On the stereoselectivity of the Paternò-Büchi reaction between carbonyl compounds and 2-furylmethanol derivatives. The case of aliphatic aldehydes and ketones

Article abstract of DOI:10.1016/S0040-4020(02)00470-2

The Paternò-Büchi reaction between 2-furylmethanol derivatives and aliphatic aldehydes and ketones induced by irradiation through Vycor at 8°C shows high regioselectivity but no stereoselectivity. This behaviour can be rationalised by assuming that this type of compound reacts through both singlet and triplet excited states. Ab initio calculations are in agreement with the formation of the 1,4-biradical. The more stable biradical accounts for the observed regioselectivity. The lack of stereoselectivity was discussed on the basis of two hypotheses. The allylic strain proposed by Adam does not account for the observed results. On the contrary, hydrogen bond interaction between (triplet excited) carbonyl oxygen and hydroxy group is able to describe the observed behaviour.

Full text of DOI:10.1016/S0040-4020(02)00470-2

TETRAHEDRON
Pergamon
Tetrahedron 58 52002) 5045±5051
Á
È
On the stereoselectivity of the Paterno±Buchi reaction between
carbonyl compounds and 2-furylmethanol derivatives. The case of
aliphatic aldehydes and ketones
Maurizio D'Auria,a,p Lucia Emanuele,a Gabriella Poggi,b Rocco Racioppia
and Gianfranco Romanielloa
a
Á
Dipartimento di Chimica, Universita della Basilicata, Via N. Sauro 85, 85100 Potenza, Italy
Á
Dipartimento di Chimica `G. Ciamician', Universita di Bologna, Via Selmi 2, 40126 Bologna, Italy
b
Received 14 February 2002; revised 8 April 2002; accepted 2 May 2002
Á
AbstractÐThe Paterno±BuÈchi reaction between 2-furylmethanol derivatives and aliphatic aldehydes and ketones induced by irradiation
through Vycor at 88C shows high regioselectivity but no stereoselectivity. This behaviour can be rationalised by assuming that this type of
compound reacts through both singlet and triplet excited states. Ab initio calculations are in agreement with the formation of the 1,4-
biradical. The more stable biradical accounts for the observed regioselectivity. The lack of stereoselectivity was discussed on the basis of two
hypotheses. The allylic strain proposed by Adam does not account for the observed results. On the contrary, hydrogen bond interaction
between 5triplet excited) carbonyl oxygen and hydroxy group is able to describe the observed behaviour. q 2002 Elsevier Science Ltd. All
rights reserved.
1. Introduction
Á
The Paterno±BuÈchi reaction between furan derivatives and
carbonyl compounds has been extensively studied and
several synthetic applications have been reported.1±44
Nevertheless, the effect of unusual substituents on the site
selectivity and stereoselectivity of the reaction has not been
studied. Recently we reported that the irradiation of 2-furyl-
methanol derivatives 1 in the presence of aromatic carbonyl
Á
compounds 2 gave the corresponding Paterno±BuÈchi
adducts 3 or 4 5Scheme 1).45
The reaction showed good regioselectivity: we obtained 3 as
the main product in most of the reactions tested. Further-
more, the reaction showed high stereoselectivity when R
was not hydrogen or methyl. In this case only one stereo-
isomer 51RS,10RS,5RS) was obtained. When an optically
active 2-furylmethanol was used 5R±H and Me), a single
enantiomer was obtained. The irradiation of 55-methyl-2-
furyl)-benzylic alcohol 55) in the presence of aromatic car-
bonyl compounds gave the corresponding adducts 6 and 7
showing a lack of regioselectivity, although, when the
reaction occurred on the side of the furan ring bearing the
alcoholic side chain, the stereoselectivity was high
5Scheme 2).46
Scheme 1.
Á
Keywords: Paterno±BuÈchi reaction; stereoselectivity; furylmethanol deri-
vatives.
Corresponding author. Tel.: 139-0971-202-240; fax: 139-0971-202-
223; e-mail: dauria@unibas.it
p
Scheme 2.
