Does substituent's conformation influence the kinetics of reduction reactions on trans-4-X-decal-1-ones and to what extent?

Article abstract of DOI:10.1016/S0040-4020(02)00303-4

Stereochemistry and relative rates k_ax and k_eq of reduction reactions on title compounds have been measured under five different reaction conditions (NaBH₄ in i-PrOH, LiBH₄ and NaAlH₄ in THF and LiAlH₄ in THF and in Et₂O). Experiments indicate that axial substituents behave as far less electronegative than their equatorial counterpart in reactions at the equatorial side of molecules.

Full text of DOI:10.1016/S0040-4020(02)00303-4

TETRAHEDRON
Pergamon
Tetrahedron 58 &2002) 3313±3318
Does substituent's conformation in¯uence the kinetics of
reduction reactions on trans-4-X-decal-1-ones and to what extent?
Giorgio Di Maio,p Maria Gabriella Mascia and Elisabetta Vecchip
Á
Dipartimento di Chimica, Universita `la Sapienza', P. le A. Moro 5, I-00185 Roma, Italy
Received 20 December 2001; accepted 14 March 2002
AbstractÐStereochemistryand relative rates kax and keq of reduction reactions on title compounds have been measured under ®ve different
reaction conditions &NaBH4 in i-PrOH, LiBH4 and NaAlH4 in THF and LiAlH4 in THF and in Et2O). Experiments indicate that axial
substituents behave as far less electronegative than their equatorial counterpart in reactions at the equatorial side of molecules. q 2002
Published byElsevier Science Ltd.
1. Introduction
C4±X bond irrespective of their axial or equatorial confor-
mation. The HOMO carbonyl orbital suffers instead
opposite distortion effects from the b-CC and the axial
C4±X bond hyperconjugation the balance being determined
bythe identityof the X group. Actually, we have found, for
instance, that the axial reactivities behave monotonicallyi.e.
theyalways increase with increasing electronegativityof the
X group, whereas the changes in equatorial reactivity
strictlydepend on the conformation of the X group and
the reaction conditions.
We have been interested in understanding p-face selectivity
in addition and reduction reactions in cyclohexanone
systems.1,2
Our previous experiments and MO considerations1 suggest
&see Schemes 1 and 2) that the LUMO carbonyl orbital is
more extended on the axial face of the molecule both under
the in¯uence of b-CC bond's hyperconjugation and the
The limit of our previous experiments was that we used two
different rigid systems, one for the axial and the second for
the equatorial substituent. Therefore, the rate values we
obtained could hardlybe removed from the intrinsic
Scheme 1. Distortions of the carbonyl group HOMO and LUMO orbitals
with a C4±X equatorial substituent.
Keywords: reduction reactions; substituents'conformation; kinetics; trans-
4-X-decal-1-ones.
p
Corresponding authors. Tel.: 139-6-49913675; fax: 139-6-490631;
e-mail: elisabetta.vecchi@uniroma1.it
Scheme 2. Distortions of the carbonyl group HOMO and LUMO orbitals
with a C4±X axial substituent.
0040±4020/02/$ - see front matter q 2002 Published byElsevier Science Ltd.
PII: S0040-4020&02)00303-4

3314
G. Di Maio et al. / Tetrahedron 58 +2002) 3313±3318
²
axial attack of the reduction agents, and &1±7)00 derived
from equatorial attack &Fig. 1).
2. Results and discussion
For each set of reaction conditions we determined the
stereochemistryof reduction reactions byGLC. Table 1
collects the stereochemical outcome of several reactions
&®ve experiments at least for each substrate under all reac-
tion conditions). Stereochemical ratios kax/keq &Table 1)
show
1. a monotonic trend, that is an increase with increasing the
axial substituent electronegativity, just for the axial
substituents and for reactions with boron reactants;
Figure 1.
