A convenient route to 1,4-monoprotected dialdehydes, 1,4-ketoaldehydes, γ-lactols and γ-lactones through radical alkylation of α,β-unsaturated aldehydes in organic and organic-aqueous media

Article abstract of DOI:10.1016/S0040-4020(02)01659-9

α,β-Unsaturated aldehydes were smoothly alkylated by radicals generated through photosensitised hydrogen abstraction of benzophenone. In this way, and by using 1,3-dioxolane as radical precursor, monoprotected 1,4-dialdehydes were obtained from crotonaldehyde, 2-hexenal, 4-methyl-2-pentenal and cyclohexencarboxyaldehyde in a moderate yield, and in a low yield from β-aryl-α,β-unsaturated aldehydes. With 2-alkyl-1,3-dioxolanes, monoprotected 1,4-ketoaldehydes were analogously prepared. By using methanol, ethanol and isopropanol as radical precursors γ-lactols were likewise obtained from the above aliphatic aldehydes. These single-step syntheses compared favorably with multi-step approaches previously proposed for some of these compounds. The lactols were conveniently oxidized to the corresponding γ-lactones. An alternative to the photosensitisation in organic medium was the use of mixed aqueous-organic solvent and a hydrosoluble photosensitiser (benzophenone disodium disulfonate was prepared for this purpose and successfully used), which allowed a more convenient work up.

Full text of DOI:10.1016/S0040-4020(02)01659-9

Tetrahedron 59 (2003) 947–957
A convenient route to 1,4-monoprotected dialdehydes,
1,4-ketoaldehydes, g-lactols and g-lactones through radical
alkylation of a,b-unsaturated aldehydes in organic and
organic-aqueous media
*
Daniele Dondi, Ilaria Caprioli, Maurizio Fagnoni, Mariella Mella and Angelo Albini
`
Dipartimento di Chimica Organica, Universita, V. Taramelli 10, 27100 Pavia, Italy
Received 14 October 2002; revised 4 December 2002; accepted 19 December 2002
Abstract—a,b-Unsaturated aldehydes were smoothly alkylated by radicals generated through photosensitised hydrogen abstraction of
benzophenone. In this way, and by using 1,3-dioxolane as radical precursor, monoprotected 1,4-dialdehydes were obtained from
crotonaldehyde, 2-hexenal, 4-methyl-2-pentenal and cyclohexencarboxyaldehyde in a moderate yield, and in a low yield from b-aryl-a,b-
unsaturated aldehydes. With 2-alkyl-1,3-dioxolanes, monoprotected 1,4-ketoaldehydes were analogously prepared. By using methanol,
ethanol and isopropanol as radical precursors g-lactols were likewise obtained from the above aliphatic aldehydes. These single-step
syntheses compared favorably with multi-step approaches previously proposed for some of these compounds. The lactols were conveniently
oxidized to the corresponding g-lactones. An alternative to the photosensitisation in organic medium was the use of mixed aqueous-organic
solvent and a hydrosoluble photosensitiser (benzophenone disodium disulfonate was prepared for this purpose and successfully used), which
allowed a more convenient work up. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
yields in water were better than in an organic medium and
the yield was still satisfactory in HCl (1 M) and NaOH
(1 M).
The use of radicals in organic synthesis has increased
dramatically during the last two decades and many methods
for the formation of C–C bonds via carbon-centred radicals
have been developed, which, among other ones, have the
advantage of tolerating the presence of water. For more than
a century, C–C bond formation in aqueous media has been
virtually limited to electrochemical processes and aldol
condensation reactions. Using radicals in water or a water-
containing mixed solvent reduces the use of toxic or
dangerous solvents, simplifies the work-up (often a simple
extraction), and takes advantage of the specific effects
occurring in water, such as hydrogen-bonding. However,
except for the pioneering work by Luche1 on the alkylation
of a,b-unsaturated carbonyl compounds under sonication,
only very recently were radicals employed in the formation
of C–C bonds in aqueous media.2,3 Such reactions were
usually carried out through some modification of the usual
methods of generation of radicals e.g. through hydrosoluble
initiators,5 the Et3B/O2 method6 and H3PO2 as the reducing
agent.7 In some of the latter experiments the chemical
An appealing target for the approach via radicals is the
conjugate alkylation of a,b-unsaturated aldehydes, in view
of the shortcomings of other methods due to the high
susceptibility of such substrates to 1,2 rather than 1,4
attack8a and to their easy polymerization. In fact, alkylation
by organometallic species such as magnesium,9a
cadmium,9b lithium,9c,d manganese9e and zirconium9f
derivatives gave good yields of the 1,4 adducts only in
some cases and under copper catalysis,10 and an improve-
ment in the regioselectivity was achieved only by
complexation of the carbonyl group8b or through a
derivatization/protection procedure (e.g. via imines or
acetals). As for radical alkylation, application to a,b-
unsaturated aldehydes is limited to a few examples
including early work on borane radical induced alkyl-
ations11a,b as well as radical generation via decomposition
of a-hydroxydiazenes11c and via photolysis of alkylmercury
halides.11d
In this paper, we report photochemical alkylations of a,b-
unsaturated aldehydes by a-oxy and a,a-dioxy substituted
radicals produced by means of photosensitised hydrogen
transfer from alcohols and 1,3-dioxolanes. Such reactions
were carried out both in organic media (benzophenone as
Keywords: alkylation; reactions in water; radical and radical reactions;
photochemistry; aldehydes.
*
Corresponding author. Tel.: þ390382507316; fax: þ390382507323;
e-mail: fagnoni@chifis.unipv.it
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01659-9

948
D. Dondi et al. / Tetrahedron 59 (2003) 947–957
the sensitiser) and in mixed aqueous media (sensitised by
benzophenone disodium disulfonate).
2. Results
In the last years our group has exploited the photochemical
hydrogen transfer method for the functionalization of
various a,b-unsaturated ketones,12a,b amides,12c nitriles12d
as well as captodative olefins.12e The same approach (see
Scheme 1) has now been applied for the synthesis of
products useful as synthetic intermediates starting from a,b-
unsaturated aldehydes. In our approach, alkyl radicals are
generated from precursors RH through hydrogen abstraction
by an excited sensitiser (Sensp). The radical thus formed
attacks the electrophilic olefin in the b position and finally
yields the alkylated aldehydes. As radical sources we chose
1,3-dioxolane derivatives and alcohols. The former ones
have been developed for this use in our laboratory and
shown to be useful for the introduction of a masked
aldehyde or ketone moiety,12a,b and the latter ones have
been employed in photoinitiated syntheses to some extent.
As shown in Scheme 1, in this way a synthesis of
g-dioxolanylaldehydes and, respectively, of g-(hydroxy-
alkyl)aldehydes (which may ring-close to lactols) is
envisaged.
Scheme 2. Reagents and conditions: (a) Procedure A: Ph2CO in neat 2 or in
2/MeCN mixtures. Procedure B: BPSS in a 2/H2O/MeCN or 2/H2O
mixtures.
polymerized under irradiation in the presence of 2k and this
precluded alkylation. However, crotonaldehyde 1b gave
the desired dioxolanyl derivatives in a significant yield
(30–40%, entries 2–7).13 Changing the conditions from the
organic to the mixed aqueous medium and using a water-
soluble sensitiser little affected the product yield and only in
the synthesis of 3bk the reaction time was lengthend.
Reactions with 1c proceeded satisfactory and the alkylation
occurred with all the dioxolanes considered (entries 8–15).