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020502)00470-2

5046
M. D'Auria et al. / Tetrahedron 58 12002) 5045±5051
In this paper we report our results obtained on irradiating
2-furylmethanol derivatives in the presence of aliphatic
aldehydes and ketones. We will show that in this case the
reaction occurs with high regioselectivity but without
stereoselectivity.
of diastereoisomers. The reaction of 8c with 9a gave 10c in
good yield 5Scheme 3, Table 1). The previously observed
trend was maintained: we obtained only one regioisomer,
with high stereoselectivity at C-6, but as a 1:1 mixture of
diastereoisomers.
The irradiation of 8a±c in the presence of heptanal 59b)
gave some unexpected results. In fact, the irradiation of
8a in the presence of 9b gave 10a as the only product
5Scheme 3, Table 1). Also in this case the product was a
single regioisomer and the exo stereoisomer at C-6. It was
also a 1:1 mixture of diastereoisomers. Surprisingly, we
obtained a product where R1 was the methyl group and
not the n-hexyl group as expected. The same result was
obtained using 8b and 8c as substrates. By using 8b as
substrate we obtained 10b as the only product 5Scheme 3,
Table 1), while the irradiation of 8c gave the adduct 10c
5Scheme 3, Table 1).
2. Results and discussion
We used as starting material 1-52-furyl)-ethanol 58a), 1-52-
furyl)-n-heptanol 58b), and 2-furyl-benzylic alcohol 58c)
5Scheme 3). These substrates were prepared from the
furan-2-carbaldehyde and the corresponding Grignard
reagent. The photochemical reactions were carried out in
benzene at 88C in the presence of a Vycor ®lter. The use
of this ®lter avoids the direct irradiation of the furan
derivatives.
The irradiation of 8a in the presence of acetaldehyde 59a)
gave 10a in good yield 5Scheme 3, Table 1). We observed
the formation of only one regioisomeric product, obtained
from attack on the most hindered side of the molecule. The
1H NMR spectrum of 10a clearly showed that the C-6
con®guration is exo. In fact, we obtained a signal at d
4.73 ppm in agreement with previous reported data.44 The
analysis of the product by using HPLC showed that 10a is a
1:1 diastereoisomeric mixture. The reaction of 8b with 9a
gave the corresponding adduct 10b in lower yield 5Scheme
3, Table 1). In this case we only observed the formation of
the product obtained on the most hindered side of the
molecule. Furthermore, we obtained good stereoselectivity
at C-6 because we observed the formation of the exo
isomer. However, HPLC showed that 10b is a 1:1 mixture
Finally, the irradiation of 8a in the presence of phenyl-
acetaldehyde 59c) gave the corresponding adduct 10d in
good yield 5Scheme 3, Table 1). We obtained a single regio-
isomeric product 5from the attack on the most hindered side
of the molecule) and an exo stereoisomer at C-6. However,
HPLC showed the presence of a 1:1 mixture of diastereo-
isomers. The irradiation of 8b with 9c gave 10e 5Scheme 3,
Table 1), while the same reaction between 8c and 9c gave
10f as the only product 5Scheme 3, Table 1).
On the basis of the above results we can draw some con-
clusions: 5i) the reaction between 2-furylmethanol deriva-
tives and aliphatic aldehydes showed higher regioselectivity
than the reactions of the same substrates with aromatic
aldehydes;45,46 5ii) the reaction between 2-furylmethanol
derivatives and aliphatic aldehydes showed lower stereo-
seletivity than the reactions of the same substrates with
aromatic aldehydes;45,46 5iii) the use of aliphatic aldehydes
induced the formation of unexpected products 5such in the
reaction of 8a±c with 9b).
Á
The use of aliphatic aldehydes in the Paterno±BuÈchi reac-
tion is often explained by a mechanism involving an excited
singlet state.47Acetaldehyde shows a low intensity absorp-
tion band at 290±293 nm due to a n!pp transition. At this
wavelength the ¯uorescence quantum yield 5Ff) is in the
range 0.50£1023±1.2£1023 48,49
;
the intersystem crossing
quantum yield 5Fisc) for this compound is 0.6;48 on the
basis of these data both singlet and triplet state can be
involved in the reaction.
Scheme 3.
Assuming that the reaction occurs in the ®rst excited singlet
state, the 0±0 transition occurs at 29,771 cm21 50
; this indi-
Table 1. The photochemical reaction between aliphatic aldehydes and 2-
furylmethanols
cates that the energy 5ES) of the excited singlet state is ca.
