Dioxolane-derived carbanions and their reactivity

Article abstract of DOI:10.1055/s-2000-8206

The generation of negatively charged species by treatment of dioxolanes with BuLi or via fluorodesilylation, results in the formation of new compounds, by spontaneous cycloelimination or upon quenching with C-electrophiles.

Full text of DOI:10.1055/s-2000-8206

1756
PAPER
Dioxolane-Derived Carbanions and Their Reactivity
Silvia Carini, Vanda Cerè, Francesca Peri, Salvatore Pollicino*
Department of Organic Chemistry, “A. Mangini” - University of Bologna, Viale Risorgimento, 4, I-40136 Bologna, Italy
Fax +39(51)2093654; E-mail: pollicin@ms.fci.unibo.it
Received 20 April 2000; 27 June 2000
Abstract: The generation of negatively charged species by treat-
ment of dioxolanes with BuLi or via fluorodesilylation, results in
the formation of new compounds, by spontaneous cycloelimination
or upon quenching with C-electrophiles.
Key words: carbanions, -eliminations, silyl dioxolanes, organo-
metallic reagents, lithium
Since their introduction, as nucleophilic acylating agents,1
1,3-dithianes have become widely used tools for the for-
mation of C C bonds. Conversely dioxolanes, which are
known to play a key role in the protection of functional
groups, have been used only seldom for promoting new
synthetically useful transformations.2 In fact whereas -
alkoxy organolithiums have been often employed in syn-
thesis,3 no simple procedures for the generation of (di-
alkoxymethyl)lithium reagents4 have been previously
devised, unless the carbanion is stabilised by conjugating
substituents.
In this paper we wish to report our results concerning the
base-promoted reactions of a representative series of
mono- and bicyclic silylated or not silylated benzaldehyde
Scheme 1
acetals 1 4.
diate 1a with the benzoate derived from the cycloelimina-
tion reaction competes with the Whitham
cycloelimination leading to the formation, in 23% yield,
of the (1R,7R)-( )-9-benzoyl-9-phenyl-8,10-dioxa-4-thi-
abicyclo 5.3.0 decane (7). Attempts at increasing the
yields of 6 by modifying the temperature and the stoichi-
ometry of the reagents were partly successful only when
2.5 equivalents of BuLi were used, leading to an increase
up to 44% of the yield of 6. Finally the unexpected forma-
tion, in 29% yield, of the (Z)-(5R)-( )-5-hydroxythiacy-
clohept-3-ene (8), configurationally and enantiomerically
pure, can only be due to a proton abstraction from the sev-
en-membered ring in position 2, leading to a -elimination
reaction (path b). Considering the low acidity of the C H
bond at this position the occurrence of path b could be as-
cribed to the higher thermodynamic stability of the cis de-
rivative 8 with respect to 5 as well as to some beneficial
effect on the proton removal due to the Li O interaction
which might favor an ortho-like proton abstraction.7
When the (1R,7R)-( )-9-phenyl-8,10-dioxa-4-thiabicyc-
lo 5.3.0 decane (1)5 was treated with 2 equivalents of
BuLi in THF at 20 °C, three main products 6 8 were
separated, by flash chromatography, from the reaction
mixture (Scheme 1).
The presence of the major product 6 (39%) suggests a re-
action outcome in line with the Whitham reaction,6 gener-
ating, via a cycloelimination (path a), a trans seven-
membered cyclic olefin 5 which, due to its instability, im-
mediately reacts with BuLi to afford the ( )-4-butylthi-
epane (6). As shown by GC and HPLC experiments using
chiral columns, 6 is obtained as an enantiopure product
whose R configuration can be assumed since the congest-
ed situation of the trans-4-thiacycloolefin 5 would allow
attack exclusively on the Si face. Reaction of the interme-
Generation of carbanionic species from 2, the silylated
counterpart of 1, by using the fluorodesilylation was per-
formed in order to obtain regiospecifically the benzylic
carbanion. This compound, obtained under acidic condi-
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PAPER
Dioxolane-Derived Carbanions and Their Reactivity
1757
tions from the corresponding trans diol and benzoyltrim- thiepan derivatives 6 and 8 of high interest as useful syn-
ethylsilane, was subjected to desilylation with anhydrous thetic intermediates and as potentially useful therapeutic
TBAF8 in THF. However, exclusively the desilylated agents,12 the reaction outcome completely changes in the
product 1 was obtained, even in the presence of 1,3-diphe- TBAF-promoted desilylation. Quenching with C-electro-
nylisobenzofuran as the trapping reagent9 for the elusive philes leads in fact (Scheme 2) to an alternative method
cyclic olefin 5. In order to verify if this result could be for generating -dialkoxy carbanionic species synthetical-
generalized for structurally different dioxolanes we syn- ly useful equivalents of fully oxygenated acyl anion syn-
thesized the eight membered carbocyclic vicinal trans thons.13 Since expectations of considerable synthetic
diol derivative 3, which does not suffer from conforma- utility rest upon the ease of acetal hydrolysis14 to alde-
tional strain, and the linear vicinal diol derivative 4, fol- hydes or ketones with respect to the corresponding
lowing the same procedure previously used for 2. In both dithianyl derivatives,15 the implementation of this concept
cases in the presence of TBAF only the desilylated prod- to a wider series of substituted dioxolanes is currently un-
ucts were recovered in high yields (96%). However the der investigation and will be reported in the due time.
