Toward the synthesis of modified carbohydrates by conjugate addition of propane-1,3-dithiol to α,β-unsaturated ketones

Article abstract of DOI:10.1002/hlca.201200423

Selected 5-substituted derivatives 4 of 1,1-diethoxy-5-hydroxypent-3-yn-2- one were treated with propane-1,3-dithiol under various conditions. The unprotected hydroxy ketones underwent cyclization during the dithiol addition and gave the corresponding 3-(diethoxymethyl)-2-oxa-6,10-dithiaspiro[4.5]decan- 3-ols 5 in 80-90% yield as the only products (Schemea 3 and Tablea 1). These products can be regarded as partly modified carbohydrates in the furanose form. When the benzyl-protected analogues 10-Bn of the 1,1-diethoxy-5-hydroxypent-3- yn-2-one derivatives were treated with the same dithiol, however, no cyclization occurred; instead the corresponding 3-{2-[(benzyloxy)methyl]-1,3-dithian-2-yl}- 1,1-diethoxypropan-2-one derivatives 11-Bn were formed in good yield (up to 99%; Table 4). These 1,3-dithianes were and are in the process of being converted to a number of new carbohydrate analogues, and here are reported high-yield syntheses of functionalized molecules 17 belonging to the 5,5-diethoxy-1,4- dihydroxypentan-2-one family of compounds (Table 7), via 15-Bn (Table 5) and 16-Bn (Table 6 and Scheme 8).

Full text of DOI:10.1002/hlca.201200423

Helvetica Chimica Acta – Vol. 95 (2012)
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Toward the Synthesis of Modified Carbohydrates by Conjugate Addition of
Propane-1,3-dithiol to a,b-Unsaturated Ketones
by Stig Valdersnes, Ingrid Apeland, Guri Flemmen, and Leiv K. Sydnes*
´
Department of Chemistry, University of Bergen, Allegt. 41, NO-5007 Bergen
Dedicated to Prof. Dieter Seebach on the occasion of his 75th birthday
Selected 5-substituted derivatives 4 of 1,1-diethoxy-5-hydroxypent-3-yn-2-one were treated with
propane-1,3-dithiol under various conditions. The unprotected hydroxy ketones underwent cyclization
during the dithiol addition and gave the corresponding 3-(diethoxymethyl)-2-oxa-6,10-dithiaspiro[4.5]-
decan-3-ols 5 in 80 – 90% yield as the only products (Scheme 3 and Table 1). These products can be
regarded as partly modified carbohydrates in the furanose form. When the benzyl-protected analogues
10-Bn of the 1,1-diethoxy-5-hydroxypent-3-yn-2-one derivatives were treated with the same dithiol,
however, no cyclization occurred; instead the corresponding 3-{2-[(benzyloxy)methyl]-1,3-dithian-2-yl}-
1,1-diethoxypropan-2-one derivatives 11-Bn were formed in good yield (up to 99%; Table 4). These 1,3-
dithianes were and are in the process of being converted to a number of new carbohydrate analogues, and
here are reported high-yield syntheses of functionalized molecules 17 belonging to the 5,5-diethoxy-1,4-
dihydroxypentan-2-one family of compounds (Table 7), via 15-Bn (Table 5) and 16-Bn (Table 6 and
Scheme 8).
Introduction. – Some time ago, we published a simple and efficient synthesis of
3,3,4,4-tetraethoxybut-1-yne (1) [1] which is called TEB and has a significant chemical
potential that has been exploited to synthesize a large variety of compounds [2 – 7]. The
first step in several of these syntheses involves generation of the TEB-derived acetylide
followed by aldehyde or ketone addition and hydrolysis, the result of which is chain
elongation and formation of propargyl alcohols, viz. 4,4,5,5-tetraethoxypent-2-yn-1-ol
derivatives 2 (Scheme 1). These alcohols show a range of chemical reactivities, and two
transformations have been particularly useful in the application of 2 in syntheses, viz.
conversion of 2 to the corresponding (E)-4,5,5-triethoxypent-3-en-1-ol derivatives 3 by
treatment with LiAlH4 [3][5], and specific removal of the ketal protection over the
acetal protection to furnish 1,1-diethoxy-5-hydroxypent-3-yn-2-one derivatives 4,
generally in excellent yield (Scheme 1) [2][4]. From 3, a number of 3-perfluoroalky-
lated carbohydrate analogues deoxygenated at C(3), C(4), and C(6) have been
prepared [3][5], and when subjected to N-nucleophiles, 4 underwent Michael addition
and appeared to be an excellent substrate for regiospecific synthesis of furan
derivatives and other heterocyclic compounds [6][7].
The reason for the furan formation in the latter case was basically that the primary
product from the first Michael addition was consumed by an intramolecular reaction
before a second Michael addition could occur [6][7]. Therefore it was envisaged that if
a better nucleophile was applied, a double Michael addition would take place and
ꢀ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 1
prevent cyclization from occurring. Studies by Ley and co-workers clearly indicated
that propane-1,3-dithiol could be such a nucleophile [8], and indeed, when 4 was
treated with this dithiol, thiolate addition occurred twice, and 1,3-dithiane formation
took place (vide infra). This is definitely an interesting reaction if the aim is to
synthesize modified carbohydrates, because when this bis-addition of thiolate to 4 takes
place, the C(a)-atom is reduced, whereas the C(b)-atom is oxidized to a ketone
equivalent. In a carbohydrate context, this dithiane formation has, therefore, resulted in
deoxygenation at C(3) and ketone formation (oxidation) at C(4), and this latter
transformation paves the way for subsequent selective alkylation at C(4).
Carbohydrates modified at both C(3) and C(4) are found as substructures in
natural and pharmaceutical products, and the activity of such products can be
synthetically modified by replacing the natural carbohydrate analogues with synthetic
ones [9][10]. On this basis, a study of the conversion of 4 to modified carbohydrate was
initiated, and some of the results obtained are reported here.
Results and Discussion. – 1. Reactions with 1,1-Diethoxy-5-hydroxypent-3-yn-2-one
Derivatives. Before the investigation with 4 started, a series of exploratory experiments
were performed with 1,1-diethoxybut-3-yn-2-one, the simple ketone derived in 96% by
deketalization of TEB [1][2]. This compound turned out to react smoothly with
propane-1,3-dithiol under a variety of conditions and gave in most cases the
corresponding 1,3-dithiane, i.e., 3-(1,3-dithian-2-yl)-1,1-diethoxypropan-2-one, in good
to excellent yield (Scheme 2). The best outcome (91%) was achieved when moderate
cooling (ꢀ108) and fairly high dilution (ca. 0.05m in ketone) were applied.
Scheme 2

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With the execution of this double conjugate addition under control, the reaction
with the simplest hydroxy ketone, 1,1-diethoxy-5-hydroxypent-3-yn-2-one (4a), was
carried out under the conditions that worked the best for 1,1-diethoxybut-3-yn-2-one.
To prevent unintentional cyclization which is a potential risk, the reaction was
quenched with H2O so that the hydrolyzate and the extract remained basic, but this
measure was apparently inadequate because the expected product, 1,1-diethoxy-3-[2-
hydroxymethyl-1,3-dithian-2-yl]propan-2-one, was not isolated at all; instead 3-
(diethoxymethyl)-2-oxa-6,10-dithiaspiro[4.5]decan-3-ol (5a) was obtained (Scheme 3,
R ¼ H). The product was isolated in 48% yield only, which is ascribed to extraction
problems caused by emulsion formation during the workup. It was therefore decided to
quench the reaction with aqueous NH4Cl solution until the hydrolyzate was slightly
acidic, and when the reaction was repeated and worked up in this way, 5a was isolated
pure in 85% yield (Table 1, Entry 1). Similar results were obtained with 1,1-diethoxy-5-
hydroxyhex-3-yn-2-one (4b) and 1,1-diethoxy-5-hydroxyundec-3-yn-2-one (4c), but
when 1,1-diethoxy-5-hydroxy-5-phenylpent-3-yn-2-one (4d) was treated under the
same conditions, the product 3-(diethoxymethyl)-1-phenyl-2-oxa-6,10-dithiaspiro[4.5]-
decan-3-ol (5d) was obtained in moderate yield only (Table 1, Entry 4). Why the
introduction of a phenyl group results in such a low yield remains a puzzle. Except for
5a, all the spiro compounds can be formed as mixtures of the cis and trans isomers, and
this was indeed the case. The isomer composition was in all cases close to 1:1 as judged
from 1H-NMR spectra of the product mixtures, but the isomers could not be separated.
Scheme 3
Table 1. Conversion of a,b-Unsaturated g-Hydroxy Ketones 4 to Spiro-Linked 1,3-Dithianes 5
Ketone
R
Product
Yield [%] after isolation
4a
4b
4c
4d
H
5a
5b
5c
5d
85
87
84
44
Me
Hex
Ph
Storage of 5 even at refrigerator temperature resulted in decomposition; it was
therefore necessary to stabilize the compounds before further studies could be carried
out. Such a stabilization is usually done by converting the compounds to the
corresponding ketals by reaction with an alcohol in the presence of an acid. Many
procedures are available for this purpose, and the first one explored, with 5a as a model
compound, was to reflux a dilute solution in dry MeOH in the presence of Dowex 50W
[11]. Regrettably the reaction was very slow, and even after a reaction time of 20 h,
only low yields of two products were obtained, viz. 3-(diethoxymethyl)-3-methoxy-2-

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Helvetica Chimica Acta – Vol. 95 (2012)
oxa-6,10-dithiaspiro[4.5]decane (6a) obtained in 41% yield and 3-[ethoxy(methoxy)-
methyl]-3-methoxy-2-oxa-6,10-dithiaspiro[4.5]decane (7a) isolated in a 7% yield
(Scheme 4). Replacing Dowex with p-toluenesulfonic acid (TsOH) was of no help,
and addition of various dehydrating agents, such as CuSO4 [12] and 4-ꢂ molecular
sieve, did not shift the equilibrium in the right direction either. Small improvements
were observed when 5a was refluxed in a mixture of trimethyl orthoformate, dry
MeOH, and a catalytic amount of TsOH acid [13], but under these conditions,
unfortunately, additional products were formed, and the method was therefore
abandoned.
Scheme 4
The results from the reactions in MeOH were not encouraging, and it was therefore
decided to use dry EtOH instead. Explorative experiments with 5a in EtOH containing
a little TsOH revealed that the ketalization was much faster than in MeOH but very
sensitive to the reaction temperature. Without warming, very little happened, but when
the reaction was performed at close to 1008, product formation followed by
decomposition of the primary product(s) took place and gave a black, intractable
reaction mixture of a large number of compounds. However, when the reaction was run
at 808, no decomposition occurred and 3-(diethoxymethyl)-3-ethoxy-2-oxa-6,10-
dithiaspiro[4.5]decane (8a) was isolated as the only product in 78% yield (Table 2,
Entry 1). Hemiketals 5b – 5d were then treated under the best conditions developed for
5a, and the corresponding ketals were formed and isolated in good yield (Table 2,
Entries 2 – 4). It is also noteworthy that the isomer composition of the spiro ketones
changed during the ketalization; whereas the hemiketals showed an approximate 1:1
isomer composition, the ratio was ca. 3 :2 for the ketals based on NMR data. Such a
change is not surprising considering the reaction mechanism for the ketalization which
Table 2. Protection of the Hydroxy Group of Spiro Compounds 5
Entry
Substrate
R
Product
Yield [%] after isolation
> 958
808
1
2
3
4
5a
5b
5c
5d
H
8a
8b
8c
8d
45
42
38
13
78
82
71
74
Me
Hex
Ph

Helvetica Chimica Acta – Vol. 95 (2012)
2103
involves a cationic intermediate that can be attacked by EtOH from two sides which are
sterically different. What is surprising, however, is that the (E)/(Z) ratio is rather
insensitive to the steric crowding of R.
2. Synthesis of OH-Protected 1,1-Diethoxy-5-hydroxypent-3-yn-2-one Derivatives.
Most carbohydrate analogues in nature are pyranose derivatives, which are, therefore,
more attractive targets than the furanose derivatives obtained from 4. To avoid
generation of five-membered rings and facilitate six-membered ring formation, three
additional steps had to be introduced. Firstly, the OH group of 4 has to be protected to
prevent cyclization during the Michael reaction; secondly, after 1,3-dithiane formation,
the keto function has to be converted to a moiety that is unable to react with the OH
group which will be regenerated by deprotection in the third step to make cyclization at
C(1) feasible.
Many protecting groups (PGs) are available for alcohols [14], but after a literature
survey, we decided to screen how effective the benzyl (Bn), benzoyl (Bz), and (2-
methoxyethoxy)methyl (MEM ¼ MeOCH2CH2OCH2) groups were as protecting
groups for our purpose. Screening experiments were carried out with 4,4,5,5-
tetraethoxypent-2-yn-1-ol (2a) as the test compound, and as the results in Scheme 5
show, the key findings are that its benzyl ether 9a-Bn and benzoate 9a-Bz were
obtained in much higher yield than the corresponding MEM ether 9a-MEM, whereas
deprotection of the ketals gave all the corresponding ketones 10a-Bn, 10a-Bz, and 10a-
MEM, respectively, in excellent yield. Due to the moderate overall yield of 10a-MEM
from 2a (45%), MEM protection was deemed unsuitable for our purpose, and the
ability to prevent cyclization in the reaction with propane-1,3-dithiol was therefore
tested for 10a-Bn and 10a-Bz only.
Scheme 5
Ether 10a-Bn and ester 10a-Bz turned out to behave rather differently when treated
with propane-1,3-dithiol. Whereas the former compound gave one product, viz. the
desired compound 3-{2-[(benzyloxy)methyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-
one (11a-Bn) in excellent yield, the ester-protected analogue 5,5-diethoxy-4-oxopent-
2-yn-1-yl benzoate (10a-Bz) afforded a 1:3 mixture of two products, the desired
analogue to 11a-Bn, i.e., [2-(3,3-diethoxy-2-oxopropyl)-1,3-dithian-2-yl]methyl ben-
zoate (11a-Bz), and 3-(diethoxymethyl)-2-oxa-6,10-dithiaspiro[4.5]decan-3-ol (5a)
(Scheme 6). The major product was identical to the furan derivative obtained from
4a, which is the unprotected analogue of 11a-Bn, and this means that the benzoate
protection is useless under the conditions prevailing during the reaction with propane-
1,3-dithiol. That is not really surprising; esters undergo after all transesterification
when exposed to alcohols under the right conditions.