356 kJ mol21. Assuming that the reaction occurs in the ®rst
excited triplet state, acetaldehyde shows a maximum in the
phosphorescence spectrum at 430 nm;51 this emission corre-
Furan
Aldehyde
Irradiation time 5h)
Product
Yield 5%)
8a
8b
8c
8a
8b
8c
8a
8b
8c
9a
9a
9a
9b
9b
9b
9c
9c
9c
8
8
8
8
8
8
8
8
8
10a
10b
10c
10a
10b
10c
10d
10e
10f
64
42
58
46
68
56
52
48
64
sponds to a triplet energy 5ET) of 276 kJ mol21
.
As reported earleir the reaction between furylmethanol
derivatives and heptanal gave unexpected products 10a±c
where R1 was CH3 instead of CH25CH2)4CH3 5Scheme 3).
This behaviour can be explained by assuming that heptanal
does not react with furan derivatives but undergoes a

M. D'Auria et al. / Tetrahedron 58 12002) 5045±5051
5047
zwitterionic intermediate: the regioselectivity in the reac-
tion between 1 and 2 can be explained by proposing the
formation of the triplet 1,4-biradical.
In our previous work we found that the reaction between
2-furylmethanol derivatives and aromatic aldehydes and
ketones gave the corresponding products with high stereo-
selectivity.45,46 In this work we found that the reaction of the
same furan derivatives with aliphatic aldehydes gave high
stereoselectivity at C-6 5in the dioxabicycloheptene skele-
ton), however, we observed that all the reactions occurred
with no stereoselectivity at C-1 and C-5. In order to explain
the observed stereoselectivity when aromatic carbonyl
compounds were used, we assume an interaction between
the hydroxyl group and the carbonyl group.45 A similar type
of interaction has been proposed in the case of the reaction
of allylic alcohols with carbonyl compounds.55,56 The lack
of stereoselectivity in the experiments reported earlier can
be explained by assuming that the interaction between the
hydroxyl and the carbonyl groups does not exist in this case.
Figure 1.
Norrish type-II reaction with g-H abstraction to give acet-
aldehyde and this product reacts with the furan ring. Norrish
type-II reactions occur from both singlet and triplet n,pp
states, but the quantum yields from the singlet state are
generally lower than from the triplet state.52 Furthermore,
it is known that aliphatic aldehydes 5capable of giving the
Norrish type-II reaction) react with furan to give the corre-
sponding adducts with high ef®ciency.6 This results the
following conclusions: 5i) if the reaction between aliphatic
aldehydes and furylmethanols occurs in the singlet excited
state, the Norrish type-II reaction must compete with the
Á
Paterno±BuÈchi reaction in this excited state; in this case,
Á
b-cleavage occurred more rapidly than the Paterno±BuÈchi
reaction; 5ii) this hypothesis is in con¯ict with both the low
ef®ciency of the Norrish type-II reaction in the singlet state
and the energetically favoured reaction between the ali-
phatic aldehyde in its excited singlet state and furan as
described above; 5iii) if the reaction between aliphatic alde-
hydes and furylmethanols occurs in the triplet excited state,
We could assume that, in a reaction involving an excited
singlet state, this short lived state cannot interact with the
hydroxyl group to give the observed stereoselectivity in the
case of reaction where the triplet state is involved.
The lack of stereoselectivity has been con®rmed by using
chiral 2-furylmethanol derivatives.45 R-51)-8a±c were
obtained through kinetic resolution of 5^)-8a±c in the
presence of Ti5OiPr)4, TBHP and l-51)-DIPT.57,58 The
substrates thus obtained were enantiomerically pure by
chiral HPLC. When the irradiation was carried out on
R-8a±c in the presence of acetaldehyde we obtained the
same products without any difference in the stereoisomeric
composition of the products.
Á
the Norrish type-II reaction must compete with the Paterno±
BuÈchi reaction in both singlet and triplet excited states.
In our previous work in this ®eld, the regioselectivity of the
Á
Paterno±BuÈchi reaction between carbonyl compounds and
2-furylmethanol derivatives was explained on the basis of
the relative stability of the possible intermediates.45,46 In
fact, theoretical work on this reaction showed that, for reac-
tions occurring in the triplet state, the reaction path could be
predicted by the most stable biradical rule.53 Semiempirical
calculations showed that only a zwitterionic intermediate
could explain the observed regiochemical behaviour.