Table 1. Stereochemical product ratios &kax/keq) for trans-4-X-decal-1-ones &1±7)
Reaction conditions
Stereochemical product ratios &kax/keq)
Axial substituent
Equatorial substituent
10/100 sIˆ0.00
20/200 sIˆ0.24
30/300 sIˆ0.38
40/400 sIˆ0.47
50/500 sIˆ0.24
60/600 sIˆ0.38
70/700 sIˆ0.47
&a) NaBH4, i-PrOH, 208C
&b) LiBH4, THF, 208C
&c) NaAlH4, THF, 208C
&d) LiAlH4, THF, 208C
&e) LiAlH4, Et2O, 208C
2.43
3.08
2.78
3.05
3.54
6.97
7.48
5.78
8.49
8.11
7.35
8.23
4.70
7.63
6.12
10.44
13.01
7.10
12.64
10.64
2.72
3.25
2.66
2.62
2.93
6.17
7.36
3.62
7.77
6.51
3.27
3.52
2.25
2.40
3.01
reactivities of the two unsubstitued systems to neatly show
the effect of changing the conformation of the C4±X group.
2. the increasing kax/keq trend is interrupted for XˆOAc
&30/300) for aluminium reactants in reactions on substrates
with Xax;
Two principal questions needed an answer. Are the axial
reactivities independent of the C4±X group conformation
as MO considerations suggest? How much does the
equatorial reactivitydepend on the C 4±X group con-
formation?
3. under all reaction conditions the reactions on Xeq bearing
substrates show a maximum in the kax/keq values when
XˆOAc &60/600).
We also performed a series of competitive kinetic experi-
ments on equimolecular mixtures of compounds 1 and
³
The title compounds having the same substituent once in the
axial and once in the equatorial conformation represent a
suitable model for exploring in more detail changes in kax
and keq.
compounds 2±7, respectively. The overall and relative
reaction rates are reported in Table 2 as the mean of at
least ®ve separate experiments.
The kinetic data show that the overall reaction rates always
increase on increasing the substituent's &both axial and
equatorial) electronegativity. Relative rates show instead a
far less homogeneous pattern: kax almost always increase
under the in¯uence of both axial and equatorial substituents.
The changes in kax between XˆH and XˆCl strictlyparallel
those previouslyfound in the b-decalone systems. The keq
show instead a less homogeneous pattern: theyalmost
always increase under the in¯uence of the equatorial sub-
stituents &columns 1, 5±7 in Table 2). Instead, the axial
substituents produce a less de®nite trend which sharply
contrasts with the behaviour previouslydescribed for the
b-decalone systems in which the keq decrease and ®nally
vanish for XˆCl thus mimicking an elecrophilic attack of
In this paper, we describe the stereochemical and kinetic
results of reduction reactions on a series of trans-4-X-
decal-1-ones namely 1 &XˆH); 2 and 5 &XˆOH); 3 and 6
&XˆOAc); 4 and 7 &XˆCl) carrying the same substituent
respectivelyin the axial & 2±4) and in the equatorial &5±7)
conformation &Fig. 1).
Their reactivityhas been compared in the following
reaction conditions: &a) NaBH4/i-PrOH; &b) LiBH4/THF;
&c) NaAlH4/THF; &d) LiAlH4/THF; &e) LiAlH4/Et2O.
Houk3 alreadystudied the stereochemical product ratios
&kax/keq) for reaction condition &a) on the same compounds.
We succeeded in separating the reaction products from
one another byHPLC &see Section 4 for full spectroscopic
characterization).
²
Compounds 20 and 500 are the same: the choice of indicating them with
different numbers is due to simplicityin reading the entries in Tables 1
and 2.
³
See Ref. 2 concerning competitive kinetic experiments, their reliability,
the methods of GLC standardization of both substrates and reaction
products and the methods used for computing the yields of reactions.
