Models studies towards the synthesis of the right-hand part of pederin

Article abstract of DOI:10.1002/hlca.200490111

Bicyclic acetal derivatives of the type 3 were prepared based either on a dihydroxyaldehyde 5 or an oxiranebutanal 6 (cf. Scheme 2). Lewis acid catalyzed reaction of the bicyclic acetal with allyltrimethylsilane introduces the side chain (as yet unfunctio

Full text of DOI:10.1002/hlca.200490111

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Helvetica Chimica Acta Vol. 87 (2004)
Model Studies towards the Synthesis of the Right-Hand Part of Pederin
by Thomas Rˆlle and Reinhard W. Hoffmann*
Fachbereich Chemie der Philipps Universit‰t Marburg, D-35032 Marburg
(fax: ‡4964212825677; e-mail: rwho@chemie.uni-marburg.de)
Bicyclic acetal derivatives of the type 3 were prepared based either on a dihydroxyaldehyde 5 or an
oxiranebutanal 6 (cf. Scheme 2). Lewis acid catalyzed reaction of the bicyclic acetal with allyltrimethylsilane
introduces the side chain (as yet unfunctionalized) and sets the stereogenic centers at the tetrahydro-2H-pyran
ring of the pederin moiety.
Introduction. The mycalamides 1 and the pederins 2 are representatives of a class
of natural products with high biological activity (Fig. 1). They inhibit protein synthesis
at subnanomolar concentrations [1], and they display a strong immunosuppressive
activity [2]. This stimulated widespread synthetic efforts culminating in several total
syntheses (mycalamides [3 9], pederin [10 16]) that had to cope with the intricate
density of functional groups in these molecules.
Fig. 1. Mycalamides and Pederins
In considering shorter syntheses to these compounds, some aspects of the previous
efforts were noteworthy: First, the sensitive aminal function can be generated by a
Curtius degradation of a carboxylic acid precursor [9][15][17][18] (Scheme 1). Second,

Helvetica Chimica Acta Vol. 87 (2004)
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the side chain R on the tetrahydro-2H-pyran ring in the right fragment of these
molecules can be attached via reaction of an oxonium ion with a suitable C-nucleophile
such as an allylsilane [4][16][18][19] (see Scheme 1).
Scheme 1
As acetals are precursors of oxonium ions, this suggested to us the following
potential synthesis of the right-hand fragment of pederin, in which the bicyclic acetal 3
is a key intermediate [20] (Scheme 2). The ring opening of a bicyclic acetal such as 3
with an allylsilane under inversion of configuration to give 4 is known [19] (cf. also
[20]). Thus, the possible synthesis of a bicylic acetal was evaluated. Two routes
appeared attractive at first sight, an acetalization of a 3,5-dihydroxyaldehyde 5, and an
acetalization of a d,e-epoxy-aldehyde (ˆoxiranebutanal) 6, which proceeds under
inversion at the stereogenic centre in d-position [21]. We report here some model
studies along both of these lines.
The Oxiranebutanal Route to Bicyclic Acetals. To evaluate the feasibility of the
route to the bicyclic acetal 3 via cyclization of an oxiran-aldehyde, we looked for a rapid
access to oxiranebutanal 6. We started from the racemic diol 7 [22], which was
converted to oxirane 8 by treatment with NaH and 1-tosyl-1H-imidazole [23]
(Scheme 3). The crude oxirane 8 was allowed to react with 3-[(tetrahydro-2H-pyran-
2-yl)oxy]prop-1-ynyllithium to give the alcohol 9 in 78% yield. Protection and
deprotection gave the primary alcohol 10. Its LiAlH4 reduction furnished the allylic
alcohol 11, which was subjected to a Sharpless epoxidation [24]. Since we started from
racemic 11, we obtained a 3 :2 mixture of diastereoisomers 12. The configuration of the
oxirane stereogenic centers was assigned on the basis of the Sharpless mnemonic [24].
MPLC Separation of the diastereoisomers became possible at the stage of 13 after
protection of the free alcohol function as a (tert-butyl)dimethylsilyl (TBDMS) ether.
3
The diastereoisomers 13 showed characteristic differences in the J(H,H) coupling
constants of HÀC(3)1). To use these for an assignment of the relative configuration, we
carried out force-field calculations with the MM3 force field implemented in the
MACROMODEL program [25], using a Monte Carlo search of the conformational
space. Boltzmann averaging over the conformers allowed an estimation of the coupling
1
)
Arbitrary numbering (see Fig. 2); for systematic names, see Exper. Part.

