Tandem Wittig-Diels-Alder reaction between sugar-derived phosphoranes and sugar aldehydes. An easy route to optically pure highly oxygenated decalins

Article abstract of DOI:10.1039/a707447f

A highly oxygenated decalin system has been obtained by a tandem Wittig-Diels-Alder reaction of sugar derived phosphoranes with sugar aldehydes.

Full text of DOI:10.1039/a707447f

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Tandem Wittig–Diels–Alder reaction between sugar-derived
phosphoranes and sugar aldehydes. An easy route to optically
pure highly oxygenated decalins
Sławomir Jarosz
Institute of Organic Chemistry, Polish Academy of Sciences ul. Kasprzaka 44,
01-224 Warszawa, Poland †
A highly oxygenated decalin system has been obtained by a
tandem Wittig–Diels–Alder reaction of sugar derived
phosphoranes with sugar aldehydes.
OBzl OBzl
SnBu3
OMe
OH
H
O
R
ref. 7
OH
O
O
OBzl
O
HO
OBzl
Several macrolide antibiotics with a decalin backbone—such as
nodusmicin (1a, isolated from Saccharopolyspora hirsuta1) or
structurally related nargenicins 1b2—are active against Gram-
OH
D-gluconolactone
BzlO
3
OBzl
3a
ref. 8
acc. to method from ref. 5
OH
O
CHO
OH
R
O
OBzl
Ph3P
O
CMe2
CMe2
O
O
O
O
OMe
HO
H
O
OBzl OBzl
H
2
4
RO
H
1a nodusmicin (R = H)
1b nargenicin (R = 2-furyl-CO)
OBzl
H
O
OBzl
6
OBzl
7
8
4
3
5
positive and drug-resistant bacteria. These antibiotics also
exhibit low toxicity and substantial oral activity.2 Several syn-
thetic approaches, based on inter- and intra-molecular Diels–
Alder methodology,3,4 have been proposed for construction of
such a system.
In this paper a convenient method leading to optically pure,
highly oxygenated decalin derivatives is presented. It is based on
the reaction of sugar-derived stabilized phosphoranes5 with
sugar aldehydes [methodology used for the synthesis of
higher (C12 to C21) carbon sugars6] followed by a [4 ϩ 2] intra-
molecular cyclization of the intermediate Wittig adduct as
shown in Scheme 1.
H
9
2
1
10
OBzl
OH
OBzl OBzl
H
H
OR
O
11
O
CMe2
CMe2
O
O
O
O
CMe2
O
O
O
CMe2
5
6
a R = H; b R = C(O)-Ph(p)NO2
6b NOE H5-H10 (6%)
H10-H11 (4.5%)
J4,5 = 10.8 Hz
Reaction of phosphorane 2 (readily available from diene
aldehyde 3, which was obtained from allyltin 3a via a
rearrangement–elimination reaction7) with an open-chain -
glucose derivative 48 in boiling benzene led to a Wittig adduct 5
which, in situ, underwent [4 ϩ 2] cyclization to give decalin 6 as
a single stereoisomer (Scheme 1). The structure of this com-
pound was assigned from high resolution NMR spectra and
NOE experiments on its p-nitrobenzoyl derivative 6b.
Reaction of phosphorane 2 with 2,3-O-isopropylidene--
glyceraldehyde 7 at 140 ЊC (boiling xylene) afforded a mixture
of stereoisomeric decalins from which the main stereoisomer 8
was isolated in 35% yield. When this reaction (2 ϩ 7) was per-
formed under high pressure (10 kbar) only one stereoisomer—
the same as the main product from thermal reaction—of
decalin 8 was isolated in 55% yield. Other sugar aldehydes with
the opposite configuration at Cα (methyl 2,3,4-tri-O-benzyl-6-
aldehyde-α--glucopyranoside, 9) afforded under high pressure
conditions decalin 10, but as an unseparable mixture of two
Scheme 1
stereoisomers. This may indicate that R-Wittig reagent 2 and
S-aldehyde 9 are a mismatched pair. If so, aldehyde 9 should
match with the isomeric S-phosphorane and give a single
decalin. Indeed, the high pressure reaction of S-phosphorane
11 (prepared from the isomeric -manno allyltin derivative7
analogously to 2) with 9 afforded decalin 12 as a single stereo-
isomer in 60% yield.
The tandem Wittig–Diels–Alder methodology presented in
this paper opens a rather convenient route for the prepar-
ation of a highly oxygenated, optically pure decalin system. The
possibility of the application of various diene-Wittig reagents
(e.g. 2 or 11, that can be readily prepared from appropriate
sugar allyltins) and various sugar aldehydes makes this
approach particularly interesting. Application of a high pres-
sure technique improves the stereoselectivity of this process and
gives chiral decalins in higher yields compared to thermal
reactions.
† E-mail: sljar@ichf.edu.pl
J. Chem. Soc., Perkin Trans. 1, 1997
3579