Under all the above-mentioned reaction conditions, the only
reaction products were alcohols &1±7)0 that derived from

G. Di Maio et al. / Tetrahedron 58 +2002) 3313±3318
Table 2. Overall ratio of rates and relative rates for trans-4-X-decal-1-ones &1±7)
3315
Reaction conditions
Overall ratio of rates
Relative rates
Xax
Xeq
kax
keq
a
a
k1/k2/k3/k4
k1/k5/k6/k7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
&a) NaBH4 i-PrOH
&b) LiBH4 THF
&c) NaAlH4 THF
&d) LiAlH4 THF
&e) LiAlH4 Et2O
1/1.23/5.35/5.83 1/2.16/6.05/6.10
1/1.50/3.81/6.43 1/2.87/5.06/5.90
1/0.79/1.66/2.53 1/1.04/2.30/2.85
1/0.83/1.65/1.94 1/0.96/1.83/1.66
1/0.97/1.28/1.63 1/1.14/1.42/1.51
1
1
1
1
1
1.53 6.61 7.52 2.23 7.34 6.57 0.41 0.22 0.90 0.72 0.82 1.19 2.01
1.72 4.44 7.94 2.89 5.89 6.05 0.32 0.23 0.54 0.61 0.89 0.80 1.72
0.92 1.88 2.98 1.04 2.46 2.68 0.36 0.16 0.40 0.42 0.39 0.68 1.19
1.02 1.91 2.40 0.92 2.18 1.56 0.33 0.12 0.25 0.19 0.35 0.28 0.65
1.13 1.41 1.91 1.08 1.56 1.44 0.28 0.14 0.23 0.18 0.37 0.24 0.48
a
Mean standard deviation: 0.02.
Table 3. LFER data &r in decreasing order and corresponding r2) in differ-
ent reaction conditions
poor correlation coef®cients. This is particularlytrue when
the axial and equatorial attack are compared for reactions
with an axial substituent. We have alreadydiscussed this
2
Reaction conditions
Axial attack
Equatorial attack
phenomenon in MO terms and de®ned equatorial reactivity
as less predictable, when the C4 substituent is axial.
r
r2
r
r2
Axial substituents
&a) NaBH4 i-PrOH
&b) LiBH4 THF
&c) NaAlH4 THF
&d) LiAlH4 THF
&e) LiAlH4 Et2O
2.03
1.91
0.98
0.83
0.55
0.87
0.93
0.69
0.79
0.84
0.75
0.67
0.2
20.36
20.31
0.32
0.45
0.05
0.16
0.24
Table 3 also contains the answers to the questions we posed
at the beginning: the rax show small changes when the
substituent conformation is changed &compare equally
lettered lines in the axial attack column). Even the reaction
rates do not change, see Table 2. One can infer that the
LUMO suffers the same distortion towards the axial side
of the molecule irrespective of substituent conformation.
Equatorial substituents
&a) NaBH4 i-PrOH
&b) LiBH4 THF
1.94
1.76
1.00
0.60
0.40
0.93
0.97
0.78
0.48
0.78
1.40
1.37
1.02
0.39
0.27
0.97
0.87
0.77
0.25
0.17
&c) NaAlH4 THF
&d) LiAlH4 THF
&e) LiAlH4 Et2O
The req, however, depend on the substituent conformation
&compare equallylettered lines in the equatorial attack
column).
the reactants and suggesting that the carbonyl group HOMO
has lesser and lesser amplitude on the equatorial side of the
molecule as described in Scheme 2. A similar conclusion is
hard to attain if one looks at the keq values in Table 2
&columns 1±4). However, that the binding of the molecule
is smaller on the equatorial side and when C4±X is axial is
evidenced bythe keq values which are systematically smaller
&244 times) in this case &compare columns 2, 3 and 4 to 5, 6
and 7, respectively). This behaviour is in keeping with the
MO description of Schemes 1 and 2 &see HOMO). The
difference in the trend of keq in the a and b-decalone
systems we mentioned above means that not only equatorial
and axial substituents behave differentlybut also that the
So, for axial attack on the molecule, we are left with the
traditional situation that is one r set and one s set inde-
pendentlyof the substituent conformation. For the equa-
torial attack on the molecule, things are less comfortable
since a choice must be made between duplicating r values
&as in Table 3) or duplicating s values: this last choice
seems, in our opinion, more reasonable. The situation
could be even more complicated in the waydescribed by
Van Bekkum et al.5 of a multiplicityof sI values. The
chlorine substituent is the onlyone for which some calcu-
lations can be done: we trust less the OH and OCOMe
substituents owing, as mentioned, to complexation or
anchimeric assistance phenomena theycan give in different
amounts on changing their conformation.6±9 Therefore,
using LFER obtained for reaction conditions &a), &b) and
&c) and adopting as r values those obtained when the sub-
stituent is equatorial &1.4, 1.37, 1.02,k Table 3) one obtains
for &sax)Cl three veryclose values which are: 0.16, 0.12, and
0.13, respectively. Perhaps close enough to rule out, so far,
the hypothesis involving a multiplicity of s values. This
means that the chlorine atom `in the axial conformation
and for reactions on the equatorial side behaves as far
less electronegative'. In other words, what is called the
`electronegativity' of a substituent can be modulated by
its MO interactions with the reacting site &and, in this
case, with the b-CC bonds).