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 2
constants for the two diastereoisomers, as shown in Fig. 2. Comparison with the
experimental coupling constants led to the above tentative assignment of the relative
configuration.
Scheme 3

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Fig. 2. Estimation of the coupling constants of the diastereoisomers 13
Next we tried to convert the alkenyloxirane 13a to the bicyclic acetal by ozonolysis
followed by treatment with TiCl4. We were, however, unable to isolate the desired
acetal 14 (Scheme 4).
Scheme 4
Rather than trying to optimize this reaction, we turned to an in situ allylation
reaction, pioneered by Rychnovsky and Dahanukar [26]. Treatment of the solution of
the crude oxirane-aldehyde with allyltrimethylsilane and TiCl4 led indeed to 55% of the
desired tetrahydro-2H-pyranmethanol 16 (Scheme 5). The acetal 14 may be involved in
this reaction in a blind-alley equilibrium. The relative configuration of product 16 was
assigned by analogy to precedents [19][26]. The 3J(H,H) coupling constants of
HÀC(4) of 10.8 and 2.6 Hz show an equatorial disposition of the silyloxy group. The
formation of 16 with the shown relative configuration requires a rapid interconversion
of the half chairs 15a and 15b of the oxonium ion prior to attack at the
allyltrimethylsilane.
The product 16 obtained in this manner was contaminated with 10% of an impurity.
Since the objective was only to demonstrate the feasibility of such an approach, 16 was
not purified further. The tetrahydro-2H-pyranmethanol 16 is, however, only a few well-
precedented steps away from the right-hand fragment of pederin: Asymmetric
dihydroxylation of the alkene moiety [3][4][6 8][16][18][27] followed by perme-
thylation of all the free alcohol functions [16][28][29], prior to the sequence of the
Curtius degradation. For this route to be viable for a synthesis of the right-hand
fragment of pederin, the starting material 7 or 8 should be enantiomerically pure. This
appears possible either by kinetic resolution of the oxirane 8 [30], or by recourse to an
asymmetric dihydroxylation reaction [31]. However, it might be preferable to use an
enantiomerically pure starting material from natural sources. This was done in the
following synthesis of the bicyclic acetal from a dihydroxy-aldehyde precursor.

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 5
The Dihydroxyaldehyde Route to Bicyclic Acetals. We felt that a dihydroxy-
aldehyde 5 could profitably be made from d-arabinose, which contains two of the
required three stereogenic centers. This would require a deoxygenation at C(2) of
arabinose and a chain extension at C(1), according to Scheme 6.
Scheme 6
To reach the first goal, d-arabinose (17) was converted to benzyl 2-deoxy-3,4-O-
isopropylidene-d-erythro-pentopyranoside (19) (Scheme 7). Benzyl 3,4-O-isopropyl-
idene-d-arabinopyranoside (18) was generated as described by Ballou [32]. The
deoxygenation at the 2-position was effected by the procedure of Barton and co-
workers [33] to give benzyl 2-deoxy-d-erythro-pentopyranoside 19 in 65% yield. Next,
the ensuing chain extension was initiated by the hydrogenation of 19 to give the 2-
deoxy-3,4-O-isopropylidene-d-erythro-pentose 20 (Scheme 8). Several attempts to
react the latter with tributyl(prenyl)stannane and Lewis acids (SnCl4, Me2SnCl2, TiCl4,
or BF3 ¥ OEt2) failed as well as indium-mediated reactions [34] of prenyl bromide.
Therefore, we turned to the reagent-controlled allylboration reaction with the

Helvetica Chimica Acta Vol. 87 (2004)
1219
allylboronate 21 [29]. The lactol 20 was allowed to react with the allylboronate 21 for
several days at room temperature under 8 9 kbar of pressure in the presence of
pyridin-2-ol as catalyst [35]. This furnished the homoallyl alcohol 22 as a single
diastereoisomer in 67% yield. The two possible diastereoisomers 22 and 23 can readily
be distinguished based on 3J(H,H) coupling constants, because each should populate a
t
preferred conformation, based on the Bu effect [36] originating from the quaternary
centre and the tendency to form an internally H-bonded structure [37] (Fig. 3). Thus, in
the 1,3-syn-diastereoisomer 22, the indicated protons should give a spin system with two
large and two small coupling constants. That of the 1,3-anti-diastereoisomer 23 should
have one large and three small coupling constants. The isolated diastereoisomer
showed coupling constants of 10.3, 1.7, 9.6, and 4.0 Hz establishing it as the 1,3-syn-
isomer 22. This is the expected one based on the preference of the reagent to generate
the homoallylic alcohol with an (R)-configuration [29]. The latter assignment is
supported by the (E)-geometry (3J(H,H) ˆ 15.6 Hz) of the newly formed CˆC bond.
Scheme 7
Fig. 3. Conformation fo the diastereoisomers 22 and 23
Next, protective groups were installed, a benzyl ether at the primary position and a
TBDMS ether at the homoallylic position to give 24. Ozonolysis furnished the
protected tetrahydroxy-aldehyde 25, which was immediately treated with TsOH in
moist benzene to effect transacetalization to the desired bicyclic acetal 26. The relative
configuration of the latter was secured by the strong NOE contacts indicated in
Scheme 8.