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 6
With benzoate protection obviously out of the question, Bn protection of the
propargyl alcohol moiety appeared to be the best alternative of those investigated.
Thus, the 4,4,5,5-tetraethoxypent-2-yn-1-ol derivatives 2b – 2f were treated as outlined
in Scheme 5 for 2a to obtain 10-Bn, the benzylated a,b-unsaturated acetylenic hydroxy
ketones required to make pyran derivatives. The results (Table 3) show that all the
syntheses, except for one (Entry 4), were successful and gave the corresponding
ketones 10-Bn via 9-Bn in excellent overall yield.
Table 3. Conversion of Propargyl Alcohol 2 to g-(Benzyloxy)-Substituted a,b-Unsaturated Acetylenic
Ketones 10-Bn
Entry
2
R
R1
Yield [%] of 9-Bna)
Yield [%] of 10-Bna)
1
2
3
4
5
6
a
b
c
d
e
f
H
H
H
H
H
72
96
88
0
85
75
99
82
99
–
94
86
Me
Hex
Ph
Me
Me
ꢀ(CH2)5ꢀ
a) After isolation.
The compound deviating from the general trend was 4,4,5,5-tetraethoxy-1-phenyl-
pent-2-yn-1-ol (2d) which was completely consumed but gave a very complex product
mixture, from which no compound could be isolated pure by chromatography.
Thorough spectroscopic and spectrometric analyses of some fractions collected after
repeated fractionations indicated that two of the products obtained were 4,5,5-
triethoxy-1-phenylpenta-2,3-dien-1-one (12) and 1-(benzyloxy)-4,5,5-triethoxy-1-phe-
nylpenta-1,2,3-triene (13) (see Scheme 7 for 12 and 13). A 13C-NMR spectrum of one
such fraction is shown in Fig. 1 and exhibits two peaks at d(C) 197 and 191 which
correlate well with a central allene C-atom and the C¼O C-atom of a conjugated
ketone moiety. DEPT-135 13C-NMR Spectra of this mixture indicated that the two C-
atoms were quaternary. Furthermore, a number of signals between d(C) 150 and 100, in
addition to those expected for the phenyl groups, are compatible with the cumulene

Helvetica Chimica Acta – Vol. 95 (2012)
2105
Fig. 1. 13C-NMR Spectrum of an impure fraction of two of the products obtained from benzylation of 2d.
Arbitrary atom numbering.
structures of 12 and 13. It is also noteworthy that some of the peaks in the d(C) 150 –
135 region appear as pairs which might indicate that penta-1,2,3-triene derivative 13
was formed as a mixture of isomers. The IR spectra of the same fractions were also
compatible with the proposed structures, as indicated by the spectrum shown in Fig. 2;
the allene moiety is supported by a peak at 1959 cmꢀ1, the absorption at 1674 cmꢀ1 is
indicative of an a,b-unsaturated C¼O group, signals from the phenyl groups appear in
the expected regions (> 3000, < 2000, and < 1000 cmꢀ1), and the strong, broad
absorption stretching from ca. 1000 to 1300 cmꢀ1 is indicative of ether CꢀO bonds, of
which there are quite a few in each compound.
The conversion of 2d to cumulenes 12 and 13 can be rationalized by invoking the
formation of the corresponding alkoxide which can form the corresponding benzyl
ether 9d-Bn (Route a) or undergo rearrangement by hydride migration to benzylic
carbanion 14 (Route b; Scheme 7). The former reaction is supported by the successful
synthesis of a number of other benzyl ethers from 2 (see below Table 4), whereas the
latter is substantiated by a number of similar transformations well documented in the
literature [15]. Subsequent 1,4-elimination of EtOH or ethoxide, a base-promoted
reaction with significant literature precedence [16], then gives 13 from 9d-Bn and 12
from carbanion intermediate 14. Why only 2d and not the other 5-hydroxypent-3-yn-2-
one derivatives behave like this is not clear, but it is well established that the phenyl
group is capable of stabilizing a carbanion in a-position to the ring.

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Fig. 2. IR Spectrum of an impure fraction of two of the products obtained from benzylation of 2d
Scheme 7

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3. Reactions of 5-(Benzyloxy)-1,1-diethoxypent-3-yn-2-one Derivatives with Pro-
pane-1,3-dithiol and Subsequent Transformations. With the adequately protected g-
hydroxy-substituted a,b-unsaturated acetylenic ketones 10-Bn at hand, Michael
addition of propane-1,3-dithiol could be carried out. The conditions that gave the
best results in the reactions with 1,1-diethoxybut-3-yn-2-one were applied (cf.
Scheme 2), and consistently the corresponding 1,3-dithiane 11-Bn was formed in good
to excellent yield (Table 4). When Method A (MeOH/CH2Cl2, MeONa, ꢀ 108 to r.t.)
was applied, small amounts of some vinyl sulfide(s) (ca. 5% yield at the most) were also
formed as judged from the presence of olefinic H-atom signals in the region d(C) 5.8 –
6.7 in the 1H-NMR spectrum of the crude product, but this by-product formation was
avoided by using Method B (THF, MeONa, ꢀ 788 to r.t.).
Table 4. Formation of 1,3-Dithiane Derivatives 11-Bn by Double Michael Addition of Propane-1,3-dithiol
to Conjugated Acetylenic Ketones 10-Bn
R
R1
Product
Yield [%] after isolation
Method A
Method B
10a-Bn
10b-Bn
10c-Bn
10e-Bn
10f-Bn
H
H
H
Me
H
11a-Bn
11b-Bn
11c-Bn
11e-Bn
11f-Bn
92
92
–
84
85
99
99
71
–
Me
Hex
Me
ꢀ(CH2)5ꢀ
93
Ketones 11-Bn constitute a versatile platform for the synthesis of a large variety of
modified carbohydrates. Compared to ordinary carbohydrates, these ketones are
modified by deoxygenation at C(3) and, with the exception of 11a-Bn, at C(6), by
aldehyde protection at C(1), by oxidation at C(2), by oxidation and protection at C(4),
and by alcohol protection at C(5), and all these functionalities make it possible to
modify 11-Bn further before the alcohol protection is removed and cyclization to
pyranose analogues is carried out. We are studying a number of approaches to reach
this goal and here one such strategy is reported.
To avoid formation of furan derivatives during or after removal of the benzyl
protection, the C¼O group has to be chemically modified and to ensure that the
reaction is regiospecific, the modification has to be carried out before dethioketaliza-
tion is performed. Several transformations are under investigation, and a variety of
derivatives have been prepared, but so far, reduction to the corresponding alcohols 15-
Bn with NaBH4 in wet THF has been most successful. All the ketones were essentially
reduced quantitatively under these conditions (Table 5), and as expected, the two
chiral ketones 3-{2-[1-(benzyloxy)ethyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-one
(11b-Bn) and 3-{2-[1-(benzyloxy)heptyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-one

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Table 5. NaBH4 Reduction of (1,3-Dithian-2-yl)methyl Ketones 11-Bn to the Corresponding Alcohols
15-Bn
R
R1
Product
Yield [%] after isolation
11a-Bn
11b-Bn
11c-Bn
11e-Bn
11f-Bn
H
H
H
Me
H
15a-Bn
15b-Bn
15c-Bn
15e-Bn
15f-Bn
99
Me
Hex
Me
99a)
99a)
96
ꢀ(CH2)5ꢀ
95
a) Essentially pure crude product.
(11c-Bn) were formed as mixtures of diastereoisomers. The diastereoisomer ratio was
ca. 1:1, and the isomers were easily separated by flash chromatography.
Cyclization and formation of modified pyranoses require removal of the benzyl
protection, and we wanted to do that with the 1,3-dithiane moiety intact. However,
when hydrogenolysis of 3-{2-[(benzyloxy)methyl]-1,3-dithian-2-yl}-1,1-diethoxypro-
pan-2-ol (15a-Bn) was attempted in the presence of Pd/C as catalyst under atmospheric
pressure of H2, no reaction took place, even with prolonged reaction time and increased
catalyst loading. This was probably due to the presence of sulfur [17], and it was
therefore decided to convert the thioketal group into a C¼O group before the Bn group
was removed. A large number of methods are available for the conversion of the 1,3-
dithiane moiety to the corresponding ketones. The reaction has traditionally been
carried out with heavy-metal reagents [14], but since they appear quite unattractive due
to their health and environmental hazards, we tried four other methods that have
been developed in recent years, using 15a-Bn as model compound (Scheme 8; R1 ¼
R2 ¼ H).
The four methods appeared to give rather different results. Method 1 furnished no
ketone at all, and the crude product consisted mainly of unreacted starting material.
Method 2 was more successful, but in spite of extensive heating, a large excess of MeI
(150 times), and a long reaction time, the corresponding ketone, 1-(benzyloxy)-5,5-
diethoxy-4-hydroxypentan-2-one (16a-Bn) was obtained in 28% yield only (Table 6,
Entry 1). However, Method 3, a simple modification of Method 2, gave a much better
result: when the reaction was performed at r.t. with less MeI (40 times excess) 16a-Bn
was isolated in 84% yield. An acceptable result, 54% yield (Table 6, Entry 3), was also
obtained with the Method 4 which is a redox process based on iodine under basic
conditions, but when 1,3-dithianes more substituted and congested than 15a-Bn were
subjected to the conditions of Method 4, the yield increased significantly and reached
91% in the best cases (Table 6, Entries 8 and 9).

Helvetica Chimica Acta – Vol. 95 (2012)
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Scheme 8. Methods Tried to Perform Dethioketalization. For R and R1, see Table 6.
a) Dithiane hydrolysis: Method 1) NaNO2, AcCl, CH2Cl2 [18]. Method 2) MeI (enormous excess),
CaCO3, MeCN, THF, H2O [19]. Method 3) MeI, CaCO3, MeCN, H2O [20]. Method 4) I2, NaHCO3 (aq.),
MeCN [8].
Table 6. Preparation of Ketones 16-Bn by Dethioketalization of 15-Bn (see Scheme 8)
Entry
Substrate
R
R1
Method
Product
Yield [%] after isolation
1
2
3
4
5
6
7
8
9
15a-Bn
15a-Bn
15a-Bn
H
H
H
H
H
H
H
Me
H
H
H
Me
Me
Hex
Hex
Me
2
3
4
4
4
4
4
4
4
16a-Bn
16a-Bn
16a-Bn
28
84
54
39
59
83
75
91
91
15b-Bn-Ia)
15b-Bn-IIa)
15c-Bn-Ia)
15c-Bn-IIa)
15e-Bn
16b-Bn-Ia)
16b-Bn-IIa)
16c-Bn-Ia)
16c-Bn-IIa)
16e-Bn
15f-Bn
ꢀ(CH2)5ꢀ
16f-Bn
a) I and II denote diastereoisomers of 15-Bn and 16-Bn.
After dethioketalization of 15-Bn, removal of the Bn protection from 16-Bn should
be straightforward, and this turned indeed out to be the case. When subjected to
catalytic hydrogenation in EtOH with 5% Pd/C as catalyst, the corresponding 1,4-
dihydroxypentan-2-ones 17 were obtained in essentially quantitative yield (Table 7).
Table 7. Conversion of Benzyloxy Ketones 16-Bn to Hydroxy Ketones 17
R
R1
Product
Yield [%] after isolation
16a-Bn
H
H
H
H
H
Me
H
17a
99
91
89
99
95
99
99
16b-Bn-Ia)
16b-Bn-IIa)
16c-Bn-Ia)
16c-Bn-IIa)
16e-Bn
Me
Me
Hex
Hex
Me
17b-Ia)
17b-IIa)
17c-Ia)
17c-IIa)
17e
16f-Bn
ꢀ(CH2)5ꢀ
17f
a) I and II denote diastereoisomers of 16-Bn and 17.

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Helvetica Chimica Acta – Vol. 95 (2012)
The reactions were in fact so clean that the crude products could be used in subsequent
reactions without purification.
With the successful debenzylation of 16-Bn, we have given access to a number of
modified carbohydrates with the general structure 17. To be applicable as modifiers of
biologically active compounds, cyclization of 17 to pyranose derivatives has to be
achieved, and this transformation is currently under investigation. So far, explorative
experiments revealed that the ultimate outcome in a given case depends on the
substrate structure as well as the reaction conditions. The importance of the reaction
conditions is illustrated by two reactions with 5,5-diethoxy-1,4-dihydroxypentan-2-one
(17a). When treated with HBF4 in acetonitrile, cyclization and dehydration took place
and gave 6-hydroxy-2H-pyran-3(6H)-one (18) as the only product in 90% yield, but
when exposed to wet acetone at 08, with concentrated sulfuric acid as catalyst,
dehydration was avoided, and dihydro-2,2-dimethyl-5H-1,3-dioxolo[4,5-b]pyran-
6(3aH)-one (19) was obtained in 60% yield (Scheme 9). Results of studies under
way will be published in due course.
Scheme 9
Financial support from the Research Council of Norway, the University of Bergen, and the Munin
Foundation is gratefully acknowledged. Thanks are also due to Dr. Bjarte Holmelid for recording mass
spectra.
Experimental Part
1. General. See [5]. FC ¼ Flash chromatography. DART-MS ¼ Direct analysis in real time mass
spectrometry.
2. Starting Materials. The 3,3,4,4-tetraethoxybut-1-yne (TEB; 1) was synthesized from ethyl vinyl
ether in a four-step synthesis in 50% total yield following published procedures [1]. Treatment of TEB
with Dowex 50W in moist acetone gave 1,1-diethoxybut-3-yn-2-one which showed spectroscopic data in
accordance with [1].
3. 3-(1,3-Dithian-2-yl)-1,1-diethoxypropan-2-one. A mixture of 1,1-diethoxybut-3-yn-2-one (11.83 g,
75.8 mmol), CH2Cl2 (1.20 l), MeOH (300 ml), MeONa (54 g, 100 mmol), and propane-1,3-dithiol (9.5 g,
88 mmol) was stirred in an dry ice/acetone bath (ꢀ108) under N2. After 16.5 h, the mixture was
concentrated, and most of the solvent was evaporated. The resulting slush was diluted with H2O and
extracted with CH2Cl2 and the combined extract dried (MgSO4) and concentrated to give 20.31 g of an
orange liquid, from which 18.1 g (91%) of the title compound was isolated as a yellow liquid by FC
(hexanes/AcOEt 95 :5). IR (film): 2973s, 2943s, 2904s, 1732s, 1420m, 1327m, 1278m, 1156m, 1068s, 949w,
910w, 871w, 810w. 1H-NMR (200 MHz, CDCl3): 4.57 (s, 1 H); 4.51 (t, J ¼ 7.0, 1 H); 3.78 – 2.49 (m, 4 H);
3.05 (d, J ¼ 7.0, 2 H); 2.93 – 2.79 (m, 4 H); 2.16 – 1.80 (m, 2 H); 1.25 (t, J ¼ 7.1, 6 H ) . 13C-NMR (50 MHz,