desilylation in the presence of a C-electrophile such as
benzaldehyde, cyclohexanecarboxaldehyde and 2-fural-
dehyde led (Scheme 2) to the desilylative hydroxyalkyla-
tion derivatives 10a c and 12a c, together with the
related protodesilylated compounds 9 and 11, from 3 and
All moisture sensitive reactions were performed in flame-dried
glassware equipped with rubber septa under positive pressure of dry
N2. Organic extracts were dried over CaSO4. Light petroleum used
had bp 35–60 °C. Preparative flash chromatographic experiments
were performed using ICN Silica gel 230-400 mesh. For TLC pre-
coated glass plates were used (Stratochrom SIF254, 0.25 mm thick)
and the spots were developed at 110 °C with an aqueous solution of
(NH4)6Mo7O24 (2.5%) and (NH4)4Ce(SO4)4 (1%) in 10% H2SO4 or
KMnO4 (0.1 M)/H2SO4 (1 M) (1:1). Yields are for isolated com-
pounds. Unless specified otherwise 1H and 13C NMR spectra were
recorded at 300 MHz and 75 MHz respectively, in CDCl3 as sol-
vent. Chemical shifts are in ppm downfield of TMS; signal multi-
plicities were established by DEPT experiments. Signal
assignments, if necessary, were elucidated by decoupling 1H NMR
experiments. Optical rotations were measured at 589 nm. THF and
MeCN were dried by distillation from Na/benzophenone and CaH2
respectively.
4, respectively.
Reaction of (1R,7R)-( )-9-Phenyl-8,10-dioxa-4-thiabicyclo-
5.3.0 decane (1) with BuLi; General Procedure
To a solution of 1 (1.180 g, 5 mmol) in THF (40 mL), cooled at
20 °C, was added dropwise a 1.6 M solution of BuLi in hexane
(6.25 mL, 10 mmol) under argon. After stirring at 20 °C for
30 min, satd aq NH4Cl (5 mL) was added, then the mixture was di-
luted with Et2O (15 mL). The organic layer was separated and dried.
After evaporation of the solvent a crude mixture was obtained
(0.995 g) which was subjected to purification by flash chromatog-
raphy to give three main products. (4R)-( )-4-Butylthiepane (6)
was eluted first with light petroleum (0.334 g, 39%).
Scheme 2
6
25
Colorless oil;
14.9 (c = 1.02, CHCl3).
D
1H NMR: = 2.78 2.55 (m, 4 H, 2 CH2S), 2.08 1.88 (m, 2 H),
1.74 1.16 (m, 11 H), 0.85 (t, 3 H, CH3).
13C NMR: = 38.6 (CH), 38.0 (CH2), 37.9 (CH2), 33.8 (CH2), 33.4
For all the substrates 2, 3 and 4 considered, the formation
of hypervalent silicon species10 may be suggested because
the formation of free carbanions would have led to Whith-
am-cycloelimination products which have never been de- (CH2), 32.2 (CH2), 30.3 (CH2), 29.6 (CH2), 23.1 (CH2), 14.3 (CH3).
tected. These results agree with our previous studies,11
dealing with the stereochemistry of the protodesilylation
of -thiasilanes, where the formation of free carbanions
was proposed only in the presence of groups able to stabi-
lize the negative charge.
