Synthesis of racemic and enantiomerically enriched α- oxyfunctionalized benzocyclanones and chromanones by dimethyldioxirane and dimethyldioxirane/Mn(III) salen system

Article abstract of DOI:10.1007/s00706-004-0159-9

Enolacetates of benzocyclanones and chromanones were synthesized and treated with dimethyldioxirane and the asymmetric oxidizing system dimethyldioxirane/chiral, non-racemic Mn(III) salen complex/axial ligand. The latter reagent resulted in the corresponding enantiomerically enriched cyclic α-hydroxy ketones and their acetates in moderate-to-good yields and modest enantioselectivity under mild and neutral conditions from tetralone and chromanone. On the contrary, flavanone provided poor yields due to the competitive C-H insertion at position 2. The use of R,R-Mn(III)salen catalyst induced an S absolute configuration at the position α in the whole series. Springer-Verlag 2004.

Full text of DOI:10.1007/s00706-004-0159-9

Monatshefte f€ur Chemie 135, 743–756 (2004)
DOI 10.1007/s00706-004-0159-9
Synthesis of Racemic and Enantiomerically
Enriched a-Oxyfunctionalized
Benzocyclanones and Chromanones
by Dimethyldioxirane and
Dimethyldioxirane=Mn(III) salen System#
ꢀ
}
´ ´ ´
Tamas Patonay , Jozsef Jeko, Attila Kiss-Szikszai, and Albert Levai
Department of Organic Chemistry, University of Debrecen, H-4010 Debrecen,
P.O. Box 20, Hungary
Received November 7, 2003; accepted (revised) January 5, 2004
Published online April 22, 2004 # Springer-Verlag 2004
Summary. Enolacetates of benzocyclanones and chromanones were synthesized and treated with
dimethyldioxirane and the asymmetric oxidizing system dimethyldioxirane=chiral, non-racemic
Mn(III) salen complex=axial ligand. The latter reagent resulted in the corresponding enantiomerically
enriched cyclic ꢀ-hydroxy ketones and their acetates in moderate-to-good yields and modest enantio-
selectivity under mild and neutral conditions from tetralone and chromanone. On the contrary, flavanone
provided poor yields due to the competitive C–H insertion at position 2. The use of R,R-Mn(III)salen
catalyst induced an S absolute configuration at the position ꢀ in the whole series.
Keywords. Dioxirane; Enantioselective epoxidation; Enolacetates; Jacobsen-Katsuki’s catalyst.
Introduction
ꢀ-Hydroxy ketones, particularly in their enantiopure form, are important synthetic
building blocks and, therefore, their synthesis has received great attention in the
last decades. Among the various approaches the oxidation of enol derivatives 2
including enolates 3 by an electrophilic oxidant is one of the most prominent
methods of high synthetic value (Scheme 1).
The oxidation of enol derivatives 2 results in the formation of epoxide inter-
mediates 4 giving the alcohols 5 by hydrolysis and=or the rearranged ꢀ-oxyfunc-
tionalized ketones 6 depending on the structure of the starting material.
ꢀ
Corresponding author. E-mail: tpatonay@tigris.klte.hu
#
Dedicated to Prof. Waldemar Adam on the occasion of his retirement

744
T. Patonay et al.
Scheme 1
à
Alkyl enol ethers 2 (R ¼ alkyl) have been oxidized by HOF MeCN complex to
yield ꢀ-ketols 5 [1]. When methyl trifluoromethyl dioxirane (MTMD) or dimethyl-
dioxirane (DMD) was applied as oxidant, the intermediate (spiro)acetals 4
(R ¼ alkyl) have been isolated [2]. An enantioselective version utilizing PhIO
and non-racemic Mn(III) salen complexes (Jacobsen-Katsuki’s catalysts) has also
been developed [3], in this latter case ꢀ-hydroxyacetals have been obtained due to
the solvolysis of the intermediate. Adam et al. [4] used peracids, H2O2, PhIO, and
bleach in combination with a chiral, non-racemic Mn(III) salen complex for this
purpose. Silyl enol ethers 2 (R ¼ TMS, TBDMS) have been oxidized by a wide
variety of oxidants such as peracids [5], lead tetrabenzoate [6], lead tetraacetate
[7], osmium tetroxide [8], DMD [9], oxaziridine [10], and tert-butyl hydroperoxide
(THBP) in the presence of titanium silicalite-1 [11]. The products were epoxides 4
(R ¼ TMS), ꢀ-silyloxy ketones 6 (R ¼ TMS), or ketols 5 depending on the condi-
tions used. Several asymmetric oxidations of silyl enol ethers by using PhIO
[12, 13] or bleach [13] in combination with a chiral, non-racemic Mn(III) salen
complex or by an optically active dioxirane generated in situ from Oxone+ and a
fructose-derived ketone (Shi’s ketone) have been performed [14]. Enol esters 2
(R ¼ acyl, phosphinyl) were also frequent substrates affording mainly the epoxides
4 (R ¼ acyl, phosphinyl) on oxidation by peracids [15, 16] or DMD [9b, 17].
Enantioselective epoxidations of enolacetates by Oxone+ and Shi’s ketone have
also been reported [14a].
It is noteworthy that ketones with high enol content could directly be oxidized
to ꢀ-hydroxyketones 5 by DMD [18]. However, the one-pot oxidation of metal
enolates by various electrophilic oxidants is a far more frequently used procedure.
Such transformation was performed by using direct oxygenation followed by the
reduction of the intermediate hydroperoxide [19] or by treating the enolate with
à
Vedejs’ reagent (MoO5 HMPA (MoOPH)) [20], oxaziridines [10, 21], bis(tri-
methylsilyl) peroxide (BTSP) [22], and DMD [18, 23, 24]. Enantioselective,
reagent-controlled ꢀ-hydroxylations upon treatment by chiral, non-racemic oxazi-
ridines such as (þ)-(camphorsulfonyl)oxaziridine have also been reported [10, 21].
Alternatively, a substrate-controlled approach utilizing titanium enolates with
chiral ligands and DMD and 3-phenyl-2-phenylsulfonyloxaziridine (PPO) as oxy-
gen source has also been developed [25].
Recently, we have disclosed that the combination of DMD and Jacobsen’s
catalyst is a useful and efficient reagent for the enantioselective epoxidation of
chromenes [26] and isoflavones [27] with ee values up to 93% under mild and