same can be done bythe C ±X axial substituents in two
4
strictlyrelated molecules. We suggest that this difference
could perhaps be related to the fact that the distances and
geometries of an axial substituent vs. the carbonyl group are
more rigidly®xed in the b-decalone system than in the
a-decalone one, thus producing either different dipole±dipole
interactions, or a different amount of the MO perturbation.§
Kinetic data in Table 2 show something more if we use them
to construct LFER &11log kax and 11log keq vs. substituents
sIs4). From each LFER we calculated the values of r and r2
respectivelywhich are reported in Table 3. Each line in
Table 3 contains ®gures originated from the same experi-
ment and should be affected bythe same systematic experi-
mental errors. Nevertheless, we go from fairlygood to very
2
Table 3 shows the same phenomenon we alreadyrecently
§
No surprise that the two hypotheses could result in the same thing in the
future.
k
Smaller r values give higher errors in reading plots.

3316
G. Di Maio et al. / Tetrahedron 58 +2002) 3313±3318
discussed, that is the reaction sensitivities are correlated
to the III Group metal which has a prominent role in
determining the structure of the transition state shape.
GLC conditions &initial oven temperature, isotherm time,
temperature increase rate, ®nal oven temperature): 808C,
4 min, 158C/min, 1808C, 20 min; TinjˆTdetˆ2308C. 1, 100
and 10 were detected during the initial isotherm. The sepa-
rations byHPLC were performed on a Varian 9001
instrument equipped with a Varian RI-4 differential
refractometer. Solvents were HPLC grade.
3. Conclusions
We determined the axial and equatorial rates of attack on a
series of trans-4-X-decal-1-ones in reduction reactions.
4.2. Starting materials
2
As formerlyevidenced, the reaction sensitivityis mainly
affected bythe changes of Group III metal &B and Al) while
changes of Group I metals &Li and Na) onlyhave a minor
in¯uence.
trans-Bicyclo[4.4.0]decan-2-one is commercially available
&Aldrich) and was used as such. Published procedures3 were
used for the preparation of &1S,5R,6S)p-5-hydroxy-
bicyclo[4.4.0]decan-2-one 2 and &1S,5S,6S)p-5-hydroxy-
bicyclo[4.4.0]decan-2-one 5, for &1S,5R,6S)p-5-acetoxy-
bicyclo[4.4.0]decan-2-one 3 and &1S,5S,6S)p-5-acetoxybi-
cyclo[4.4.0]decan-2-one 6, for &1S,5R,6S)p-5-chlorobicyclo-
[4.4.0]decan-2-one 4 and for &1S,5S,6S)p-5-chlorobicyclo-
[4.4.0]decan-2-one 7.
The LUMO of a carbonyl group is more distorted on the
axial face of a cyclohexanone system irrespective of the
conformation of the remote substituent.
Axial reactivityis independent from the substituent's
conformation, but axial substituents behave differently
depending on which molecular skeleton theyare bonded to.
4.3. Preparation of reagents, reactions and competition
experiments
2
Standard procedures previouslydescribed were adopted.
