Ring-fused gem-dibromocyclopropanes as precursors to enantiomerically pure D- and L-series 3-deoxy- and 2-amino-2,3-dideoxyaldohexose derivatives

Article abstract of DOI:10.1039/b008146i

The gem-dibromocyclopropanes that undergo silver(1)-promoted electrocyclic ring-opening and the resulting π-allyl cations trapped with a range of nucleophiles to give mixtures of cyclohexenyl bromides were discussed. It was found that the subjection of these products to ozonolytic cleavage afforded differentially protected and enantiopure D- and L-series 3-deoxy- and 2-amino-2,3-dideoxyaldohexoses. The results showed that monosaccharide derivatives, as well as related compounds were likely to prove useful as 'building blocks' in the construction of a range of carbohydrates.

Full text of DOI:10.1039/b008146i

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Ring-fused gem-dibromocyclopropanes as precursors to
enantiomerically pure D- and L-series 3-deoxy- and
-amino-2,3-dideoxyaldohexose derivatives
2
1
Martin G. Banwell,* Wolfgang Ebenbeck and Alison J. Edwards
Research School of Chemistry, Institute of Advanced Studies, The Australian National
University, Canberra, ACT 0200, Australia
Received (in Cambridge, UK) 9th October 2000, Accepted 24th November 2000
First published as an Advance Article on the web 18th December 2000
The readily available gem-dibromocyclopropanes 5 and 6
undergo silver(I)-promoted electrocyclic ring-opening and
the resulting ꢀ-allyl cations trapped with a range of
nucleophiles to give mixtures of cyclohexenyl bromides
such as 7–9 and 17–19, respectively. Subjection of certain
of these products to ozonolytic cleavage followed by
reduction protocols then affords differentially protected
and enantiopure D- and L-series 3-deoxy- and 2-amino-2,3-
dideoxyaldohexoses.
derived “naked sugars” as synthons for the preparation of a
wide-variety of - and -forms of various monosaccharides
1,7
including members of the title classes of compound. It
is against this background that we now describe new and
flexible methods for the synthesis of enantiomerically pure
- and -series 3-deoxyaldohexoses and 2-amino-2,3-di-
deoxyaldohexoses from ring-fused gem-dibromocyclopropanes.
The present work also serves to highlight the value of
8
menthanediyls as protecting groups for cis-vicinal diols and
as auxiliaries for effecting the resolution of racemic mixtures
of such diols.
3
-Deoxyaldohexoses and 2-amino-2,3-dideoxyaldohexoses are
of significance because of their occurrence as substructures
within more complex carbohydrates and/or their potential as
biochemical tools for use in the study of a variety of bio-
chemical transformations. Furthermore, compounds such as
2
The pivotal early stages of the present work are outlined9
in Scheme 1 and involve formation of the previously reported
cis-1,2-diol (±)-2 via lead tetraacetate-mediated dihydroxyl-
ation of freshly cracked cyclopentadiene (1). Treatment of
compound (±)-2 with (Ϫ)-menthone (p-menthan-3-one)
and catalytic amounts of toluene-p-sulfonic acid (p-TsOH)
in refluxing pentane resulted in the smooth formation of
1
-amino-2,3-dideoxy--arabino-hexose (2-amino-2,3-dideoxy-
2

-manno-pyranose) have been shown to act as inhibitors of
angiogenesis and, therefore, have potential for the treatment
of chronic inflamation, diabetic retinopathy, psoriasis and
rheumatoid arthritis as well as the suppression of metastases.
As such these rare sugars represent attractive synthetic targets
and they have most frequently been prepared by traditional
methods involving, inter alia, selective deoxygenation of com-
mon aldohexoses or desulfurisation of related thiosugars.