ꢀ-Oxyfunctionalized Benzocyclanones and Chromanones
745
neutral conditions. In continuation of this work we wished to test our system in ꢀ-
oxyfunctionalization, as well. Cyclic ketones were used as substrates for our
studies since
(i) these derivatives were much more rarely used model compounds and fewer
procedures have been developed for their asymmetric oxidation, moreover,
(ii) usually poorer enantioselective discrimination was observed in their reaction
probably due to the fixed cyclic system. E.g., Reddy and Thornton [12]
reported only 14–62% ee in the oxidation of cyclic silyl enol ethers by PhIO
and Mn(III) salen complexes. Similarly, a poor (20–30%) enantioselectivity
was found [28] in the oxidation of 1-(trimethylsilyloxy)-3,4-dihydronaphtalene
by PhIO or bleach and Jacobsen’s catalyst, a reagent which was very efficient
for acyclic substrates [13]. We have chosen enol acetates 2 (R ¼ Ac) as starting
materials owing to the higher persistency of the intermediates 4 and in the
hope that the lower reactivity of enol acetates toward the oxidant may result in
a higher enantioselectivity.
Results and Discussion
Starting material enolacetates 8a–8d have been synthesized by the classical acid-
catalyzed transesterification of the corresponding ketones 7a–7d and isopropenyl
acetate (12) using modified Saito’s conditions [29].
When enolacetates 8a–8c were allowed to react with DMD (as acetone solu-
tion) [30] without any chiral catalyst mixtures of ꢀ-hydroxy ketones 10a–10c and
ꢀ-acetoxy ketones 11a–11c were obtained in moderate yields (15–57% and 34–
48%, respectively) and no intermediate 9 could be detected (Scheme 2). Oxidation
of chromanone derivative 8c gave lower yields due to the instability of products
10c and 11c, particularly ꢀ-ketol 10c was sensitive for the exposure to air.
Scheme 2