MS (EI): m/z (%) = 172 (71, M+), 157 (7.0), 143 (71), 129 (65), 115
(100), 87 (78), 81 (69), 55 (75).
HRMS (EI): m/z calcd for C10H20S: 172.1286, found: 172.1198.
The configurational homogeneity of this compound was confident-
ly proved by chromatographic analysis. In fact, using two different
GC chiral columns, (Megadex 5, 25 m, 0.25 mm ID and Rt DEX-
sm, 30 m, 0.32 mm ID) and by HPLC analysis using a chiral column
(Supelcosil LC (R)-naphthyl urea, 25 cm, 4.6 mm ID) only one ste-
reoisomer was detected.
No matter what the mechanistic implication of these re-
sults they appear synthetically promising and envision a
flexible method for a straightforward transformation of
dioxolanes into new interesting compounds. In fact if on
one side the metallation of 1 with BuLi promotes (Scheme
1), via cycloelimination, the formation of configurational-
ly and enantiomerically pure saturated and unsaturated
(1R,7R)-( )-9-Benzoyl-9-phenyl-8,10-dioxa-4-thiabicyclo 5,3,0
decane (7) was eluted next with 40% Et2O/light petroleum (0.383 g,
23%).
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1758
7
S. Carini et al.
PAPER
(1R,7R)-( )-9-phenyl-9-trimethylsilyl-8,10-dioxa-4-thiabicyc-
28
Colorless oil;
89.0 (c = 1.11, CHCl3).
lo 5.3.0 decane (2)
Yield: 0.462 g (75%).
24
D
1H NMR: = 8.55 7.80 (m, 2 H, 2 CHAr), 7.63 7.48 (m, 2 H, 2
CHAr), 7.22 7.45 (m, 6 H, 6 CHAr), 4.32 4.11 (m, 2 H, 2 CHO),
2.75 2.45 (m, 6 H, 2 CH2S and 2 CHH), 1.98 1.70 (m, 2 H, 2
CHH).
13C NMR: = 195.5 (CO), 138.3 (CAr), 133.8 (CAr), 133.0 (CHAr),
130.7 (CHAr), 129.2 (CHAr) 128.7 (CHAr), 128.2 (CHAr) 125.7
(CHAr), 108.9 (C), 82.0 (CHO), 81.8 (CHO), 32.5 (2 CH2), 30.9
(CH2), 30.5 (CH2).
58.3 (c = 0.64, MeOH).
D
1H NMR: = 7.62 7.42 (m, 5 H, CHAr), 4.25 4.16 (m, 1 H, CHO),
4.12 4.03 (m, 1 H, CHO), 3.08 2.71 (m, 6 H), 2.18 2.03 (m, 1 H),
1.91 1.77 (m, 1 H), 0.28 [s, 9 H, Si(CH3)3].
13C NMR: = 144.4 (CAr), 127.9 (2 CHAr), 126.8 (CHAr), 125.5 (2
CHAr), 109.9 (OCO), 82.3 (CHO), 79.9 (CHO), 34.2 (CH2), 32.0
(CH2), 31.2 (CH2), 31.2 (CH2), 4.3 [Si(CH3)3].
MS (EI): m/z (%) = 235 (35), 105 (100), 77 (44), 51 (12).
MS (EI): m/z (%) = 235 (95), 105 (100), 77 (63), 73 (59).
HRMS (EI): m/z calcd for C20H20O3S: 340.1133, found 340.1211.
HRMS (EI): m/z calcd for C16H24O2SSi: 308.1266, found 308.1238.
(Z)-(5R)-( )-5-Hydroxythiacyclohept-3-ene (8) was eluted last
with Et2O (0.188 g, 29%).
10-Phenyl-10-trimethylsilyl-9,11-trans-dioxabicyclo 6.3.0 un-
decane (3)
8
Yield: 0.513 g (84%).
1H NMR: = 7.29 7.10 (m, 5 H, CHAr), 3.90 3.61 (m, 2 H, 2
CHO), 2.61 1.02 (m, 12 H), 0.29 [s, 9 H, Si(CH3)3].
13C NMR: = 144.4 (CAr), 127.5 (2 CHAr), 126.4 (CHAr), 125.5 (2
CHAr), 107.5 (OCO), 83.6 (CHO), 80.7 (CHO), 35.2 (CH2), 33.2
(CH2), 27.8 (CH2), 27.5 (CH2), 23.9 (2 CH2), 4.5 [Si(CH3)3].