In order to obtain further information about the reactivity of
Á
2-furylmethanol derivatives, we studied the Paterno±BuÈchi
reaction of these substrates with aliphatic ketones. The
irradiation of 8c in the presence of acetone 513a) gave 14a
in good yields 5Scheme 4, Table 2). We observed the forma-
tion of only one regioisomeric product, obtained from the
attack on the most hindered side of the molecule. The analy-
sis of the product by using HPLC showed that 14a is a 1:1
diastereoisomeric mixture.
In order to test this hypothesis we performed ab initio calcu-
lations on the triplet 1,4-biradicals 11 and 12 5Fig. 1). The
structures were optimized at B3LYP/3-21Gp level by means
of the Gaussian94 package of programs on a K200 Pentium
II/400 MHz SCSI system.54
The results of the calculations showed that 11 is more stable
than 12 by 0.8 kJ mol21. On the basis of this result we must
revise our previous hypothesis on the formation of a
The irradiation of 8c in the presence of 2,4-dimethyl-3-
pentanone 513b) gave the same type of results. In fact, the
irradiation of 8c in the presence of 13b gave 14b as the only
Scheme 4.

5048
M. D'Auria et al. / Tetrahedron 58 12002) 5045±5051
Table 2. The photochemical reaction between aliphatic ketones and 8c
3. Experimental
Aldehyde
Irradiation time 5h)
Solvent
Product
Yield 5%)
NMR spectra were recorded on a Bruker 300 AM instru-
ment. Elemental analyses were obtained using a Carlo Erba
Elemental Analyzer 1106. 2-Furylmethanol was obtained
by Aldrich. 2-Furylmethanol derivatives were prepared
through the reaction of suitable Grignard reagents with
furan-2-carbaldehyde.61
13a
13a
13b
13c
13d
13e
8
8
8
8
8
8
Benzene
Acetone
Benzene
Benzene
Benzene
Benzene
14a
14a
14b
14c
14d
14e
33
47
45
30
25
40
3.1. Caution
product 5Scheme 4, Table 2). Also in this case the product
was a single regioisomer. It was also a 1:1 mixture of
diastereoisomers.
Performing the NMR spectra of cycloadducts we observed
that deuterated chloroform purchased from Aldrich induced
a retro-cycloaddition reaction giving, within an hour, the
starting materials. We did not observe this behaviour
using deuterated chloroform from Fluka or Carlo Erba.
We asked Aldrich about the presence of metals or some
other trace impurities in deuterated chloroform which
could give this type of reaction. Until now, we did not obtain
any reply from Aldrich and we think we should advice
readers on this possible problem.
The irradiation of 8c in the presence of cyclohexanone 513c)
gave the corresponding adduct 14c in good yields 5Scheme
4, Table 2). We obtained a single regioisomeric product
5that from the attack on the most hindered side of the
molecule). Furthermore, in this case HPLC again showed
the presence of a 1:1 mixture of diastereoisomers.
When 8c is irradiated in the presence of 4-t-butylcyclo-
hexanone 513d) the product 14d is obtained 5Scheme 4,
Table 2). Also in this case we obtained only one regio-
isomer. Furthermore, 14d appeared as a 1:1 diastereo-
isomeric mixture 51H NMR).
3.2. Cycloaddition reaction between 2-furylmethanols
and carbonyl compoundsÐgeneral procedure
2-Furylmethanol derivative 58a±c) 510 mmol) was
dissolved in benzene 570 ml) in the presence of the carbonyl
compound 515 mmol) in a quartz vessel. The mixture was
¯ushed with nitrogen for 1 h and, then, maintained at 88C
with a Haake F3 thermostat. The mixture was irradiated
with a 500 W high-pressure mercury arc 5Helios±Italquartz)
with Vycor ®lter. After 8 h, the irradiation was stopped.
After this time 50% conversion of the starting material
was observed. The removal of the solvent yielded a crude
product that was chromatographed on silica gel. Elution
with n-hexane/ethyl acetate 9:1 gave pure products 5Table 1)
Finally, the reaction of 8c in the presence of cycloheptanone
513e) gave 14e as a single regioisomeric product but as a
mixture of stereoisomeric compounds 5Scheme 4, Table 2).