Equatorial reactivityis instead related to the substituent
conformation. We suggest that HOMO is less developed
on the equatorial side of the molecule under the in¯uence
of an axial C4±X substituent.
4.3.1. Reaction products. We performed separate reduction
reactions on compounds &1±7) using standard procedure.
After working up, the crude reaction mixtures were sepa-
rated into their components byHPLC: the purityof each
compound was tested byGLC. Besides physical chemical
properties, we report the most suitable HPLC solvent
composition and the elution order of compounds from
each mixture.
Our data suggest that axial substituents have a much lower
electronegativitythan their equatorial counterparts in
reactions on the equatorial side of the molecule.
Additions to a trigonal stereogenic centre occur at quite
different reaction rates, one on each side of the molecule
and each one with its own controls. The idea which persists
in questions focussed on `p-face diastereoselection' that it is
possible to infer what happens on both sides of a molecule
bysimple determinations of the kax/keq ratios should be
de®nitivelyabandoned.
Puri®cation byHPLC &CH 2Cl2/EtOAcˆ80:20), gave, in
order, 100 and 10
Compound 10. White needles, mp 60±618C &lit.10 638C);
nmax &CHCl3) 3620, 3460, 3020, 2930, 2860, 1620, 1450,
1365, 1260, 1240, 1100, 1020, 950, 810 cm21; m/z &%): 154
&M1, 11) 136 &100), 121 &43), 111 &39), 94 &60), 81 &43), 67
&66), 55 &36), 41 &38); 1H NMR d &200 MHz CDCl3) 3.15±
3.08 &bm, 1H, CHaxOH) &lit.10 3.05), 2.07±1.87 &m, 4H),
1.68±0.81 &m, 12H); 13C NMR d 74.04 &CHOH), 49.44,
40.11, 34.80, 32.58, 32.42, 27.99, 25.33, 25.14, 23.03.
4. Experimental
4.1. Instruments
Melting points were determined on a Mettler FP82HP
apparatus and are uncorrected. HRMS were performed on
a Bruker Spectrospin APEX TM 47e FT-IRC instrument.
Microanalyses were carried out on a CE instrument EA
1110. IR spectra were recorded on a Perkin±Elmer 1600
Series FTIR. GC-MS analyses were performed with a
GC-MS HP 5970 Chemstation Mass Selective Detector
connected with a HP 5890 gas chromatograph using a
capillarycolumn coated with ¯uid methly silicone
Compound 100. Pale yellow viscous oil &lit.10 498C); nmax
&CHCl3) 3620, 2930, 2860, 1460, 1260, 1230, 1100, 1015,
820 cm21; m/z &%): 154 &M1, 3.1), 136 &100), 121 &36), 111
&26), 107 &34), 95 &43), 94 &57), 81 &39), 67 &64), 57 &22), 55
1
&36), 41 &42); H NMR d &300 MHz, CDCl3) 3.73 &bs, 1H,
CHeqOH) &lit.10 3.7), 1.58±1.42 &m, 8H), 1.23±1.2 &m, 8H);
13C NMR d: 70.66 &CHOH), 47.13, 35.56, 34.31, 33.84,
33.67, 29.69, 26.71, 26.36, 19.96.
1
&12.5 m, 0.2 mm i.d.). H and 13C NMR spectra &CDCl3)
were recorded on a GEMINI 200 and on a VARIAN XL
300 spectrometers with CHCl3 as internal standard. GLC
analyses were carried out on a Carlo Erba HRGC Mega
Series 5300 apparatus using a 25 m, 0.25 mm i.d. fused
silica capillarycolumn &stationaryphase CARBOWAX
20 M), He ¯owˆ0.5 ml/min. Reaction mixtures were eluted
in the order &1, 100, 10), &200, 2, 20), &3, 300, 30), &4, 400, 40), &5,
500, 50), &6, 600, 60) and &7, 70,700). We report the most suitable
Puri®cation byHPLC &H 2O/CH3CNˆ90:10), gave, in order,
20 and 200.