746
T. Patonay et al.
The immediate formation of secondary products 10 and 11 by ring-opening of
the oxirane functionality can be explained by the presence of a small amount
of water in the DMD solution. When the oxidation was performed in the presence
of anh. K2CO3 as additive, the intermediate 1-acetoxy-1,2-epoxytetralin (9b) was
obtained in excellent yield but other enolacetates 8a and 8c gave only the second-
ary products, again. The treatment of 4-acetoxy-2-phenyl-2H-1-chromene (8d)
with DMD in the presence of anh. K2CO3 resulted in the formation of trans-3-
hydroxyflavanone (trans-10d) (40%), trans-3-acetoxyflavanone (trans-11d) (25%),
and flavone (13) (10%). The complete diastereoselectivity of the reaction is note-
worthy, no cis diastereomers could be detected in the reaction mixture by 1H NMR.
To our best knowledge, this was the first isolation of epoxide 9b, although
Spanish authors [31] postulated its intermediacy in the photolysis of enolacetate
8b. The observed high lability of ꢀ-acetoxy epoxides 9 can be attributed to various
reasons. These epoxides are known to be sensitive to traces of acid [16, 32]. Shi
and coworkers [14a] purified ꢀ-benzoyloxy epoxides on silica pretreated with
NEt3. In the non-selective bleach=Mn(III) salen-mediated oxidation of 2-acet-
oxy-1,3-cycloalkadienes Jacobsen et al. [33] obtained only the corresponding ꢀ-
hydroxy and ꢀ-acetoxy ketone derivatives. Any ring-strain seems to increase the
lability of the epoxides 9. Tetralines still show modest stability since 1-benzoy-
loxy-1,2-epoxytetraline has been also prepared [14a] but incorporation of the larger
oxygen heteroatom in the cyclanone ring or the change for a five-membered indane
ring makes the epoxide unstable.
Mapping the reactivity of the stable epoxide 9b we found that it reacted
smoothly in the presence of acids even with silica gel to afford 2-hydroxytetralone
(10b) and 2-acetoxytetralone (11b). The formation of acetate 11b in a thermal
process (vide infra) could be excluded since a prolonged (50 h) heating of epoxide
9b gave the mixture of 10b and 11b only in a very low (13%) conversion.
The asymmetric epoxidation of enolacetate 8b by DMD and Jacobsen’s cata-
lyst 14 was tested next (Table 1). Enantioselectivity was determined by measuring
the optical rotation of the isolated pure epoxide 9b after a fast short-column chro-
matography to remove the catalyst. Attempts to determine ee values by chiral
HPLC failed due to the slow hydrolysis of the product 9b during the sample
preparation and the elution. On the basis of our experiments with different catalyst
loading we chose amounts of 10 mol% for the further oxidations. By switching
from R,R-14 to S,S-14, nearly the same optical purity was measured for the other
enantiomer. This observation clearly proves an asymmetric oxidation process.
In the 1980s Kochi and coworkers [34] observed that efficiency of metal salen
catalysts can be improved by adding donor ligands and this finding was also suc-
cessfully used in the Jacobsen-Katsuki epoxidation [35, 36]. In our previous work
we have also perceived the beneficial effect of nitrogen-containing axial ligands
both on the yields and ee values [26a, 27b]. Therefore, we have performed oxida-
tion of enolacetate 8b by using imidazole, N-methylimidazole, 4-picoline N-oxide,
and 4-phenylpyridine N-oxide (PPNO) (ca. 40 mol%) as axial ligand and, as
expected, an improved enantiopurity of both the intermediate epoxide 9b and
the cleaved products 10b and 11b was observed. The data summarized in Table
1 clearly show the advantageous effect of the ligands, the best enantioselectivities
were obtained by using imidazole or PPNO (ee values up to 66% for 10b and 58%

ꢀ-Oxyfunctionalized Benzocyclanones and Chromanones
747
Table 1. Results of the synthesis of chiral, non-racemic epoxide 9b by oxidation with DMD and Mn(III) salen catalyst 14 and
their silica gel-induced ring-opening to alcohol 10b and acetate 11b
Catalyst (14)
Axial ligand
Epoxide 9b
Alcohol 10ba
Acetate 11bb
Config. Amount= Type
mol%
Amount= Yield= [ꢀ]D
%
Yield= Config. eec= Yield= Config. eec=
mol%
%
%
%
%
R,R-(ꢁ) 10.2
6.3
none
ꢁ
52
60
39
19d
26
34
þ26.2 38
ꢁ16.5 37
ꢁ23.3 39
ꢁ5.9 23
S-(ꢁ)
R-(þ)
R-(þ)
R-(þ)
R-(þ)
R-(þ)
R-(þ)
R-(þ)
26
33
20
33
66
52
47
62
31
49
47
31
21
28
30
17
S-(ꢁ)
R-(þ)
R-(þ)
R-(þ)
R-(þ)
R-(þ)
R-(þ)
R-(þ)
20
30
26
30
49
52
36
58
S,S-(þ)
none
ꢁ
S,S-(þ) 10.2
S,S-(þ) 14.9
S,S-(þ) 10.2
S,S-(þ) 10.2
S,S-(þ) 10.2
S,S-(þ) 10.2
none
ꢁ
none
ꢁ
imidazole
N-Me-imidazole
42.9
42.8
ꢁ40.1 17
ꢁ39.1 17
ꢁ36.2 32
4-picoline N-oxide 40.2
PPNOe
40.0
45
f
ꢁ
59
a
Absolute configuration was determined on the basis of the sign of specific rotation [21, 53]
Absolute configuration was determined on the basis of the sign of specific rotation [21]
Determined by HPLC
b
c
d
e
f
Contaminated with alcohol 10b and acetate 11b
PPNO ¼ 4-phenylpyridine N-oxide
Decomposed to alcohol 10b and acetate 11b during chromatography
for 11b). The major enantiomer of both the alcohol and the acetate had the same
absolute configuration; the formation of R-(þ)-10b and R-(þ)-11b was preferred in
the presence of S,S-(þ)-14.
In continuation we checked our optimized system (DMD=10 mol% 14=
40 mol% imidazole or PPNO) in the oxidation of heterocyclic enolacetates 8c
and 8d and the results are shown in Tables 2 and 3.
Oxidation of both substrates resulted in poor ee values without axial ligands but
considerably higher enantioselectivity was obtained in the presence of imidazole or
PPNO. As before, these two additives gave comparable ee values (up to 50% for
alcohols and 45% for acetates) but the values were somewhat lower than those
found for the tetralone derivatives. It seems that the incorporation of oxygen into
the ring decreases the stereodifferentiation in the attack of the chiral Mn(V) salen
Table 2. Results of the enantioselective oxidation of enolacetate 8c with DMD and Mn(III) salen
catalyst (R,R)-14 (10 mol%)
DMD=equiv.
Axial liganda
Alcohol 10c
Yield=%
Acetate 11c
Yield=%
Config.b
ee=%
Config.c
ee=%
4.0
2.9
2.5
none
19
26
16
S-(ꢁ)
S-(ꢁ)
S-(ꢁ)
8
37
33
24
23
16
S-(ꢁ)
S-(ꢁ)
S-(ꢁ)
8
33
31
imidazole
PPNO
a
40 mol% of axial ligand were added
b
c
Absolute configuration was determined on the basis of the sign of specific rotation [54]
Absolute configuration was deduced from the Sc(OTf)3-mediated hydrolysis of (ꢁ)-11c giving
(ꢁ)-10c [55]