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Scheme 8
Further Exploratory Experiments. With the acetal 26 in hand, we could explore
the feasibility of the Curtius degradation. While not directly relevant to a synthesis of
pederin, we did these studies on the bicyclic structure 26. To this end, the benzyl ether
in 26 was deprotected by hydrogenolysis, and the resulting alcohol 27 was oxidized to a
carboxylic acid 28 [38] (Scheme 9). The latter was subjected as obtained to a Curtius
degradation furnishing carbamate 30 in 56% yield.
Scheme 9

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It appeared attractive to couple [14][39] carbamate 30 with the left-hand part of
pederin to provide a pederin analogon with a bicyclic acetal as a right-hand part. These
studies and the further elaboration of the right-hand fragment of pederin were,
however, postponed until a reliable coupling method for the two fragments will be at
hand. Such reservation was indicated after some initial attempts to couple the
isocyanate 29 with the left-hand fragment of pederin following our earlier model
studies [40] failed [41].
In summary, these studies indicate that a short and efficient synthesis of a right-
hand building block for pederin and its analogues via a Lewis acid catalyzed ring
opening of bicyclic acetals of type 14 or 26 with an allylsilane is feasible. This would
require subsequent refunctionalization of the side chain such as asymmetric dihydrox-
ylation, O-methylation of alcohols, and a Curtius degradation. The studies reported
here and precedents from previous studies bode well for such an approach.
We would like to thank the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie for
support of this study.
Experimental Part
General. See [42].
1. rac-3,3-Dimethyl-8-[(tetrahydro-2H-pyran-2-yl)oxy]oct-1-en-6-yn-4-ol (9). At 08, an 80% NaH suspen-
sion in white oil (8.00 g, 0.26 mol) was added in small portions to a soln. of 3,3-dimethylpent-4-en-1,2-diol [22]
(7; 13.8 g, 106 mmol) in THF (350 ml). The mixture was stirred for 2 h at r.t. and then cooled again to 08. A soln.
of 1-tosyl-1H-imidazole (25.0 g, 115 mmol) in THF (100 ml) was added dropwise. The mixture was stirred for
1 h at r.t. and for 30 min under reflux, and then the soln. of oxirane 8 was cooled to À 788.
A soln. of the lithiated acetylide was prepared from 3-[(tetrahydro-2H-pyran-2-yl)oxy]prop-1-yne (17.0 g,
125 mmol) in THF (150 ml) and 1.84m BuLi in hexane (68.0 ml, 125 mmol). This soln. was cooled to 08 and
added via canula to the precooled soln. of oxirane 8. BF3 ¥ Et2O (50 ml, 0.4 mol) was added dropwise resulting in
strong frothing. The mixture was stirred for 12 h at À 788. Sat. aq. NaHCO3 soln. (300 ml) was added slowly at
t
À 608. The mixture was allowed to reach r.t. The aq. layer was extracted with BuOMe (3 Â 100 ml), the
combined org. layer washed with brine (150 ml), dried (Na2SO4), and evaporated, and the residue filtered with