Helvetica Chimica Acta – Vol. 95 (2012)
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CDCl3): 201.2 (C); 102.2 (CH); 63.2 (2 CH2); 42.0 (CH2); 40.1 (CH); 29.5 (2 CH2); 25.1 (CH2); 14.9
(2 Me). EI-MS: 264 (9, Mþ), 219 (14), 189 (11), 119 (17), 103 (63), 84 (13), 75 (55), 59 (27), 49 (7). HR-
MS: 264.085320 (Mþ, C11H20O3Sþ2 ; calc. 264.085388).
4. Reaction of 4 with Propane-1,3-dithiol. 3-(Diethoxymethyl)-2-oxa-6,10-dithiaspiro[4.5]decan-3-ol
(5a). Propane-1,3-dithiol (0.90 ml, 8.9 mmol) and MeONa (0.48 g, 8.9 mmol) were dissolved in dry THF
(200 ml) under N2. The mixture was cooled to ꢀ 788, and 1,1-diethoxy-5-hydroxypent-3-yn-2-one (4a;
1.50 g, 8.1 mmol) was dissolved in dry THF (50 ml) and added dropwise during 30 min. The mixture was
stirred overnight and allowed to reach r.t. The reaction was quenched with sat. aq. NH4Cl soln. (150 ml),
the mixture extracted with CH2Cl2 (3 ꢁ 150 ml), the combined org. extract dried (MgSO4) and
concentrated and the product isolated by FC (hexanes/AcOEt 3 :2): 5a (2.02 g, 85%). Yellow liquid. IR
(film): 3466s, 2977s, 2931s, 2987s, 1778w, 1423m, 1366m, 1324m, 1278m, 1114s, 1071s, 967m, 912m, 839w,
808w, 736w. 1H-NMR (200 MHz, CDCl3): 4.45 (s, 1 H); 4.35 (d, J ¼ 9.1, 1 H); 4.21 (d, J ¼ 9.1, 1 H); 3.93 –
3.46 (m, 5 H); 3.05 – 2.72 (m, 4 H); 2.59 (d, J ¼ 14.5, 1 H); 2.39 (d, J ¼ 14.5, 1 H); 2.16 – 1.90 (m, 2 H); 1.25
(m, 6 H). 13C-NMR (50 MHz, CDCl3): 106.5 (C); 103.8 (CH); 79.0 (CH2); 65.2 (CH2); 64.4 (CH2); 52.6
(C); 48.6 (CH2); 28.8 (CH2); 28.7 (CH2); 25.1 (CH2); 15.4 (Me). DART-MS: 312 (40, [M þ H2O]þ), 294
(35, Mþ), 277 (95, [M ꢀ OH]þ), 231 (100), 203 (40), 189 (15). HR-MS: 277.0937 ([M ꢀ OH]þ,
C12H21O3Sþ2 ; calc. 277.0932).
3-(Diethoxymethyl)-1-methyl-2-oxa-6,10-dithiaspiro[4.5]decan-3-ol (5b). As described for 5a, with
propane-1,3-dithiol (1.15 ml, 11 mmol), MeONa (0.61 g, 11 mmol), and 1,1-diethoxy-5-hydroxyhex-3-yn-
2-one (4b; 2.02 g, 10 mmol). The product was isolated by FC (hexanes/AcOEt 7:3): 5b (2.70 g, 87%).
Yellow liquid. IR (film): 3479s, 2983s, 2939s, 1766w, 1449m, 1433m, 1373m, 1328m, 1113s, 1069s, 917m,
824w, 797w, 724w. 1H-NMR (400 MHz, CDCl3): 4.50, 4.38 (2s, ratio 5 :4, 1 H); 4.39, 4.03 (2q ratio 5 :4, J ¼
6.4 and 6.5, resp., 1 H); 4.11 (s, 0.5 H); 3.86 – 3.54 (m, 4.5 H); 3.12 – 2.76 (m, 5.5 H); 2.59 (d, B part of AB
system, J ¼ 14.3, 0.5 H); 2.18 – 2.09, 2.00 – 1.84 (2m, ratio 4 :5, 2 H); 1.45, 1.40 (2d, ratio 4 :5, J ¼ 6.5 and
6.4, resp., 3 H); 1.32 – 1.18 (m, 6 H). 13C-NMR (100 MHz, CDCl3): 105.4, 104.9 (2 C); 104.4, 103.8
(2 CH); 83.9, 83.2 (2 CH); 65.6, 65.4 (2 CH2); 64.8, 64.1 (2 CH2); 57.2, 57.1 (2 C); 49.9, 47.9 (2 CH2); 28.6,
28.6 (2 CH2); 27.4, 27.0 (2 CH2); 25.8, 25.7 (2 CH2); 16.5, 16.3 (2 Me); 15.6, 15.5 (2 Me); 15.4, 15.3 (2 Me).
DART-MS: 308 (5, Mþ), 291 (70, [M ꢀ OH]þ), 245 (100), 217 (10), 113 (15). HR-MS: 291.1093 ([M ꢀ
OH]þ, C13H23O3Sþ2 ; calc. 291.1087).
3-(Diethoxymethyl)-1-hexyl-2-oxa-6,10-dithiaspiro[4.5]decan-3-ol (5c). As described for 5a, with
propane-1,3-dithiol (0.55 ml, 5.5 mmol), MeONa (0.32 g, 5.9 mmol), and 1,1-diethoxy-5-hydroxyundec-
3-yn-2-one (4c; 1.02 g, 3.7 mmol). The product was isolated by FC (hexane/AcOEt 8 :2): 5c (1.20 g,
84%). Yellow liquid. IR (film): 3483s, 2923s, 2985s, 1736w, 1445m, 1429m, 1370m, 1332m, 1285m, 1217m,
1069s, 913m, 812w, 721w. 1H-NMR (400 MHz, CDCl3): 4.49, 4.37 (2s, ratio 1:1, 1 H); 4.20 – 4.05 (m,
0.5 H); 4.14 (s, 0.5 H); 3.86 (m, 5 H); 3.21 – 2.73 (m, 5.5 H); 2.63 (d, B part of AB system, J ¼ 14.3, 0.5 H);
2.25 – 2.09, 2.00 – 1.83 (2m, ratio 1:1, 2 H); 1.84 – 1.64 (m, 2 H); 1.60 – 1.51 (m, 1 H); 1.47 – 1.16 (m, 13 H);
0.88 (t, J ¼ 6.8, 3 H). 13C-NMR (100 MHz, CDCl3): 105.4, 104.9 (2 C); 104.4, 104.0 (2 CH); 87.9, 87.0
(2 CH), 65.9, 65.8 (2 CH2); 64.6, 63.9 (2 CH2); 57.4, 57.0 (2 C); 50.1, 47.8 (2 CH2); 31.9 (CH2); 31.2, 30.9
(2 CH2); 29.3, 29.3 (2 CH2); 28.8, 28.6 (2 CH2); 27.4, 27.1 (2 CH2); 27.0 (CH2); 26.0 (CH2); 22.8 (CH2);
15.6 (Me); 15.4, 15.3 (2 Me); 14.2 (Me). DART-MS: 378 (10, Mþ), 361 (30, [M ꢀ OH]þ), 315 (100), 275
(10), 183 (5). HR-MS: 361.1845 ([M ꢀ OH]þ, C18H33O3S2þ ; 361.1871).
3-(Diethoxymethyl)-1-phenyl-2-oxa-6,10-dithiaspiro[4.5]decan-3-ol (5d). As described for 5a, with
propane-1,3-dithiol (0.55 ml, 5.5 mmol), MeONa (0.30 g, 5.7 mmol), and 1,1-diethoxy-5-hydroxy-5-
phenylpent-3-yn-2-one (4d; 0.95 g, 3.6 mmol). The crude product was purified by FC (hexanes/AcOEt
4 :1): benzyl alcohol and 5d in a ratio of ca. 1:1 (0.59 g, 44%). Yellow liquid. IR (film): 3459s, 3068m,
3030m, 1603w, 1499m, 1461m, 1419m, 1366m, 1325m, 1281m, 1209m, 1117s, 1069s, 945m, 921m, 877m,
1
805w, 756s, 700s. H-NMR (400 MHz, CDCl3): 7.65 – 7.47 (m, 2 H); 7.45 – 7.28 (m, 8 H); 5.36, 5.00 (2s,
ratio ca. 1:1, 1 H); 4.69 (s, 2.5 H); 4.49 (s, 0.5 H); 4.35 (s, 0.5 H); 3.97 – 3.51 (m, 5.5 H); 3.07 (d, A part of
AB system, J ¼ 14.6, 0.5 H); 3.04 – 2.95 (m, 1 H); 2.91 – 2.77 (m, 2 H); 2.72 (d, B part of AB system, J ¼
14.6, 0.5 H); 2.60 – 2.43 (m, 1 H); 2.16 – 2.11 (m, 0.5 H); 2.06 – 1.96 (m, 0.5 H); 1.95 – 1.84 (m, 0.5 H);
1.81 – 1.64 (m, 1.5 H); 1.34 – 1.19 (m, 6 H). 13C-NMR (100 MHz, CDCl3): 136.4 (C); 136.3 (C); 128.8
(CH); 128.8 (CH); 128.1 (CH); 128.0 (CH); 127.9 (CH); 127.8 (CH); 127.4 (CH); 127.2 (CH); 105.8,
104.5 (2 C); 104.3, 104.2 (2 CH); 90.0, 89.1 (2 CH); 66.1, 65.9 (2 CH2); 65.6, 65.0, 64.1 (3 CH2); 57.5, 56.9

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Helvetica Chimica Acta – Vol. 95 (2012)
(2 C); 51.2, 48.0 (2 CH2); 28.7, 28.5 (2 CH2); 27.5, 27.2 (2 CH2); 25.2, 24.9 (2 CH2); 15.7 (CH2); 15.5
(CH2); 15.4 (CH2). DART-MS: 370 (10, Mþ), 353 (20, [M ꢀ OH]þ), 307 (100), 263 (10), 175 (10), 103
(5). HR-MS: 353.1211 ([M ꢀ OH]þ, C18H25O3Sþ2 ; calc. 353.1245).
5. Experiments Aiming at Stabilizing Hemiketal 5. 5.1. 3-(Diethoxymethyl)-2-oxa-6,10-dithiaspiro-
[4.5]decan-3-ol (5a) in MeOH Containing Dowex 50W. Dry MeOH (100 ml), 5a (0.70 g, 2.4 mmol), and a
spatula of Dowex 50W-X8 (H) were mixed in a dry reaction flask under N2. The mixture was heated to
reflux and stirred for 22 h. After cooling to r.t., the Dowex was removed by filtration. H2O (50 ml) was
added, and 2/3 of the MeOH was evaporated. CH2Cl2 (3 ꢁ 75 ml) was used for extraction, the combined
org. phase dried (MgSO4) and concentrated, and the residue subjected to FC (hexanes/AcOEt 3 :2): 3-
(diethoxymethyl)-3-methoxy-2-oxa-6,10-dithiaspiro[4.5]decane (6a; 0.30 g, 41%) and 3-[ethoxy(meth-
oxy)methyl]-3-methoxy-2-oxa-6,10-dithiaspiro[4.5]decane (7a; 0.047 g, 7%). Yellowish liquids. Data of
6a: IR (film): 2973s, 2939s, 2904s, 1427m, 1366m, 1324m, 1274m, 1118s, 1072s, 954m, 912m, 873m, 801w.
1H-NMR (400 MHz, CDCl3): 4.55 (s, 1 H); 4.32 (d, J ¼ 9.0, 1 H); 4.26 (d, J ¼ 9.0, 1 H); 3.88 – 3.54 (m,
4 H); 3.37 (s, 3 H); 3.08 – 2.77 (m, 4 H); 2.69 (d, J ¼ 14.5, 1 H); 2.25 (d, J ¼ 14.5, 1 H); 2.17 – 1.88 (m,
2 H); 1.25 (t, J ¼ 7.0, 6 H). 13C-NMR (100 MHz, CDCl3): 109.7 (C); 101.7 (CH); 80.0 (CH2); 65.5 (CH2);
63.9 (CH2); 52.5 (C); 50.0 (CH2); 47.6 (CH2); 29.2 (CH2); 29.1 (CH2); 25.1 (CH2); 15.5 (Me); 15.4 (Me).
DART-MS: 277 ([75 M ꢀ MeO]þ), 231 (100), 145 (5). HR-MS: 277.0945 (C12H21O3Sþ2 , [M ꢀ MeO]þ;
calc. 277.0932).
Data of 7a: IR (film): 2977s, 2931s, 2898s, 2828s, 1736w, 1423m, 1370m, 1320m, 1274m, 1110s, 1080s,
969m, 945m, 801m, 725w. 1H-NMR (400 MHz, CDCl3): 4.47 (s, 1 H); 4.33 – 4.23 (m, 2 H); 3.77 – 3.71 (m,
2 H); 3.50 (s, 1 H); 3.47 (s, 2 H); 3.37 (s, 2 H); 2.93 – 2.81 (m, 4 H); 2.67 – 2.63 (m, 1 H); 2.27 – 2.21 (m,
1 H); 2.12 – 1.89 (m, 2 H); 1.26 (m, 3 H). 13C-NMR (100 MHz, CDCl3): 109.7, 109.6 (2 C); 103.2, 103.0
(2 CH); 80.1, 79.93 (2 CH2); 66.0, 64.4 (2 CH2); 57.3, 55.9 (2 Me); 52.5, 52.4 (2 C); 50.0 (Me); 47.9, 47.4
(2 CH2); 29.24, 29.16 (2 CH2); 29.1 (CH2); 25.07, 25.05 (2 CH2); 15.49, 15.43 (2 Me).
5.2. Ketal 8 from Hemiketal 5 in EtOH Containing TsOH. 3-(Diethoxymethyl)-3-ethoxy-2-oxa-6,10-
dithiaspiro[4.5]decane (8a). Abs. EtOH (60 ml), 5a (0.37 g, 1.3 mmol), and TsOH (0.048 g, 0.25 mmol,
20 mol-%) were mixed and heated to 808. The mixture was left overnight (12 h). After cooling to r.t.,
H2O (60 ml) was added. CH2Cl2 was used for extraction, the combined org. phase dried (MgSO4) and
concentrated, and the residue subjected to FC (hexanes/AcOEt 4 :1): 8a (0.32 g, 78%). Yellow liquid. IR
(film): 2983s, 2935s, 2903s, 1433m, 1370m, 1316m, 1286m, 1232m, 1121s, 1077s, 965m, 904m, 866w, 816w.
1H-NMR (400 MHz, CDCl3): 4.52 (s, 1 H); 4.31 (d, J ¼ 8.9, 1 H); 4.25 (d, J ¼ 8.9, 1 H); 3.87 – 3.51 (m,
6 H); 3.03 – 2.76 (m, 4 H); 2.69 (d, J ¼ 14.5, 1 H); 2.24 (d, J ¼ 14.5, 1 H); 2.15 – 1.83 (m, 2 H); 1.24 (td, J ¼
2.1, 7.0, 6 H); 1.18 (t, J ¼ 7.1, 3 H ) . 13C-NMR (100 MHz, CDCl3): 109.7 (C); 102.2 (CH); 79.8 (CH2); 65.4
(CH2); 64.0 (CH2); 57.9 (C); 52.7 (CH2); 48.0 (CH2); 29.3 (CH2); 29.2 (CH2); 25.2 (CH2); 16.0 (Me); 15.5
(Me); 15.4 (Me). DART-MS: 277 (95, [M ꢀ EtO]þ), 231 (100). HR-MS: 277.0952 ([M ꢀ EtO]þ,
C12H21O3Sþ2 ; calc. 277.0932).
3-(Diethoxymethyl)-3-ethoxy-1-methyl-2-oxa-6,10-dithiaspiro[4.5]decane (8b). As described for 8a,
with abs. EtOH (70 ml), 5b (1.29 g, 4.2 mmol), and TsOH (0.160 g, 0.84 mmol, 20 mol-%). FC (hexanes/
AcOEt 4 :1) gave 8b (0.84 g, 42%). Yellow liquid. IR (film): 2975s, 2935s, 2899s, 1425m, 1377m, 1305m,
1274m, 1213m, 1125s, 1069s, 909m. 1H-NMR (400 MHz, CDCl3): 4.52, 4.43 (2s, ratio 3 :2, 1 H); 4.27 (q,
J ¼ 6.4, 1 H); 3.75 – 3.58 (m, 6 H); 3.07 (d, A part of AB system, J ¼ 14.1, 1 H); 3.03 – 2.79 (m, 5 H); 2.66
(d, B part of AB system, J ¼ 14.5, 1 H); 2.50 (d, B part of AB system, J ¼ 14.1, 1 H); 2.14 – 2.02, 2.02 – 1.87
(2m, ratio 3 :2, 2 H); 1.49 – 1.40 (m, 3 H); 1.26 – 1.21 (m, 6 H); 1.17 (t, J ¼ 7.1, 3 H ) . 13C-NMR (100 MHz,
CDCl3): 108.0, 107.6 (2 C); 103.8, 101.8 (2 CH); 85.0, 83.7 (2 CH); 65.5, 65.3 (2 CH2); 64.5, 64.2 (2 CH2);
58.2, 57.8 (2 CH2); 57, 56.6 (2 C); 51.2, 47.8 (2 CH2); 29.0, 28.9 (2 CH2); 27.7, 27.5 (2 CH2); 25.7, 25.6
(2 CH2); 17.1, 16.3 (2 Me); 16.1, 15.8 (2 Me); 15.5, 15.4 (2 Me); 15.4, 15.4 (2 CH). DART-MS: 291 (65,
[M ꢀ EtO]þ), 245 (100), 203 (10), 113 (20). HR-MS: 291.1099 ([M ꢀ EtO]þ, C13H23O3þ2 ; calc. 291.1089).
3-(Diethoxymethyl)-3-ethoxy-1-hexyl-2-oxa-6,10-dithiaspiro[4.5]decane (8c). As described for 8a,
with abs. EtOH (60 ml), 5c (0.85 g, 2.20 mmol), and TsOH (0.085 g, 0.45 mmol, 20 mol-%). FC (hexanes/
AcOEt 4 :1) gave 8c (0.65 g, 71%). Yellow liquid. IR (film): 2983s, 2931s, 2863s, 1689w, 1473m, 1375m,
1312m, 1270m, 1125s, 1077s, 942m, 908m, 797w, 721w. 1H-NMR (400 MHz, CDCl3): 4.52, 4.42 (2s, ratio
3 :2, 1 H); 4.07 – 3.96 (m, 1 H); 3.83 – 3.54 (m, 6 H); 3.14 (d, A part of AB system, J ¼ 14.0, 0.5 H); 3.09 –
2.71 (m, 5 H); 2.54 (d, B part of AB system, J ¼ 14.0, 0.5 H); 2.12 – 2.07 (m, 1 H); 2.01 – 1.85 (m, 1 H);