748
T. Patonay et al.
Table 3. Results of the enantioselective oxidation of enolacetate 8d with DMD and Mn(III) salen catalyst (R,R)-12
(10 mol%)
DMD=equiv.
Axial liganda
Alcohol 10d
Yield=%
Acetate 11d
Yield=%
Flavone (13)
Yield=%
Config.b
ee=%
Config.b
ee=%
7.0
6.5b
5.4
6.0
none
29
29
12
11
2R,3R-(ꢁ)
2R,3R-(ꢁ)
2S,3S-(þ)
2S,3S-(þ)
2
4
2.5
3
n.d.
n.d.
3
37
42
52
73
none
2S,3S-(ꢁ)
2S,3S-(ꢁ)
2S,3S-(ꢁ)
imidazole
PPNO
44
50
13
8
45
35
a
40 mol% of axial ligand were added
b
Absolute configuration was determined on the basis of the sign of rotation [51]
oxo complex on the double bond of enolacetate. Absolute configuration of products
10c, 11c, trans-10d, and trans-11d has been assigned on the basis of the sign of the
specific rotation or by chemical correlation. When the oxidation was performed by
using catalyst R,R-(ꢁ)-14, all these products had the same S absolute configuration
at stereogenic center C-3. This observation is in accordance with the preferred
configuration of tetralones (vide supra).
Data given in Table 3 have also revealed another interesting point. Namely,
when enolacetate 8d was oxidized by DMD without catalyst 14 the major products
were trans-10d and trans-11d (in 65% total isolated yields, see Experimental) but
the amount of the previous by-product flavone (13) was highly increased when
Jacobsen’s catalyst was applied. The use of catalyst 14 combined with axial
ligands led to the formation of 13 as major product (in isolated yields up to
73%). Due to this unfortunate side reaction the asymmetric ꢀ-oxyfunctionalization
of flavanone has no significant synthetic value. The preferred formation of flavone
(13) can be explained by the increased reactivity of the oxidizing species, i.e. the
Mn(V) salen oxo complex, compared to DMD. The more reactive oxidizing agent
can attack not only the C¼C double bond but competitively the doubly activated
(benzylic and allylic at the same time) position 2 of the enolacetate 8d, too, form-
ing the 2-hydroxylated intermediate 15 by a C–H insertion reaction. This inter-
mediate 15 affords flavone (13) after hydrolysis and water elimination (Scheme 3).
The ease of this latter elimination step has been documented [37a]. It is noteworthy
that the oxidation of flavanones by DMD was also reported but it takes place very
slowly on the parent compound 7d and requires the activation of C-2 by electron-
donating substituents in ring B [37].
Scheme 3

ꢀ-Oxyfunctionalized Benzocyclanones and Chromanones
749
The transformation of ꢀ-acetoxy epoxides into ꢀ-acetoxy ketones has been
known for a long time and the suggested mechanisms are reviewed [38]. This
rearrangement can take place both upon treatment of acids (or silica gel, as in
our case) and heating. The configuration at the position adjacent to the ketone
group is usually retained in the presence of acids but the thermal procedure may
give either the product with inverted [14a, 38] or, in some particular case [38, 39],
with retained configuration. This duality indicates the existence of at least two
independent mechanisms. Considering the facts that in our reactions
(i) the obtained ꢀ-hydroxy- and ꢀ-acetoxybenzo(hetera)cyclanones had the same
absolute configuration and the formation of ꢀ-hydroxy ketones does not entail
the breaking of the Cꢀ–O bond,
(ii) the oxyfunctionalization of flavanone (7d) took place with complete diastero-
selectivity, and
(iii) the possibility of thermolysis was excluded (vide supra) we suggest the
mechanism shown in Scheme 4 to account all the listed observations the ring
opening of intermediate 9d is depicted.
The formation of alcohol trans-10d can be interpreted in terms of a protonation
of the epoxide giving the oxonium ion A and its resonance stabilized form A0. The
hydration of the latter species followed by elimination of acetic acid from the
intermediate B results in the product trans-10d. The pathway leading to trans-
11d involves an intramolecular migration of the acetyl group via a zwitterion with
a dioxolan ring (C) which leaves the Cꢀ–O bond intact.
As mentioned before, catalyst R,R-(ꢁ)-14 induced a preferred S whereas cat-
alyst S,S-(þ)-14 induced R absolute configuration of the ꢀ-hydroxy and ꢀ-acetoxy
ketones. These selectivities are consistent with the configurations expected on the
basis of a recently published model of the transition state [36b and the references
Scheme 4