Noteworthy, neither using the dioxolane 1 M (as it is the
case for 2n) rather than neat (as with 2k), nor increasing
steric hindrance (using 2-substituted dioxolanes rather than
parent 2k) lowered the product yield, although such changes
prolonged the required reaction time (compare entry 14 and
entry 8, 16 h rather than 3). The reaction took place in the
same way with 1d, showing that branching in the b position
did not hinder radical addition.
2.1. Synthesis of monoprotected 1,4-dialdehydes
(ketoaldehydes)
These compounds were prepared by photosensitised
addition of 1,3-dioxolane (used neat), or respectively,
2-substituted-1,3-dioxolanes (as 1 M solution). Irradiation
of aldehydes 1 with phosphor-coated lamps (center of
emission 315 nm) in solution containing an excess of
dioxolanes 2 in the absence of the sensitiser did not lead to
alkylated products 3. Sensitisation under the same
conditions afforded in most cases the expected 3-[2-(1,3-
dioxolanyl)]aldehydes 3 (Scheme 2). Yields and reaction
times were dependent on the substrate employed and
conditions and the results are shown in Table 1. Acrolein
1a was the only substrate studied which readily (3 h)
Incorporating the double bond in a ring as with cyclo-
hexencarboxylaldehyde 1e did not inhibit the alkylation,
which however in this case gave a poor yield in acetonitrile,
while the result was much better in mixed aqueous solvent.
A mixture of the cis and trans diastereoisomers was formed
(4:1). Due to the superimposition of NMR signals, the
assignment was mainly based on the close analogy with the
previously studied reaction of 2k with 1-acetylcyclohexene,
where the cis was the only isomer obtained.12a
Aromatic a,b- unsaturated aldehydes were less suited for
the reaction under the above conditions, due to their high
absorption at 315 nm. Unsensitised irradiation at this
wavelength caused very little alkylation. Using the
sensitiser and shifting to lamps with the emission centered
at 366 nm gave better, though not satisfactory, yields of
products 3fk and 3gk. With doubly unsaturated 1h no
significant amount of product 3hk was obtained, although
the aldehyde was consumed during the irradiation.
2.2. Synthesis of g-butyrolactols or lactones
These compounds were prepared by using alcohols as
radical precursors and the results are presented in Scheme 3
and Table 2. Acrolein (1a) polymerized by photosensitisa-
tion in the presence of alcohols (Table 2, entry 1). However,
alkylation was satisfactory with the other aliphatic
Scheme 1.

D. Dondi et al. / Tetrahedron 59 (2003) 947–957
Table 1. Alkylation yields from a,b-unsaturated aldehydes and dioxolanes 2
949
Entry
Aldehydes
Dioxolane
Products
Procedure
Reactions time (h)
Product yield (%)a
d
1
2
3
4
5
6
7
8
1a
1b
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
1c
1c
1c
1d
1d
1e
1e
1f
2k
2k
2k
2m
2m
2n
2n
2k
2k
2l
3ak
3bk
3bk
3bm
3bm
3bn
3bn
3ck
3ck
3cl
3cl
3cm
3cm
3cn
3cn
3dk
Ab/Bc
Ab
Bc
3
3
40
43
38
42
30
36
39
32
49
44
28
24
40
38
38
36
10
49
25
16
16
16
16
16
3
16
16
16
16
16
16
16
3
16
16
16
6
6
3
Ae
Bf
Ae
Bf
Ab
Bc
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Ae
2l
Bf
2m
2m
2n
2n
2k
2k
2k
2k
2k
2k
2k
Ae
Bg
Ae
Bg
Ab
Bb
3dk
3ek (cisþtrans)
Ab
Bb
3ek (cisþtrans)
3fk
3gk
3hk
Ab
Ab
Ab/Bc
1g
1h
18
h
a
Isolated yield.
Irradiation in neat dioxolane.
Irradiation in 1:1 2k–water mixture.
Polymerization occurred during the irradiation.
Irradiation in 1 M 2 in MeCN.
b
c
d
e
f
Irradiation in 1 M 2 in 1:1 MeCN–water.
Irradiation in 1 M 2 in 7:10 MeCN–water.
No alkylation occurred while 1 was completely consumed. See Section 5.
g
h
aldehydes. In the case of crotonaldehyde (1b) alkylation
with 2-propanol (4q) occurred smoothly leading to the
desired lactol 5bq as a 2:1 mixture of the two dia-
stereomers.14 The residue obtained from the irradiated
solution could be directly oxidized to lactone 6bq without
isolating 5bq by using Br2/BaCO3, with an overall yield of
31% for the two steps (entry 3, Table 2). Lactol 5bq was
likewise synthesised in water–alcohol mixture (procedure
B) in a similar yield (48%, entry 4).
also by using ethanol (4r) and methanol (4s). As an
example, lactol 5br was obtained as a mixture of the four
possible diastereoisomers. When the above oxidation
procedure was applied, the cis and trans isomers of lactones
6br (in about 1:1 ratio) were obtained and characterized
after careful chromatographic separation. Better yields were
reached in the alkylation of 1c (entries 9–13), probably
owing to the lower volatility of the final products. As an
example, lactone 6cs was prepared from 1c by direct
oxidation of the non-purified lactol intermediate. The same
procedure was applied to carbocyclic aldehyde 1e, with
similar results in the formation of lactones 6 eq. (cisþtrans
isomers).
Alkylated products 5 were obtained in a reasonable yield
On the other hand, the alkylation by alcohols was
unsuccessful not only, as in the case of dioxolanes, with
doubly unsaturated aldehyde 1h, but also with aromatic
aldehydes 1f, g.
2.3. Assessment of the efficiency of different water-
soluble sensitisers
We prepared a water-soluble sensitiser, benzophenone
disodium disulfonate (BPSS), for the experiments in
mixed aqueous media. This salt is prepared in one-step
(see Section 5) and we were curious to examine how it
compared with other hydrosoluble sensitisers. We therefore
tested three further sensitisers in the reaction of 1c with 4q,
viz. the sodium salts of antraquinone 2-sodium sulfonic acid
(AQSS, commercially available) and of 2- or 4-benzoyl-
benzoic acid (2-BBSC and 4-BBSC, the corresponding
acids are both commercialized). Irradiation for 8 h gave the
results shown in Table 3. It is apparent that only 4-BBSC
Scheme 3. Reagents and conditions: (a) Procedure A: Ph2CO in neat 4.
Procedure B: BPSS in a 4/H2O mixtures. (b) Br2, BaCO3.

950
D. Dondi et al. / Tetrahedron 59 (2003) 947–957
Table 2. Yield of alkylated lactols (or lactones) from a,b-unsaturated aldehydes and alcohol 4
Entry
Aldehydes
Alcohols
Lactols
Lactonesa
Procedure
Irradiation time (h)
Product yield (%)b
e
1
2
3
4
5
6
7
8
1a
1b
1b
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
1e
1e
1f
4q
4q
4q
4q
4r
4r
4s
5aq
5bq
Ac/Bd
Ac
Ac
Bd
3
7
7
44
31
48
41
6bq
5bq
5br
7
Ac
Bd
15
15
15
15
7
7
7
7
15
16
16
16
16
16
6br (cisþtrans)
14 (cis) þ12 (trans)
5bs
B
58f
39
4s
6bs
B
9
4q
4q
4q
4q
4s
4q
4q
4q
4q
4q
5cq
5cq
5cq
Ac
Bd
63
10
11
12
13
14
15
16
17
18
50
Bd
57f,g
35
6cq
6cs
Bd
Ac
Ac
Bd
42
32
37
h
6eq (cisþtrans)
6eq (cisþtrans)
5fq
5gq
5hq
Ac
Ac
Ac/Bd
h
h
1g
1h
a
Lactones were obtained by direct oxidation of the raw photolisates. See text.