Compound 20ˆ500. White needles, mp 161±1628C; Anal.
calcd for C10H18O2: C, 70.53; H, 10.66; found: C, 70.56;
H, 10.68; nmax &CHCl3) 3690, 3605, 2930, 2855, 1600, 1230,
790 cm21; m/z &%): 170 &M1, 3), 152 &8), 134 &56), 123 &39),
112 &100), 108 &77), 95 &85), 81 &67), 79 &65), 67 &86), 58

G. Di Maio et al. / Tetrahedron 58 +2002) 3313±3318
3317
&78), 41 &60); 1H NMR d &300 MHz, CDCl3) 3.62 &bd, 1H,
CHeqOH, Jˆ2.4 Hz), 3.18±3.14 &dt, 1H, CHaxOH, Jtˆ
9.9 Hz, Jdˆ4.8 Hz), 2.15±2.11 &m, 1H), 1.80±1.16 &m,
14415H); 13C NMR &d): 74.00 &CHOHeq), 68.54 &CHOHax),
43.85, 41.84, 30.32, 28.27, 28.18, 28.12, 25.29, 24.79.
Puri®cation byHPLC &H 2O/CH3CNˆ87:13), gave, in order,
50 and 500.
Compound 50. White needles, mp 156±1578C; Anal. calcd
for C10H18O2: C, 70.53; H, 10.66; found: C, 70.50; H, 10.68;
nmax &CHCl3) 3640, 2930, 2860, 1450, 1380, 1260, 1230,
1100, 1030 cm21; m/z &%): 170 &M1, 1), 152 &76), 134 &77),
123 &43), 112 &53), 108 &71), 95 &80), 81 &64), 79 &62), 67
Compound 200. White needles, mp 137±1388C; Anal. calcd
for C10H18O2: C, 70.53; H, 10.66; found: C, 70.49; H, 10.68;
nmax &CHCl3) 3690, 3605, 3020, 2930, 2860, 1600, 1230,
1210 cm21; m/z &%): 152 &100), 134 &91), 123 &57), 108
1
&100), 55 &58), 41 &66); H NMR d &300 MHz, CDCl3)
3.32±3.12 &bm, 2H, CHaxOH), 2.06±0.84 &m, 14H); 13C
NMR &d) 74.09 &CHOH), 47.46, 32.96, 28.93, 25.55.
1
&79), 95 &83), 79 &75), 67 &97), 55 &65), 41 &81); H NMR
d &300 MHz, CDCl3) 3.71±3.69 &bm, 2H, CHeqOH), 1.86±
1.84 &bd, 2H, Jˆ9.3 Hz) 1.60±1.18 &m, 12H); 13C NMR &d):
70.08 &CHOH), 39.13, 29.39, 27.25, 26.31.
Puri®cation byHPLC & n-hexane/EtOAcˆ80:20), gave, in
order, 600 and 60.
Puri®cation byHPLC &CH 2Cl2/EtOAcˆ80:20), gave, in
order, 30and 300.
Compounf 60. White needles, mp 95.0±95.58C; Anal. calcd
for C12H20O3: C, 67.88; H, 9.50; found: C, 67.91; H, 9.48;
nmax &CHCl3) 3620, 3470, 2950, 2860, 1725, 1450, 1380,
1270, 1130, 1030 cm21; m/z &%):152 &11), 134 &100), 119
&16), 108 &45), 95 &14), 92 &31), 79 &27), 67 &23), 43 &47); 1H
NMR d &300 MHz, CDCl3): 4.49±4.41 &dt, 1H, CHOAc,
Jtˆ10.2 Hz, Jdˆ3.6 Hz), 3.24±3.17 &m, 1H, CHaxOH),
2.00 &s, 3H), 1.81±1.6 &m, 6H), 1.42±1.12 &m, 8H); 13C
NMR &d):170.83, 75.96 &CHOAc), 73.73 &CHOH), 47.62,
44.62, 32.73, 29.30, 28.93, 28.78, 25.46, 25.39, 21.15.
Compound 30. White viscous oil; HRMS: found 212.1416.