750
T. Patonay et al.
Fig. 1. Suggested way of attack of substrate 8b on Jacobsen’s catalyst
cited therein]. The two possible approaches of an enolacetate to the oxidizing
species are shown for catalyst S,S-(þ)-14 and substrate 8b in Fig. 1.
The enolacetate comes to the Mn(V) oxo complex of folded structure from the
open side above the phenyl ring of the catalyst (Katsuki trajectory, ꢁ ffi ꢁ90ꢂ) with
a parallel or slightly skewed side-on approach. Approach from the opposite side
(ꢁ ffi 90ꢂ) is hindered due to the substituted phenyl group of the catalyst lying
above the plane of the cyclohexyl ring. From the two possible orientations of
the enolacetate, the attack to its si face is favored because of less steric repulsion.
This attack leads to R configuration at position 2 which is retained in the products
10b and 11b. In the case of attack to the re face the benzene ring and the acetoxy
group of the substrate 8 come too close to the phenyl ring of the salen unit bearing
two bulky tert-butyl groups which make this approach highly disfavored (Fig. 1).
In conclusion, the asymmetric oxidation of enolacetates of benzocyclanones
and chromanone 8a–8c by DMD=chiral, non-racemic Mn(III) salen complex=axial
ligand system offers a new method for the synthesis of enantiomerically enriched
cyclic ꢀ-hydroxy ketones 10a–10c and their acetates 11a–11c with moderate-to-
good yields and modest enantioselectivities under mild and neutral conditions. 4-
Acetoxy-2-phenyl-2H-1-chromene (8d) reacts smoothly with DMD itself to afford
the corresponding ꢀ-oxyfunctionalized products 10d and 11d with complete trans
diastereoselectivity but the chiral reagent provides only flavone (13) as the major
product. The stereochemical control of the epoxidation is in accordance with the
side-on approach to the Mn(V) oxo complex along the Katsuki trajectory.
Experimental
All solvents and reagents were purchased from commercial suppliers and used as received. Caroate+
(potassium monoperoxysulfate), the triple salt 2KHSO5 Á KHSO4 Á K2SO4, was used as received from
€
Peroxid-Chemie GmbH (Hollriegelskreuth, Germany). DMD solution was prepared as indicated in
Ref. [30], its peroxide content was determined by iodometry. Melting points were determined on a
Boetius hot-stage apparatus and are uncorrected. IR spectra were recorded with a Perkin-Elmer 16 PC
1
FT-IR instrument in KBr pellets unless otherwise specified. H and 13C NMR data were recorded on
Bruker WP 200SY and Bruker AM400 spectrometers. Chromatographic separations were performed