Fischer–Kiliani chain extension of 2-deoxyaldopentoses has
also been employed together with enzymatic processes
involving aldolases. A rather versatile approach has been
,
the corresponding menthanediyls 3† ‡ and 4 (81% combined
yield) which were not readily separable by conventional
means. As a consequence this mixture of diastereoisomers
was subjected to reaction with dibromocarbene (generated
under phase-transfer conditions) and in this manner the cyclo-
propanes 5 {[α] = Ϫ10 (c 1.0)§} and 6 {[α] = Ϫ30 (c 1.1)} were
3
4
D
D
obtained (98% combined yield) and these could be separated
from one another by careful gravity column chromatography
involving gradient elution techniques. The assignment of
the illustrated structures to compounds 5 and 6 follows from
5
6
pursued by Vogel and co-workers using non-carbohydrate
Scheme 1 Reagents and conditions: (i) Pb(OCOMe) (0.68 mol equiv.), MeCO H, H O, 0–18 ЊC, 1 h then K CO , MeOH, 18 ЊC, 2 h; (ii) (Ϫ)-
4
2
2
2
3
menthone (1.2 mol equiv.), p-TsOH (trace), pentane, 36 ЊC, 48 h then DBU (1.1 mol equiv. wrt p-TsOH); (iii) CHBr , 50% aq. NaOH, C H , TEBAC,
3
6
6
0
–18 ЊC, 48 h (TEBAC = triethylbenzylammonium chloride).
1
14
J. Chem. Soc., Perkin Trans. 1, 2001, 114–117
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b008146i

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t
Scheme 2 Reagents and conditions: (i) AgOCN (7.0 mol equiv.), Bu OH, 80 ЊC, 72 h; (ii) O , CH Cl –MeOH, pyridine (4.0 mol equiv.), Ϫ90 ЊC,
3
2
2
0
.2 h; (iii) KI (1.5 mol equiv.), NaBH (6.0 mol equiv.), Ϫ90–0 ЊC, 1 h; (iv) TBDMSOTf (1.5 mol equiv.), 2,6-dimethylpyridine, CH Cl , 0–18 ЊC, 0.5
4
2
2
h (for 10→12) or TBDMSCl (1.3 mol equiv.), Et N (1.8 mol equiv.), DMAP (trace), CH Cl , 18 ЊC, 7 h (for 11→13); (v) DIBAL-H (2.0 mol equiv.),
3
2
2
CH Cl , Ϫ78–18 ЊC, 8 h; (vi) Dess–Martin reagent (1.5 mol equiv.), pyridine, CH Cl , 0–18 ЊC, 4 h; (vii) 36% HCl (trace) in MeOH, 0–18 ЊC, 18 h;
2
2
2
2
(
viii) Ac O (mol equiv.), pyridine, 0–18 ЊC, 3 h.
2
The trioxygenated bromocyclohexenes 8 and 9 were inde-
pendently subjected to ozonolytic cleavage in methanol–
dichloromethane to give, after subsequent reduction of the
ensuing hydroperoxide, the methyl esters 10 {94%, [α] = Ϫ29
D
11
(
c 1.0)} and 11 {89%, [α] = Ϫ42 (c 1.0)}, respectively. The
D
C-6 hydroxy group within these latter compounds was pro-
tected as the corresponding TBDMS-ethers so as to form the
fully protected hexanoic acid derivatives 12 {84%, [α] = Ϫ31
D
(
c 1.0)} and 13 {99%, [α] = Ϫ27 (c 1.0)}, respectively. Reduc-
D
tion of the ester moiety within the latter pair of compounds
was effected using DIBAL-H and the resulting 1Њ-alcohols then
oxidised to the corresponding aldehydes, 14 {93%, [α] = Ϫ35
D
Fig. 1 ORTEP (with 50% probability ellipsoids) of compound 9
(
c 1.3)} and 15 {80%, [α] = Ϫ42 (c 1.1)}, using the Dess–
D
derived from X-ray crystallographic data.
Martin periodinane. Sequential treatment of compound 15
with acidic methanol then acetic anhydride afforded an
inseparable and ca. 6.3:1 mixture of the α- and β-forms of 2-
amino-2,3-dideoxy--arabino-hexose derivative 16 {88% from
X-ray crystallographic analyses and a chemical correlation
study (vide infra).¶
The reaction sequences outlined in Scheme 2 serve to high-
light the utility of compound 5 as a synthon for the preparation
of various “-series” deoxyaldohexoses. Thus, treatment of this
ring-fused cyclopropane with silver isocyanate in the presence
of tert-butyl alcohol afforded a mixture of bromocyclohexenes
15, [α] = Ϫ8.6 (c 1.1)} and thereby demonstrating that the
D
menthanediyl protecting group is readily removed under rather
mild conditions.