By using acetone as model compound for aliphatic ketones,
the singlet excited acetone is converted with an ef®ciency of
unity into triplet acetone via rapid intersystem crossing.59
It is noteworthy that both the reactions of 2-furylmethanols
with aliphatic aldehydes and ketones do not show stereo-
selectivity. Furthermore, in the case of aliphatic ketones we
can exclude that this effect is due to a short lived singlet
excited state. Our results can not be explained on the basis
of 1,3 allylic strain as reported by Adam.55,56 In fact, the
same `allylic' substrates were used giving high stereo-
selectivity with aromatic aldehydes and ketones and no
stereoselectivity when using aliphatic aldehydes and
ketones.
3.2.1.
1-31-Hydroxyethyl)-6-methyl-2,7-dioxabicyclo-
1
[3.2.0]hept-3-ene 310a). Viscous oil; H NMR 5CDCl3) d:
6.60 5dd, J1ˆ2.5 Hz, J2ˆ0.5 Hz, 1H, 3-H), 5.30 5dd,
J1ˆJ2ˆ2.5 Hz, 1H, 4-H), 4.73 5m, 1H, 6-H), 3.90 5m, 1H,
CHOH), 3.36 5m, 1H, 5-H), 2.2 5br s, 1H, OH), 1.48 5d,
Jˆ6 Hz, 3H, CH3), 1.18 5d, Jˆ6.6 Hz, 3H, CH3). 13C
NMR 5CDCl3) d: 148.4 5C-3), 117.5 5C-1), 104.8 5C-4),
87.3 5C-6), 67.4 5CHOH), 47.6 5C-5), 21.7 5CH3), 15.3
5CH3). C8H12O3 5156.2): calcd C 61.52, H 7.74; found C
61.55, H, 7.70.
Recently, Griesbeck reported that stereoselectivity in 212
cycloaddition reactions between carbonyl compounds and
allylic alcohol derivatives can increase with the possibility
of hydrogen-bonding interactions with singlet as well as
triplet excited carbonyl states prior to bond formation.60
However, aliphatic and aromatic ketones could give the
same hydrogen bond interaction with the hydroxy group
in the furan derivatives, while the stereoselectivity is
different. In order to understand if the strength of the hydro-
gen bond interaction can be different in aromatic and
aliphatic aldehydes and ketones, we calculated 5PM3) the
charge on carbonyl oxygen in the triplet state of benzo-
phenone and acetone: while in benzophenone the charge
was 20.076, in acetone we obtained 20.066. This
difference could possibly justify the observed lack in stereo-
selectivity observed when using aliphatic aldehydes and
ketones.
3.2.2. 1-31-Hydroxy-n-heptyl)-6-methyl-2,7-dioxabicyclo-
[3.2.0]-hept-3-ene 310b). Viscous oil; H NMR 5CDCl3)
1
d: 6.59 5dd, J1ˆ2.6 Hz, J2ˆ0.5 Hz, 1H, 3-H), 5.29 5dd,
J1ˆ2.6 Hz, J2ˆ2.5 Hz, 1H, 4-H), 4.71 5m, 1H, 6-H), 3.68
5m, 1H, CHOH), 3.34 5m, 1H, 5-H), 2.3 5br s, 1H, OH), 1.49
5d, Jˆ6 Hz, 3H, CH3), 1.31 5m, 10H, CH2), 1.31 5t, Jˆ7 Hz,
3H, CH3). 13C NMR 5CDCl3) d: 148.4 5C-3), 117.1 5C-1),
104.7 5C-4), 87.25C-6), 71.5 5CHOH), 48.25C-5), 32.0,
30.8, 30.1, 29.5, 25.6, 22.7, 21.7 5CH3), 14.9 5CH3).
C13H22O3 5226.3): calcd C 68.99, H 9.80; found C 68.89,
H, 9.87.