ꢀ-Oxyfunctionalized Benzocyclanones and Chromanones
751
using 70–230 or 230–400 mesh (Merck) silica gel. Thin-layer chromatography (TLC) was carried out
on Macherey-Nagel silica plates (0.25 mm layer thickness). HPLC analyses were performed with a
Hewlett-Packard chromatograph with Chiralcel OB (10a, 11a) or OD (10c, 10d, 11c, 11d)
(250 mm 0.46 cm) chiral columns, (eluent: n-hexane:2-propanol¼ 9:1, v=v). Optical rotations were
measured at 20ꢂC with a Perkin-Elmer 341 instrument at 589 nm (cell width¼ 100 mm). Elemental
analyses (C, H) were conducted using the Carlo Erba 1106 EA instrument; their results were found to
be in good agreement (Æ0.2%) with the calculated values.
General Method for the Preparation of Enolacetates 8a, 8c, and 8d
To a solution of the corresponding ketone 7a–7c (27.00mmol) in 2-acetoxypropene (12) (16 cm3,
0.145 mmol), 0.4 g (4.162mmol) of methanesulfonic acid were added and the mixture was stirred at
reflux temperature for 24h under N2 atmosphere. After cooling to room temperature it was diluted with
toluene (100 cm3) and washed with a saturated solution of NaHCO3 (20 cm3). The organic phase was
dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent: toluene:EtOAc¼ 4:1, v=v).
1-Acetoxyindene (8a)
White crystals, 3.283 g (62%); mp 40–41ꢂC (Ref. [40] 45–46ꢂC); 1H NMR spectrum was found to be
identical with the one described in Ref. [40].
4-Acetoxy-2H-1-chromene (8c)
1
Yellowish crystals, 4.311 g (74%); mp 49.5–50.5ꢂC (Ref. [29] bp 150–152ꢂC=1.733 kPa); H NMR
spectrum was found to be identical with the one described in Ref. [29].
4-Acetoxy-2-phenyl-2H-1-chromene (8d)
Yellowish crystals, 3.523 g (49%); mp 52–54ꢂC (Ref. [40] oil); 1H NMR (200 MHz, CDCl3): ꢂ ¼ 7.50
(d, J ¼ 7.8 Hz, 20,60-H), 7.36 (m, 30,40,50-H), 7.14 (m, 7-H), 7.10 (dd, J ¼ 7.2, 1.2Hz, 5-H), 6.88 (m, 6-
H), 6.80 (d, J ¼ 8.4 Hz, 8-H), 6.08 (d, J ¼ 3.7Hz, 2-H), 5.62 (d, J ¼ 3.7Hz, 3-H), 2.30 (s, 3H, Ac); 13C
NMR (100 MHz, CDCl3): ꢂ ¼ 168.5 (s, Ac), 153.9 (s, C-8a), 142.6 (s, C-4), 140.0 (s, C-10), 130.4 (d, 5-
C), 128.7 (d, 30,50-C), 127.3 (m, 20,40,60-H), 121.4, 121.0 (2d, 6,7-C), 118.2 (s, C-4a), 116.3 (d, C-8),
111.6 (d, C-3), 79.6 (d, C-2), 20.9 (q, Ac).
1-Acetoxy-3,4-dihydronaphtalene (8b)
In a three-necked flask fitted with a Vigreux column and equipped with a gas inlet, a mixture of 1-
tetralone (7b) (13.885 g, 94.99 mmol), 2-acetoxypropene (12) (22 cm3, 0.199mmol), and methanesul-
fonic acid (0.550 g, 5.722 mmol) was stirred under N2 atmosphere for 23h while the head temperature
was kept below 60ꢂC. The mixture was diluted with n-hexane (100cm3), saturated NaHCO3 solution
(150 cm3) was added, and it was stirred for 15min at room temperature. The brown crystals formed
were filtered off, dissolved in CH2Cl2 (10 cm3), and the solution was filtered through a mixture of silica
gel and MgSO4 (1:1). The filtrate was concentrated under reduced pressure and the oily residue was
allowed to stand with n-hexane to give 13.624g (76%) of 8b as light brown crystals. Mp 54–56ꢂC
(Ref. [40] 54–56ꢂC); 1H NMR spectrum was found to be identical with the one described in Ref. [40].
1-Acetoxy-1,2-epoxytetralin (9b, C12H12O3)
1-Acetoxy-3,4-dihydronaphthalene (8b, 380 mg, 2.019 mmol) and anh. K2CO3 (1.00 g) were added to a
solution of DMD in acetone (83 cm3, 0.049 M, ca. 2.01 equiv) and the mixture was allowed to react at