Access to the enantiomeric series of aldohexose derivatives
involved, in the initial stages (Scheme 3), treatment of the gem-
dibromocyclopropane 6 with silver isocyanate in the presence
of tert-butyl alcohol so as to form the anticipated mixture of
7
9
{26%, [α] = ϩ76 (c 1.1)}, 8 {17%, [α] = Ϫ17 (c 1.0)} and
D
D
{49%, mp = 55–56 ЊC, [α] = ϩ4 (c 1.0)} that were readily
D
separated from one another by flash chromatography on silica.
The carbamates most likely arise via silver()-promoted electro-
cyclic ring-opening of the gem-dibromocyclopropyl moiety
cyclohexenyl bromides 17 {23%, [α] = Ϫ104 (c 1.1)}, 18 {13%,
D
[α] = Ϫ5 (c 1.2)} and 19 {55%, mp = 112–114 ЊC, [α] = Ϫ73
D
D
10
(c 1.1)} which could be separated from one another by flash
chromatography. Independent subjection of the latter products
to ozonolytic cleavage in methanol–dichloromethane followed
by reductive work-up then afforded the hexanoic acid deriv-
atives 20 {95%, [α] = Ϫ25 (c 1.0)} and 21 {95%, [α] = Ϫ16
and interception of the resulting π-allyl cation with isocyanate.
The ensuing allylic isocyanates then react, at the sp-hybridised
carbon, with tert-butyl alcohol to give compounds 7 and 9.
The structure of compound 9 was established by single crystal
X-ray analysis (Fig. 1)|| which also served to confirm the
structures of compounds 3 and 5. The all cis-relationship of
the oxygen-containing groups associated with menthanediyl
D
D
(c 1.5)}, respectively. These were each converted, by standard
means, into the corresponding TBDMS-ether derivatives,
22 {81%, [α] = Ϫ8 (c 1.0)} and 23 {90%, [α] = Ϫ8 (c 1.2)}
D
D
8
, which was established by chemical correlation studies,**
respectively, which were, in turn, transformed into the alde-
presumably arises via an S 2 reaction between tert-butyl
hydes 24 {98%, [α] = Ϫ13 (c 1.0)} and 25 {88%, [α] = Ϫ5
N
D
D
alcohol and the allylic isocyanate that also serves as a precursor
to carbamate 9.
(c 0.9)}. Sequential treatment of compound 25 with acidic
methanol then acetic anhydride afforded an inseparable and
J. Chem. Soc., Perkin Trans. 1, 2001, 114–117
115

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t
Scheme 3 Reagents and conditions: (i) AgOCN (7.0 mol equiv.), Bu OH, 80 ЊC, 72 h; (ii) O , CH Cl –MeOH, pyridine (4.0 mol equiv.), Ϫ90 ЊC,
3
2
2
0
0
.2 h; (iii) KI (1.5 mol equiv.), NaBH (6.0 mol equiv.), Ϫ90 to 0 ЊC, 1 h; (iv) TBDMSOTf (1.5 mol equiv.), 2,6-dimethylpyridine, CH Cl , 0–18 ЊC,
4
2
2
.5 h (for 20→22) or TBDMSCl (1.3 mol equiv.), Et N (1.8 mol equiv.), DMAP (trace), CH Cl , 18 ЊC, 7 h (for 21→23); (v) DIBAL-H (2.0 mol
equiv.), CH Cl , Ϫ78–18 ЊC, 8 h; (vi) Dess–Martin reagent (1.5 mol equiv.), pyridine, CH Cl , 0–18 ЊC, 4 h; (vii) 36% HCl (trace) in MeOH, 0–18 ЊC,
3
2
2
2
2
2
2
1
8 h; (viii) Ac O (mol equiv.), pyridine, 0–18 ЊC, 3 h.
2
ca. 2.2:1 mixture of the α- and β-forms of 2-amino-2,3-
dideoxy--arabino-hexose derivative ent-16 {83% from 25,
TLC-grade silica gel. The pad was washed with diethyl ether
(1 × 200 ml) and the combined filtrates concentrated under
reduced pressure. The resulting light-yellow oil was subjected to
[
α] = ϩ4.5 (c 1.2)}.