3.2.3. 1-31-Hydroxybenzyl)-6-methyl-2,7-dioxabicyclo-
[3.2.0]-hept-3-ene 310c). Viscous oil; H NMR 5CDCl3)
d: 7.5±7.25m, 5H, aromatic protons), 6.66 5dd,
1

M. D'Auria et al. / Tetrahedron 58 12002) 5045±5051
5049
J1ˆ2.7 Hz, J2ˆ0.5 Hz, 0.5H, 3-H), 6.46 5dd, J1ˆ2.7 Hz,
J2ˆ0.5 Hz, 0.5H, 3-H), 5.29 5dd, J1ˆ2.7 Hz, J2ˆ2.5 Hz,
0.5H, 4-H), 5.14 5dd, J1ˆ2.7 Hz, J2ˆ2.5 Hz, 0.5H, 4-H),
4.85 5m, 0.5H, 6-H), 4.80 5m, 0.5H, 6-H), 4.75 5m, 0.5H,
CHOH),), 4.61 5m, 0.5H, CHOH), 3.325m, 1H, 5-H), 2.97
5s, 0.5H, OH), 2.62 5s, 0.5H, OH), 1.50 5d, Jˆ6.4 Hz, 3H,
CH3). 13C NMR 5CDCl3) d: 148.4 5C-3), 148.3 5C-3), 134.9,
129.8, 129.7, 127.6, 116.9 5C-1), 105.0 5C-4), 104.8 5C-4),
87.8 5C-6), 87.5 5C-6), 74.1 5CHOH), 73.0 5CHOH), 48.4
5C-5), 48.25C-5), 21.5 5CH 3). C13H14O3 5218.3): calcd C
71.54, H 6.47; found C 71.76, H, 6.55.
5CDCl3) d: 7.5±7.25m, 5H, aromatic protons), 6.58 5d,
Jˆ3.3 Hz, 0.5H, 3-H), 5.61 5d, Jˆ3.5 Hz, 0.5H, 3-H),
5.31 5m, 1H, 4-H), 4.93 5d, Jˆ2.5 Hz, 1H, CHOH), 3.88
5m, 1H, 5-H), 2.61 5s, 1H, OH), 1.56 5m, 2H, CH), 1.35
5m, 12H, CH3). 13C NMR 5CDCl3) d: 149.25C-3), 142.9
5C-3), 135.1, 129.9, 127.5, 119.5 5C-1), 112.8 5C-4), 111.1
5C-4), 104.9 5C-6), 90.4 5C-6), 73.5 5CHOH), 72.9 5CHOH),
49.5 5C-5), 30.3 5CH), 29.7 5CH) 22.7 5CH3). C18H24O3
5288.4): calcd C 74.97, H 8.39; found C 74.90, H, 8.45.
3.2.9. 1-31-Hydroxybenzyl)-6,6-pentamethylene-2,7-dioxa-
bicyclo-[3.2.0]hept-3-ene 314c). Viscous oil; 1H NMR
5CDCl3) d: 7.5±7.3 5m, 5H, aromatic protons), 6.45 5m,
0.5H, 3-H), 6.25 5d, Jˆ3 Hz, 0.5H, 4-H), 5.625d, Jˆ3 Hz,
0.5H, 3-H), 5.35 5s, 1H, CHOH), 5.00 5m, 0.5H, 4-H), 3.88
5m, 0.5H, 5-H), 3.38 5m, 0.5H, 5-H), 2.5 5s, 1H, OH), 1.25
5s, 10H, CH2). 13C NMR 5CDCl3) d: 149.25C-3), 142.9
5C-3), 134.8, 129.8, 127.8, 119.5 5C-1), 112.8 5C-4), 112.4
5C-4), 104.9 5C-6), 90.4 5C-6), 73.5 5CHOH), 72.9 5CHOH),
49.5 5C-5), 30.3 5CH2), 29.7 5CH2), 27.7 5CH2), 23.9 5CH2),
22.2 5CH2). C17H20O3 5272.3): calcd C 74.97, H 7.40; found
C 75.04, H, 7.32.
3.2.4.