Helvetica Chimica Acta – Vol. 95 (2012)
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1.85 – 1.68 (m, 2 H); 1.57 – 1.53 (m, 1 H); 1.50 – 1.13 (m, 16 H); 0.90 (t, J ¼ 9.2, 3 H). 13C-NMR (100 MHz,
CDCl3): 108.1, 107.5 (2 C); 104.1, 102.0 (2 CH); 88.7, 87.2 (2 CH); 65.8, 65.2 (2 CH2); 64.5, 64.4 (2 CH2);
58.3, 57.8 (2 CH2); 57.4, 56.8 (2 C); 51.7, 47.5 (2 CH2); 31.9, 31.9 (2 CH2); 31.5, 30.6 (2 CH2); 29.4, 29.3
(2 CH2); 29.2, 27.4 (2 CH2); 27.3, 26.1 (2 CH2); 26.0, 22.8 (2 CH2); 22.8 (CH2); 16.2 (Me); 15.9, 15.6
(2 Me); 15.4 (Me); 14.2 (Me). DART-MS: 361 (75, [M ꢀ EtO]þ), 315 (100), 183 (5). HR-MS: 361.1843
([M ꢀ EtO]þ, C18H33O3Sþ2 ; calc. 361.1871).
3-(Diethoxymethyl)-3-ethoxy-1-phenyl-2-oxa-6,10-dithiaspiro[4.5]decane (8d). As described for 8a,
with abs. EtOH (40 ml), 5d (0.30 g, 0.0.81 mmol), and TsOH (0.0.031 g, 0.16 mmol, 20 mol-%). FC
(hexanes/AcOEt 4 :1) gave 8d (0.24 g, 74%). Yellow liquid. IR (film): 3065m, 3034m, 2987s, 2935s, 2895s,
2254w, 1496m, 1457m, 1435m, 1381m, 1320m, 1278m, 1217m, 1121s, 1077s, 954m, 912m, 870m, 820w,
1
744m, 702m. H-NMR (400 MHz, CDCl3): 7.66 – 7.61 (m, 2 H); 7.39 – 7.36 (m, 3 H); 5.24, 5.21 (2s, ratio
3 :2, 1 H); 4.68, 4.53 (2s, 1 H); 4.00 – 3.56 (m, 6 H); 3.08 (d, A part of AB system, J ¼ 14.2, 0.5 H); 3.00 (d,
A part of AB system, J ¼ 14.5, 0.5 H); 2.91 – 2.72 (m, 3 H); 2.68 (d, B part of AB system, J ¼ 14.4, 0.5 H);
2.57 (d, B part of AB system, J ¼ 14.3, 0.5 H); 2.52 – 2.35 (m, 1 H); 1.90 – 1.79, 1.79 – 1.65 (2m, ratio 3 :2,
2 H); 1.35 – 1.22 (m, 6 H); 1.20 (t, J ¼ 7.1, 3 H ) . 13C-NMR (100 MHz, CDCl3): 137.5, 136.7 (2 C); 128.8
(CH); 128.7 (CH); 128.1 (CH); 128.0 (CH); 127.9 (CH); 107.6, 107.4 (2 C); 103.8, 101.7 (2 CH); 91.4, 89.6
(2 CH); 65.9, 65.7 (2 CH2); 64.6, 64.3 (2 CH2); 58.2, 58.0 (2 CH2); 56.6, 55.6 (2 C); 51.9, 47.9 (2 CH2);
28.8, 28.5 (2 CH2); 27.6, 27.2 (2 CH2); 24.8 (CH2); 16.1, 16.0 (2 Me); 15.7, 15.6 (2 Me); 15.5 (Me). DART-
MS: 353 (30, [M ꢀ EtO]þ), 307 (100), 261 (5), 233 (5), 175 (10). HR-MS: 353.1215 ([M ꢀ EtO]þ,
C18H25O3Sþ2 ; calc. 353.1245).
6. Exploratory Experiments with 2a to Assess Protection of Hydroxy Ketone 4. 6.1. Synthesis of 9a-PG
(PG ¼ Bz, Bn, MEM). 4,4,5,5-Tetraethoxypent-2-yn-1-yl Benzoate (9a-Bz). To a mixture of 2a (4.01 g,
15.38 mmol) and pyridine (30 ml) in CH2Cl2 (40 ml) kept at 08 under N2 was added dropwise during 1.5 h
a soln. of benzoyl chloride (2.8 g, 20 mmol) in CH2Cl2 (20 ml). After stirring for 16 h, H2O was added and
the hydrolyzate extracted by CH2Cl2 (4 ꢁ 30 ml). The combined org. extract was dried (MgSO4) and
concentrated and the residual orange liquid (6.69 g) of purified by FC (hexanes/AcOEt 4 :1): 5.13 g
(92%) of 9a-Bz. Yellow liquid. IR (film): 3066w, 2977s, 2931s, 2892s, 1788w, 1728s, 1601w, 1480m, 1448s,
1373s, 1319m, 1264s, 1173s, 1074s, 1026s, 947m, 879m, 806w, 714s. 1H-NMR (200 MHz, CDCl3): 8.09 – 8.03
(m, 2 H); 7.57 – 7.40 (m, 3 H); 5.02 (s, 2 H); 4.42 (s, 1 H); 3.89 – 3.63 (m, 8 H); 1.25 (t, J ¼ 7.0, 6 H); 1.22 (t,
J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 165.5 (C); 133.0 (CH); 129.5 (2 CH); 129.3 (C); 128.2 (2 CH);
103.6 (CH); 98.4 (C); 81.4 (C); 80.6 (C); 64.7 (2 CH2); 59.4 (2 CH2); 52.6 (CH2); 15.1 (2 Me); 15.0
(2 Me). EI-MS: 320 (12), 261 (10), 187 (17), 140 (10), 112 (10), 103 (100), 84 (8), 75 (58), 67 (8), 47 (51).
HR-MS: 261.111519 ([M ꢀ CH(OEt)2]þ, C15H17O4þ ; calc. 261.112684).
6.2. 1-(Benzyloxy)-4,4,5,5-tetraethoxypent-2-yne (9a-Bn). Alcohol 2a (26.0 g, 0.10 mol) was mixed
with CH2Cl2 (80 ml), benzyl chloride (16.4 g, 130 mmol), and tetrabutylammonium hydrogensulfate
((Bu4N)HSO4; 1.0 g, 2.9 mmol), and to this mixture was added 50% aq. NaOH soln. (50 g, 0.125 mol).
The mixture was refluxed, and extra benzyl chloride (5.0 g, 39.7 mmol) was added after 2.5 h (TLC
monitoring). After a total of 5 h, the mixture was allowed to cool. H2O was added followed by extraction
with CH2Cl2. The combined org. extract was dried (MgSO4) and concentrated and the crude product
purified by FC (hexanes/AcOEt 95 :5): 25.2 g (72%) of 9a-Bn. Yellowish liquid. IR (film): 3030m, 2976s,
2934s, 2885s, 1448m, 1287m, 1351m, 1244m, 1080s, 884w, 811w, 743m, 700m. 1H-NMR (200 MHz, CDCl3):
7.38 – 7.27 (m, 5 H); 4.63 (s, 2 H); 4.41 (s, 1 H); 4.27 (s, 2 H); 3.89 – 3.63 (m, 8 H); 1.25 (t, J ¼ 7.6, 6 H); 1.23
(t, J ¼ 7.6, 6 H). 13C-NMR (50 MHz, CDCl3): 137.3 (C); 128.2 (2 CH); 128.0 (2 CH); 127.6 (CH); 103.8
(CH); 98.6 (C); 82.7 (C); 81.2 (C); 71.1 (CH2); 64.6 (2 CH2); 59.4 (2 CH2); 57.1 (CH2); 15.1 (2 Me); 15.0
(2 Me). EI-MS: 305 (5, [M ꢀ EtO]þ), 247 (13), 200 (18), 171 (17), 157 (6), 141 (7), 127 (6), 119 (13), 103
(100), 91 (75), 83(7), 75 (53), 55 (7), 47 (38). HR-MS: 305.174667 ([M ꢀ EtO]þ, C18H25O4þ ; calc.
305.175285).
6.3. 4,4,5,5-Tetraethoxy-1-[(2-methoxyethoxy)methoxy]pent-2-yne (9a-MEM). To 2a (1.00 g,
i
3.80 mmol) mixed with CH2Cl2 (10 ml) and Pr2EtN (0.52 g, 4.00 mmol) at 08 under N2 was added
dropwise MeOCH2CH2OCH2Cl (0.52 g, 4.17 mmol). After stirring overnight, H2O was added and the
hydrolyzate worked up with CH2Cl2. The combined org. extract was dried (MgSO4) and concentrated
and the crude product (1.22 g) purified by FC (hexanes/AcOEt): 0.64 g (48%) of 9a-MEM. Yellow
liquid. IR (film): 2983s, 2885s, 2249w, 1702w, 1620w, 1449m, 1371m, 1341m, 1294m, 1083s, 929m, 902m,

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849m, 756 w. lH-NMR (200 MHz, CDCl3): 4.81 (s, 2 H); 4.28 (s, 1 H); 4.34 (s, 2 H); 3.87 – 3.53 (m, 12 H);
3.40 (s, 3 H); 1.24 (t, J ¼ 7.0, 6 H); 1.21 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 103.7 (CH); 98.5 (C);
93.5 (CH2); 82.3 (C); 80.5 (C); 71.5 (CH2); 66.9 (CH2); 64.6 (2 CH2); 59.3 (2 CH2); 58.8 (Me); 54.2
(CH2); 15.1 (2 Me); 15.0 (2 Me). EI-MS: 347 (22), 334 (100), 171 (10), 159 (35), 148 (10), 142 (12), 125
(15), 113 (17), 103 (88), 97 (24), 85 (53), 75 (64). HR-MS: 348.2137 (Mþ, C17H32O7þ ; calc. 348.2148).
6.4. Deketalization of 9a-PG, Formation of 10a-PG (PG ¼ Bz, Bn, MEM). General Procedure.
Alkyne 9a-PG (1.0 mmol) was refluxed in a mixture of acetone (10 ml), H2O (0.5 ml), and Dowex 50W
(0.35 g) (TLC monitoring). The reaction was stopped when it was finished according to TLC (3 – 6 h).
The mixture was allowed to cool to r.t. and filtered to remove the Dowex 50W. Evaporation of the
acetone gave a crude product which was purified by FC (hexanes/AcOEt): corresponding ketone 10a-
PG.
5,5-Diethoxy-4-oxopent-2-yn-1-yl Benzoate (10a-Bz): Yield 91%. Slightly yellow liquid. IR (film):
3067w, 2979s, 2934s, 2889s, 2222s, 1728s, 1694s, 1601m, 1480m, 1448m, 1369m, 1317m, 1261s, 1170s, 1105s,
1
957m, 911m, 832w, 809w, 714s. H-NMR (200 MHz, CDCl3): 8.10 – 8.04 (m, 2 H); 7.65 – 7.42 (m, 3 H);
5.12 (m, 2 H); 4.76 (s, 1 H); 3.81 – 3.56 (m, 4 H); 1.26 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 182.1
(C); 165.4 (C); 133.5 (CH); 129.7 (2 CH); 128.8 (C); 128.4 (2 CH); 101.3 (CH); 89.1 (C); 83.4 (C); 63.1
(2 CH2); 51.9 (CH2); 12.9 (2 Me). EI-MS: 245 (1), 217 (1), 187 (2), 143 (1), 122 (4), 103 (100), 75 (54), 66
(14), 58 (7), 47 (95). HR-MS: 290.1162 (Mþ, C16H18O5þ ; calc. 290.1154).
5-(Benzyloxy)-1,1-diethoxypent-3-yn-2-one (10a-Bn): Yield 99%. Slightly yellow liquid. IR (film):
3031m, 2979s, 2934s, 2884s, 2211m, 1691s, 1450m, 1387m, 1351s, 1322m, 1246s, 1103s, 905m, 836w, 743s,
701m. 1H-NMR (200 MHz, CDCl3): 7.38 – 7.30 (m, 5 H); 4.80 (s, 1 H); 4.64 (s, 2 H); 4.35 (s, 2 H), 3.82 –
3.56 (m, 4 H); 1.27 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 182.2 (C); 136.6 (C); 128.3 (2 CH); 128.0
(2 CH); 127.9 (CH); 101.4 (CH); 91.6 (C); 83.6 (C); 71.6 (CH2); 63.0 (2 CH2); 56.8 (CH2); 14.9 (2 Me).
EI-MS: 185 (4), 173 (4), 149 (6), 129 (6), 115 (13), 103 (100), 91 (57), 83 (8), 75 (47), 83 (10), 75 (47), 65
(15), 55 (9), 47 (70). HR-MS: 276.133476 (Mþ, C16H20O4þ ; calc. 276.136159).
5-[(2-Methoxyethoxy)methoxy]-1,1-diethoxypent-3-yn-2-one (10a-MEM). Yield 93%. Slightly yel-
low liquid. IR (film): 2978s, 2931s, 2890s, 2213m, 1693s, 1459m, 1366m, 1244m, 1122s, 1049s, 990m, 907m,
846m, 781w. 1H-NMR: (200 MHz, CDCl3): 4.83 (s, 2 H); 4.74 (s, 1 H); 4.46 (s, 2 H); 3.80 – 3.55 (m, 8 H);
3.40 (s, 3 H); 1.27 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 182.1 (C); 101.2 (CH); 93.8 (CH2); 91.4
(C); 83.1 (C); 71.4 (CH2); 67.1 (CH2); 62.9 (2 CH2); 58.7 (Me); 53.8 (CH2); 14.8 (2 Me). EI-MS: 273 (1),
247 (1), 229 (1), 199 (1), 185 (1), 169 (1), 155 (1), 141 (5), 113 (5), 103 (100), 75 (57), 66 (11), 59 (22), 47
(97). HR-MS: 229.1075 ([M ꢀ EtO]þ, C11H17O5þ ; calc. 229.1076).
6.5. Double Conjugate Addition of Propane-1,3-dithiol to 10a-PG, Formation of 11a-PG (PG ¼ Bz,
Bn): General Procedures. Method A. Protected 10a-PG (10 mmol) and propane-1,3-dithiol (1.2 g,
11 mmol) were dissolved in MeOH (170 ml) and CH2Cl2 (42 ml) and cooled to ꢀ 108 before MeONa
(0.82 g, 15 mmol) was added. The mixture was stirred overnight and allowed to reach r.t. The reaction
was quenched by adding sat. aq. NH4Cl soln. followed by extraction with CH2Cl2 (3 ꢁ 40 ml). The
combined extract was dried (MgSO4) and concentrated crude 11a-PG.
Method B. Propane-1,3-dithiol (1.51 ml, 15 mmol) and MeONa (0.81 g, 15 mmol) was dissolved in
dry THF (200 ml) at r.t. under N2. The mixture was then cooled to ꢀ 788, and the a,b-unsaturated ketone
10a-PG (10 mmol) was dissolved in THF (50 ml) and added dropwise during 20 min. The mixture was
stirred overnight and allowed to reach r.t. The reaction was quenched by adding sat. aq. NH4Cl soln.
followed by extraction with CH2Cl2 (3ꢁ). The combined extract was dried (MgSO4) and concentrated:
crude 11a-PG.
[2-(3,3-Diethoxy-2-oxopropyl)-1,3-dithian-2-yl]methyl Benzoate (11a-Bz): From 10a-Bz (3.67 g,
12.66 mmol) with Method A. The crude orange liquid (5.75 g) was purified by FC (hexanes/AcOEt
95 :5): 1.28 g (25%) of 11a-Bz and 2.74 g (74%) of 5a both as a yellow liquid. 11a-Bz: IR (film): 3064w,
2877s, 2900s, 1726s, 1601w, 1451m, 1422m, 1366m, 1315m, 1269m, 1103m, 1065m, 956m, 910m, 878w,
1
810w, 712s, 677w. H-NMR (200 MHz, CDCl3): 8.07 – 8.03 (m, 2 H); 7.60 – 7.40 (m, 3 H); 4.97 (s, 2 H);
4.57 (s, 1 H); 3.79 – 3.49 (m, 4 H); 3.29 (s, 2 H), 3.16 – 3.02 (m, 2 H); 2.76 – 2.65 (m, 2 H); 2.15 – 1.82 (m,
2 H); 1.23 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 200.8 (C); 165.6 (C); 132.9 (CH); 129.7 (C);
129.6 (2 CH); 128.2 (2 CH); 102.8 (CH); 63.9 (CH2); 63.4 (2 CH2); 48.8 (C); 42.8 (CH2); 26.0 (2 CH2);
24.3 (CH2), 14.9 (2 Me). EI-MS: 398 (1, Mþ), 370 (1), 353 (1), 263 (1), 253 (1), 231 (1), 203 (1), 203 (1),