D
9
Compounds 14 and 24 represent differentially protected 3-
distillation thereby affording diol (±)-2 (33.1 g, 60%) as a clear
deoxy--ribo-hexose and 3-deoxy--ribo-hexose derivatives,
respectively, while congeners 15 and 25 are orthogonally pro-
tected forms of 2-amino-2,3-dideoxy--arabino-hexose and
colourless oil, bp 96–98 ЊC (0.1 mm Hg). This material was
1
13
identical, as judged by H and C NMR spectroscopic analysis,
9
with authentic material.
2
-amino-2,3-dideoxy--arabino-hexose, respectively. These rare
monosaccharide derivatives, as well as related compounds that
should be readily accessible by the rather simple methods
described herein, are likely to prove useful as “building blocks”
in the construction of a range of carbohydrates of biological
interest.
Compounds 3 and 4
A mixture of diol (±)-2 (26.1 g, 261 mmol), (Ϫ)-menthone
(
48.3 g, 313 mmol) and p-TsOH (20 mg) in pentane (300 ml)
was heated at reflux in an apparatus connected to a Dean–Stark
trap. After 48 h the reaction mixture was cooled then treated
with DBU (18 µL) and concentrated under reduced pressure to
afford a light-yellow oil. Subjection of this material to flash
chromatography (silica gel, 40:1 v/v hexane–ethyl acetate
elution) afforded, after concentration of the appropriate
Experimental
(
± ±-cis-Cyclopent-3-ene-1,2-diol [(± ±-2]
fractions [R = 0.4 (15:1 hexane–diethyl ether elution)], a 1:1
f
Freshly cracked and twice-distilled cyclopentadiene (1) (62.0 g,
mixture of the diastereoisomeric menthanediyls 3 and 4 (50.2
0
.938 mol) was slowly added to a magnetically stirred and
ϩ
ؒ
g, 81%) as a clear, colourless oil [Found: M , 236.1776.
chilled (ice–water-bath) mixture of lead tetraacetate (284 g,
ϩ
ؒ
Ϫ1
C H O requires: M , 236.1776]; ν (KBr)/cm 3057, 2869,
15
24
2
max
0
1
.642 mol), acetic acid (580 ml, 10.2 mol) and water (24 ml,
.32 mol) maintained under a nitrogen atmosphere. Shortly
2
8
844, 1615, 1455, 1365, 1304, 1161, 1117, 1091, 1082, 1042,
1
54, 720; H NMR (300 MHz, CDCl ) δ 0.71–0.93 (complex
3
after completion of the addition of cyclopentadiene the
reaction mixture became homogeneous and at this point the
ice–water-bath was removed. Stirring was continued for 1 h
then the reaction mixture was poured into diethyl ether (1200
ml) and the supernatant liquid decanted then filtered through a
pad of TLC-grade silica gel. The filtrate was treated with
Na CO (300 g) and the resulting mixture stirred vigorously
m, 22H), 1.20–1.39 (complex m, 4H), 1.56–1.69 (complex m,
6
2
H), 1.82 (m, 1H), 1.87 (m, 1H), 2.05 (septet, J = 7.2 Hz, 2H),
.44–2.52 (complex m, 4H), 4.65 (m, 1H), 4.73 (m, 1H), 5.01
13
(
d, J = 6.2 Hz, 1H), 5.06 (d, J = 5.9 Hz, 1H), 5.72 (m, 4H);
C
NMR (75 MHz, CDCl ) δ 18.8 (CH or CH ), 19.3 (CH or CH ),
3
3
3
2
2.6 (CH or CH ), 22.7 (CH or CH ), 23.8 (CH ), 24.1(0) (CH
3 3 2
2
3
or CH ), 24.1(3) (CH ), 24.6(1) (CH or CH ), 24.6(4) (CH or
3
2
3
at 18 ЊC overnight. The resulting precipitate was removed by
filtration and washed with diethyl ether (1 × 300 ml) then the
combined filtrates were concentrated under reduced pressure
to give a light-yellow oil. Distillation of this material afforded
a ca. 1:1 mixture of regioisomeric mono-acetates (64.5 g, 48%)
associated with diol (±)-2 as a clear colourless oil, bp 101–
CH ), 30.8(9) (CH or CH ), 30.9(3) (CH or CH ), 35.1 (CH ),
3
3
3
2
3
4
5.2 (CH ), 38.8 (CH ), 38.9 (CH ), 44.4 (CH ), 44.7 (CH ),
8.3 (CH), 48.7 (CH), 77.0 (CH), 77.5 (CH), 85.0 (CH), 85.4
2 2 2 2 2
(
CH), 113.2 (C), 130.6 (CH), 130.8 (CH), 132.3 (CH); m/z (EI,
ϩ
ؒ
ؒ
ϩ
7
0 eV) 236 [49%, M ], 221 [44, (M Ϫ CH ) ], 179 (59), 151
3
(
83), 69 (100).