Isolated yield.
Irradiation in neat alcohol.
b
c
d
e
f
Irradiation in 1:1 alcohol 4–water mixture.
Polymerization occurred during the irradiation.
Reactions carried out in an immersion reactor.
Product 5cq isolated by bulb to bulb distillation.
No alkylation occurred while starting aldehyde 1 was wholly consumed. See text.
g
h
gives results comparable with BPSS, with essentially the
same yield of 5cq, even though the reaction was slightly
slower. On the contrary, aldehyde 1c was photostable in the
presence of AQSS and 2-BBSC, just as it happened in the
absence of the sensitisers. One may notice that the only
alternative to BPSS is the most expensive one of the
commercial photosensitisers tested.
is efficient by using the sensitiser at a substoichiometric
concentration (20–40%), and the relative independence of
the results on the structure of R–H suggests that path a is the
most important one. Path c, on the contrary, leads to
stoichiometrical consumption of the sensitiser and produces
pinacols.16
Under our conditions, where [RH] (in any case a better
hydrogen donor than aldehydes)17 exceeds by a factor $10
the concentration of the unsaturated aldehyde, no competing
hydrogen abstraction occurs neither from the formyl group,
3. Discussion
3.1. General course of the reaction
The mild conditions of photosensitisation appear well suited
for the radical alkylation of such sensitive substrates as
unsaturated aldehydes. The mechanism leading to alkylated
aldehydes 3 and 5 is depicted in Scheme 4. Promotion of the
sensitiser to the triplet state leads to hydrogen abstraction
from the donors (RH) and radical Rz is trapped by the
unsaturated aldehydes leading to an adduct radical.15 The
sequence is completed by hydrogen abstraction from either
the ketyl radical (path a) or a reagent, such as RH, (1, path b)
or the solvent (path c). The first two paths do not consume
the sentisitizer stoichiometrically, as path a regenerates it
and path b leads to a chain alkylation. The present reaction
Table 3. Comparison of different water soluble sensitisers in the reaction of
1c and 4q after 8 h of irradiation
Sensitiser
Conversion of 1c (%)
Relative yield of 5cq
None
BPSS
AQSS
4-BBSC
2-BBSC
,5
100
,5
90
–
1
a
0.88
a
,5
a
Scheme 4.
Product 5cq not detected by GC analysis.

D. Dondi et al. / Tetrahedron 59 (2003) 947–957
951
although such abstraction by excited benzophenone has
been reported,18 nor from the g-position.
using a water soluble sensitiser. The fact that procedure B is
feasible is significant for different reasons: (a) the amount of
toxic organic solvents such as MeCN is reduced (b) the final
products are obtained by simple extraction of the irradiated
mixtures often with a satisfactory degree of purity, either for
isolation requiring a less elaborated chromatography than
after irradiation in organic medium or for simplified further
elaboration, (c) during the extraction procedure all of the
byproducts arising from the sensitiser remain in the aqueous
phase. A water-soluble sensitiser, BPSS, was obtained by
sulfonation of the inexpensive benzophenone; of the
commercial sensitisers tested, only 4-BBSC comes near to
the results with BPSS (see Table 3). Previously, both
4-BBSC22a,b and p-sulfonated benzophenones22c,d have
been reported to abstract hydrogen in alcohol–water
mixtures with efficiency similarly to non-sulfonated benzo-
phenone through laser flash photolysis studies.22a,d On the
contrary, sensitisers with slightly different structures, such
2-BBSC and AQSS were much less effective. This
peculiarity is presently under investigation.
3.2. Scope of the method
Yields are mostly moderate, but this does not deprive the
method of interest in view of the mild conditions, the
simplicity and directness of the method, leading through a
single photochemical reaction to products that are
otherwise obtained in several steps, and avoiding the use
of heavy metals. Both dioxolanes and alcohols are
suitable radical precursors. The irradiation time depends
on the concentration of these hydrogen donor (e.g. compare
entry 2 in Table 1 with 2k used neat and entry 4 with 2m
used 1 M) and on their structure (e.g. alkylations with
isopropanol are in every case about twice as fast as with
ethanol and methanol, see Table 2), but the yield reached
after the appropriate irradiation time are not much different.
a,b-Unsaturated aldehydes proved to be efficient radical
traps. Indeed, in the alkylation with 2-alkyl-dioxolanes 2l–n
yields are better than with structurally similar ketones.12b
Exceptions are acrolein 1a, which undergoes a fast
polymerization under this conditions and doubly unsatu-
rated aldehyde 1h that likewise is consumed efficiently thus
precluding alkylation. Aromatic aldehydes have a triplet
energy close to that of the sensitiser (cinnamaldehyde, 1f,
300 kJ mol21, benzophenone, 287)19 and thus energy
transfer and geometric isomerization greatly hinders
hydrogen abstraction from the radical precursors R–H.
Nevertheless, some alkylation takes place with dioxolanes,
if not with the alcohols.
3.4. Synthetic significance
The present method offers an easy entry to different
succinaldehyde monoacetals23 and g-(monoprotected)
ketoaldehydes. As for the latter compounds, the photo-
chemical procedure gives selectively masked dicarbonyls
that can not be obtained in a single step from the
corresponding g-ketoaldehydes because the protection
involves the less electrophilic ketone function. Noteworthy,
compounds 3dk, 3bm and 3gk have been previously
reported in the literature as intermediates for the synthesis
of molecules having biological activity but have been
obtained through several steps. For example, aldehyde 3dk
has been obtained in five steps and employed in the
synthesis of ryanodol.24a Likewise, the dioxolanyl deriva-
tives 3bm is a building block for the synthesis of sordinin (a
male pheromone compound emitted by Cosmopolites
sordidus)24b and O-methyljoubertiamine (a seco-
mesembrane alkaloid) has been obtained from 3gk.24c
In the alkylation with alcohols, g-butyrolactols are obtained
often as a diastereoisomeric mixture. Such products can be
further transformed without purification, however; in
particular we oxidized them directly to the corresponding
lactones. This simple preparation of b-alkyl-g-lactones is of
interest also because the alternative approach from a,b-
unsaturated acids through the same photosensitised radical
method was previously found to give poor yields.20,21 In the
present case, the preparation of the lactones was cleaner
when the photoalkylation had been carried out in mixed
aqueous solution (procedure B), since the oxidation step was
facilitated by the elimination of most byproducts by
extraction (see further below).
g-Lactols are another important class of compounds in
organic synthesis; this importance is especially due to their
easy transformation to tetrahydrofuran derivatives or
lactones.25 We will not deal with this point in detail, but
g-butyrolactones are ubiquitous in nature and many of them
are biologically significant (alkaloids, macrocyclic anti-
biotics and pheromones).26,27 Thus a new mild access to this
class of compounds is of interest.
With cyclohexencaboxylaldeyde (1e) in mixed aqueous
solvent the addition is somewhat diastereoselective, both
when using isopropanol (cis/trans 2:1 for lactone 6eq) and,
to a larger degree, with dioxolane (4.6:1 for the cis isomer in
the formation of compound 3ek). Addition of ethanol to
crotonaldehyde is unselective (see entry 6 in Table 2).
