Soc.
2004, 126, 1307.
7. (a) Lee, N. H.; Muci, A. R.; Jacobsen, E. N. Tetrahedron Lett.
1991, 32, 5055; (b) Deng, L.; Jacobsen, E. N. J. Org. Chem.
1992, 57, 4320; (c) Brandes, B. D.; Jacobsen, E. N.
Tetrahedron Lett. 1995, 36, 5123; (d) Brandes, B. D.;
Jacobsen, E. N. J. Org. Chem. 1994, 59, 4378; (e) Fukuda,
T.; Irie, R.; Katsuki, T. Synlett 1995, 197; (f) Sakaki, H.; Irie,
R.; Katsuki, T. Synlett 1993, 300; (g) Hosoya, N.; Hatayama,
A.; Ianai, K.; Fujii, H.; Irie, R.; Katsuki, T. Synlett 1993, 641;
(h) Hamada, T.; Irie, R.; Katsuki, T. Synlett 1994, 479.
8. (a) Fukuda, T.; Katsuki, T. Tetrahedron Lett. 1996, 37, 4389; (b)
20. (a) Krohn, K. Angew. Chem., Int. Ed. Engl. 1986, 25, 790; (b)
Schultz, A. G. Chem. Rev. 1973, 73, 385.
21. (a) Sharpless, K. B.; Teranishi, A. Y.; Backwall, J. E. J. Am.
Chem. Soc. 1977, 99, 3120; (b) Hamada, T.; Fukuda, T.;
Imanishi, H.; Katsuki, T. Tetrahedron 1996, 52, 515; (c)
Norrby, P.-O.; Linde, C.; Akermark, B. J. Am. Chem. Soc.
1995, 117, 11035; (d) Linde, C.; Arnold, M.; Norrby, P.-O.;
Akermark, B. Angew. Chem., Int. Ed. 1997, 36, 1723.
22. (a) Palucki, M.; Finney, N. S.; Pospisil, P. J.; Guler, M. L.;
Ishida, T.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 948;
(b) Jacobsen, E. N.; Zhang, W.; Muci, A. R.; Ecker, J. R.;
Deng, L. J. Am. Chem. Soc. 1991, 113, 7063.
23. Kawai, N.; Shioiri, T. Chem. Pharm. Bull. 1983, 31, 2564.
24. Craig, J. C.; Moyle, M. J. Chem. Soc. 1963, 3712.
25. Xi, Q.; Lin, X.; Chang, J.; Ding, Y. Phosphorus, Sulfur Silicon
2003, 178, 47.
26. Chopa, A. B.; Dorn, V. B.; Badajoz, M. A.; Lockhart, M. T.
J. Org. Chem. 2004, 69, 3801.
€
Adam, W.; Fell, R. T.; Mock-Knoblauch, C.; Saha-Moller,
C. R. Tetrahedron Lett. 1996, 37, 6531.
27. No analytically pure epoxides 3a–i and 6a–c were obtained
owing to their instability during purification. These compounds
were characterized by NMR, IR, and HRMS. Crude epoxides
3j and 6d–f could not be fully characterized by NMR and
MS spectra owing to their instability during measurements
performed at room temperature.
28. Vedejs, E.; Engler, D. A.; Telschow, J. E. J. Org. Chem. 1978,
43, 188.
29. Kajiro, H.; Mitamura, S.; Mori, A.; Hiyama, T. Bull. Chem.
Soc. Jpn. 1999, 72, 1553.
9. (a) Eto, M. Organophosphorus Pesticides: Organic and
Biological Chemistry; CRC: Cleveland, Ohio, 1974; (b)
Stowell, J. K.;Widluaski, T. S. J. Am. Chem. Soc. 1994, 116, 789.
10. (a) Lichtenthaler, F. W. Chem. Rev. 1961, 61, 607; (b)
Meisters, A.; Swann, J. W. Aust. J. Chem. 1965, 18, 168; (c)
Borowitz, I. J.; Firstenberg, S.; Caspar, E. W. R.; Crouch,
R. K. J. Org. Chem. 1971, 36, 3282; (d) Hayashi, T.;
Fujiwa, T.; Okamoto, Y.; Katsuro, Y.; Kumada, M. Synthesis

12374
M. Koprowski et al. / Tetrahedron 62 (2006) 12363–12374
30. Honda, Y.; Ori, A.; Tsuchihashi, G. Bull. Chem. Soc. Jpn. 1987,
60, 1027.
31. Marcune, B. F.; Karady, S.; Reider, P. J.; Miller, R. A.; Biba, M.;
Di Michele, L.; Reamer, R. A. J. Org. Chem. 2003, 68, 8088.
33. (a) Davis, F. A.; Weismiller, M. C.; Murphy, Ch. K.; Reddy,
R. T.; Chen, B.-C. J. Org. Chem. 1992, 57, 7274; (b) Davis,
F. A.; Sheppard, A. C.; Chen, B. C.; Haque, M. S. J. Am.
Chem. Soc. 1990, 112, 6679.
€
32. (a) Ziehe, H.; Wartchow, R.; Butenschon, H. Eur. J. Org. Chem.
34. Demir, A. S.; Hamaruci, H.; Tanyeli, C.; Akhmedow, J. M.;
Doganel, F. Tetrahedron: Asymmetry 1998, 9, 1673.
35. Ohta, H.; Ikemoto, N.; Hiroyuki, II; Okamoto, Y.; Tsuchinashi,
G.-I. Chem. Lett. 1986, 1169.
1999, 823; (b) Morikawa, K.; Park, J.; Andersson, P. G.;
Hashiyama, T.; Sharpless, K. B. J. Am. Chem. Soc. 1993,
115, 8463.