1
04 ЊC, 15 mm Hg. A reaction mixture comprising these mono-
acetates (79.0 g, 0.556 mol), K CO3 (84.7 g, 0.614 mol)
2
Compounds 5 and 6
and MeOH (640 ml) was stirred vigorously at 18 ЊC while
being protected from light. After 2 h diethyl ether (700 ml) was
added and the ensuing mixture was filtered through a pad of
Bromoform (121 g, 478 mmol) was added to a vigorously
stirred mixture of menthanediyls 3 and 4 (7.38 g of a 1:1
1
16
J. Chem. Soc., Perkin Trans. 1, 2001, 114–117

View Article Online
mixture, 31.2 mmol), benzene (40 ml), TEBAC (300 mg, mmol)
and NaOH (56 ml of 50% w/v aqueous solution) maintained
at ca. 0 ЊC (ice-bath). After 1 h the cooling bath was removed
and stirring continued at ca. 18 ЊC for 48 h. The ensuing
thick, brown reaction mixture was diluted with petroleum
spirit (40–60 fraction, 300 ml) and the separated organic phase
§ All optical rotations were determined in chloroform solution at
2
¶
0 ЊC.
The illustrated anti-relationship between the cyclopropyl and
menthanediyl moieties within compounds 5 and 6 has not been
rigorously proven but follows by analogy with stereochemical outcomes
9
of reactions leading to closely related compounds. Further support
for the structure of compound 6 follows from single crystal X-ray
analysis of benzyl ether i which is obtained, as the major reaction prod-
uct, upon treatment of the former compound with silver isocyanate
in neat benzyl alcohol.
washed with brine (1 × 100 ml) then dried (MgSO ), filtered
4
and concentrated under reduced pressure (ca. 10 mm Hg).
The resulting yellow oil was subjected to heating at 45–55 ЊC
and 12 mm Hg in order to remove excess bromoform. The
ensuing brown residue was subjected to flash chromatography
(
silica gel, 35:1 v/v 40–60 petroleum spirit–diethyl ether
elution) and concentration of the appropriate fractions
afforded a ca. 1:1.2 mixture of the diastereomeric gem-di-
bromocyclopropanes 5 and 6 (12.5 g, 98%) as a pale-yellow oil.
A 1.2 g sample of this material was subjected to gravity column
chromatography [330 g of TLC-grade silica gel contained in a
7
4
cm id chromatography column, gradient elution from neat
0–60 petroleum spirit to 80:1 v/v 40–60 petroleum spirit–
|| Crystal data for 9: C H BrO , M = 435.407, T = 200.0(1) K, mono-
2
3
31
3
r
diethyl ether] and in this manner two fractions, A and B, were
obtained.
clinic, space group P2 , Z = 2, a = 8.2977(13), b = 8.1755(12), c =
1
3 Ϫ3
1
6.318(2) Å, β = 94.645(11)Њ, U = 1103.3(3) Å , ρ = 1.31 g cm ,
calc
Ϫ1
F(000) = 456, µ(MoKα) = 1.88 mm , 4562 unique data (2θmax = 55Њ),
2418 with I > 3σ(I); R = 0.051, R = 0.060, S = 1.03.
Concentration of fraction A (R = 0.2) afforded compound 5
f
ϩ
ؒ
w
as a clear, colourless oil, [α] = Ϫ9.45 (c 1.00) [Found: M ,
D
79
ϩ
ؒ
Data were measured on a Nonius Kappa CCD diffractometer
4
06.0145. C H Br O requires: M , 406.0143]; ν
(KBr)/
16
24
2
2
max
(
graphite crystal monochromator, λ = 1.54180 Å). Refinement was by
Ϫ1
cm 2950, 2930, 2868, 1455, 1305, 1158, 1117, 1082, 1053, 996;
12
full-matrix least squares analysis on F using the CRYSTALS structure
analysis suite. Structure solution was by direct methods (SIR92).