25
Colorless oil;
67.9 (c 1.50, CHCl3).
D
1H NMR: = 5.99 (m, 1 H, C3H), 5.82 (dd, 1 H, C4H, J = 11.2, 1.3
Hz), 4.68 4.62 (m, 1 H, C5H), 3.27 (m, 1 H, C2HH, irradiation at
= 5.99 resolved the multiplet into a doublet, J 14.3 Hz), 3.04 (m,
1 H, C2HH irradiation at = 5.99 resolved the multiplet into a dou-
blet, J 14.4 Hz), 3.02 2.92 (m, 2 H, C7H2), 2.18 (br s, 1 H, OH),
2.16 1.86 (m, 2 H, C6H2).
MS (EI): m/z (%) = 231 (22), 135 (10), 109 (17), 105 (100), 77 (35),
73 (43), 67 (31).
13C NMR: = 139.3 (C4), 128.7 (C3), 70.8 (C5), 35.8 (C2), 30.3 (C7),
28.9 (C6).
HRMS (EI): m/z calcd for C18H28O2Si: 304.1858, found 304.1879.
MS (EI): m/z (%) = 130 (64, M+), 115 (31), 97 (51), 84 (93), 69
(100), 55 (47).
4-Benzyl-5-methyl-2-phenyl-2-trimethylsilyl-1,3-trans-diox-
olane (4)
Yield: 0.615 g (94%); only one diastereoisomer.
HRMS (EI): m/z calcd for C6H10OS: 130.0452, found 130.0395.
1H NMR: = 7.68 7.52 (m, 10 H, CHAr), 4.52 4.41 (m, 2 H,
CHO), 3.30 (dd, 1 H, PhCHH, J = 14.3, 8.5 Hz) 3.05 (dd, 1 H, Ph-
CHH, J = 14.2, 4.0 Hz), 1.59 (d, 3 H, CH3, J = 6.1 Hz), 0.43 [s, 9 H,
Si(CH3)3].
13C NMR: = 143.4 (CAr), 139.2 (CAr), 129.3 (2 CHAr), 128.4 (2
CHAr), 128.0 (2 CHAr), 126.8 (CHAr), 126.2 (CHAr), 125.6 (2 CHAr),
108.1 (OCO), 77.9 (CHO), 73.5 (CHO), 36.5 (CH2), 16.1 (CH3),
4.1 [Si(CH3)3].
Mosher’s Ester of Alcohol 8
To establish the optical purity of the allyl alcohol 8 obtained we
converted it to the corresponding Mosher’s ester.16 To a mixture of
4-(dimethylamino)pyridine (37 mg, 0.3 mmol) and Et3N (200 L)
dissolved in CH2Cl2 (1 mL) was added 8 (39 mg, 0.3 mmol). Imme-
diately after, neat ( )- -methoxy- -(trifluoromethyl)phenylacetyl
chloride (60 L, 0.32 mmol) was added. The solution became warm
and turned to orange. After 10 min the reaction was quenched by the
addition of 3-(dimethylamino)propylamine (110 L). After evapo-
ration of the solvent, a residue was obtained which was passed
through a short plug of silica gel in order to remove polar impurities
(5% Et2O/light petroleum). Exclusively one product (98 mg, 95%)
was obtained.
MS (EI): m/z (%) = 326 (M+ 1), 253 (14), 131 (44), 105 (100), 91
(42), 77 (57), 73 (70).
HRMS (EI): m/z calcd for C20H26O2Si: 326.1702, found 326.1622.
Fluorodesilylation of 2, 3 and 4; General Procedure
TBAF (0.630 g, 2 mmol) was dissolved in anhyd MeCN (3.5 mL).
After evaporation of the solvent, the solid residue was maintained
at 40 °C/0.001 Torr for 48 h. To the residue dissolved in anhyd THF
(5 mL) was added a solution of silyldioxolanes 2-4 (2 mmol) in an-
hyd THF (2 mL). The mixture was stirred for 3 h at r.t. and parti-
tioned between Et2O (5 mL) and 10% aq NH4Cl solution (1 mL).