4. Conclusions
In this work, radicals generated by photosensitised hydro-
gen abstraction were successfully used for the synthesis of
1,4-monoprotected dialdehydes and ketoaldehydes as well
of g-lactols and lactones starting from a,b-unsaturated
aldehydes, a class of substrates to which radical addition
processes had been only rarely applied up to now. The
reactions could be performed both in organic media and in
mixed aqueous media; in the last case water-soluble
sensitisers were used and work up was simplified. 1,3-
Dioxolane and its 2-substituted derivatives or respectively
3.3. Water-containing solvent and hydrophylic
sensitisers
As can be seen from Tables 1 and 2, the presence of water
did not influence the alkylation processes (except for the
irradiation time in some cases) and the overall yields in the
formation of either dioxolanyl aldehydes 3 or lactols 5 were
about the same both by procedure A and B, the latter
involving a mixed solvent containing up to 50% water and

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D. Dondi et al. / Tetrahedron 59 (2003) 947–957
alcohols were used as radical precursors, obtaining
moderate yields from aliphatic unsaturated aldehydes,
though less positive results were obtained with the arylated
derivatives.
Calcd for C13H8Na2O4S2·H2O containing 5% Na2SO4: C,
36.77; H, 2.37.
5.2. Photochemical synthesis of substituted aldehydes 3.
General procedure
Procedure A: A solution of the aldehyde 1 (0.05–0.1 M),
dioxolane 2 (used as the solvent in the case of 2k or 1 M in
the other cases) and the sensitiser (benzophenone, 0.02 M)
in acetonitrile was irradiated until 1 was consumed. Workup
of the photolytes involved concentration in vacuo and
chromatographic separation.
5. Experimental
5.1. General
Unsaturated aldehydes 1 were of commercial origin except
for 1d28 1e,29 which were prepared according to literature
procedures, and were freshly distilled (or purified) just
before use. Dioxolanes 2k and 2l were commercial samples
and used as received whereas 2m and 2n were prepared
from the corresponding aldehydes.12b 2-BBSC and 4-BBSC
were obtained from the commercial acids. The photo-
chemical reactions were performed in quartz tubes by using
nitrogen-purged solution and external illumination by
means of a multilamp reactor fitted with six 15 W
phosphor-coated lamps (maximum of emission 315 or
366 nm). Workup of the photolytes involved concentration
in vacuo followed by chromatographic separation (cyclo-
hexane/ethyl acetate mixtures as eluants) using Millipore
Procedure B: A solution of the aldehyde 1 (0.1 M),
dioxolane 2 (1 M) and the sensitiser (BPSS 0.02 M) in
acetonitrile/water (a 1:1 mixture of 2-water in the case of
2k) was irradiated until 1 was consumed. Workup of the
photolytes involved elimination of the organic solvents in
vacuo, extraction with CH2Cl2 (4 times) of the resulting
aqueous phase and, when appropriate, chromatographic
purification of the residue.
5.2.1. 3-(1,3-Dioxolan-2-yl)-butyraldehyde (3bk). Proc.
A: From 205 mL of 1b (2.5 mmol, 0.05 M) and 180 mg of
benzophenone (1 mmol, 0.02 M) in 50 mL of 1,3-dioxolane
irradiated for 3 h at 315 nm. After column chromatography
(C6H12/EtAc 9:1 containing 0.2% Et3N) 144 mg of the title
compound 3bk (oil) were isolated (40% yield).
˚
60 A 35–70 mm silica gel (otherwise indicated). The
structural attribution of new products was made mainly on
1
the basis of H and 13C NMR, recorded on a 300 MHz
spectrometer; chemical shifts are reported in ppm downfield
from TMS.
Proc. B: From 500 mL of 1b (6 mmol, 0.1 M) and 485 mg of
BPSS (1.2 mmol, 0.02 M) in 60 mL of a 1:1 mixture of 1,3-
dioxolane/water irradiated for 16 h at 315 nm. Purification
by column chromatography yielded 372 mg of 3bk (43%
yield).
5.1.1. Synthesis of benzophenone disodium disulfonate
(BPSS). Benzophenone (50 g, 274 mmol) was heated at
608C under mechanical stirring until melting. Oleum
(90 mL, 20% SO3 content) was then slowly added and the
resulting mixture was heated to 1608C for 4 h. The solution
was then allowed to cool down to room temperature and
poured into 150 g of crushed ice under vigorous stirring. A
white solid (unreacted benzophenone) separated out and
was filtered off. The filtrate was cautiously neutralized
under stirring with 40% NaOH aqueous solution. The milky
solid thus formed was again eliminated and the filtrate was
evaporated in vacuo. The resulting solid was dissolved in
water and MeOH was added in order to precipitate most of
the Na2SO4 present. The last procedure (dissolution in water
and precipitation of Na2SO4 with MeOH) was repeated a
few times until the resulting solid showed a satisfactory
degree of purity (.90%).30 The resulting BPSS (after
reaching constant weight in vacuum essicator, 12.7 g, 12%
yield) was a mixture of 3,30- and 4,40-benzophenone
disodium disulfonate (bis-meta/bis-para ratio ca. 2:1) as
shown by NMR analysis. Ionic chromatographic sulfate
determination revealed the presence of 5% Na2SO4. These
data, coupled with elemental analysis, were consistent with
a BPSS monohydrate structure.
3bk: Spectroscopic data in accord with the literature.31
Chromatography in the absence of Et3N yielded the trans-
acetalized product 1,2-bis-[(1,3-dioxolan-2-yl)propane as
the only isolated product. 1H NMR (CDCl3): d 1.05 (3H, d,
J¼7.0 Hz, CH3CHx), 1.40–1.60 (1H, m, CHaHb-
CH(OCH2)2, A part of an ABX system), 1.80–1.90 (1H,
m, CHaHbCH(OCH2)2, B part of an ABX system), 1.90–
2.05 (1H, m, CH3CHx, X part of an ABX system), 3.70–
3.85 (4H, m, OCH2CH2O), 3.90–4.10 (4H, m, OCH2CH2-
O), 4.70 (1H, d, J¼4.0 Hz, OCHO), 4.90 (1H, t, J¼5.0 Hz,
OCHO). 13C NMR: d 14.3 (CH3), 32.9 (CH), 35.0 (CH2),
64.6 (CH2), 64.7 (CH2), 64.8 (CH2), 64.9 (CH2), 103.3
(CH), 108.9 (CH). IR (neat) n, (cm21) 2945, 1101. Anal.
Calcd for C9H16O4: C, 57.43; H, 8.57. Found: C, 57.70; H,
8.31.
Compound 3bk was very sensitive to oxidation in solution
forming the corresponding acid [3-(1,3-dioxolan-2-yl)-
butyric acid]. This was detected in mixture with 3bk after
some time in solution. 1H NMR (CDCl3, from the mixture):
d 1.00 (3H, d, J¼7.0 Hz, CH3CHx), 2.15–2.25 (1H, m,
CHaHbCOOH, A part of an ABX system), 2.45–2.50 (1H,
m, CH3CHx, X part of an ABX system), 2.55–2.60 (1H, m,
CHaHbCOOH, B part of an ABX system), 4.00 (4H, m,
OCH2CH2O), 4.90–5.00 (1H, m, OCHO). 13C NMR
(CDCl3): d 15.1 (CH3), 34.3 (CH), 35.8 (CH2), 65.5
(CH2), 65.6 (CH2), 106.7 (CH), 177.8 (COOH).
1H (D2O, from the mixture) d 7.65 (2H, t, J¼6.0 Hz, meta),
7.85–7.95 (8H, m, 4H meta and 4H para), 8.05 (4H, d,
J¼6.0 Hz, para), 8.15 (2H, bs, meta). 13C (D2O, from the
mixture) d 125.6 (CH), 126.7 (CH), 129.4 (CH), 130.0
(CH), 130.7 (CH), 136.8 (meta), 138.6 (para), 142.9 (meta),
146.3 (para), 197.8 (CO, meta), 198.1 (CO, para). IR (KBr)
n, (cm21) 2950, 1642, 1100. Anal. Found: C, 36.30; H, 2.32.