1
H NMR (300 MHz, CDCl ) δ 0.79–0.93 (complex m, 10H),
13
3
1
.32–1.76 (complex m, 6H), 1.83 (d, J = 15.5 Hz, 1H), 2.19–2.24
CCDC reference number 207/500. See http://www.rsc.org/suppdata/p1/
b0/b008146i/ for crystallographic files in .cif format.
** Compound 8 was subject to treatment with trifluoroacetic acid
then aqueous trifluoroacetic acid which resulted in cleavage of both
the menthanediyl and tert-butyl ether moieties. The ensuing triol
was converted into the corresponding acetonide under standard
conditions and the latter compound {mp 68–70 ЊC, [α]D ϩ143.4 (c
(
4
complex m, 3H), 2.43 (m, 1H), 2.51 (d, J = 7.1 Hz, 1H),
.51 (d, J = 5.6 Hz, 1H), 4.61 (td, J = 5.6 and 2.6 Hz, 1H);
C NMR (75 MHz, CDCl ) δ 19.2 (CH or CH ), 22.6 (CH or
13
3
3
CH ), 23.9 (CH ), 24.2 (CH or CH ), 25.1 (CH or CH ), 30.9
3
2
3
3
(
(
CH or CH ), 35.1 (CH ), 35.5 (C), 36.9 (CH ), 38.5 (CH), 41.4
CH), 43.6 (CH ), 48.4 (CH), 84.2 (CH), 84.8 (CH), 115.9 (C);
3
2
2
2
0
.64, CHCl )} proved spectroscopically identical with its optical
ϩ
ؒ
3
m/z (EI, 70 eV) 410 (31%) 408 (58) 406 (32) (M ), 395 (32)
antipode {mp 69–70 ЊC, [α]D Ϫ141 (c 1.03, CHCl )} that has been
3
ؒ
ϩ
3
6
93 (54) 391 (31) [(M Ϫ CH ) ], 239 (73) 237 (100) 235 (73),
3
prepared from (Ϫ)-quinic acid (1,3,4,5-tetrahydroxycyclohexanecarb-
oxylic acid) by Paquette and co-workers (J. Am. Chem. Soc., 1997, 119,
3038).
9 (99).
Concentration of fraction B (R = 0.25) afforded compound
f
ϩ
ؒ
6
4
as a light-yellow oil, [α] = Ϫ30.4 (c 1.06) [Found: M ,
D
79 ϩ
ؒ
06.0147. C H Br O requires: M , 406.0143]; ν (KBr)/
max
1 For useful reviews of this area see (a) D. Fattori and P. Vogel,
The Syntheses of 3- and 4-Deoxyhexoses, in Studies in Natural
Products Chemistry, ed. Atta-ur-Rahman, Elsevier Science B. V.,
Amsterdam, 1994, vol. 14, pp. 143–200; (b) A. Kirschning,
A. F.-W. Bechthold and J. Rohr, Top. Curr. Chem., 1997, 188, 1.
16
24
2
2
Ϫ1
cm 2950, 2869, 1455, 1305, 1161, 1112, 1082, 1051, 1006, 743;
1
H NMR (300 MHz, CDCl ) 0.83–0.93 (complex m, 10H),
3
1
.24–1.75 (complex m, 6H), 1.82 (dm, J = 15.4 Hz, 1H), 2.10
(
dd, J = 15.4 and 5.5 Hz, 1H), 2.20–2.31 (complex m, 2H), 2.42
t, J = 7.2 Hz, 1H), 2.52 (d, J = 7.2 Hz, 1H), 4.52 (d, J = 5.3 Hz,
2
N. Mongelli, A. Bargiotti, N. Oneto and C. Geroni, Eur. Pat. Appl.,
EP 527042 A2 19930210 (1993) (Chem. Abstr., 1993, 119, 226337).