C12H20O3 requires 212.1412; nmax &CHCl3) 3620, 3010,
2930, 2860, 1720, 1450, 1380, 1260, 1025, 760 cm21; m/z
&%):152 &18), 135 &14), 134 &100), 108 &30), 92 &25), 79
1
&20), 67 &18), 43 &32); H NMR d &300 MHz, CDCl3) 4.84
&bt, 1H, CHOAc), 3.29±3.21 &m, 1H, CHaxOH), 2.18 &d, 2H,
Jˆ9 Hz), 2.01 &s, 3H, OCOCH3), 1.94 &d, 2H, Jˆ9 Hz),
1.80±1.52 &m, 4H), 1.26±1.18 &m, 8H); 13C NMR &d):
170.61, 74.51 &CHOAc), 72.04 &CHOH), 43.67, 43.50,
29.74, 29.35, 28.87, 28.54, 26.13, 25.75, 21.27.
Compound 600. Pale yellow oil; HRMS: found 212.1416.
C12H20O3 requires 212.1412: nmax &CHCl3) 3620, 3480,
2930, 2860, 1720, 1600, 1450, 1375, 1260, 1130, 1030,
950 cm21; m/z &%): 152 &15), 134 &100), 119 &21), 108
Compound 300. Pale yellow viscous oil; HRMS: found
212.1418. C12H20O3 requires 212.1412: nmax &CHCl3)
3695, 3620, 2930, 2860, 1725, 1260, 1210 cm21; m/z
&%):152 &33), 135 &15), 134 &100), 119 &17), 108 &24), 92
1
&37), 92 &26), 81 &17), 79 &23), 67 &20), 43 &38); H NMR
d &300 MHz, CDCl3) 4.53±4.44 &dt, 1H, CHOAc, Jtˆ
10.5 Hz, Jdˆ5.1 Hz), 3.70 &bd, 1H, CHeqOH, Jˆ2.1 Hz),
2.05 &s, 3H), 1.95±1.76 &m, 6H), 1.63±1.59 &m, 8H); 13C
NMR &d): 171.03, 76.92 &CHOAc), 69.19 &CHOH), 45.02,
39.71, 31.14, 29.19, 29.14, 26.18, 25.62, 25.46, 21.49.
1
&28), 79 &23), 67 &22), 43 &42); H NMR d &300 MHz,
CDCl3) 4.85 &bs, 1H, CHOAc), 3.73 &s, 1H, CHeqOH),
2.00 &s, 3H, OCOCH3), 1.80±1.48 &m, 6H), 1.24±1.18 &m,
8H); 13C NMR &d): 170.86, 72.99 &CHOAc), 69.79
&CHOH), 40.21, 37.84, 29.68, 29.42, 27.99, 26.22, 26.09,
24.37, 21.24.
Puri®cation byHPLC &H 2O/CH3CNˆ60:40), gave, in order,
70and 700.
Puri®cation byHPLC &CH 2Cl2/EtOAcˆ80:20), gave, in
order, 40and 400.
Compound 70. Pale yellow needles; mp 97±988C; HRMS:
found 188.0970. C10H17ClO requires 188.0968; nmax
&CHCl3) 3620, 3465, 3028, 2920, 2860, 1450, 1260,
1120, 1040, 920 cm21; m/z &%): 188 &M1, 5), 152 &15),
135 &100), 111 &89), 108 &40), 93 &29), 79 &26), 67 &43),
Compound 40. Pale yellow oil; HRMS: found 188.0969.
C10H17ClO requires 188.0968; nmax &CHCl3) 3620, 2930,
2860, 1450, 1370, 1260, 1100, 1060, 1020, 808 cm21; m/z
&%):188 &M1, 2.8), 135 &57), 134 &100), 108 &46), 93 &23),
67 &31), 57 &24), 41.00 &17); 1H NMR d &300 MHz,
CDCl3) 4.06 &bd, 1H, CHCl, Jˆ2.2 Hz), 3.20±3.10 &m,
1H, CHaxOH), 2.20±2.12 &m, 1H), 2.03±1.96 &m, 1H),
1.80±1.68 &m, 4H), 1.45±1.15 &m, 8H); 13C NMR &d)
74.74 &CHOH), 64.29 &CHCl), 45.26, 42.48, 32.64, 30.51,
29.18, 29.08, 25.86, 25.50.