Helvetica Chimica Acta – Vol. 95 (2012)
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189 (2), 161 (1), 146 (3), 132 (1), 122 (1), 103 (100), 75 (32), 47 (33). HR-MS: 398.121704 (Mþ,
C19H26O5Sþ2 ; calc. 398.122168).
2-{2-[(Benzyloxy)methyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-one (11a-Bn): From 10a-Bn with
Methods A and B. After purification by FC (hexanes/AcOEt 95 :5), the yield of 11a-Bn was 92% and
99%, resp. Yellow liquid. IR (film): 3030w, 2976s, 2901s, 1731s, 1450m, 1420m, 1391m, 1355m, 1318m,
1
1282m, 1244m, 1095s, 1067s, 910w, 975w, 815w, 741m, 700m, 654w. H-NMR (200 MHz, CDCl3): 7.37 –
7.25 (m, 5 H); 4.60 (s, 2 H); 4.58 (s, 1 H); 3.97 (s, 2 H); 3.74 – 3.64 (m, 4 H); 3.34 (s, 2 H); 2.86 – 2.80
(m, 4 H); 2.02 – 1.90 (m, 2 H); 1.22 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 201.4 (C); 137.8 (C);
128.1 (2 CH); 127.4 (3 CH); 102.6 (CH); 73.1 (CH2); 72.9 (CH2); 63.0 (2 CH2); 49.9 (CH2); 42.5 (C); 25.9
(2 CH2); 24.7 (CH2); 15.0 (2 Me). EI-MS: 384 (1, Mþ), 356 (1), 338 (1), 293 (1), 146 (10), 103 (100), 91
(57), 75 (34), 65 (7), 47 (37). HR-MS: 384.143028 (Mþ, C19H28O4S2þ ; calc. 384.142903).
7. Conversion of 2b – 2f to 11b-Bn – 11f-Bn via 9b-Bn – 9f-Bn and 10b-Bn – 10f-Bn. 7.1. Benzylation
of 2b – 2f: General Procedure. Alcohol 2 (100 mmol) was dissolved in CH2Cl2 (80 ml), benzyl chloride
(16.4 g, 130 mmol), (Bu4N)HSO4 (1.0 g, 2.9 mmol), and 50% of aq. NaOH soln. (50 g) were added, and
the mixture was refluxed. Extra benzyl chloride (5.0 g, 39.7 mmol) was added after 2.5 h. After a total of
5 – 10 h (TLC monitoring), the mixture was allowed to cool down, and H2O was added followed by
extraction with CH2Cl2. The combined org. extracts was dried (MgSO4) and concentrated and the crude
product purified by FC: 9-Bn.
5-(Benzyloxy)-1,1,2,2-tetraethoxyhex-3-yne (9b-Bn): Yield 96%. Slightly yellow liquid. IR: 3031m,
2978s, 2931s, 2887s, 1450m, 1375m, 1329m, 1243m, 1080s, 1025s, 916m, 881w, 813w, 741s, 700s, 616m.
1H-NMR (200 MHz, CDCl3): 7.40 – 7.25 (m, 5 H); 4.84 – 4.50 (m, 2 H); 4.42 (s, 1 H); 4.30 (q, J ¼ 6.0, 1 H);
3.89 – 3.67 (m, 8 H); 1.48 (d, J ¼ 6.0, 3 H); 1.28 – 1.19 (m, 12 H). 13C-NMR (50 MHz, CDCl3): 137.7 (C);
128.0 (2 CH); 127.8 (2 CH); 127.3 (CH); 103.8 (CH); 98.5 (C); 86.5 (C); 79.9 (C); 70.1 (CH2); 64.3
(CH2); 64.2 (CH2); 64.0 (CH); 59.4 (CH2); 59.3 (CH2); 21.5 (Me); 15.1 (2 Me); 15.0 (2 Me). EI-MS: 319
(1, [M ꢀ EtO]þ), 289 (2), 273 (1), 261 (10), 214 (8), 185 (15), 119 (12), 103 (100), 91 (68), 75 (47), 65 (6),
47 (43). HR-MS: 319.1909 ([M ꢀ EtO]þ, C19H32O5þ ; calc. 319.1909).
5-(Benzyloxy)-1,1,2,2-tetraethoxyundec-3-yne (9c-Bn): Yield 88%. Clear liquid. IR (film): 3088w,
3031m, 1975s, 2956s, 2930s, 2862s, 2241w, 1496m, 1455s, 1390m, 1333m, 1241m, 1120s, 1082s, 1027s, 1020s,
913m, 878m, 845w, 816w, 806w, 737m, 699m. 1H-NMR (200 MHz, CDCl3): 7.40 – 7.23 (m, 5 H); 4.85 – 4.51
(m, 2 H); 4.41 (s, 1 H); 4.18 (t, J ¼ 6.5, 1 H); 3.90 – 3.63 (m, 8 H); 1.84 – 1.72 (m, 2 H); 1.54 – 1.28 (m, 8 H);
1.24 (t, J ¼ 7.0, 3 H); 1.23 (t, J ¼ 7.0, 3 H); 1.22 (t, J ¼ 7.0, 6 H); 0.87 (t, J ¼ 6.5, 3 H). 13C-NMR (50 MHz,
CDCl3): 138.0 (C); 128.2 (2 CH); 128.0 (2 CH); 127.5 (CH); 104.0 (CH); 98.7 (C); 86.2 (C); 80.7 (C);
70.4 (CH2); 68.6 (CH); 64.4 (CH2); 64.3 (CH2); 59.8 (CH2); 59.7 (CH2); 35.5 (CH2); 31.6 (CH2); 28.9
(CH2); 25.1 (CH2); 22.5 (CH2); 15.3 (2 Me); 15.2 (Me); 15.1 (Me); 14.0 (Me). EI-MS: 434 (2, Mþ), 390
(7), 359 (9), 331 (80), 284 (20), 259 (30), 255 (35), 225 (20), 119 (65), 103 (50), 75 (100). HR-MS:
389.2692 ([M ꢀ EtO]þ, C24H37O4þ ; calc. 389.2692).
5-(Benzyloxy)-1,1,2,2-tetraethoxy-5-phenylpent-3-yne (9d-Bn). Instead of 9d-Bn, complex mixture
of products including 4,5,5-triethoxy-1-phenylpenta-2,3-dien-1-one (12) and 1-(benzyloxy)-4,5,5-trieth-
oxy-1-phenylpenta-1,2,3-triene (13). IR: Fig. 2. 13C-NMR: Fig. 1.
Data of 12. EI-MS: 290 (10, Mþ), 261 (30), 187 (20), 159 (40), 103 (100), 75 (90). HR-MS: 245.1180
([M ꢀ EtO]þ, C15H17Oþ3 ; calc. 245.1178). Data of 13: EI-MS: 380 (20, Mþ), 352 (85), 335 (60), 323 (100),
249 (80), 221 (80), 185 (70), 143 (90), 104 (95).
5-(Benzyloxy)-1,1,2,2-tetraethoxy-5-methylhex-3-yne (9e-Bn): Yield 85%. Clear, yellowish liquid.
IR(film): 3090w, 3065w, 3031w, 2977s, 2931s, 2889s, 2247w, 1498w, 1480w, 1454m, 1380m, 1360m, 1330m,
1258m, 1186m, 1159s, 1117s, 1081s, 1028m, 1020m, 961w, 952w, 902m, 877m, 839w, 801w, 736m, 697m.
1H-NMR (200 MHz, CDCl3): 7.40 – 7.20 (m, 5 H); 4.67 (s, 2 H); 4.41 (s, 1 H); 3.87 – 3.61 (m, 8 H); 1.57 (s,
6 H); 1.21 (t, J ¼ 7.1, 12 H). 13C-NMR (50 MHz, CDCl3): 139.0 (C); 128.2 (2 CH); 127.8 (2 CH); 127.3
(CH); 103.9 (CH); 98.6 (C); 89.1 (C); 79.4 (C); 70.7 (C); 66.7 (CH2); 64.3 (2 CH2); 59.7 (2 CH2); 28.7
(2 Me); 15.3 (2 Me); 15.2 (2 Me). EI-MS: 378 (2), 285 (5), 199 (10), 133 (30), 117 (25), 103 (65), 89 (95),
73 (90), 59 (100). HR-MS: 333.2067 ([M ꢀ EtO]þ, C20H29O4þ ; calc. 333.2066).
1-[1-(Benzyloxy)cyclohexyl]-3,3,4,4-tetraethoxybut-1-yne (9f-Bn): Yield 75%. Yellow liquid. IR
(film): 3029m, 2974s, 2934s, 2239w, 1710w, 1449m, 1382m, 1333m, 1294m, 1086s, 1026s, 940m, 905m, 850w,
801w, 727m, 700m. 1H-NMR (200 MHz, CDCl3): 7.14 – 7.23 (m, 5 H); 4.69 (s, 2 H); 4.41 (s, 1 H); 3.89 –

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Helvetica Chimica Acta – Vol. 95 (2012)
3.60 (m, 8 H); 2.07 – 2.01 (m, 2 H); 1.75 – 1.48 (m, 8 H); 1.21 (t, J ¼ 7.0, 6 H); 1.20 (t, J ¼ 7.0, 6 H).
13C-NMR (50 MHz, CDCl3): 139.1 (C); 128.0 (2 CH); 127.7 (2 CH); 127.1 (CH); 104.0 (CH); 98.8 (C);
88.4 (C); 81.1 (C); 74.1 (C); 65.6 (CH2); 64.1 (2 CH2); 59.8 (2 CH2); 37.1 (2 CH2); 25.3 (CH2); 22.7
(2 CH2); 15.3 (2 Me); 15.1 (2 Me). EI-MS: 418 (1, Mþ), 373 (1), 343 (2), 327 (7), 315 (12), 266 (6), 103
(100), 91 (42), 75 (36), 47 (37). HR-MS: 418.2708 (Mþ, C25H38O5þ ; calc. 418.2719).
7.2. Deketalization of 9-Bn, Formation of 10-Bn. The reactions were carried out following the
General Procedure used to prepare 10a-PG (see above, Exper. 6.4).
5-(Benzyloxy)-1,1-diethoxyhex-3-yn-2-one (10b-Bn): Yield 82%. Slightly yellow liquid. IR: 3031m,
2981s, 2933s, 2878s, 2214s, 1691s, 1451m, 1387m, 1325s, 1242m, 1103s, 936m, 909w, 838w, 803w, 744m,
700m. 1H-NMR (200 MHz, CDCl3): 7.38 – 7.27 (m, 5 H); 4.84 – 4.50 (m, 2 H); 4.75 (s, 1 H); 4.38 (q, J ¼ 6.7,
1 H); 3.81 – 3.56 (m, 4 H); 1.51 (d, J ¼ 6.7, 3 H); 1.26 (t, J ¼ 7.1, 6 H ) . 13C-NMR (50 MHz, CDCl3): 182.4
(C); 137.1 (C); 128.2 (2 CH); 127.9 (2 CH); 127.7 (CH); 101.3 (CH); 95.0 (C); 82.4 (C); 70.7 (CH2); 64.0
(CH); 62.9 (CH2); 62.8 (CH2); 20.9 (Me); 14.9 (2 Me). EI-MS: 245 (1), 215 (1), 187 (1), 187 (1), 169 (1),
157 (1), 145 (1), 129 (2), 103 (100), 91 (32), 75 (31), 65 (7), 47 (37). HR-MS: 290.1540 (Mþ, C17H22O4þ ;
calc. 290.1518).
5-(Benzyloxy)-1,1-diethoxyundec-3-yn-2-one (10c-Bn): Yield 99%. Yellow liquid. IR (film): 3089w,
3065w, 3032m, 2977s, 2954s, 2929s, 2861s, 2209m, 1694s, 1497m, 1479m, 1455s, 1392m, 1371m, 1332m,
1242m, 1206w, 1159m, 1111s, 1072s, 1029s, 909m, 839w, 818w, 787w, 738m, 699m, 617m. 1H-NMR
(200 MHz, CDCl3): 7.39 – 7.26 (m, 5 H); 4.86 – 4.50 (m, 2 H); 4.76 (s, 1 H); 4.26 (t, J ¼ 6.6, 1 H); 3.82 – 3.57
(m, 4 H); 1.88 – 1.76 (m, 2 H); 1.59 – 1.40 (m, 8 H); 1.27 (t, J ¼ 7.1, 6 H); 0.87 (t, J ¼ 6.5, 3 H). 13C-NMR
(50 MHz, CDCl3): 182.7 (C); 137.3 (C); 128.4 (2 CH); 128.1 (2 CH); 127.9 (CH); 101.5 (CH); 95.1 (C);
83.3 (C); 70.9 (CH2); 68.4 (CH); 63.0 (CH2); 62.9 (CH2); 34.9 (CH2); 31.6 (CH2); 28.8 (CH2); 25.1 (CH2);
22.5 (CH2); 15.1 (2 Me); 14.0 (Me). EI-MS: 360 (1, Mþ), 330 (5), 314 (4), 287 (6), 255 (20), 227 (15), 209
(25), 169 (30), 143 (35), 129 (55), 115 (82), 92 (100), 65 (100). HR-MS: 359.2238 ([M – H]þ, C22H31O4þ ;
calc. 359.2222).
5-(Benzyloxy)-1,1-diethoxy-5-methylhex-3-yn-2-one (10e-Bn): Yield 94%. Slightly yellow liquid. IR
(film): 3031m, 2981s, 2932s, 2889s, 2213s, 1691s, 1452m, 1383m, 1319s, 1249s, 1161s, 1087s, 957w, 912m,
841w, 741s, 699m. 1H-NMR (200 MHz, CDCl3): 7.39 – 7.25 (m, 5 H); 4.73 (s, 1 H); 4.66 (s, 2 H); 3.79 – 3.53
(m, 4 H); 1.60 (s, 6 H); 1.23 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 182.7 (C); 138.1 (C); 128.1
(2 CH); 127.6 (2 CH); 127.4 (CH); 101.3 (CH); 97.4 (C); 81.7 (C); 70.4 (C); 66.9 (CH2); 62.7 (2 CH2); 27.9
(2 Me); 14.9 (2 Me). EI-MS: 259 (1), 229 (1), 201 (1), 183 (1), 171 (1), 152 (2), 103 (100), 91 (43), 75
(47), 65 (8), 47 (61). HR-MS: 304.1681 (Mþ, C18H24O4þ ; calc. 304.1675).
4-[1-(Benzyloxy)cyclohexyl]-1,1-diethoxybut-3-yn-2-one (10f-Bn): Yield 86%. Slightly yellow liquid.
IR (film): 3062m, 3031m, 2936s, 2207s, 1690s, 1450s, 1382m, 1318m, 1290m, 1093s, 941m, 910m, 848w,
739m, 700m. 1H – NMR (200 MHz, CDCl3): 7.40 – 7.23 (m, 5 H); 4.75 (s, 1 H); 4.67 (s, 2 H); 3.79 – 3.54 (m,
4 H); 2.10 – 2.00 (m, 2 H); 1.84 – 1.52 (m, 8 H); 1.24 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 182.8
(C); 138.4 (C); 128.1 (2 CH); 127.6 (2 CH); 127.3 (CH); 101.3 (CH); 97.3 (C); 83.7 (C); 74.0 (C); 65.9
(CH2); 62.7 (2 CH2); 36.5 (2 CH2); 25.1 (CH2); 22.4 (2 CH2); 15.0 (2 Me). EI-MS: 241 (1), 229 (1), 211
(1), 200 (2), 185 (1), 229 (10), 117 (6), 111 (23), 103 (83), 97 (10), 91 (52), 83 (24), 75 (44), 58 (27). HR-
MS: 344.2003 (Mþ, C21H28Oþ4 ; calc. 344.1988).
7.3. Addition of Propane-1,3-dithiol to 10-Bn, Formation of 11-Bn. Methods A and B used to perform
double conjugate addition of propane-1,3-dithiol to protected 10a-Bn were applied (see above,
Exper. 6.5).
3-{2-[1-(Benzyloxy)ethyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-one (11b-Bn): From 10b-Bn.
Method A: After FC, 92% yield. Method B: After FC, 99% yield. Yellow liquid. IR (film): 3030m,
2975s, 2926s, 1729s, 1449m, 1375m, 1320m, 1283m, 1242m, 1069s, 972m, 908m, 812w, 740s, 700m, 656w.
1H-NMR (200 MHz, CDCl3): 7.36 – 7.23 (m, 5 H); 4.67 (s, 1 H); 4.64 – 4.74 (m, 2 H); 4.28 (q, J ¼ 6.3, 1 H);
3.70 – 3.39 (m, 4 H); 3.43 (m, 2 H); 2.96 – 2.81 (m, 4 H); 2.04 – 1.84 (m, 2 H); 1.42 (d, J ¼ 6.3, 3 H); 1.20 (t,
J ¼ 7.0, 3 H); 1.19 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 201.7 (C); 138.2 (C); 127.9 (2 CH); 127.5
(2 CH); 127.2 (CH); 102.5 (CH); 79.7 (CH); 71.8 (CH2); 62.9 (2 CH2); 55.5 (C); 42.7 (CH2); 26.6 (CH2);
26.0 (CH2); 24.6 (CH2); 15.0 (Me); 14.9 (Me); 14.8 (Me). EI-MS: 398 (1, Mþ), 353 (1), 308 (1), 263 (25),
103 (100), 91 (50), 75 (35), 47 (36). HR-MS: 398.1593 (Mþ, C20H30O4S2þ ; calc. 398.1586).