The organic layer was separated, dried, and evaporated to afford 1,
9 and 11 respectively. The spectral data of 1 (0.401 g, 85%) were
identical to the one we have previously reported.5 The spectral data
of 9 (0.443 g, 96%) were identical to the one reported in the litera-
ture.6a
1H NMR: = 7.48 7.42 (m, 2 H, 2 CHAr), 7.36 7.30 (m, 3 H,
3CHAr), 6.03 5.94 (m, 1 H, C3H), 5.82 5.75 (m, 1 H, C5H), 5.64
5.59 (m, 1 H, C4H), 3.48 (s, 3 H, OCH3), 3.19 3.12 (dd, 1 H, C2HH,
J = 15.4, 6.9 Hz), 3.02 2.95 (dd, 1 H, C2HH, J = 15.4, 7.0 Hz),
2.94 2.91 (m, 2 H, C7H2), 2.18 1.97 (m, 2 H, C6H2).
13C NMR: = 165.7 (CO), 133.2 (CH), 132.3 (CAr), 131.2 (CH),
129.8 (CH), 128.6 (CH), 127.4 (CH), 129.3 (q, CF3, J = 298.22 Hz),
84.6 (q, CCF3, J = 28.84 Hz), 75.1 (CHO), 55.6 (OCH3), 32.6
(CH2), 30.1 (CH2), 28.7 (CH2).
2-Silyldioxolanes 2, 3 and 4; General Procedure
4-Benzyl-5-methyl-2-phenyl-1,3-trans-dioxolane (11)
To a solution of the appropriate trans-1,2-diol (2 mmol) in benzene
(10 mL), were added benzoyltrimethylsilane (0.356 g, 2 mmol) and
p-toluenesulfonic acid (12 mg). The mixture was heated at reflux
for 3 h with continuous removal of H2O by means of a Dean Stark
separator. After cooling the solution was extracted with 5% aq
NaHCO3 solution (5 mL) and dried. Evaporation of the solvent led
to a crude mixture which was subjected to flash-chromatography
(2% Et2O/light petroleum) to afford the title compounds 2 4 as vis-
cous colorless oils.
Yield: 0.490 g (96%); only one diastereoisomer;colorless oil.
1H NMR: = 7.75 7.63 (m, 10 H, CHAr), 6.14 (s, 1 H, CHPh),
4.83 4.64 (m, 2 H, CHO), 3.41 3.25 (m, 1 H, PhCHH), 3.21 3.09
(m, 1 H, PhCHH), 1.69 (d, 3 H, CH3, J = 6.1 Hz).
13C NMR: = 138.4 (CAr), 138.2 (CAr), 129.2 (2 CHAr), 129.0 (2
CHAr), 128.0 (2 CHAr), 126.9 (2 CHAr), 126.4 (CHAr), 126.2 (CHAr),
103.1 (OCO), 79.9 (CHO), 75.0 (CHO), 36.4 (CH2), 16.1 (CH3).
MS (EI): m/z (%) = 253 (10), 163 (67), 105 (55), 91 (100), 77 (52),
51 (20).
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PAPER
Dioxolane-Derived Carbanions and Their Reactivity
1759
HRMS (EI): m/z calcd for C17H18O2: 254.1307, found 254.1342.
127.7 (CHAr), 126.5 (CHAr), 126.4 (CHAr), 110.3 (CH=), 110.2
(CH=), 108.8 (CH=), 108.6 (CH=), 107.6 (2 OCO), 84.2 (CHO),
83.7 (CHO), 82.1 (CHO), 81.8 (CHO), 73.0 (CHOH), 72.8
(CHOH), 34.3 (CH2), 34.2 (CH2), 33.1 (CH2), 33.0 (CH2), 27.8
(2CH2), 27.7 (CH2), 27.6 (CH2), 24.2 (CH2), 23.9 (CH2), 23.8
(CH2), 23.7 (CH2).
Carbodesilylation of 3 and 4; General Procedure
A solution of anhyd TBAF (0.313 g, 1.2 mmol) in anhyd THF (5
mL) was added dropwise at 20 °C to a solution of the silylketal 3
or 4 (0.5 mmol) in anhyd THF (4 mL) and freshly distilled aldehyde
(2.4 mmol). The mixture was cooled at 20 °C for 1 h and then
warmed to r.t. After 2 h, the solvent was evaporated and the crude
product was purified by flash chromatography (50% Et2O/light pe-
troleum) to afford 10a c and 9 from 3, and 12a c and 11 from 4,
respectively.