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38.6 (C9), 47.1 (C10), 83.5 (C3), 84.0 (C4), 86.0 (C2), 109.0
(C1), 126.7 (C6), 128.3 (C7).
O
OBzl
O
OBzl
Ph3P
Ph3P
R
S
Reaction of stabilized Wittig reagents (2 and 11) with aldehydes
under high pressure
OBzl OBzl
OBzl OBzl
2
11
A solution of the appropriate phosphorane (ca. 0.5 mmol) and
aldehyde (ca. 0.6 mmol) in dry toluene (10 ml) was placed
in a piston-type apparatus and kept under high pressure (ca.
10 kbar) for 2 d. Products were isolated by column chrom-
atography.
Decalin 8. (Single isomer, 55%) [HRMS: calcd. for
C36H40O6Na (M ϩ Naϩ): 591.2726. Found: 591.2762]; δH 1.78
and 2.01 (2m, both H8), 2.19 (m, H9), 2.42 (m, H5), 2.56 (dd,
J9,10 11.8, J5,10 5.6, H10), 3.68 (dd, J2,3 10.2, J3,4 9.1, H3), 3.82
(dd, J4,5 10.5, H4), 4.65 (d, H2), 5.75 (H6), 6.01 (H7); δC 27.2
(C8), 37.5 (C9), 38.6 (C5), 53.5 (C10), 83.3 (C4), 85.5 (C3), 85.6
(C2), 126.0 and 127.8 (C6,7), 207.0 (CO).
CHO
S
CHO
O
O
OBzl
R
10 kbar
toluene
10 kbar
toluene
CMe2
BzlO
OMe
OBzl
O
7
9
OBzl
OBzl
OBzl
H
H
H
6
OBzl
OBzl
OBzl
OBzl
OBzl
7
4
3
5
H
9
2
1
8
10
OBzl
H
H
O
O
O
Decalin 12. (Single isomer, 60%) [HRMS: calcd. for C58-
H60O9Na (M ϩ Naϩ): 923.4135. Found: 923.4146] νmax/cmϪ1
1730; δH 2.06 and 2.39 (2m, both H8), 2.91 (m, H9), 2.98 (dd,
J9,10 7.0, J5,10 6.4, H10), 3.03 (m, H5), 3.85 (dd, J2,3 2.9, J3,4 6.6,
H3), 3.94 (dd, J4,5 4.3, H4), 4.40 (d, H2), 5.75 (m, H6,7); δC 28.0
(C8), 34.5 (C9), 37.0 (C5), 48.5 (C10), 78.1 (C4), 79.9 (C3), 81.0
(C2), 124.5 and 128.9 (C6,7).
Decalin 10. (50%) [HRMS: calcd. for C58H60O9Na (M ϩ
Naϩ): 923.4135. Found: 923.4149]. Two major products were
seen in the NMR spectra [1H- 3.34, 3.49 (OMe) and 13C- 98.2,
97.7 ppm (C1 of glucose moiety)]. Signals at 3.10, 2.89 (H5 of
both isomers), 34.4, 31.2 (C5), 2.64, 2.46 (H10), 49.9, 43.6
(C10), and 5.85–5.6 (H6,7), 129.8, 127.4, 126.2, 123.0 (C7,8)
proved the decalin structure of both isomers of 10.
5′
O
O
O
O
CMe2
1′
OBzl
OBzl
BzlO
OMe
OBzl
10
(2 isomers)
BzlO
OMe
OBzl
8
NOE H5-H10 (7.5%)
H5-H3 (4%)
12
H9-H2 (7%)
H9-H4 (7%)
NOE H4-H5 (6%)
H4-H10 (3%)
H10-H5′ (3%)
H5–H10 and H9–H2 (from NOESY)
Scheme 2
Experimental
All H- and 13C-resonances were assigned by 2D experiments.
The configuration of 12 was proved also by NOESY spectro-
scopy.
1
Acknowledgements
(3R,4S,5R)-3,4,5-Tribenzyloxy-2-oxonona-6,8-dienylidene-
triphenylphosphorane 2
Dr Marek Tkacz (Institute of Physical Chemistry, PAS) is
thanked for conducting the high pressure experiments.
Diene aldehyde 37 (1.1 g, 2.49 mmol) was oxidized to an acid
with Jones’ reagent. To a solution of this crude acid (1.04 g,
2.26 mmol, 90%) in dry THF (10 ml), N,N-carbonyldiimidazole
(1.1 equiv., 0.4 g) was added and after 15 min this solution of
crude imidazolide was added to a cooled (Ϫ78 ЊC) solution of
References
1 H. A. Whalley, C. G. Chidester, S. A. Miszak and R. J. Wnuk,
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Ph P᎐CH (4 equiv.; generated from Ph PCH I and BuLi for 2 h
᎐
3
2
3
3
at Ϫ78 ЊC) in THF. After stirring for 30 min at Ϫ78 ЊC the
mixture was partitioned between water–benzene and the
product 2 was purified by column chromatography to afford 2
(0.98 g, 1.37 mmol, 55%) [HRMS calcd. for C48H46O4P
(M ϩ Hϩ): 717.3134. Found: 717.3131]. Similarly, phosphorane
11 was prepared (HRMS: 717.3130).
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therein.
Synthesis of decalin 6 under atmospheric pressure
Phosphorane 2 (0.35 g, 0.49 mmol) and aldehyde 48 (0.15 g,
0.58 mmol) in dry benzene (20 ml) were heated under reflux for
20 h. The product, decalin 6a, was isolated by column chrom-
atography (0.18 g, 0.26 mmol, 53%) [HRMS calcd. for
C42H50O9Na (M ϩ Naϩ): 721.3352. Found: 721.3349]. p-
Nitrobenzyl derivative 6b (prepared from 6a by the action of
p-nitrobenzoyl chloride–Et3N–DMAP): δH 2.08 and 2.30 (2m,
both H8), 2.32 (m, H9), 2.80 (m, H5), 3.13 (dd, J9,10 13.6, J5,10
6.8, H10), 3.55 (dd, J3,4 9.7, J4,5 10.8, H4), 3.90 (dd, J2,3 10.3,
H3), 3.99 (d, H2), 5.81 (H6), 6.01 (H7); δC 27.2 (C8), 38.1 (C5),
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˙
10 775.
Paper 7/07447F
Received 15th October 1997
Accepted 28th October 1997
3580
J. Chem. Soc., Perkin Trans. 1, 1997