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3-{2-[1-(Benzyloxy)heptyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-one (11c-Bn): From 10c-Bn with
Method B. After FC, 71% yield. Yellow liquid. IR (film): 3088w, 3063w, 3030m, 2954s, 2926s, 2857s, 2870s,
1728s, 1605w, 1585w, 1549w, 1454m, 1424m, 1394m, 1371m, 1342m, 1314m, 1278m, 1240w, 1206w, 1164m,
1097s, 1065s, 1028s, 926w, 910m, 874w, 816w, 787w,735m, 698m, 678w, 650w. 1H-NMR (200 MHz, CDCl3):
7.39 – 7.21 (m, 5 H); 4.86 – 4.62 (m, 2 H); 4.66 (s, 1 H); 4.10 (dd, J ¼ 2.7, 9.0, 1 H); 3.69 – 3.41 (m, 4 H); 3.39
(s, 2 H); 3.03 – 2.76 (m, 4 H); 2.71 – 2.57 (m, 1 H); 2.33 – 2.19 (m, 1 H); 2.11 – 1.27 (m, 10 H); 1.21 (t, J ¼
7.0, 3 H); 1.18 (t, J ¼ 7.0, 3 H); 0.88 (t, J ¼ 6.3, 3 H). 13C-NMR (50 MHz, CDCl3): 202.1 (C); 138.5 (C);
128.1 (2 CH); 127.6 (2 CH); 127.3 (CH); 102.6 (CH); 84.3 (CH); 75.2 (CH2); 63.1 (CH2); 63.1 (CH2); 56.4
(C); 42.7 (CH2); 31.8 (CH2); 31.7 (CH2); 29.4 (CH2); 27.3 (CH2); 26.4 (CH2); 26.3 (CH2); 24.7 (CH2); 22.5
(CH2); 15.1 (Me); 15.0 (Me); 14.0 (Me). DART-MS: 468 (52, Mþ), 460 (22), 459 (38), 455 (33), 449
(10), 442 (52), 430 (31), 423 (100), 404 (8). HR-MS: 423.2029 ([M ꢀ EtO]þ, C23H35O3S2þ ; calc.
423.2028).
3-{2-[1-(Benzyloxy)-1-methylethyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-one (11e-Bn): From 10e-
Bn with Method A. After FC, 84% yield. Yellow liquid. IR (film): 3029m, 2975s, 2928s, 1721s, 1447m,
1418m, 1288m, 1317m, 1286m, 1244m, 1160m, 1088m, 1065s, 963m, 910w, 848w, 811w, 737m, 698m, 609m.
1H-NMR (200 MHz, CDCl3): 7.40 – 7.19 (m, 5 H); 5.20 (s, 1 H); 4.36 (s, 2 H); 3.36 (s, 2 H); 3.39 – 3.14 (m,
4 H); 3.12 – 2.98 (m, 2 H); 2.87 – 2.75 (m, 2 H); 2.14 – 2.03 (m, 1 H); 1.95 – 1.83 (m, 1 H); 1.58 (s, 6 H);
1.06 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 201.6 (C); 138.8 (C); 127.9 (2 CH); 126.8 (3 CH); 100.9
(CH); 82.4 (C); 63.4 (CH2); 62.2 (C); 61.6 (2 CH2); 44.7 (CH2); 26.4 (2 CH2); 24.5 (CH2); 20.8 (2 Me);
15.0 (2 Me). EI-MS: 412 (3, Mþ), 367 (1), 321 (1), 281 (1), 263 (28), 103 (100), 91 (80), 75 (39), 65 (5), 47
(48). HR-MS: 412.1760 (Mþ, C21H32O4S2þ ; calc. 412.1742).
3-{2-[1-(Benzyloxy)cyclohexyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-one (11f-Bn). From 10f-Bn.
Method A: After FC, 85% yield. White solid. M.p. 89 – 908. Method B: After FC, 93% yield. White solid.
M.p. 87 – 888. IR (KBr): 3083w, 2919s, 2863s, 1710s, 1442m, 1390w, 1367m, 1327m, 1291m, 1259m, 1196m,
1134s, 1057s, 934m, 910m, 858m, 737m, 694m, 662w, 638w, 582w, 563w. 1H-NMR (200 MHz, CDCl3):
7.38 – 7.19 (m, 5 H); 4.66 (s, 2 H); 4.56 (s, 1 H); 3.51 – 3.25 (m, 6 H); 3.10 – 2.96 (m, 2 H); 2.88 – 2.75 (m,
2 H); 2.43 – 2.36 (m, 2 H); 2.08 – 1.78 (m, 4 H); 1.65 – 1.48 (m, 6 H); 1.10 (t, J ¼ 7.0, 6 H). 13C-NMR
(50 MHz, CDCl3): 202.1 (C); 139.4 (C); 128.0 (2 CH); 127.3 (2 CH); 126.9 (CH); 101.7 (CH); 83.1 (C);
65.7 (C); 65.6 (CH2); 62.5 (2 CH2); 40.2 (CH2); 29.6 (2 CH2); 27.0 (2 CH2); 25.2 (CH2); 24.0 (CH2); 22.0
(2 CH2); 15.0 (2 Me). EI-MS: 407 (1, [M ꢀ EtO]þ), 361 (1), 349 (1), 315 (1), 299 (1), 263 (1), 189 (15),
103 (88), 91 (100), 75 (32), 47 (35). HR-MS: 407.172951 ([M ꢀ EtO]þ, C22H31O3S2þ ; calc. 407.171464).
8. Conversion of Ketones 11-Bn to Alcohols 15-Bn. Typical Procedure. The ketone 11-Bn (7.2 mmol)
in THF (10 ml) was added to a soln. of NaBH4 (0.32 g, 8.5 mmol) in THF (20 ml) and H2O (1 ml) at r.t.
The mixture was stirred overnight before H2O was added, and the hydrolyzate was extracted with CH2Cl2
(3 ꢁ 50 ml). The combined extract was dried (MgSO4) and concentrated to give a residue from which 15-
Bn was isolated by FC.
3-{2-[(Benzyloxy)methyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-ol (15a-Bn): From 11a-Bn (5.09 g,
13.2 mmol). Yield 99% (5.12 g) after FC. Slightly yellow liquid. IR (film): 3471s, 3086w, 3061w, 3030m,
2974s, 2902s, 1496m, 1452s, 1421s, 1372s, 1277s, 1244m, 1206m, 1095s, 1028s, 944m, 909m, 817m, 738s, 699s,
679w, 660w. 1H-NMR (200 MHz, CDCl3): 7.39 – 7.29 (m, 5 H); 4.65 (s, 2 H); 4.34 (d, J ¼ 5.2, 1 H); 4.07 –
3.97 (m, 1 H); 3.86 – 3.50 (m, 6 H); 3.14 (d, J ¼ 3.5, 1 H); 2.85 – 2.73 (m, 4 H); 2.44 (dd, J ¼ 1.4, 15.2, 1 H);
2.10 – 1.90 (m, 3 H); 1.23 (t, J ¼ 7.0, 3 H); 1.22 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 137.5 (C);
128.3 (2 CH); 127.6 (3 CH); 104.4 (CH); 74.4 (CH2); 73.4 (CH2); 68.8 (CH); 63.3 (CH2); 63.2 (CH2); 51.8
(C); 39.8 (CH2); 26.2 (CH2); 25.7 (CH2); 25.0 (CH2); 15.3 (2 Me). EI-MS: 385 (2), 322 (22), 277 (8), 263
(14), 247 (15), 230 (15), 216 (10), 203 (12), 186 (32), 175 (21), 157 (20), 133 (67), 106 (100), 91 (91), 72
(73), 59 (98). HR-MS: 386.1601 (Mþ, C19H30O4S2þ ; calc. 386.1586).
3-{2-[1-(Benzyloxy)ethyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-ol (15b-Bn): From 11b-Bn (2.71 g,
6.8 mmol). The crude product (2.71 g, 99%) consisted of two diastereoisomers. A pure sample of each
diastereoisomer was obtained by FC (hexanes/AcOEt 95 :5).
Diastereoisomer 15b-Bn-I: IR (film): 3463m, 3087w, 3062m, 3030m, 2973s, 2929s, 2902s, 1497m,
1454m, 1443m, 1423m, 1417m, 1394m, 1374m, 1342m, 1328m, 1277m, 1242m, 1210m, 1093s, 1027s, 946w,
908m, 886w, 845w, 806w, 739m, 698m, 681w. 1H-NMR (200 MHz, CDCl3): 7.39 – 7.27 (m, 5 H); 4.72 – 4.59
(m, 2 H); 4.2 (d, J ¼ 4.8, 1 H); 4.14 – 4.05 (m, 1 H); 4.02 (d, J ¼ 2.9, 1 H); 3.95 (q, J ¼ 6.5, 2 H); 3.85 – 3.52

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(m, 4 H); 3.03 – 2.53 (m, 4 H); 2.19 – 1.76 (m, 3 H); 1.41 (d, J ¼ 6.5, 3 H); 1.23 (t, J ¼ 7.0, 6 H). 13C-NMR
(50 MHz, CDCl3): 137.3 (C); 128.4 (2 CH); 127.9 (2 CH); 127.8 (CH); 104.6 (CH); 81.2 (CH); 72.9
(CH2); 69.6 (CH); 63.8 (CH2); 62.8 (CH2); 57.4 (C); 35.7 (CH2); 26.3 (CH2); 25.1 (CH2); 25.0 (CH2); 15.4
(Me); 15.3 (Me); 14.6 (Me). EI-MS: 399 (1), 383 (5), 276 (4), 248 (6), 216 (8), 201 (11), 175 (24), 145
(21), 133 (67), 117 (53), 105 (80), 91 (90), 77 (83), 59 (100). HR-MS: 400.1732 (Mþ, C20H32O4S2þ ; calc.
400.1742).
Diastereoisomer 15b-Bn-II: IR (film): 3462m, 3087w, 3062w, 3029w, 2973s, 2927s, 2897s, 1496m,
1453m, 1423m, 1341m, 1277m, 1244m, 1208m, 1094s, 1070s, 1028s, 952w, 909m, 886w, 878w, 801w, 737s,
698s, 676w, 665w. 1H-NMR (200 MHz, CDCl3): 7.41 – 7.24 (m, 5 H); 4.70 – 4.54 (m, 2 H); 4.32 (d, J ¼ 5.1,
1 H); 4.28 – 4.19 (m, 1 H); 3.97 (q, J ¼ 6.3, 1 H); 3.82 – 3.48 (m, 4 H); 3.25 (d, J ¼ 2.7, 1 H); 2.89 – 2.81 (m,
4 H); 2.42 (dd, J ¼ 1.4, 15.4, 1 H); 2.25 – 2.04 (m, 2 H); 2.01 – 1.58 (m, 1 H); 1.39 (d, J ¼ 6.3, 3 H); 1.21 (t,
J ¼ 7.0, 3 H); 1.20 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 138.2 (C); 128.1 (2 CH); 127.4 (2 CH);
127.3 (CH); 104.4 (CH); 81.3 (CH); 72.2 (CH2); 69.2 (CH); 63.2 (CH2); 62.9 (CH2); 56.8 (C); 37.2 (CH2);
26.2 (CH2); 26.0 (CH2); 24.6 (CH2); 15.2 (Me); 15.1 (Me); 14.8 (Me). EI-MS: 397 (1), 383 (2), 353 (2),
310 (3), 293 (4), 260 (6), 219 (18), 160 (10), 145 (13), 133 (34), 108 (40), 89 (91), 73 (87), 59 (100). HR-
MS: 400.1740 (Mþ, C20H32O4Sþ2 ; calc. 400.1742).
3-{2-[1-(Benzyloxy)heptyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-ol (15c-Bn): From 11c-Bn (1.69 g,
3.6 mmol). The crude product (1.69 g, 99%) consisted of two diastereoisomers. A pure sample of each
diastereoisomer was obtained by FC.
Diastereoisomer 15c-Bn-I: IR (film): 3462s, 3088w, 3063m, 3030m, 2973s, 2919s, 2871s, 1497m, 1454s,
1418s, 1395m, 1375m, 1343m, 1276m, 1242m, 1213m, 1063s, 1027s, 952m, 909m, 870m, 816w, 802w 727s,
1
698s, 679w, 665w, 605w. H-NMR (200 MHz, CDCl3): 7.40 – 7.26 (m, 5 H); 5.01 – 4.63 (m, 2 H); 4.42 (d,
J ¼ 4.6, 1 H); 4.17 (d, J ¼ 2.7, 1 H); 4.15 – 4.07 (m, 1 H); 3.84 – 3.50 (m, 5 H); 3.06 – 2.54 (m, 5 H); 2.12 –
2.00 (m, 2 H); 1.96 – 1.76 (m, 3 H); 1.28 (br. m, 8 H); 1.23 (t, J ¼ 7.0, 3 H); 1.22 (t, J ¼ 7.0, 3 H); 0.91 – 0.84
(m, 3 H). 13C-NMR (50 MHz, CDCl3): 137.5 (C); 128.4 (2 CH); 127.9 (CH); 127.8 (2 CH); 104.6 (CH);
86.2 (CH); 77.5 (CH2); 69.7 (CH); 63.9 (CH2); 62.7 (CH2); 58.1 (C); 36.1 (CH2); 31.7 (CH2); 31.2 (CH2);
29.2 (CH2); 27.1 (CH2); 26.3 (CH2); 25.1 (CH2); 25.0 (CH2); 22.6 (CH2); 15.4 (Me); 15.3 (Me); 14.0
(Me). EI-MS: 448 (2), 408 (7), 374 (2), 347 (17), 316 (15), 257 (68), 209 (25), 169 (24), 145 (49), 133
(58), 106 (84), 91 (93), 73 (68), 59 (100). HR-MS: 470.2520 (Mþ, C25H42O4S2þ ; calc. 470.2525).
Diastereoisomer 15c-Bn-II: IR (film): 3472m, 3087w, 3063w, 3029m, 2973s, 2930s, 1497m, 1454s,
1423s, 1394s, 1374s, 1342m, 1306m, 1277m, 1240m, 1211m, 1099s, 1028s, 946w, 910m, 886w, 843m, 815w,
1
802w, 735m, 697m, 676w, 666w, 600m. H-NMR (200 MHz, CDCl3): 7.42 – 7.25 (m, 5 H); 4.98 – 4.62 (m,
2 H); 4.34 – 4.25 (m, 2 H); 3.87 – 3.47 (m, 5 H); 3.21 (d, J ¼ 2.2, 1 H); 2.94 – 2.82 (m, 4 H); 2.42 (dd, J ¼
1.4, 15.7, 1 H); 2.19 – 1.55 (m, 5 H), 1.27 (br. m, 8 H); 1.21 (t, J ¼7.1, 3 H); 1.20 (t, J ¼ 7.1, 3 H); 0.88 (t, J ¼
6.4, 3 H). 13C-NMR (50 MHz, CDCl3): 138.6 (C); 128.2 (2 CH); 127.4 (2 CH); 127.4 (CH); 104.5 (CH);
85.5 (CH); 75.8 (CH2); 69.4 (CH); 63.4 (CH2); 63.0 (CH2); 57.7 (C); 37.3 (CH2); 31.7 (CH2); 31.7 (CH2);
29.4 (CH2); 27.3 (CH2); 26.4 (CH2); 26.2 (CH2); 24.7 (CH2); 22.6 (CH2); 15.3 (Me); 15.2 (Me); 14.1
(Me). EI-MS: 431 (2), 385 (1), 364 (3), 319 (9), 301 (5), 270 (8), 257 (38), 243 (13), 231 (28), 217 (37),
169 (58), 145 (52), 132 (34), 103 (100), 91 (95), 75 (92), 59 (100). HR-MS: 470.2513 (Mþ, C25H42O4S2þ ;
calc. 470.2525).
3-{2-[1-(Benzyloxy)-1-methylethyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-ol (15e-Bn): From 11e-
Bn (2.97 g, 7.2 mmol). Yield 96% (2.69 g) after FC. Clear liquid. IR (film): 3452m, 3088w, 3062w, 2974s,
2928s, 1497w, 1454m, 1444m, 1418m, 1389m, 1369m, 1343m, 1320m, 1278m, 1243m, 1203m, 1158s, 1139s,
1086s, 1062s, 1027s, 944w, 908w, 864w, 847w, 801w, 735s, 698s, 681w. 1H-NMR (200 MHz, CDCl3): 7.38 –
7.24 (m, 5 H); 4.64 – 4.50 (m, 2 H); 4.38 (d, J ¼ 4.9, 1 H); 4.27 – 4.20 (m, 1 H); 3.96 (br. s, 1 H); 3.82 – 3.48
(m, 4 H); 3.06 – 2.57 (m, 5 H); 2.26 – 2.14 (m, 1 H), 2.06 – 1.78 (m, 2 H) ,1.65 (s, 3 H); 1.56 (s, 3 H); 1.21 (t,
J ¼ 7.1, 3 H); 1.19 (t, J ¼ 7.1, 3 H ) . 13C-NMR (50 MHz, CDCl3): 138.4 (C); 128.3 (2 CH); 127.4 (CH); 127.4
(2 CH); 104.6 (CH); 83.8 (C); 70.0 (CH); 64.7 (CH2); 63.8 (CH2); 62.4 (C); 62.2 (CH2); 37.3 (CH2); 26.9
(CH2); 26.9 (CH2); 24.8 (CH2); 21.7 (2 Me); 15.3 (2 Me). EI-MS: 368 (4), 323 (10), 261 (15), 236 (28),
203 (69), 175 (30), 165 (70), 145 (100), 107 (76), 87 (63), 73 (68). HR-MS: 369.1555 ([M ꢀ EtO]þ,
C19H29O3Sþ2 ; calc. 369.1558).
3-{2-[1-(Benzyloxy)cyclohexyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-ol (15f-Bn): From 11f-Bn
(1.65 g, 3.7 mmol). Yield 95% (1.58 g) after FC. Clear liquid. IR (film): 3454m, 3088w, 3063w, 3031w,