D. Dondi et al. / Tetrahedron 59 (2003) 947–957
953
5.2.2. 3-(2-Ethyl-1,3-dioxolan-2-yl)-butyraldehyde
(3bm). Proc. A: From 205 mL of 1b (2.5 mmol, 0.05 M),
5.2 mL of 2m (50 mmol, 1 M) and 180 mg of benzophenone
(1 mmol, 0.02 M) in 45 mL of acetonitrile irradiated for
16 h at 315 nm. After column chromatography (C6H12/EtAc
95:5) 164 mg of the title compound 3bm (oil) were isolated
(38% yield).
2882, 1707, 1101. Anal. Calcd for C9H16O3: C, 62.77; H,
9.36. Found: C, 62.79; H, 9.33.
5.2.5. 3-(2-Methyl-1,3-dioxolan-2-yl)-hexanal (3cl). Proc.
A: From 580 mL of 1c (5 mmol, 0.1 M), 4.5 mL of 2l
(50 mmol, 1 M) and 180 mg of benzophenone (1 mmol,
0.02 M) in 45.5 mL of acetonitrile irradiated for 16 h at
315 nm. After column chromatography (Cy/EtAc 92:8)
455 mg of the title compound 3cl (oil) were isolated (49%
yield).
Proc. B: From 500 mL of 1b (6 mmol, 0.1 M), 6.2 mL of 2m
(60 mmol, 1 M) and 485 mg of BPSS (1.2 mmol, 0.02 M) in
54 mL of a 1:1 mixture of acetonitrile/water irradiated for
16 h at 315 nm. Purification on column yielded 435 mg of
3bm (42% yield).
Proc. B: From 700 mL of 1c (6 mmol, 0.1 M), 5.4 mL of 2l
(60 mmol, 1 M) and 485 mg of BPSS (1.2 mmol, 0.02 M) in
54.5 mL of a 1:1 mixture of acetonitrile/water irradiated for
16 h at 315 nm. Purification on column yielded 492 mg of
3cl (44% yield).
3bm: Spectroscopic data in accord with the literature.32
5.2.3. 3-(2-Hexyl-1,3-dioxolan-2-yl)-butyraldehyde
(3bn). Proc. A: From 205 mL of 1b (2.5 mmol, 0.05 M),
8.5 mL of 2n (50 mmol, 1 M) and 180 mg of benzophenone
(1 mmol, 0.02 M) in 41.5 mL of acetonitrile irradiated for
16 h at 315 nm. Most of compound 2n was then eliminated
by distillation in vacuo and after column chromatography
(C6H12/EtAc 95:5) of the resulting raw material, 170 mg of
the title compound 3bn (oil) were isolated (30% yield).
3cl: colourless oil, 1H NMR (CDCl3): d 0.95 (3H, t,
J¼7.0 Hz, CH3CH2), 1.10–1.60 (4H, m, CH3CH2CH2),
1.30 (3H, s, CH3C(OCH2)2), 2.20–2.50 (3H, m, CHxCHa-
Hb), 3.80–3.90 (4H, m, OCH2CH2O), 9.65 (1H, d,
J¼3.0 Hz, CHaHbCHO). 13C NMR: d 14.0 (CH3), 20.7
(CH2), 20.9 (CH3), 32.4 (CH), 42.3 (CH2), 43.8 (CH2), 63.9
(CH2), 64.5 (CH2), 201.8 (CO). IR (neat) n, (cm21) 2958,
2872, 1708, 1037. Anal. Calcd for C10H18O3: C, 64.49; H,
9.74. Found: C, 64.55; H, 9.66.
Proc. B: From 250 mL of 1b (3 mmol, 0.06 M), 1.5 mL of
2n (9 mmol, 0.2 M) and 243 mg of BPSS (0.6 mmol,
0.012 M) in 50 mL of a 7:3 mixture of acetonitrile/water
irradiated for 16 h at 315 nm. Purification on column
yielded 245 mg of 3bn (36% yield).
5.2.6. 3-(2-Ethyl-1,3-dioxolan-2-yl)-hexanal (3cm). Proc.
A: From 290 mL of 1c (2.5 mmol, 0.05 M), 5.2 mL of 2m
(50 mmol, 1 M) and 180 mg of benzophenone (1 mmol,
0.02 M) in 45.5 mL of acetonitrile irradiated for 16 h at
315 nm. After column chromatography (C6H12/EtAc 95:5)
140 mg of the title compound 3cl (oil) were isolated (28%
yield).
3bn: colourless oil, 1H NMR (CDCl3): d 0.85 (3H, t,
J¼7.0 Hz, CH3CH2), 1.00 (3H, d, J¼7.0 Hz, CH3CH),
1.15–1.40 (8H, m, CH2CH2CH2CH2), 1.50–1.70 (2H, m,
CH2CH(OCH2)2), 2.15–2.25 (1H, m, CH3CHx, X part of an
ABX system), 2.45–2.55 (2H, m, CHaHbCHO, AB part of
an ABX system), 3.90 (4H, m, OCH2CH2O), 9.60 (1H, bs,
CHaHbCHO). IR (neat) n, (cm21) 2955, 2877, 1708, 1103.
Anal. Calcd for C13H24O3: C, 68.38; H, 10.59. Found: C,
68.24; H, 10.51.
Proc. B: From 170 mL of 1c (1.5 mmol, 0.03 M) 1 mL of
2m (10 mmol, 0.2 M) and 242 mg of BPSS (0.6 mmol,
0.012 M) in 50 mL of a 7:10 mixture of MeCN/water
irradiated for 16 h at 315 nm. Purification on column
yielded 72 mg of 3cm (24% yield).
5.2.4. 3-[1,3]Dioxolan-2-yl-hexanal (3ck). Proc. A: From
290 mL of 1c (2.5 mmol, 0.05 M) and 180 mg of benzo-
phenone (1 mmol, 0.02 M) in 50 mL of 1,3-dioxolane
irradiated for 3 h at 315 nm. After column chromatography
(C6H12/EtAc 9:1) 168 mg of the title compound 3ck (oil)
were isolated (39% yield).
3cm: colourless oil, 1H NMR (CDCl3): d 0.85 (3H, t,
J¼7.0 Hz, Me), 0.90 (3H, t, J¼7.0 Hz, Me), 1.15–1.80 (6H,
m, 3CH2), 2.15–2.50 (3H, m, CHxCHaHb), 3.80–4.00 (4H,
m, OCH2CH2O), 9.60 (1H, dd, J¼2.0, 3.0 Hz, CHaHbCHO).
IR (neat) n, (cm21) 2952, 2868, 1708, 1098. Anal. Calcd for
C11H20O3: C, 65.97; H, 10.07. Found: C, 66.01; H, 10.01.
Proc. B: From 700 mL of 1c (6 mmol, 0.1 M) and 485 mg of
BPSS (1.2 mmol, 0.02 M) in 60 mL of a 1:1 mixture of 1,3-
dioxolane/water irradiated for 16 h at 315 nm. Purification by
column chromatography yielded 330 mg of 3ck (32% yield).
5.2.7. 3-(2-Hexyl-1,3-dioxolan-2-yl)-hexanal (3cn). Proc.
A: From 290 mL of 1c (2.5 mmol, 0.05 M), 8.5 mL of 2n
(50 mmol, 1 M) and 180 mg of benzophenone (1 mmol,
0.02 M) in 41.5 mL of acetonitrile irradiated for 16 h at
315 nm. Compound 3cn (255 mg, oil, 40% yield) was
isolated by bulb to bulb distillation.