1-31-Hydroxyethyl)-6-benzyl-2,7-dioxabicyclo-
1
[3.2.0]hept-3-ene 310d). Viscous oil; H NMR 5CDCl3) d:
7.5±7.25m, 5H, aromatic protons), 6.625dd, J1ˆ2.6 Hz,
J2ˆ0.5 Hz, 1H, 3-H), 5.28 5dd, J1ˆJ2ˆ2.6 Hz, 1H, 4-H),
4.73 5m, 1H, 6-H), 4.69 5s, H, CH2), 4.67 5s, 1H, CH2),
3.85 5m, 1H, CHOH), 3.34 5m, 1H, 5-H), 2.2 5br s, 1H,
OH), 1.18 5d, Jˆ6.6 Hz, 3H, CH3). 13C NMR 5CDCl3) d:
148.4 5C-3), 138.5, 132.9, 129.6, 126.2, 117.3 5C-1), 105.0
5C-4), 87.3 5C-6), 70.3 5CHOH), 48.25C-5), 29.3 5CH 2),
15.25CH 3). C14H16O3 5232.3): calcd C 72.39, H 6.94;
found C 72.25, H, 7.00.
3.2.10. 1-31-Hydroxybenzyl)-6,6-33-t-butyl)pentamethyl-
ene-2,7-dioxa-bicyclo[3.2.0]hept-3-ene 314d). Viscous oil;
1H NMR 5CDCl3) d: 7.5±7.25m, 5H, aromatic protons),
6.57 5dd, J1ˆJ2ˆ3.3 Hz, 0.5H, 3-H), 5.59 5dd,
J1ˆJ2ˆ3.2Hz, 0.5H, 3-H), 5.30 5m, 1H, C HOH), 4.94 5m,
1H, 4-H), 3.725m, 1H, 5-H), 2.73 5s, 1H, OH), 1.68 5m, 9H,
CH2 e CH), 1.18 5s, 9H, CH3). 13C NMR 5CDCl3) d: 149.2
5C-3), 135.2, 130.0, 127.8, 117.3 5C-1), 104.9 5C-4), 90.4
5C-6), 73.4 5CHOH), 49.5 5C-5), 47.6, 37.5, 34.3, 27.7, 15.3
5CH3). C21H28O3 5328.5): calcd C 76.79, H 8.59; found C
76.60, H, 8.72.
3.2.5. 1-31-Hydroxy-n-heptyl)-6-benzyl-2,7-dioxabicyclo-
[3.2.0]-hept-3-ene 310e). Viscous oil; 1H NMR 5CDCl3) d:
7.5±7.25m, 5H, aromatic protons), 6.60 5dd, J1ˆ2.6 Hz,
J2ˆ0.5 Hz, 1H, 3-H), 5.29 5dd, J1ˆ2.6 Hz, J2ˆ2.5 Hz, 1H,
4-H), 4.75 5s, 1H, CH2), 4.73 5s, 1H, CH2), 4.71 5m, 1H,
6-H), 3.80 5m, 1H, CHOH), 3.30 5m, 1H, 5-H), 2.3 5br s, 1H,
OH), 1.30 5m, 10H, CH2), 1.28 5t, Jˆ7 Hz, 3H, CH3). 13C
NMR 5CDCl3) d: 148.4 5C-3), 138.6, 133.0, 129.4, 126.0,
117.0 5C-1), 104.6 5C-4), 87.4 5C-6), 71.5 5CHOH), 48.2
5C-5), 38.5, 32.0, 30.8, 30.0, 29.5, 25.6, 22.7, 14.1.
C19H26O3 5302.4): calcd C 75.46, H 8.67; found C 75.55,
H, 8.63.
3.2.11. 1-31-Hydroxybenzyl)-6,6-hexamethylene-2,7-dioxa-
bicyclo-[3.2.0]hept-3-ene 314e). Viscous oil; 1H NMR
5CDCl3) d: 7.5±7.3 5m, 5H, aromatic protons), 6.45 5m,
0.5H, 3-H), 6.28 5d, Jˆ3 Hz, 0.5H, 4-H), 5.625d, Jˆ3 Hz,
0.5H, 3-H), 5.34 5m, 1H, CHOH), 5.00 5m, 0.5H, 4-H), 3.90
5m, 0.5H, 5-H), 3.37 5m, 0.5H, 5-H), 2.63 5s, 1H, OH), 1.28
5s, 12H, CH2). 13C NMR 5CDCl3) d: 149.25C-3), 135.2,
129.8, 127.8, 117.8 5C-1), 112.8 5C-4), 112.4 5C-4), 104.9
5C-6), 90.4 5C-6), 73.5 5CHOH), 65.8 5CHOH), 49.5 5C-5),
34.1, 29.5, 23.9. C18H22O3 5286.4): calcd C 75.50, H 7.74;
found C 75.38, H, 7.85.