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2971s, 2930s, 2863s, 1496m, 1449m, 1421m, 1392m, 1374m, 1348m, 1325m, 1306m, 1276m, 1258m, 1242w,
1211w, 1142s, 1063s, 1026s, 944m, 909m, 886m, 854m, 817w, 785w, 734m, 697m. 1H-NMR (200 MHz,
CDCl3): 7.41 – 7.21 (m, 5 H); 5.03 – 4.80 (m, 2 H); 4.56 (s, 1 H); 4.41 (d, J ¼ 4.7, 1 H); 4.10 – 4.03 (m, 1 H);
3.85 – 3.50 (m, 4 H); 3.29 – 3.07 (m, 2 H); 2.89 (d, J ¼ 16.2, 1 H); 2.80 – 2.53 (m, 3 H); 2.32 – 1.41 (m,
12 H); 1.22 (t, J ¼ 7.0, 3 H); 1.21 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 138.4 (C); 128.4 (2 CH);
127.5 (CH); 127.4 (2 CH); 104.8 (CH); 83.6 (C); 69.8 (CH); 67.2 (CH2); 64.1 (CH2); 63.9 (C); 62.3 (CH2);
36.9 (CH2); 31.1 (CH2); 28.6 (CH2); 27.3 (CH2); 25.1 (2 CH2); 24.6 (CH2); 22.2 (CH2); 22.0 (CH2); 15.4
(2 Me). EI-MS: 408 (1), 383 (1), 361 (2), 337 (1), 302 (3), 284 (1), 243 (3), 214 (4), 177 (4), 133 (11), 108
(100), 91 (84), 79 (97), 59 (31). HR-MS: 409.1883 ([M ꢀ EtO]þ, C22H33O3S2þ ; calc. 409.1871).
9. Synthesis of 16-Bn by Dethioketalization of 15-Bn. 9.1. Method 2: Typical Procedure. To a soln. of
15a-Bn (2.13 g, 5.50 mmol) and CaCO3 (5.52 g, 55.2 mmol) in MeCN (48 ml), H2O (12 ml), and THF
(12 ml) at r.t., MeI (51.5 ml, 0.83 mol) was added. The mixture was heated to 508 and stirred for 42 h
before quenching with sat. aq. NH4Cl soln., followed by extracting with CH2Cl2 (3ꢁ). The combined
extract was dried (MgSO4) and concentrated and the crude green liquid (0.92 g) purified by FC: 0.46 g
(28%) of 16a-Bn. Yellow liquid.
9.2. Method 3: Typical Procedure. To a soln. of 15a-Bn (0.39 g, 1.00 mmol) and CaCO3 (0.25 g,
2.5 mmol) in MeCN (40 ml) and H2O (10 ml) at r.t., MeI (2.5 ml) was added. The mixture was stirred at
r.t. for 47 h before quenching with sat. aq. NH4Cl soln., followed by extracting with CH2Cl2 (3ꢁ). The
combined extract was dried (MgSO4) and concentrated and the crude clear liquid (0.30 g) purified by
FC: 0.25 g (84%) of 16a-Bn. Clear liquid.
9.3. Method 4: Typical Procedure. A soln. of 15-Bn (6.5 mmol) in MeCN (50 ml) and sat. aq.
NaHCO3 soln. (50 ml) was cooled to 08, and I2 (6.6 g, 26 mmol) was added portionwise during 10 min
before stirring and attaining r.t. overnight. The mixture was quenched by adding sat. aq. NaHCO3/sat. aq.
Na2S2O4 soln. 1:1 (50 ml) followed by extraction with CH2Cl2 (3ꢁ). The combined extract was dried
(MgSO4) and concentrated an the crude product subjected to FC (SiO2, hexane/AcOEt): 16-Bn.
9.4. Products 16-Bn. 1-(Benzyloxy)-5,5-diethoxy-4-hydroxypentan-2-one (16a-Bn): All the three
methods were used at various scales. Method 4 applied to 4.93 g (12.8 mmol) of 15a-Bn gave, beside
unreacted starting material, 2.02 g (54%) of 16a-Bn. Yellowish liquid. IR (film): 3479m, 3088w, 3063w,
3031w, 2975s, 2928s, 2883s, 1725s, 1497m, 1454m, 1389m, 1374m, 1341m, 1310m, 1277m, 1208m, 1095s,
1063s, 1028s, 909w, 888w, 841w, 817w, 740m, 699m. 1H-NMR (200 MHz, CDCl3): 7.37 – 7.27 (m, 5 H); 4.60
(s, 2 H); 4.39 (d, J ¼ 5.1, 1 H); 4.17 – 4.06 (m, 3 H); 3.82 – 3.48 (m, 4 H); 3.73 – 2.68 (m, 3 H); 1.21 (t, J ¼
7.0, 3 H); 1.20 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 207.9 (C); 137.1 (C); 128.4 (2 CH); 127.9
(CH); 127.9 (2 CH); 103.9 (CH); 75.3 (CH2); 73.2 (CH2); 68.5 (CH); 63.8 (CH2); 63.5 (CH2); 40.6 (CH2);
15.3 (Me); 15.2 (Me). EI-MS: 295 (2), 278 (2), 265 (2), 251 (2), 233 (1), 219 (2), 205 (3), 187 (2), 175 (4),
157 (2), 144 (18), 129 (13), 107 (23), 103 (74), 91 (100), 75 (43), 65 (15), 59 (16).
2-(Benzyloxy)-6,6-diethoxy-5-hydroxyhexan-3-one (16b-Bn): Diastereoisomer 16b-Bn-I. Method 4
applied to 0.79 g (2.0 mmol) of 15b-Bn-I gave 0.24 g (39%) of 16b-Bn-I. Slightly yellow liquid. IR (film):
3475m, 3088w, 3063w, 3031w, 2976s, 2930s, 2898s, 2874s, 1720s, 1497m, 1454m, 1372m, 1326m, 1308m,
1208m, 1095s, 1067s, 1028s, 912w, 818w, 788w, 737m, 698m, 665w. 1H-NMR (200 MHz, CDCl3): 7.37 – 7.28
(m, 5 H); 5.64 – 4.46 (m, 2 H); 4.42 (d, J ¼ 5.2, 1 H); 4.20 – 4.10 (m, 1 H), 3.97 (q, J ¼ 6.8, 1 H); 3.83 – 3.50
(m, 4 H); 2.85 (d, J ¼ 6.4, 2 H); 2.32 – 2.13 (m, 1 H); 1.35 (d, J ¼ 6.8, 3 H); 1.22 (t, J ¼ 7.0, 3 H); 1.21 (t, J ¼
7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 212.4 (C); 137.5 (C); 128.4 (2 CH); 127.8 (CH); 127.7 (2 CH);
103.8 (CH); 80.6 (CH); 71.8 (CH2); 68.3 (CH); 63.7 (CH2); 63.4 (CH2); 39.1 (CH2); 17.1 (Me); 15.3
(Me); 15.2 (Me). EI-MS: 365 (1), 219 (3), 201 (4), 175 (13), 158 (36), 135 (18), 129 (54), 103 (98), 91
(100), 75 (67), 59 (38). HR-MS: 265.1440 ([M ꢀ EtO]þ, C15H21O4þ ; calc. 265.1440).
Diastereoisomer 16b-Bn-II. Method 4 applied to 0.28 g (0.70 mmol) of 15b-Bn-II gave 0.18 g (59%)
of 16b-Bn-II. Slightly yellow liquid. IR (film): 3467m, 3088w, 3063w, 3030w, 2976s, 2930s, 2899s, 1728m,
1497m, 1453m, 1420w, 1389w, 1373w, 1341w, 1315w, 1278w, 1257w, 1242w, 1207w, 1095s, 1064s, 1028m,
1
960w, 909w, 737m, 698m, 667w. H-NMR (200 MHz, CDCl3): 7.36 – 7.26 (m, 5 H); 5.61 – 4.45 (m, 2 H);
4.40 (d, J ¼ 5.2, 1 H); 4.18 – 4.07 (m, 1 H); 3.97 (q, J ¼ 6.9, 1 H), 3.82 – 3.49 (m, 4 H); 2.81 (d, J ¼ 6.2, 2 H);
2.27 – 2.19 (m, 1 H); 1.34 (d, J ¼ 6.9, 3 H); 1.21 (t, J ¼ 7.0, 3 H); 1.20 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz,
CDCl3): 212.2 (C); 137.4 (C); 128.3 (2 CH); 127.7 (CH); 127.7 (2 CH); 103.8 (CH); 80.6 (CH); 71.7
(CH2); 68.3 (CH); 63.6 (CH2); 63.3 (CH2); 39.1 (CH2); 16.9 (Me); 15.2 (Me); 15.1 (Me). EI-MS: 309 (1),

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292 (2), 281 (1), 265 (3), 247 (2), 219 (5), 201 (7), 175 (40), 158 (75), 135 (58), 129 (90), 103 (93), 92
(77), 75 (100), 65 (72), 59 (90). HR-MS: 265.1452 ([M ꢀ EtO]þ, C15H21O4þ ; calc. 265.1440).
5-(Benzyloxy)-1,1-diethoxy-2-hydroxyundecan-4-one (16c-Bn): Diastereoisomer 16c-Bn-I. Method 4
applied to 0.73 g (1.50 mmol) of 15c-Bn-I gave 0.49 g (83%) of 16c-Bn-I. Slightly yellow liquid. IR (film):
3483m, 3089w, 3064w, 3031m, 2973s, 2955s, 2928s, 2871s, 2860s, 1716s, 1497m, 1455s, 1394m, 1375s, 1334m,
1307m, 1286m, 1207m, 1066s, 1028s, 942w, 911w, 889w, 846w, 817w, 787w, 737m, 698s. 1H-NMR (200 MHz,
CDCl3): 7.36 – 7.30 (m, 5 H); 4.67 – 4.37 (m, 2 H); 4.42 (d, J ¼ 5.1, 1 H); 4.20 – 4.09 (m, 1 H); 3.84 – 3.50
(m, 5 H); 2.86 – 2.79 (m, 2 H); 2.29 – 2.19 (m, 1 H); 1.70 – 1.62 (m, 2 H); 1.43 – 1.26 (m, 8 H); 1.22 (t, J ¼
7.0, 3 H); 1.21 (t, J ¼ 7.0, 3 H); 0.90 – 0.83 (m, 3 H). 13C-NMR (50 MHz, CDCl3): 212.8 (C); 137.5 (C);
128.3 (2 CH); 127.8 (2 CH); 127.7 (CH); 103.8 (CH); 84.8 (CH); 72.2 (CH2); 68.2 (CH); 63.6 (CH2); 63.2
(CH2); 39.2 (CH2); 31.8 (CH2); 31.5 (CH2); 28.9 (CH2); 25.1 (CH2); 22.4 (CH2); 15.2 (Me); 15.1 (Me);
13.9 (Me). EI-MS: 379 (1), 362 (2), 335 (4), 317 (6), 289 (10), 271 (62), 259 (32), 243 (3), 228 (96), 206
(57), 199 (73), 175 (75), 157 (56), 149 (38), 129 (74), 110 (96), 102 (100), 88 (73), 71 (85), 59 (93). HR-
MS: 352.2230 ([M ꢀ EtO]þ, C20H31O4þ ; calc. 335.2222).
Diastereoisomer 16c-Bn-II. Method 4 applied to 0.59 g (1.30 mmol) of 15c-Bn-II gave 0.36 g (75%)
of 16c-Bn-II. Slightly yellow liquid. IR (film): 3488m, 3089w, 3064w, 3031w, 2972s, 2955s, 2870s, 2859s,
1717s, 1497m, 1455m, 1394m, 1375m, 1333m, 1307m, 1287m, 1207w, 1070s, 1028m, 943w, 910w, 887w,
1
847w, 817w, 786w, 736m, 698m. H-NMR (200 MHz, CDCl3): 7.36 – 7.30 (m, 5 H); 4.62 – 4.37 (m, 2 H);
4.41 (d, J ¼ 5.2, 1 H); 4.18 – 4.07 (m, 1 H); 3.85 – 3.49 (m, 5 H); 2.80 – 2.77 (m, 2 H); 2.32 – 2.12 (m, 1 H);
1.73 – 1.62 (m, 2 H); 1.43 – 1.25 (m, 8 H); 1.22 (t, J ¼ 7.0, 3 H); 1.20 (t, J ¼ 7.0, 3 H); 0.90 – 0.83 (m, 3 H).
13C-NMR (50 MHz, CDCl3): 212.7 (C); 137.5 (C); 128.3 (2 CH); 127.8 (2 CH); 127.7 (CH); 103.8 (CH);
85.0 (CH); 72.3 (CH2); 68.3 (CH); 63.5 (CH2); 63.3 (CH2); 39.3 (CH2); 31.6 (CH2); 31.5 (CH2); 28.9
(CH2); 25.0 (CH2); 22.4 (CH2); 15.2 (Me); 15.2 (Me); 13.9 (Me). EI-MS: 380 (1), 337 (1), 323 (1), 309
(1), 295 (2), 281 (1), 270 (1), 248 (1), 208 (9), 175 (6), 131 (14), 103 (13), 91 (100), 73 (30), 59 (41). HR-
MS: 352.2214 ([M ꢀ EtO]þ, C20H31O4þ ; calc. 335.2222).
2-(Benzyloxy)-6,6-diethoxy-5-hydroxy-2-methylhexan-3-one (16e-Bn): Method 4 applied to 2.68 g
(6.50 mmol) of 15e-Bn gave 1.90 g (91%) of 16e-Bn. Slightly yellow liquid. IR (film): 3479m, 3089w,
3064w, 3031w, 2977s, 2930m, 2898m, 2877m, 1716s, 1497w, 1466m, 1454m, 1383m, 1344w, 1285w, 1232w,
1168m, 1139m, 1063s, 1029s, 933w, 911w, 888w, 781w, 736m, 698m. 1H-NMR (200 MHz, CDCl3): 7.39 – 7.24
(m, 5 H); 4.49 – 4.35 (m, 2 H); 4.42 (d, J ¼ 5.3, 1 H); 4.21 – 4.10 (m, 1 H); 3.82 – 3.47 (m, 4 H); 3.08 – 2.80
(m, 3 H); 1.41 (s, 6 H); 1.21 (t, J ¼ 7.0, 3 H); 1.18 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 213.9 (C);
138.3 (C); 128.2 (2 CH); 127.4 (CH); 127.3 (2 CH); 103.8 (CH); 82.0 (C); 68.4 (CH); 66.1 (CH2); 63.5
(CH2); 63.2 (CH2); 37.9 (CH2); 22.9 (Me); 22.8 (Me); 15.2 (Me); 15.1 (Me). EI-MS: 323 (2), 305 (2), 279
(4), 261 (3), 233 (3), 215 (18), 175 (78), 150 (83), 129 (68), 104 (77), 92 (100), 83 (91), 73 (89), 65 (97),
60 (88). HR-MS: 279.1590 ([M ꢀ EtO]þ; C16H23O4þ ; calc. 279.1596).
1-[1-(Benzyloxy)cyclohexyl]-4,4-diethoxy-3-hydroxybutan-1-one (16f-Bn): Method 4 applied to
1.43 g (3.20 mmol) of 15f-Bn gave 1.04 g (91%) of 16f-Bn. Clear, colorless liquid. IR (film): 3498m,
3089w, 3064w, 3031w, 2974s, 2933s, 2860s, 1710s, 1497m, 1451m, 1377m, 1343m, 1280m, 1257m, 1212w,
1
1140s, 1084s, 1063s, 1028s, 956m, 914w, 890w, 852w, 736w. H-NMR (200 MHz, CDCl3): 7.43 – 7.26 (m,
5 H); 4.39 (d, J ¼ 5.3, 1 H); 4.40 – 4.25 (m, 2 H); 4.20 – 4.09 (m, 1 H); 3.81 – 3.46 (m, 4 H); 3.03 – 2.78 (m,
2 H); 2.73 (d, J ¼ 4.2, 1 H); 1.98 – 1.56 (m, 10 H); 1.21 (t, J ¼ 7.0, 3 H); 1.17 (t, J ¼ 7.0, 3 H). 13C-NMR
(50 MHz, CDCl3): 214.7 (C); 138.3 (C); 128.3 (2 CH); 127.5 (2 CH); 127,4 (CH); 103.9 (CH); 82.9 (C);
68.5 (CH); 65.7 (CH2); 63.6 (CH2); 63.2 (CH2); 37.7 (CH2); 30.9 (CH2); 30.7 (CH2); 25.3 (CH2); 21.4
(CH2); 21.3 (CH2); 15.3 (Me); 15.2 (Me).
10. Dihydroxylated Ketones 17 by Hydrogenolytic Removal of the Bn Protection from 16-Bn: Typical
Procedure. To a soln. of 16-Bn (2.40 mmol) in 96% EtOH (50 ml), 5% Pd/C (0.4 g) was added. The
mixture was stirred under H2 for 1 – 3 d (TLC monitoring). Then the mixture was filtered through a
Celite plug and the filtrate concentrated: 17 which appeared to be essentially pure.
5,5-Diethoxy-1,4-dihydroxypentan-2-one (17a): With 0.70 g (2.4 mmol) of 16a-Bn: 0.48 g (99%) of
17a. Clear, colorless liquid. IR (film): 3437s, 2976s, 2929s, 2900s, 1721s, 1481m, 1444m, 1398m, 1375m,
1
1345m, 1285m, 1121s, 1066s, 884w, 841w, 807w. H-NMR (200 MHz, CDCl3): 4.39 (d, J ¼ 5.1, 1 H); 4.30
(m, 2 H); 4.11 (m, 1 H); 3.83 – 3.50 (m, 4 H); 3.29 (br. s, 1 H); 2.87 (br. s, 1 H); 2.75 – 2.56 (m, 2 H); 1.22
(t, J ¼ 7.0, 3 H); 1.21 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 209.1 (C); 103.9 (CH); 68.9 (CH2); 68.7