3ck: colourless oil, 1H NMR (CDCl3): d 0.95 (3H, t,
J¼7.0 Hz, CH3CH2), 1.10–1.60 (4H, m, CH3CH2CH2),
2.25 (1H, ddd, J¼2.0, 4.0, 15.0 Hz, CHaHbCHO, A part of
an ABX system), 2.35–2.40 (1H, m, CH3CHx, X part of an
ABX system), 2.45 (1H, ddd, J¼3.0, 7.0, 15.0 Hz, CHaHb-
CHO, B part of an ABX system), 3.80–4.00 (4H, m,
OCH2CH2O), 4.90 (1H, d, J¼3.0 Hz, OCHO), 9.60 (1H, dd,
J¼2.0, 3.0 Hz, CHaHbCHO). 13C NMR: d 13.8 (CH3), 20.1
(CH2), 32.3 (CH2), 37.1 (CH), 42.7 (CH2), 54.6 (CH2), 54.8
(CH2), 105 (CH), 202 (CHO). IR (neat) n, (cm21) 2968,
Proc. B: From 170 mL of 1c (1.5 mmol, 0.03 M) 1.5 mL of
2n (10 mmol, 0.2 M) and 242 mg of BPSS (0.6 mmol,
0.012 M) in 50 mL of a 7:10 mixture of MeCN/water
irradiated for 16 h at 315 nm. Purification by column
chromatograph yielded 146 mg of 3cn (38% yield).
3cn: colourless oil, 1H NMR (CDCl3): d 0.78 (3H, t,
J¼7.0 Hz, Me), 0.80 (3H, t, J¼7.0 Hz, Me), 1.20–1.70

954
D. Dondi et al. / Tetrahedron 59 (2003) 947–957
(14H, m, 7CH2), 2.10–2.40 (3H, m, CHxCHaHb), 3.85–4.00
(4H, m, OCH2CH2O), 9.6 (1H, dd, J¼2.0, 3.0 Hz, CHaHb-
CHO). IR (neat) n, (cm21) 2956, 2871, 1710, 1090. Anal.
Calcd for C15H28O3: C, 70.27; H, 11.01. Found: C, 70.22; H,
10.98.
3fk: colourless oil, 1H NMR (CDCl3): d 2.70–2.80 (1H, m,
CHaHbCHO, A part of an ABX system), 2.95–3.05 (1H, m,
CHaHbCHO, B part of an ABX system), 3.55–3.65 (1H,
m, PhCHx, X part of an ABX system), 3.80–4.00 (4H, m,
OCH2CH2O), 5.05–5.15 (1H, m, OCHO), 7.20–7.40 (5H,
m, Ph), 9.75 (1H, bs, CHO). 13C NMR: (CDCl3) d 43.7
(CH2), 43.8 (CH), 65.1 (CH2), 65.3 (CH2), 105.6
(CH),138.8, 126.2 (CH), 127.8 (CH), 128.5 (CH), 201
(CHO). IR (neat) n, (cm21) 2938, 2858, 1721, 1617, 1089,
840. Anal. Calcd for C12H14O3: C, 69.89; H, 6.84. Found: C,
69.78; H, 6.77.
5.2.8. 3-(1,3-Dioxolan-2-yl)-4-methylpentanal (3dk).
Proc. A: From 245 mg of 1d (2.5 mmol, 0.05 M) and
180 mg of benzophenone (1 mmol, 0.02 M) in 50 mL of
1,3-dioxolane irradiated for 3 h at 315 nm. After column
chromatography (C6H12/EtAc 85:15) 164 mg of the title
compound 3dk (oil) were isolated (38% yield).
5.2.11. 3-[1,3]Dioxolan-2-yl-3-(4-methoxyphenyl)propa-
nal (3gk). Proc. A: From 425 mg of 1g (2.5 mmol, 0.05 M)
and 180 mg of benzophenone (1 mmol, 0.02 M) in 50 mL of
1,3-dioxolane irradiated for 6 h at 366 nm. After column
chromatography (neutral alumina, C6H12/EtAc 8:2) 106 mg
of the title compound 3gk (oil) were isolated (18% yield).
Proc. B: From 590 mg of 1d (6 mmol, 0.1 M) and 485 mg of
BPSS (1.2 mmol, 0.02 M) in 60 mL of a 1:1 mixture of 1,3-
dioxolane/water irradiated for 16 h at 315 nm. Purification by
column chromatography yielded 372 mg of 3dk (36% yield).
3dk: Spectroscopic data in accord with the literature.33
1
3gk: H NMR (CDCl3):34 d 2.70 (1H, ddd, J¼2.0, 7.0,
5.2.9. 3-(1,3-Dioxolan-2-yl)-cyclohexancarbaldehyde
(3ek). Proc. A: From 285 mg of 1e (2.5 mmol, 0.05 M)
and 180 mg of benzophenone (1 mmol, 0.02 M) in 50 mL of
1,3-dioxolane irradiated for 3 h at 315 nm. Purification by
column chromatography (C6H12/EtAc 80:20) was tedious
owing to the interference of different byproducts and only
37 mg of slighty impure 3ek (oil, cisþtrans) were isolated
(10% yield).
16.5 Hz, CHaHbCHO, A part of an ABX system), 2.95 (1H,
ddd, J¼2.5, 7.0, 16.5 Hz, CHaHbCHO, B part of an ABX
system), 3.55 (1H, dt, J¼3.6, 7.0 Hz, 4-MeOPhCHx, X part
of an ABX system), 3.80 (3H, s, Me), 3.90–4.00 (4H, m,
OCH2CH2O), 5.00 (1H, d, J¼3.6 Hz, OCHO), 6.80–6.90
(2H, m, AA0BB0 system), 7.20–7.30 (2H, m, AA0BB0
system), 9.70 (1H, dd, J¼2.0, 2.5 Hz, CHO). 13C NMR
(CDCl3): d 42.9 (CH), 43.8 (CH2), 55.1 (CH3O), 64.8
(CH2), 65.3 (CH2), 105.7 (CH), 113.9 (CH), 129.4 (CH),
130.8, 158.6, 201 (CHO). IR (neat) n, (cm21) 2941, 2862,
1720, 1618, 1093, 842. Anal. Calcd for C13H16O4: C, 66.09;
H, 6.83. Found: C, 66.00; H, 6.85.
Proc. B: From 570 mL of 1e (5 mmol, 0.1 M) and 405 mg of
BPSS (1 mmol, 0.02 M) in 50 mL of a 1:1 mixture of 1,3-
dioxolane/water irradiated for 16 h at 315 nm. Purification
by column chromatography yielded 358 mg of 3ek (49%
yield) as a mixture of the two diastereoisomers in the ratio
4.6:1. The cis configuration was assigned to the major
component on the basis of the comparison with the
corresponding adduct with 1-acetylcyclohexene,12a for
which double irradiation experiments, not carried out here
due to the close superimposition of signals, had supplied
evidence.
5.3. Attempted synthesis of dioxolanes 3ak and 3hk
Application of the above procedures to aldehydes 1a and 1h
both in organic and in aqueous media gave no detectable
amount of the expected products 3ak or 3hk, while 1h was
consumed through undetermined paths and 1a polymerized.
5.4. Photochemical synthesis of lactols 5. General
procedure
1H NMR (CDCl3, mixture of the two diastereoisomers): d
1.00–2.50 (18H, m, 8CH2 and 2CH), 2.50–2.65 (2H, m,
2CHCHO), 3.70–4.00 (8H, m, 2 OCH2CH2O), 4.7 (1H, d,
J¼3.0 Hz, OCHO, minor isomer), 4.95 (1H, d, J¼5.5 Hz,
OCHO, major isomer), 9.35 (1H, d, J¼5.0 Hz, CHO, minor
isomer), 9.80 (1H, bs, CHO, major isomer).