MS (EI): m/z (%) = 310(7), 31(11), 184(8), 157(10), 128(10),
105(100), 95(29), 79(24), 77(38), 67(33).
Phenyl-(4-benzyl-5-methyl-2-phenyl-1,3-trans-dioxolanyl)-
methanol (12a)
Yield: 0.120 g (67%); 1:1 diasteroisomeric mixture.
Phenyl-(10-phenyl-9,11-trans-dioxabicyclo 6.3.0 undecanyl)-
methanol (10a)
Yield: 0.145 g (86%); 1:1 diastereomeric mixture.
1H NMR: = 7.29 7.02 (m, 10 H, CHAr), 4.80 (br s, 1 H, CHOH),
3.98 3.50 (m, 2 H, CHO), 2.71 (br s, 1 H, OH), 2.30 1.02 (m, 12
H).
13C NMR: = 140.9 (CAr), 140.8 (CAr), 138.2 (CAr), 137.9 (CAr),
128.1 (CHAr), 127.8 (CHAr), 127.4 (CHAr), 127.3 (CHAr), 127.2
(CHAr), 126.8 (CHAr), 126.7 (CHAr), 108.9 (OCO), 83.8 (CHO),
81.8 (CHO), 78.6 (2 CHO), 34.3 (CH2), 34.2 (CH2), 33.0 (CH2),
33.0 (CH2), 27.8 (CH2), 27.7 (CH2), 27.6 (CH2), 24.0 (CH2), 23.9
(CH2), 23.8 (CH2).
1H NMR: = 7.64 7.36 (m, 15 H, CHAr), 5.12 (br s, 1 H, CHOH),
4.58 4.42 (m, 2 H, CHO), 3.29 3.20 (m, 2 H, OH and PhCHH),
3.07 2.98 (m, 1 H, PhCHH), 1.55 (d, 3 H, CH3, J = 6.1 Hz).
13C NMR: = 139.7 (CAr), 138.4 (CAr), 138.1 (CAr), 137.9 (CAr),
137.8 (CAr), 129.2 (CHAr), 129.1 (CHAr), 128.5 (CHAr), 128.4
(CHAr), 128.3 (CHAr), 128.2 (CHAr), 128.1 (CHAr), 127.6 (CHAr),
127.6 (CHAr), 127.3 (CHAr), 127.0 (CHAr), 126.4 (CHAr), 126.3
(CHAr), 109.4 (OCO), 109.3 (OCO), 78.7 (CHO), 78.4 (CHO), 78.2
(CHO), 74.2 (CHO), 36.3 (CH2Ph), 35.9 (CH2Ph), 15.9 (CH3), 15.6
(CH3).
MS (EI): m/z (%) = 360 (M+ 1), 254 (17), 253 (89), 131 (44), 105
(100), 77 (28)
MS (EI): m/z (%) = 231 (85), 123 (15), 109 (24), 106 (11), 105
(100), 86 (17), 84 (25), 77 (28), 67 (26).
Cyclohexyl-(4-benzyl-5-methyl-2-phenyl-1,3-trans-dioxolanyl)-
methanol (12b)
Yield: 0.271g (74%); 1:1 diasteroisomeric mixture. An analytical
sample of the diasteroisomeric mixture was separated by prepara-
tive TLC (SiO2, 15% Et2O/light petroleum) into two separate dias-
teroisomers as viscous oils.
Cyclohexyl-(10-phenyl-9,11-trans-dioxabicyclo 6.3.0 undecan-
yl)methanol (10b)
Yield: 0.274g (79%); 1:1 diasteroisomeric mixture. An analytical
sample of the diasteroisomeric mixture was purified by preparative
TLC (SiO2, 5% Et2O/light petroleum) to give the two separate di-
asteroisomers as colorless oils.
First diasteroisomer
1H NMR: = 7.45 7.38 (m, 2 H, CHAr), 7.34 7.19 (m, 8 H, CHAr),
4.26–4.09 (m, 2 H, CHO), 3.59 (d, 1 H, CHOH, J = 3.0 Hz), 2.97
(dd, 1 H, PhCHH, J = 14.3, 8.8 Hz), 2.73 (dd, 1 H, PhCHH,
J = 14.5, 4.6 Hz), 2.25 (br s, 1 H, OH), 1.96 1.80 (m, 1 H), 1.70
1.40 (m, 4 H), 1.29 (d, 3 H, CH3, J = 6.25 Hz), 1.15 0.92 (m, 6 H).