1
57 &21), 41 &20); H NMR d &200 MHz, CDCl3) 3.55±
3.42 &ddd, 1H, CHaxCl, Jd1ˆ11.6 Hz, Jd2ˆ10.4 Hz, Jd3ˆ
4.2 Hz), 3.28±3.15 &ddd, 1H, CHOH, Jd1ˆ11.0 Hz, Jd2ˆ
9.2 Hz, Jd3ˆ4.4 Hz), 2.26±2.05 &m, 2H), 1.8±1.6 &m, 4H),
1.43±1.1 &m, 8H); 13C NMR &d): 73.53 &CHOH), 65.08
&CHCl), 49.58, 48.35, 35.20, 34.71, 30.65, 29.11, 25.79,
25.73.
Compound 700. Pale yellow oil; HRMS: found 188.0965.
C10H17ClO requires 188.0968; nmax &CHCl3) 3620, 3014,
2930, 2856, 1450, 1260, 1210, 1118, 1025, 940 cm21; m/z
&%):188 &M1, 6), 152 &12), 135 &65), 111 &100), 93 &28),
Compound 400. Pale yellow oil; HRMS: found 188.0963.
C10H17ClO requires 188.0968; nmax &CHCl3) 3020, 2930,
2860, 1455, 1260, 1210, 1100, 1020, 810 cm21; m/z
&%):188 &M1, 4), 135 &100), 134 &28), 108 &26), 67 &29),
41 &17); 1H NMR d &300 MHz CDCl3) 4.26 &bd, 1H CHCl,
Jˆ2.9 Hz), 3.57±3.55 &m, 1H, CHeqOH), 2.10±1.8 &m, 2H),
1.6±1.3 &m, 4H), 1.22±1.18 &m, 8H); 13C NMR &d) 69.54
&CHOH), 66.17 &CHCl), 39.44, 39.04, 30.80, 28.97, 28.67,
27.58, 26.03, 25.91.
1
67 &42), 41 &23); H NMR d &300 MHz, CDCl3) 3.66 &bd,
1H, CHeqOH, Jˆ2.4 Hz), 3.55±3.46 &td, 1H, CHCl, Jtˆ
11.1 Hz, Jdˆ4.5 Hz), 2.10±1.93 &m, 2H), 1.70±1.50 &m,
4H), 1.25±1.10 &m, 8H). 13C NMR &d): 68.27 &CHOH),
65.11 &CHCl), 45.74, 42.34, 32.04, 30.17, 29.85, 28.46,
25.31, 24.80.

3318
G. Di Maio et al. / Tetrahedron 58 +2002) 3313±3318
3. Wu, Y.-D.; Tucker, J. A.; Houk, K. N. J. Am. Chem. Soc.
1991, 113, 5018±5027.
Acknowledgements
4. Charton, M. Prog. Phys. Org. Chem. 1981, 13, 119±251.
5. Van Bekkum, H.; Verkade, P. E.; Wepster, B. M. Rec. Trav.
Chim. 1959, 78, 815±850.
We are indebted to the Italian MURST and to the University
of Rome `La Sapienza' &National Project `Stereoselezione
in Sintesi Organica. Metodologie ed Applicazioni') for
®nancial support.
6. Kwart, H.; Miller, L. J. J. Am. Chem. Soc. 1961, 83, 4552±
4559.
7. Kwart, H.; Takeshita, T. J. Am. Chem. Soc. 1962, 84, 2833±
2835.
8. Cianetti, C.; Di Maio, G.; Pignatelli, V.; Tagliatesta, P.;
Vecchi, E.; Zeuli, E. Tetrahedron 1983, 39, 657±666.
9. Migneco, L. M.; Vecchi, E. Gazz. Chim. Ital. 1997, 127,
19±24.
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