Procedure A: A solution of the aldehyde 1 (0.05–0.1 M),
the sensitiser (benzophenone, 0.02 M) in neat alcohol 4 was
irradiated until 1 was consumed. Workup of the photolytes
involved concentration in vacuo and chromatographic
separation.
13C NMR: (CDCl3, major isomer from the mixture) d 22.9
(CH2), 24.3 (CH2), 25.0 (CH2), 25.1 (CH2), 42.1 (CH), 48.2
(CH), 64.5 (CH2), 64.6 (CH2), 104.7 (CH), 204.2 (CHO).
13C NMR: (CDCl3, minor isomer from the mixture) d 24.4
(CH2), 24.7 (CH2), 25.6 (CH2), 25.8 (CH2), 41.3 (CH), 49.7
(CH), 64.5 (CH2), 64.6 (CH2), 105.8 (CH), 203.0 (CHO). IR
(neat, mixture) n, (cm21) 1730, 1085. Anal. Calcd for
C10H16O3: C, 65.19; H, 8.75. Found: C, 65.25; H, 8.80.
Procedure B: A solution of the aldehyde 1 (0.05–0.1 M),
the sensitiser (BPSS 0.02 M) in a 1:1 mixture of 4-water
was irradiated until 1 was consumed. Workup of the
photolytes involved elimination of the organic solvents in
vacuo, extraction with CH2Cl2 (4 times) of the resulting
aqueous phase and chromatographic purification of the
residue.
5.2.10. 3-(1,3-Dioxolan-2-yl)-3-phenylpropanal (3fk).
Proc. A: From 315 mL of 1f (2.5 mmol, 0.05 M) and
180 mg of benzophenone (1 mmol, 0.02 M) in 50 mL of
1,3-dioxolane irradiated for 6 h at 366 nm. After column
chromatography (neutral alumina, C6H12/EtAc 8:2) 129 mg
of the title compound 3fk (oil) were isolated (25% yield).
5.5. Conversion to lactones 6. General procedure
Lactones 6 were obtained from crude lactols 5 by oxidation
of the previous crude photolisates employing Br2/BaCO3 as
an oxidant. The reaction was carried out dissolving the
residue in H2O/ dioxane 2:1 at room temperature in the dark

D. Dondi et al. / Tetrahedron 59 (2003) 947–957
955
under stirring for 2 h.35 The reaction was quenched with an
aqueous saturated Na2S2O3 solution until decoloration and
then extracted with AcOEt (3 times). The crude lactone was
purified on column chromatography.
irradiated for 16 h at 315 nm. The residue obtained from the
irradiation was dissolved in 30 mL of H2O/dioxane 2:1
mixture and oxidized by treatment with 1.3 g of BaCO3 and
770 mL of Br2. Chromatographic purification (C6H12/EtAc
8:2 as the eluant) afforded 98 mg of the cis-4,5-dimethyl-
tetrahydro-furan-2-one (14% yield) and 80 mg of trans-4,5-
dimethyl-tetrahydro-furan-2-on (12% yield). Spectroscopic
data were in accord with the literature.37
5.5.1. 4,5,5-Trimethyltetrahydrofuran-2-ol (5bq). Proc.
A: From 207 mL of 1b (2.5 mmol, 0.05 M) and 180 mg of
benzophenone (1 mmol, 0.02 M) in 50 mL of 4q irradiated
for 16 h at 315 nm. After column chromatography
(C6H12/EtAc 8:2) 143 mg of the title compound 5bq were
obtained as a mixture of two diastereoisomer in a 2:1 ratio
(44% yield).
5.5.5. 4-Methyltetrahydrofuran-2-ol (5bs). Proc. B (in the
immersion well photochemical reactor): The reaction was
performed in an immersion well apparatus fitted with a
Pyrex glass filtered 150 W medium-pressure mercury lamp
starting from 2 mL of 1b (24 mmol, 0.1 M) and 2.33 g of
BPSS (4.8 mmol, 0.02 M) in 240 mL of a 1:1 mixture of
4s/water (irradiation time¼15 h). Purification by column
chromatography (C6H12/EtAc 8:2) yielded 1.42 g of 5bs
(58% yield) as a mixture of two diastereoisomers in a 1.5:1
ratio.
Proc. B: From 500 mL of 1b (6 mmol, 0.1 M) and 485 mg of
BPSS (1.2 mmol, 0.02 M) in 60 mL of a 1:1 mixture of
4q/water irradiated for 16 h at 315 nm. Purification by
column chromatography yielded 372 mg of 5bq (48%
yield).
1
5bq: colourless oil, H NMR (CDCl3, major isomer, from
1
the mixture) d 0.95 (6H, s, 2 Me), 1.15 (3H, d, J¼7.0 Hz,
Me), 1.70 (1H, ddd, J¼5.0, 7.0, 12.0 Hz, CHaHbCHOH),
1.95 (1H, dd, J¼7.0, 12.0 Hz, CHaHbCHOH), 2.20–2.30
(1H, m, CHMe), 5.30 (1H, d, J¼5.0 Hz, CHOH). 13C NMR
(CDCl3, from the mixture): d 13.8 (CH3), 22.8 (CH3), 28.8
(CH3), 39.5 (CH), 41.0 (CH2), 84.2, 95.9 (CH).
5bs: The H NMR spectra (CDCl3) corresponded to those
previously reported.38
13C (CDCl3, major isomer) d 17.3 (CH3), 30.8 (CH), 41.3
(CH2), 73.7 (CH2), 98.3 (CH).
13C (CDCl3, minor isomer) d 16.7 (CH3), 32.8 (CH), 41.2
(CH2), 72.9 (CH2), 98.8 (CH).
1H NMR (CDCl3, minor isomer, from the mixture) d 0.90
(3H, d, J¼7.0 Hz, Me), 1.30 (6H, s, 2 Me), 1.55–1.65 (1H,
m, CHaHbCHOH), 1.85–1.95 (1H, m, CHaHbCHOH),
2.30–2.40 (1H, m, CHMe), 5.30 (1H, t, J¼5.0 Hz,
CHOH). 13C NMR (CDCl3, from the mixture): d 14.0
(CH3), 22.9 (CH3), 27.4 (CH3), 41.3 (CH2), 42.7 (CH), 83.3,
95.8 (CH). IR (neat, mixture) n, (cm21) 3425, 2978, 1450,
1360, 980. Anal. Calcd for C7H14O2: C, 64.58; H, 10.84.
Found: C, 64.63; H, 10.89.
IR (neat, mixture) n, (cm21) 3420, 2950, 2865, 1710
(traces), 1459, 1002. Anal. Calcd for C5H10O2: C, 58.80; H,
9.87. Found: C, 58.71; H, 9.81.
5.5.6. 4-Methyltetrahydrofuran-2-one (6bs). 1.4 g
(13.7 mmol) of lactol 5bs (obtained as above) were
dissolved in 70 mL of H2O/dioxane 2:1 mixture and
oxidized by treatment with 3 g of BaCO3 and 1.7 mL of
Br2. The resulting mixture after quenching with Na2S2O3
was extracted with Et2O and the organic phase was distilled
affording 937 mg of 6bs (39% yield based on starting 1b).
5.5.2. 4,5,5-Trimethyltetrahydrofuran-2-one (6bq). The
residue obtained from the procedure B irradiation was
dissolved in 30 mL of H2O/dioxane 2:1 mixture and
oxidized by treatment with 1.3 g of BaCO3 and 770 mL of
Br2. Chromatographic purification (C6H12/EtAc 8:2 as the
eluant) afforded 238 mg of 6bq (31% yield based on starting
1b).