First diasteroisomer
1H NMR: = 7.58 7.45 (m, 2 H, CHAr), 7.39 7.27 (m, 3 H, CHAr),
4.14 3.94 (m, 1 H, CHO), 3.63 3.52 (m, 1 H, CHO), 3.57 (d, 1 H,
CHOH, J = 2.9 Hz), 2.45 2.11 (m, 2 H and OH), 1.95 0.96 (m, 21
H).
13C NMR: = 140.8 (CAr), 138.4 (CAr), 129.2 (CHAr), 128.6 (CHAr),
128.5 (CHAr), 128.2 (CHAr), 128.1 (CHAr), 126.6 (2 CHAr), 126.4
(CHAr), 110.3 (OCO), 79.4 (CHO), 77.8 (CHO), 74.3 (CHOH), 38.6
(CH), 36.1 (CH2), 31.4 (CH2), 26.7 (CH2), 26.6 (CH2), 26.5 (CH2),
26.2 (CH2), 16.1 (CH3).
13C NMR: = 142.1 (CAr), 128.1 (CHAr), 127.9 (2 CHAr), 126.6 (2
CHAr), 109.2 (OCO), 84.3 (CHO), 80.8 (CHO), 79.3 (CHOH), 38.4
(CH), 34.6 (CH2), 33.2 (CH2), 31.6 (2 CH2), 28.0 (CH2), 27.9 (CH2),
26.6 (CH2), 26.4 (CH2), 26.3 (CH2), 24.2 (CH2), 24.1 (CH2).
MS (EI): m/z (%) = 327( 1), 231(24), 105(100), 93 (18), 83(39),
79(40), 77(45), 67(38), 55(83), 51(14).
MS (EI): m/z (%) = 348( 1), 253 (27), 128 (17), 115 (15), 105
(100), 91 (58), 83 (26), 77 (46), 55 (38).
Second diasteroisomer
Second diasteroisomer
1H NMR: = 7.80 7.73 (m, 2 H, CHAr), 7.63 7.54 (m, 3 H, CHAr),
4.27 4.16 (m, 1 H, CHO), 4.05 3.96 (m, 1 H, CHO), 3.77 (d, 1 H,
CHOH, J = 3.2 Hz), 2.67 2.33 (m, 2 H + OH) 2.17 1.13 (m, 21 H).
1H NMR: = 7.47 7.36 (m, 2 H, CHAr), 7.36 7.20 (m, 8 H, CHAr),
4.28 4.22 (m, 1 H, CHO), 4.11 4.02 (m, 1 H, CHO), 3.61 (d, 1 H,
CHOH, J = 2.53 Hz), 2.94 (dd, 1 H, PhCHH, J = 14.1, 9.62 Hz),
2.73 (dd, 1 H, PhCHH, J = 14.1, 4.22 Hz), 2.33 (br s, 1 H, OH),
1.92 1.79 (m, 1 H), 1.68 1.42 (m, 4 H), 1.29 (d, 3 H, CH3, J = 6.4
Hz), 1.17 0.92 (m, 6 H).
13C NMR: = 141.9 (CAr), 127.9 (3 CHAr), 126.4 (2 CHAr), 109.0
(OCO), 83.1 (CHO), 82.2 (CHO), 79.9 (CHOH), 38.5 (CH), 34.5
(CH2), 33.3 (CH2), 31.5 (CH2), 27.9 (CH2), 27.7 (CH2), 26.6 (CH2),
26.5 (CH2), 26.4 (CH2), 26.3 (CH2), 24.0 (CH2), 23.9 (CH2).
13C NMR: = 140.8 (CAr), 138.6 (CAr), 129.4 (CHAr), 128.5 (CHAr),
128.2 (CHAr), 128.1 (CHAr), 126.5 (CHAr), 126.4 (CHAr), 110,4
(OCO), 79.2 (CHO), 79.1 (CHO), 73.2 (CHOH), 38.4 (CH), 36.6
(CH2), 31.6 (CH2), 26.6 (CH2), 26.5 (CH2), 26.3 (CH2), 15.5 (CH3).
MS (EI): m/z (%) = 327( 1), 231(30), 105(100), 93 (15), 83(39),
79(43), 77(44), 67(38), 55(83), 51(14).