752
T. Patonay et al.
ꢁ20ꢂC for 2 h. The insoluble part was filtered off and the solvent was removed under reduced pressure
at room temperature. The crude product was recrystallised from n-hexane to afford 346 mg (84%) of
epoxide 9b as white crystals. Mp 96–98ꢂC; 1H NMR (200MHz, CDCl3): ꢂ ¼ 7.43 (dd, J ¼ 7.3, 2.5 Hz,
8-H), 7.26 (m, 6,7-H), 7.15 (dd, J ¼ 8.0, 2.5 Hz, 5-H), 3.88 (d, J ¼ 2.7 Hz, 2-H), 2.56–2.86 (m, 2H, 4-
H), 2.40 (m, 3-Heq), 2.26 (s, 3H, Ac), 2.02 (m, 1H, 3-Hax); 13C NMR (50 MHz, CDCl3): ꢂ ¼ 169.0 (s,
C¼O), 136.0 (s, C-8a), 130.9 (s, C-4a), 128.9, 128.5, 126.3, 125.1 (m, C-5,6,7,8), 79.8 (s, C-1), 62.0 (d,
C-2), 24.9 (t, C-4), 21.5 (t, C-3), 20.8 (q, Ac); IR (KBr): ꢃꢀ¼ 2908, 1746 (C¼O), 1426, 1376, 1216
(C–O–C), 1180, 1064 (C–O–C), 974, 760 cmꢁ1
.
Typical Procedure for the Enantioselective Oxidation of Enolacetate 8b
A DMD solution in acetone (164 cm3, 0.051M, ca. 2.02 equiv) was added to the solution of enolacetate
8b (779mg, 4.139 mmol) and R,R-(ꢁ)-Jacobsen’s catalyst (R,R-14) (271mg, 0.427 mmol) and the
mixture was stirred at room temperature for 10min. The solvent was removed under reduced pressure
at room temperature. The crude oily residue was passed through a silica gel pad wetted with n-
hexane:EtOAc (1:1, v=v) to remove the catalyst. The eluted fraction was concentrated under reduced
pressure and the residue was treated with n-hexane to yield crystalline epoxide 9b. Further experi-
mental details are given in Table 1.
Typical Procedure for the Silica Gel-induced Ring-opening of 1-Acetoxy-1,2-epoxytetralin (9b) to 2-
Hydroxytetralone (10b) and 3-Acetoxytetralone (11b)
A mixture of racemic epoxide 9b (275 mg, 1.346 mmol), silica gel (1.5g), and CH2Cl2 (25 cm3) was
stirred at room temperature for 17h, the completion of the reaction was checked by TLC (n-
hexane:EtOAc¼ 1:1, v=v). After filtration the solvent was removed in vacuo and the residue (mixture
of 48% alcohol 10b and 52% acetate 11b according to 1H NMR) was submitted to column chromato-
graphy (eluent: toluene:EtOAc¼ 4:1, v=v) to give 77mg (35%) of 2-hydroxytetralone (10b) and
109 mg (40%) of 2-acetoxytetralone (11b).
2-Hydroxytetralone (10b)
Yellow oil (Ref. [41] mp 36–37ꢂC, Ref. [23] ‘‘slightly yellow coloured oil which darkens on exposure
1
on air’’); H NMR (200MHz, CDCl3): ꢂ ¼ 8.15 (dd, J ¼ 7.7, 1.3 Hz, 5-H), 7.54 (m, 7-H), 7.26–7.39
(m, 6,8-H), 4.40 (dd, J ¼ 13.5, 5.4Hz, 2-H), 3. 81 (br s, 2-OH), 3.10 (m, 2H, 4-H), 2.52 (m, 3-Heq),
2.02 (m, 3-Hax).
2-Acetoxytetralone (11b)
White crystals; mp 66.5–68ꢂC (Ref. [21] 58–59ꢂC, Ref. [42] 72–73ꢂC); 1H NMR spectrum was found
to be identical with the one described in Ref. [21].
The same reaction conditions were also applied to the chiral, non-racemic epoxide 9b obtained in
the presence of catalyst 14 (vide supra), the results are shown in Table 1.
When 2-acetoxytetralone (11b) was treated under the same conditions for 50h no reaction was
observed.
Acid-induced Ring-opening of 1-Acetoxy-1,2-epoxytetralin (9b)
Trifluoroacetic acid (209mg, 1.833 mmol) was added to the solution of racemic epoxide 9b (211 mg,
1.033 mmol) in methanol (15 cm3) and stirred at room temperature for 10 min, the completion of the
reaction was checked by TLC (toluene:EtOAc¼ 4:1, v=v). The mixture was evaporated under reduced