Helvetica Chimica Acta – Vol. 95 (2012)
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(CH); 64.0 (CH2); 63.7 (CH2); 40.1 (CH2); 15.2 (Me); 15.1 (Me). EI-MS: 205 (1), 175 (63), 161 (38), 143
(88), 129 (90), 115 (63), 104 (79), 88 (80), 73 (90), 60 (100). HR-MS: 161.0811 ([M ꢀ EtO]þ, C7H13O4þ ;
calc. 161.0814).
6,6-Diethoxy-2,5-dihydroxyhexan-3-one (17b): Diastereoisomer 17b-I. With 0.22 g (0.70 mmol) of
16b-Bn-I: 0.14 g (91%) of 17b-I. Clear, slightly yellow liquid. IR (film): 3420s, 2976s, 2931s, 2904s, 1717s,
1447m, 1374s, 1276m, 1023s, 913m, 733s, 666m. 1H-NMR (200 MHz, CDCl3): 4.41 (d, J ¼ 5.1, 1 H); 4.29
(q, J ¼ 7.1, 1 H); 4.13 (dt, J ¼ 7.1, 5.1, 1 H); 3.83 – 3.49 (m, 6 H); 2.87 – 2.66 (m, 2 H); 1.38 (d, J ¼ 7.1, 3 H ) ;
1.22 (t, J ¼ 7.0, 3 H); 1.21 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 212.2 (C); 103.7 (CH); 73.0 (CH);
68.7 (CH); 64.0 (CH2); 63.6 (CH2); 39.1 (CH2); 19.3 (Me); 15.2 (Me); 15.1 (Me). EI-MS: 219 (1), 207
(2), 203 (3), 175 (52), 157 (18), 129 (72), 117 (18), 101 (100), 89 (63), 73 (71), 59 (88). HR-MS: 175.0966
([M ꢀ EtO]þ, C8H15Oþ4 ; calc. 175.0970).
Diastereoisomer 17b-II. With 0.12 g (0.40 mmol) of 16b-Bn-II: 0.070 g (89%) of 17b-II. Clear,
colorless liquid. IR (film): 3454s, 2979s, 2931s, 2900s, 1766w, 1716s, 1481m, 1447s, 1374s, 1277s, 1052s,
1
912m, 818w, 805w, 733m. H-NMR (200 MHz, CDCl3): 4.42 (d, J ¼ 5.0, 1 H); 4.29 (q, J ¼ 7.1, 1 H); 4.13
(dt, J ¼ 5.0, 7.0, 1 H); 3.84 – 3.50 (m, 6 H); 2.84 – 2.64 (m, 2 H); 1.38 (d, J ¼ 7.1, 3 H); 1.22 (t, J ¼ 7.1, 3 H ) ;
1.21 (t, J ¼ 7.1, 3 H ) . 13C-NMR (50 MHz, CDCl3): 212.2 (C); 103.8 (CH); 73.4 (CH); 68.7 (CH); 64.0
(CH2); 63.7 (CH2); 39.0 (CH2); 19.2 (Me); 15.2 (Me); 15.1 (Me). EI-MS: 203 (1), 185 (2), 175 (3), 157
(6), 129 (33), 103 (100), 88 (27), 75 (70), 59 (26). HR-MS: 175.0964 ([M ꢀ EtO]þ, C8H15O4þ ; calc.
175.0970).
1,1-Diethoxy-2,5-dihydroxyundecan-4-one (17c): Diastereoisomer 17c-I. With 0.46 g (1.2 mmol) of
16c-Bn-I: 0.36 g (99%) of 17c-I. Clear, colorless liquid. IR (film): 3461s, 2973s, 2956s, 2927s, 2859s, 2872s,
1713s, 1456m, 1445m, 1394m, 1376m, 1344m, 1284m, 1221m, 1116s, 1066s, 1029s, 946w, 909w, 888w, 842w,
803w, 725w. 1H-NMR (200 MHz, CDCl3): 4.42 (d, J ¼ 5.1, 1 H); 4.24 – 4.08 (m, 2 H); 3.83 – 3.49 (m, 5 H);
2.84 – 2.64 (m, 3 H); 1.91 – 1.73 (m, 2 H); 1.63 – 1.28 (m, 8 H); 1.22 (t, J ¼ 7.0, 6 H); 0.91 – 0.85 (m, 3 H).
13C-NMR (50 MHz, CDCl3): 212.0 (C); 103.7 (CH); 76.8 (CH); 68.8 (CH); 64.0 (CH2); 63.7 (CH2); 39.4
(CH2); 33.3 (CH2); 31.6 (CH2); 29.0 (CH2); 24.7 (CH2); 22.5 (CH2); 15.2 (Me); 15.1 (Me); 14.0 (Me). EI-
MS: 289 (1), 277 (1), 272 (1), 260 (1), 245 (2), 227 (3), 199 (16), 175 (3), 158 (4), 131 (40), 113 (14), 103
(100), 88 (73), 75 (61), 55 (54). HR-MS: 245.1759 ([M ꢀ EtO]þ, C13H25O4þ ; calc. 245.1753).
Diastereoisomer 17c-II. With 0.34 g (0.90 mmol) of 16c-Bn-II: 0.25 g (95%) of 17c-II. Slightly yellow
liquid. IR (film): 3465s, 2974s, 2956s, 2929s, 2872s, 2859s, 1764w, 1713s, 1456m, 1446m, 1393w, 1376s,
1344m, 1280m, 1066s, 910w, 886w, 844w, 803w, 733w. 1H-NMR (200 MHz, CDCl3): 4.42 (d, J ¼ 4.9, 1 H);
4.24 – 4.09 (m, 2 H); 3.84 – 3.50 (m, 5 H); 3.11 (br. s, 1 H); 2.74 – 2.71 (m, 2 H); 1.91 – 1.72 (m, 2 H); 1.63 –
1.28 (m, 8 H); 1.23 (t, J ¼ 7.1, 3 H); 1.22 (t, J ¼ 7.1, 3 H); 0.91 – 0.85 (m, 3 H). 13C-NMR (50 MHz, CDCl3):
212.1 (C); 103.8 (CH); 77.3 (CH); 68.9 (CH); 64.0 (CH2); 63.7 (CH2); 39.2 (CH2); 33.2 (CH2); 31.6
(CH2); 29.0 (CH2); 24.8 (CH2); 22.5 (CH2); 15.3 (Me); 15.2 (Me); 14.0 (Me). EI-MS: 277 (1), 262 (2),
251 (1), 243 (1), 226 (1), 199 (8), 170 (2), 141 (9), 131 (100), 113 (12), 103 (7), 85 (36), 75 (4), 59 (86).
HR-MS: 245.1757 ([M ꢀ EtO]þ, C13H25O4þ ; calc. 245.1753).
6,6-Diethoxy-2,5-dihydroxy-2-methylhexan-3-one (17e): With 0.16 g (0.50 mmol) of 16e-Bn: 0.11 g
(99%) of 17e. Clear, colorless liquid. IR (film): 3461s, 2976s, 2931s, 1713s, 1463m, 1446m, 1374s, 1288m,
1
1440s, 1059s, 1029s, 969m, 910m, 889w, 796w, 783w, 665w. H-NMR (200 MHz, CDCl3): 4.43 (d, J ¼ 5.0,
1 H); 4.20 – 4.10 (m, 1 H); 3.95 (br. s, 1 H); 3.83 – 3.47 (m, 4 H); 3.08 (br. s, 1 H); 2.96 – 2.73 (m, 2 H); 1.37
(s, 6 H); 1.22 (t, J ¼ 7.0, 6 H). 13C-NMR (50 MHz, CDCl3): 214.2 (C); 103.7 (CH); 76.4 (C); 68.6 (CH);
63.7 (CH2); 63.5 (CH2); 37.3 (CH2); 26.1 (Me); 26.0 (Me); 15.1 (2 Me). EI-MS: 233 (1), 215 (1), 207 (1),
189 (2), 171 (18), 158 (8), 146 (18), 130 (15), 125 (14), 112 (86), 103 (100), 88 (94), 75 (70), 59 (88). HR-
MS: 189.1111 ([M ꢀ EtO]þ, C9H17O4þ ; calc. 189.1127).
4,4-Diethoxy-3-hydroxy-1-(1-hydroxycyclohexyl)butan-1-one (17f). With 1.00 g (2.8 mmol) of 16f-
Bn: 0.74 g (99%) of 17f. Clear, colorless liquid. IR (film): 3463s, 2975s, 2931s, 2862s, 1705s, 1481m, 1448s,
1375s, 1345m, 1262s, 1124s, 1061s, 1038s, 986m, 914w, 888w, 850w, 834w, 814w, 770w. 1H-NMR (200 MHz,
CDCl3): 4.43 (d, J ¼ 5.0, 1 H); 4.17 – 4.07 (m, 1 H); 3.84 – 3.50 (m, 5 H); 2.97 – 2.74 (m, 3 H); 1.75 – 1.48
(m, 10 H); 1.23 (t, J ¼ 7.0, 3 H); 1.22 (t, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 214.7 (C); 103.8 (CH);
78.2 (C); 67.0 (CH); 63.9 (CH2); 63.6 (CH2); 37.5 (CH2); 33.6 (CH2); 33.5 (CH2); 25.2 (CH2); 21.0 (CH2);
20.9 (CH2); 15.3 (2 Me). EI-MS: 229 (2), 211 (14), 186 (51), 158 (25), 130 (46), 99 (100), 88 (43), 75 (94),
55 (96). HR-MS: 229.1429 ([M ꢀ EtO]þ, C12H21O4þ ; calc. 229.1440).

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Helvetica Chimica Acta – Vol. 95 (2012)
11. 6-Hydroxy-2H-pyran-3(6H)-one (18). A mixture of 17a (40 mg, 0.19 mmol), MeCN (10 ml), and
50% HBF4 soln. (0.5 ml) was stirred at r.t. After 18 h, H2O was added, and the hydrolyzate was extracted
with CH2Cl2. The combined org. extract was dried (MgSO4) and concentrated: 20 mg (90%) of
essentially pure 18. Brown liquid. Spectroscopic data: in agreement with those reported in [15].
12. Dihydro-2,2-dimethyl-5H-1,3-dioxolo[4,5-b]pyran-6(3aH)-one (19). To a soln. of 17a (0.060 g,
0.29 mmol) in acetone (20 ml), H2O (3 drops) and conc. H2SO4 soln. (0.4 ml) were added. The mixture
was stirred at 08 for 1 h, and H2O was added before extraction with CH2Cl2. The combined org. extract
was dried (MgSO4) and concentrated and the crude product (0.35 g) purified by FC: 30 mg (60 %) of 19.
Clear liquid. IR (film): 2983s, 2935s, 1740s, 1675m, 1615w, 1454m, 1418m, 1380s, 1311m, 1256s, 1216s,
1179s, 1117s, 1070s, 1027s, 993s, 928s, 868s, 806m, 746w, 671m. 1H-NMR (200 MHz, CDCl3): 5.67 (d, J ¼
5.1, 1 H); 4.70 (dt, J ¼ 3.1, 5.1, 1 H); 4.09 (m, 2 H); 2.75 (m, 2 H); 1.53 (s, 3 H); 1.37 (s, 3 H). 13C-NMR
(50 MHz, CDCl3): 207.1 (C); 109.2 (C); 96.9 (CH); 72.7 (CH); 66.5 (CH2); 39.0 (CH2); 25.6 (Me); 25.0
(Me). EI-MS: 172 (Mþ, 1), 157 (20), 126 (10), 115 (12), 97 (8), 85 (20), 59 (31), 55 (11), 43 (100). HR-
MS: 172.073124 (Mþ, C8H12Oþ4 ; calc. 172.073559).
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Received August 7, 2012