2-Furyl-(10-phenyl-9,11-trans-dioxabicyclo 6.3.0 undecanyl)-
methanol (10c)
Yield: 0.223 g (68%); 1:1 diasteroisomeric mixture
MS (EI): m/z (%) = 348( 1), 253 (28), 128 (19), 115 (15), 105
(100), 91 (56), 83 (26), 77 (46), 55 (37).
1H NMR: = 7.42 7.25 (m, 2 H, CHAr), 7.32 7.23 (m, 4 H, 3 CHAr
and CH=), 6.26 6.22 (m, 1 H, CH=), 6.16 6.14 (m, 1 H, CH=),
4.82 (br s, 1 H, CHOH), 3.98 3.83 (m, 1 H, CHO), 3.78 3.68 (m,
1 H, CHO), 2.74 (br s, 1 H, OH), 2.28 2.12 (m, 2 H), 1.83 1.50 (m,
4 H), 1.43 0.98 (m, 6 H).
13C NMR: = 152.1 (CAr), 151.7 (CAr), 141.9 (CH=), 141.7 (CH=),
141.0 (C=), 140.9 (C=), 128.2 (CHAr), 128.0 (CHAr), 127.8 (CHAr),
2-Furyl-(4-benzyl-5-methyl-2-phenyl-1,3-trans-dioxolanyl)-
methanol (12c)
Yield: 0.266g (76%); 1:1 diasteroisomeric mixture.
1H NMR: = 7.31 7.19 (m, 11 H, 10 CHAr and CH=), 6.25 6.12
(m, 2 H, CH=), 4.88 (br s, 1 H, CHOH), 4.28 4.13 (m, 2 H, CHO),
3.03 2.90 (m, 1 H, PhCHH), 2.76 2.66 (m, 1 H, PhCHH), 1.27 (br
s, 3 H, CH3).
Synthesis 2000, No. 12, 1756–1760 ISSN 0039-7881 © Thieme Stuttgart · New York

1760
S. Carini et al.
PAPER
13C NMR: = 151.6 (C=), 143.0 (C=), 141.8 (CH=), 141.7 (CH=),
139.8 (CHAr), 138.3 (CHAr), 138.2 (CHAr), 129.3 (CH), 129.2 (CH),
129.1 (CH), 128.5 (CH), 128.4 (CH), 128.3 (CH), 127.8 (CH), (2
CH), 126.6 (CH), 126.5 (CH), 126.4 (CH), 126.3 (CH), 110.4
(CH=), 110.3 (OCO), 109.0 (OCO), 108.9 (CH=), 79.0 (CHO), 78.4
(CHO), 74.6 (CHO), 74.3 (CHO), 72.4 (CHOH), 36.2 (CH2), 35.9
(CH2), 15.8 (CH3), 15.5 (CH3).
(6) Hines, J. N.; Peagram, M. J.; Thomas, E. J.; Whitham, G. H.
J. Chem. Soc. Perkin Trans.1 1973, 2332.
Bridges, A.J.; Whitham, G. H. J. Chem. Soc.,Chem. Commun.
1974, 142.
Jones, M.; Temple, P.; Thomas, E. J.; Whitham, G. H. J.
Chem. Soc. Perkin Trans, 1 1974, 433.
Connell, A.C.; Whitham, G. H. J. Chem. Soc., Perkin Trans. 1
1983, 989.
MS (EI): m/z (%): 332(5), 253(21), 148(16), 129(31), 115(24),
105(100), 95(41), 91(58), 77(40).
(7) Snieckus, V. Chem. Rev. 1990, 90, 879.
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1965, 87, 934.
(10) McDougal, P. G.; Condon, B. D. Tetrahedron 1989, 30, 789.
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4599.
Acknowledgement
This work has been supported by University of Bologna (Funds for
Selected Research Topics, A. A. 1995-97) and by the National Pro-
ject “Stereoselezione in Chimica Organica, Metodologie ed Appli-
cazioni”.
Soderquist, J. S.; de Puy, C. H. J. Am. Chem. Soc. 1985, 45,
3385.
(11) Cerè, V.; Peri, F.; Pollicino, S. Heterocycles 1999, 51, 1025.
(12) Lautens, M.; Fillion, E.; Sampat, M. Tetrahedron Lett. 1998,
39, 1501.
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Article Identifier:
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Synthesis 2000, No. 12, 1756–1760 ISSN 0039-7881 © Thieme Stuttgart · New York