(
1
13
H), 4.55 (m, 1H); C NMR (75 MHz, CDCl ) δ 19.2 (CH or
3
3 D. H. R. Barton and R. Subramanian, J. Chem. Soc., Chem.
CH ), 22.6 (CH or CH ), 24.0 (CH ), 24.2 (CH or CH ), 25.1
Commun., 1976, 867.
3
3
2
3
(
CH or CH ), 30.9 (CH or CH ), 35.0 (CH ), 36.0 (C), 36.5
4 M. Gut, D. A. Prins and T. Reichstein, Helv. Chim. Acta, 1947, 30,
3
3
2
(
CH ), 38.5 (CH), 41.9 (CH), 43.6 (CH ), 48.4 (CH), 84.5 (CH),
743.
2
2
5
(a) P. M. Scensny, S. G. Hirschhorn and J. R. Rasmussen,
Carbohydr. Res., 1983, 112, 307; (b) W. McDowell, T. J. Grier,
J. Rasmussen and R. T. Schwarz, Biochem. J., 1987, 248, 523.
J. R. Durrwachter, H. M. Sweers, K. Nozaki and C.-H. Wong,
Tetrahedron Lett., 1986, 27, 1261.
8
5.3 (CH), 115.9 (C); m/z (EI, 70 eV) 410 (40%) 408 (58) 406
ϩ
ؒ
ϩ
(
41) (M ), 395 (34) 393 (53) 391 (31) [(M Ϫ CH ) ], 239 (67)
3
2
37 (100) 235 (67), 69 (100).
Each “cycle” of above-mentioned gravity column chrom-
6
7
atographic procedure provides 350–400 mg samples of the
diastereomerically pure cyclopropanes 5 and 6 and those
fractions containing mixtures of these compounds are readily
recycled.
(a) E. de Guchteneere, D. Fattori and P. Vogel, Tetrahedron, 1992,
4
8, 10603; (b) P. Vogel, Curr. Org. Chem., 2000, 4, 455 and references
cited therein.
8 (a) T. Harada, I. Wada and A. Oku, J. Org. Chem., 1989, 54, 2599;
b) T. Harada and A. Oku, Synlett, 1994, 95 and references cited
(
therein. For a useful review of closely related work see A. P. Davis,
Angew. Chem., Int. Ed. Engl., 1997, 36, 591.
M. G. Banwell, C. J. Cowden and R. W. Gable, J. Chem. Soc., Perkin
Trans. 1, 1994, 3515.
Acknowledgements
9
We thank the Institute of Advanced Studies for financial
support and the Deutsche Forschungsgemeinschaft (DFG) for
provision of a post-doctoral stipend (to W. E.). Ms Vanessa
Bridges and Mr Robert Longmore are thanked for conducting
some preliminary experiments.
10 For an excellent discussion of such processes see E. N. Marvell,
Thermal Electrocyclic Reactions, Academic Press, New York, 1980,
pp. 23–53.
1 Hudlicky et al. were the first to highlight the utility of tetra-
oxygenated halogenocyclohexenes as precursors to aldohexoses
1
[
see: (a) T. Hudlicky and J. W. Reed, in Advances in Asymmetric
Synthesis, ed. A. Hassner, JAI Press, Greenwich, CT, 1995, p. 271;
b) T. Hudlicky, D. A. Entwistle, K. K. Pitzer and A. J. Thorpe,
Chem. Rev., 1996, 96, 1195].
Notes and references
(
†
All new and stable compounds had spectroscopic data [IR, NMR,
mass spectrum] consistent with the assigned structure. Satisfactory
combustion and/or high resolution mass spectral analytical data were
obtained for new compounds and/or suitable derivatives.
12 D. J. Watkin, C. K. Prout, J. R. Carruthers and P. W. Betteridge,
CRYSTALS Issue 10, 1996, Chemical Crystallography Laboratory,
Oxford, UK.
‡
The use of higher boiling solvents in this acetalisation reaction leads
13 A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi,
M. C. Burla, G. Polidori and M. Camalli, J. Appl. Cryst., 1994, 27,
435.
to the formation of samples of compounds 3 and 4 which appear to be
contaminated with the epimeric (at the spiro-carbon) menthanediyls.
J. Chem. Soc., Perkin Trans. 1, 2001, 114–117
117