ꢀ-Oxyfunctionalized Benzocyclanones and Chromanones
753
1
pressure. The residue (mixture of 91% alcohol 10b and 9% acetate 11b according to H NMR) was
submitted to column chromatography (eluent: toluene:EtOAc¼ 4:1, v=v) to give 143mg (85%) of 2-
hydroxytetralone (10b) and 19 mg (9%) of 2-acetoxytetralone (11b).
Base-induced Ring-opening of 1-Acetoxy-1,2-epoxytetralin (9b)
Anh. K2CO3 (1.000g, 7.236 mmol) was added to the solution of epoxide 9b (240 mg, 1.175mmol) in
methanol (15 cm3) and stirred at room temperature under N2 atmosphere for 10 min, the completion
of the reaction was checked by TLC (toluene:EtOAc¼ 4:1, v=v). After filtration the solvent was
removed under reduced pressure. The residue was submitted to column chromatography (eluent:
toluene:EtOAc¼ 4:1, v=v) to give 164 mg (86%) of 2-hydroxytetralone (10b).
Typical Procedure for the One-step Synthesis of Racemic ꢀ-Hydroxy Ketones
10a–10c and ꢀ-Acetoxy Ketones 11a–11c
A DMD solution in acetone (45 cm3, 0.069 M, ca. 2.03 equiv) was added to enolacetate 9b (287 mg,
1.523 mmol) and the mixture was stirred at room temperature until completion of the reaction (mon-
itored by TLC, toluene:EtOAc¼ 4:1, v=v). Then it was concentrated in vacuo and submitted to column
chromatography (eluent: toluene:EtOAc ¼ 4:1, v=v) to give 141 mg (57%) of 2-hydroxytetralone (10b)
and 123 mg (40%) of 2-acetoxytetralone (11b).
Analogous treatment of enolacetate 8a afforded 2-hydroxyindanone (10a, 31%) and 2-acetoxyte-
tralone (11a, 48%).
2-Hydroxyindanone (10a)
1
Yellowish oil (Ref. [43] mp 34–36ꢂC, Ref. [44] colourless, viscous liquid, bp 152ꢂC=0.267kPa); H
NMR spectrum was found to be identical with the one described in Ref. [45].
2-Acetoxyindanone (11a)
White crystals; mp 68–70ꢂC (Ref. [43] bp 124–128ꢂC=13 Pa, Ref. [44] bp 140ꢂC=0.267 kPa); 1H NMR
(200 MHz, CDCl3): ꢂ ¼ 7.85 (d, J ¼ 7.5 Hz, 4-H), 7.65 (m, 6-H), 7.45 (m, 5,7-H), 5.45 (dd, J ¼ 8.0,
5.0 Hz, 2-H), 3.67 (dd, J ¼ 17.1, 8.0 Hz, 3-Hcis), 3.05 (dd, J ¼ 17.1, 5.0 Hz, 3-Htrans), 2.20 (s, 3H, Ac);
13C NMR (100MHz, CDCl3): ꢂ ¼ 201.2 (s, C-1), 170.4 (s, Ac), 150.3 (s, C-4a), 135.8 (d, C-5), 134.4
(s, C-7a), 128.1 (d, C-7), 126.6 (d, C-4), 124.4 (d, C-6), 74.0 (d, C-2), 33.4 (t, C-3), 20.7 (q, Ac).
Analogous treatment of enolacetate 8c afforded 3-hydroxy-4-chromanone (10c, 15%) and 3-acet-
oxy-4-chromanone (11c, 34%).
When the reaction was repeated in the presence of 1.000 g (7.236mmol) of anh. K2CO3 using 2.8
equiv of DMD 22% alcohol 10c and 36% acetate 11c were obtained.
3-Hydroxy-4-chromanone (10c)
Pale yellow crystals; mp 51–55ꢂC (Ref. [45] 58–59ꢂC); 1H NMR spectrum was found to be identical
with the one described in Ref. [46].
3-Acetoxy-4-chromanone (11c)
1
Pale yellow crystals; mp 66–68ꢂC (Ref. [47] 74ꢂC); H NMR (200MHz, CDCl3): ꢂ ¼ 7.91 (dd,
J ¼ 7.8, 1.7 Hz, 5-H), 7.55 (m, 7-H), 7.05 (m, 6, 8-H), 5.66 (dd, J ¼ 11.4, 5.6 Hz, 3-H), 4.45 (dd,
J ¼ 11.3, 5.6 Hz, 2-Heq), 4.40 (dd, J ¼ 11.4, 11.3 Hz, 2-Hax), 2.25 (s, 3H, Ac); 13C NMR (100 MHz,

754
T. Patonay et al.
CDCl3): ꢂ ¼ 188.0 (s, C-4), 169.5 (s, Ac), 161.3 (s, C-8a), 136.4 (d, C-7), 127.6 (d, C-5), 122.1 (d, C-
6), 119.8 (s, C-4a), 177.8 (d, C-8), 69.4 (d, C-3), 68.3 (t, C-2), 20.5 (q, Ac).
One-step Synthesis of Racemic trans-3-Hydroxyflavanone (10d)
and trans-3-Acetoxyflavanone (10d)
A DMD solution in acetone (180 cm3, 0.069M, ca. 4.00 equiv) was added to a mixture of 4-acetoxy-2-
phenyl-2H-1-chromene (8d, 827 mg, 4.106 mmol) and anh. K2CO3 (1.013g, 7.329 mmol) and allowed
to react at ꢁ20ꢂC. After filtration the solvent was removed in vacuo at room temperature and the
residue was submitted to column chromatography (eluent: toluene:EtOAc¼ 4:1, v=v) to yield 251 mg
(40%) of alcohol 10d, 140 mg (25%) of acetate 11d, and 66 mg (10%) of flavone (13).
trans-3-Hydroxyflavanone (10d)
White crystals; mp 182–185ꢂC (Ref. [48] 183–184ꢂC, Ref. [49] 188ꢂC); 1H NMR spectrum was found
to be identical with the one described in Ref. [50].
trans-3-Acetoxyflavanone (11d)
White crystals; mp 92–95ꢂC (Ref. [50] 96–97ꢂC); 1H NMR spectrum was found to be identical with
the one described in Ref. [51].
Flavone (13)
White crystals; mp 93–96ꢂC (Ref. [52] 97ꢂC).
Typical Procedure for the Enantioselective Oxidation of Enolacetates 8c and 8d
A DMD solution in acetone (180cm3, 0.058M, ca. 2.90 equiv) was added to the mixture of enolacetate
8c (697mg, 3.665 mmol), imidazole (100mg, 1.469mmol), and R,R-(ꢁ)-Jacobsen’s catalyst (R,R-12)
(240 mg, 0.378mmol) and stirred at room temperature for 6 h. The solvent was removed under reduced
pressure at room temperature and the residue was submitted to column chromatography (eluent: n-
hexane:EtOAc (4:1, v=v)). Further experimental details are shown in Tables 2 and 3.
Acknowledgement
This work was financially supported by the Hungarian Scientific Research Fund (OTKA #T029171).
+
€
We thank Peroxid-Chemie GmbH (Hollriegelskreuth, Germany) for the generous gift of Caroate .
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