3.2.6. 1-31-Hydroxybenzyl)-6-benzyl-2,7-dioxabicyclo-
[3.2.0]hept-3-ene 310f). Viscous oil; H NMR 5CDCl3) d:
1
7.5±7.25m, 10H, aromatic protons), 6.63 5dd, J1ˆ2.6 Hz,
J2ˆ0.5 Hz, 1H, 3-H), 5.31 5dd, J1ˆ2.6 Hz, J2ˆ2.5 Hz, 1H,
4-H), 4.87 5m, 1H, 6-H), 4.75 5m, 2H, CH2), 4.60 5m, 1H,
CHOH), 3.325m, 1H, 5-H), 3.0 5bs, 1H, OH). 13C NMR
5CDCl3) d: 148.4 5C-3), 138.4, 134.9, 132.9, 129.8, 129.6,
127.6, 126.3, 116.9 5C-1), 105.1 5C-4), 87.7 5C-6), 72.5
5CHOH), 48.4 5C-5), 30.1 5CH2). C19H18O3 5294.4): calcd
C 77.53, H 6.16; found C 77.61, H, 6.11.
3.3. Optically active 2-furylmethanolsÐgeneral
procedure
3.2.7. 1-31-Hydroxybenzyl)-6,6-dimethyl-2,7-dioxabicyclo-
[3.2.0]-hept-3-ene 314a). Viscous oil; 1H NMR 5CDCl3) d:
7.5±7.25m, 5H, aromatic protons), 6.56 5dd, J1ˆJ2ˆ3.5 Hz,
0.5H, 3-H), 5.59 5dd, J1ˆJ2ˆ3.2Hz, 0.5H, 3-H), 5.47 5s,
0.5H, CHOH), 5.43 5s, 0.5H, CHOH), 5.36 5dd,
J1ˆJ2ˆ2.5 Hz, 0.5H, 4-H), 5.27 5d, Jˆ2.5 Hz, 0.5H, 4-H),
3.68 5m, 1H, 5-H), 2.88 5s, 1H, OH), 1.22 5s, 3H, CH3), 1.18
5s, 3H, CH3). 13C NMR 5CDCl3) d: 148.4 5C-3), 148.3 5C-3),
135.2, 129.7, 127.7, 116.8 5C-1), 105.2 5C-4), 104.9 5C-4),
87.8 5C-6), 87.6 5C-6), 74.1 5CHOH), 72.9 5CHOH), 48.3
5C-5), 48.1 5C-5), 21.6 5CH3), 20.3 5CH3). C14H16O3 5232.3):
calcd C 72.39, H 6.94; found C 72.45, H, 6.89.
A solution of Ti5OiPr)4 56.84 ml, 46 mmol) in CH2Cl2
5112ml) was treated at 2208C with l-51)-DIPT 55.77 ml,
55 mmol). After 10 min at 2308C a 52-furyl)methanol
derivative 546 mmol) dissolved in CH2Cl2 55.5 ml) and
t-butylhydroperoxide 54.6 ml) were added. The solution
was stirred at 2218C for 40 h and then poured into a mixture
of 10% tartaric acid 50.94 ml), ether 537.4 ml), and NaF
55.6 g). The mixture was stirred for 3 h at room temperature.
The mixture was ®ltered on Celite. The organic phase was
concentrated to give an oil which was dissolved in ether
5187 ml) and treated with 1N NaOH 593.5 ml) for 30 min
at 08C. The ethereal phase was washed with brine and dried
5Na2SO4). Evaporation of the solvent gave an oil that was
3.2.8. 1-31-Hydroxybenzyl)-6,6-di3methylethyl)-2,7-dioxa-
bicyclo-[3.2.0]hept-3-ene 314b). Viscous oil; 1H NMR

5050
M. D'Auria et al. / Tetrahedron 58 12002) 5045±5051
30. Pelzer, R.; JuÈtten, P.; Scharf, H.-D. Chem. Ber. 1989, 122,
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chromatographed on silica gel to give pure R-51)-8
derivatives. The ee was estimated by using chiral HPLC
on Chiralcel OD using as eluent n-hexane/i-propanol 95:5
at 1 ml min21. The chromatograms were detected with an
UV detector at 235 nm.
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