1
6bs: The H NMR spectra (CDCl3) corresponded to those
previously reported.39
5.5.7. 5,5-Dimethyl-4-propyltetrahydrofuran-2-ol (5cq).
Proc. A: From 290 mL of 1c (2.5 mmol, 0.05 M) and
180 mg of benzophenone (1 mmol, 0.02 M) in 50 mL of 4q
irradiated for 16 h at 315 nm. After column chromatography
(C6H12/EtAc 7:3) 249 mg of the title compound 5cq (oil)
were obtained as a mixture of two diastereoisomer in a 2:1
ratio (63% yield).
6bq: Spectroscopic data in accord with the literature.36
5.5.3. 4,5-Dimethyltetrahydrofuran-2-ol (5br). Proc. A:
From 207 mL of 1b (2.5 mmol, 0.05 M) and 180 mg of
benzophenone (1 mmol, 0.02 M) in 50 mL of 4r irradiated
for 16 h at 315 nm. After column chromatography
(C6H12/EtAc 8:2) 119 mg of the title compound 5br (oil)
were obtained (41% yield). NMR analysis (1H NMR and
13C NMR) is consistent with a mixture of the four possible
diastereoisomers of compound 5br due to the presence of
four emiacetalic hydrogens d¼4.35, 4.1, 3.8, 3.55 in a
3.2:1:1.5:1.5 ratio. The structure of this compound was also
supported by the ensuing oxidation leading to compound
6br (see below).
Proc. B: From 700 mL of 1c (6 mmol, 0.1 M) and 485 mg of
BPSS (1.2 mmol, 0.02 M) in 60 mL of a 1:1 mixture of
4q/water irradiated for 6 h at 315 nm. Purification by
column chromatography yielded 475 mg of 5cq (50%
yield).
Proc. B (in the immersion well photochemical reactor): The
same reaction was repeated in a higher scale in an
immersion well apparatus fitted with a Pyrex glass filtered
150 W medium-pressure mercury lamp starting from
3.5 mL of 1c (30 mmol, 0.1 M) and 2.9 g of BPSS
5.5.4. 4,5-Dimethyltetrahydrofuran-2-one (6br). Proc. B:
From 500 mL of 1b (6 mmol, 0.1 M) and 485 mg of BPSS
(1.2 mmol, 0.02 M) in 60 mL of a 1:1 mixture of 4r/water

956
D. Dondi et al. / Tetrahedron 59 (2003) 947–957
(6 mmol, 0.02 M) in 300 mL of a 1:1 mixture of 4q/water
(irradiation time¼6 h). The residue was bulb to bulb
distilled affording 2.67 g of the title compound (57% yield).
mixture.41 The same synthesis was performed analogously
with procedure A with an overall yield of 32%.
6eq (transþcis): 1H NMR (CDCl3) d 1.1–1.2 (6H, m, H ring),
1.25 (3H, s, Me, trans), 1.30 (3H, s, Me, cis), 1.35 (3H, s, Me,
cis), 1.40 (3H, s, Me, trans), 1.55–1.80 (8H, m, H ring), 2.10–
2.25 (4H, m, H ring), 2.95–3.05 (2H, m, H ring).
1
5cq: colourless oil, H NMR (CDCl3, major isomer, from
the mixture) d 0.95 (3H, t, J¼7.0 Hz, Me), 1.15 (3H, s, Me),
1.15–1.45 (4H, m, 2CH2), 1.30 (3H, s, Me), 1.65 (1H, ddd,
J¼5.0, 7.0, 12.0 Hz, CHaHbCHOH), 1.95 (1H, dd, J¼7.0,
12.0 Hz, CHaHbCHOH), 2.30–2.40 (1H, m, CH2CHCHa-
Hb), 4.80 (1H, bd, J¼5 Hz, OH), 5.30 (1H, t, J¼5 Hz,
CHOH). 13C NMR (CDCl3): d 14.2 (CH3), 22.4 (CH2),
23.3 (CH3), 29.8 (CH3), 32.5 (CH2), 45.6 (CH), 96.4
(CH).
cis isomer: 13C (CDCl3, from the mixture) d 23.0 (CH2),
23.3 (CH3), 23.4 (CH2), 24.1 (CH2), 25.6 (CH2), 26.6 (CH3),
40.4 (CH), 43.9 (CH), 84.5, 178.2 (CO).
trans isomer: 13C (CDCl3, from the mixture) d 21.1 (CH3),
25.7 (CH2), 25.8 (CH2), 26.0 (CH2), 26.5 (CH2), 27.6 (CH3),
44.3 (CH), 52.8 (CH), 86.1, 177.3 (CO).
1H NMR (CDCl3, minor isomer, from the mixture) d 0.95
(3H, t, J¼7.0 Hz, Me), 1.10 (3H, s, Me), 1.15–1.45 (4H, m,
2CH2), 1.30 (3H, s, Me), 1.55 (1H, ddd, J¼5.0, 11.0,
13.0 Hz, CHaHbCHOH), 1.75–1.85 (1H, m, CHaHbCHOH),
2.10–2.20 (1H, m, CHCHaHb), 5.00 (1H, bd, J¼5 Hz, OH),
5.40 (1H, dq, J¼5.0, 6.0 Hz, CHOH). 13C NMR (CDCl3): d
14.2 (CH3), 22.3 (CH2), 23.6 (CH3), 28.2 (CH3), 32.7 (CH2),
49.2 (CH), 97.3 (CH).
IR (neat) n, (cm21) 2929, 2857, 1765, 1449, 1376, 1268,
1124. Anal. Calcd for C10H16O2: C, 71.39; H, 9.59. Found:
C, 71.33; H, 9.63.
5.6. Attempted synthesis of lactols 5aq, 5fq, 5gq and 5hq
Application of the above methods to aldehydes 1a and 1f–h
(both procedure A and B) did not lead to expected
alkylation. Aldehyde 1a polymerized while the other
aldehydes were consumed forming no detected products.
IR (neat, mixture) n, (cm21) 3415, 2962, 2869, 1456, 1381,
1142. MS (m/z) 157 (1, M21), 141 (19), 97 (13), 69 (15), 59
(18), 43 (100). Anal. Calcd for C9H18O2: C, 68.31; H, 11.47.
Found: C, 68.23; H, 11.43.
5.5.8. 5,5-Dimethyl-4-propyltetrahydrofuran-2-one
(6cq). The residue obtained from the procedure B was
dissolved in 30 mL of H2O/dioxane 2:1 mixture and
oxidized by means of 1.3 g of BaCO3 and 770 mL of Br2.
Purification (C6H12/EtAc 8:2 as the eluant) afforded 330 mg
of 6cq (35% yield based on starting 1c).
Acknowledgements
We are indebted to Millipore for the grant of silica gel. A
fellowship by Federchimica (to D. D.) and the interest by Dr
P. Rossi (Solchem) are gratefully acknowledged. Partial
support of this work by Consiglio Nazionale delle Ricerche,
Rome and Murst, Rome is gratefully acknowledged.
6cq: colourless oil, 1H NMR (CDCl3) d 0.90 (3H, t,
J¼7.0 Hz, Me), 1.20 (3H, s, Me), 1.2–1.5 (4H, m, 2CH2),
1.4 (3H, s, Me), 2.1–2.3 (2H, m, CH2COO), 2.55–2.65 (1H,
m, CHCH2COO). IR (neat) n, (cm21) 2959, 2931, 2872,
1775, 1464, 1375, 1261, 1097. Anal. Calcd for C9H16O2: C,
69.19; H, 10.32. Found: C, 69.09; H, 10.24.
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´
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¨ ¨
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