petroleum ether/tBuOMe 3 :1 over silica gel. The crude product was heated for 5 h to 508 at 2 ¥ 10À2 mbar to
remove excess 3-[(tetrahydro-2H-pyran-2-yl)oxy]prop-1-yne: 9 (diastereoisomer mixture; 20.9 g, 78%).
Colorless oil. 1H-NMR (300 MHz, CDCl3): 0.98 (s, Me); 0.99 (s, Me); 1.46 1.75 (m, CH2CH2CH2 (thp));
2.11 (dd, 3J ˆ 3.6, 8.5, CHOH); 2.20 (dABdt, 2JAB ˆ À16.7, 3J ˆ 8.5, 5J ˆ À2.4, CH2CꢀC); 2.35 (t, CH2CꢀC);
3.42 3.48 (m, HeqÀCHO (thp) and OH); 3.79 3.84 (m, HaxÀCHO (thp)); 4.12 4.23 (m, CꢀCCH2); 4.75 (q,
OCHO); 4.96 (dABd, 2JAB ˆ À1.3, 3J ˆ 17.4, HcisÀCHˆCH); 5.02 (dABd, 2JAB ˆ À1.3, 3J ˆ 10.9, HtransÀCHˆCH);
5.84 (dd, 3J ˆ 10.9, 3J ˆ 17.4, CH2ˆCH). 13C-NMR (75 MHz, CDCl3): 19.0; 22.4; 23.0; 23.1; 25.3; 30.2; 41.0; 54.6;
54.7; 61.8; 76.3; 78.2; 84.0; 96.9; 113.0; 144.4. Anal. calc. for C15H24O3 (252.35): C 71.39, H 9.59; found: C 71.48, H
9.81.
2. rac-4-{[(tert-Butyl)dimethylsilyl]oxy}-3,3-dimethyl-8-[(tetrahydro-2H-pyran-2-yl)oxy]oct-1-en-6-yne.
(tert-Butyl)chlorodimethylsilane (50% in hexane; 10.0 g, 33.2 mmol) and 1H-imidazole (3.20 g, 47.0 mmol)
were added to a soln. of 9 (7.89 g, 31.3 mmol) in DMF (30 ml). After stirring for 10 h at 458, MeOH (5 ml) was
added, and stirring was continued for 15 min. H2O (40 ml) was added, and the mixture was extracted with
petroleum ether (3 Â 100 ml). The combined org. layers were washed with brine (100 ml) and evaporated. FC
(petroleum ether/tBuOMe 10 :1 ! 1:1) furnished the product (diastereoisomer mixture; 6.71 g, 59%), besides
recovered 9 (2.52 g, 32%). 1H-NMR (300 MHz; CDCl3): 0.06 (s, MeSi); 0.11 (s, MeSi); 0.88 (s, tBuSi); 0.97 (s,
Me); 0.98 (s, Me); 1.45 1.73 (m, CH2CH2CH2 (thp)); 2.11 (dABdt, 2JAB ˆ À17.2, 3J ˆ 6.5, 5J ˆ 2.1, CH2CꢀC);
3
5
3
2.41 (dABdt, 2JAB ˆ À17.2, J ˆ 4.0, J ˆ 2.3, CH2CꢀC); 3.46 3.54 (m, HeqÀCHO (thp), overlapped by dd, J ˆ
4.0, 6.5, CHOSi); 3.77 3.85 (m, HaxÀCHO (thp)); 4.12 4.23 (m, CꢀCCH2); 4.75 (m, OCHO); 4.96
(dABd, 2JAB ˆ À1.9, 3J ˆ 18.0, HcisÀCHˆCH); 4.97 (dABd, 2JAB ˆ À1.9, 3J ˆ 10.6, HtransÀCHˆCH); 5.84 (dd, 3J ˆ
10.6, 3J ˆ 18.0, CH2ˆCH). 13C-NMR (75 MHz, CDCl3): À 4.5; À 3.8; 18.2; 19.1; 22.3; 24.2; 24.3; 25.4; 26.0;
30.3; 42.5; 54.6; 54.7; 61.8; 77.5; 78.6; 85.6; 85.7; 96.6; 96.7; 112.1; 145.3. Anal. calc. for C21H38O3Si (366.62): C
68.80, H 10.66; found: C 68.68, H 10.48.

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3. rac-5-{[(tert-Butyl)dimethylsilyl]oxy}-6,6-dimethyloct-7-en-2-yn-1-ol (10). TsOH (ca. 10 mg) was added
to a soln. of rac-4-{[(tert-butyl)dimethylsilyl]oxy}-3,3-dimethyl-8-[(tetrahydro-2H-pyran-2-yl)oxy]oct-1-en-6-
yne (3.60 g, 9.82 mmol) in EtOH (150 ml). After stirring for 1 d at r.t., the mixture was poured into a vigorously
t
stirred emulsion of H2O (100 ml) and BuOMe (100 ml). K2CO3 (1 g) was added, the aq. layer extracted with
tBuOMe (5 Â 100 ml), the combined org. layer washed with brine (50 ml), dried (Na2SO4), and evaporated, and
the residue filtered with petroleum ether/tBuOMe 3 :1 over silica gel: 10 (2.61 g, 94%). Colorless oil. 1H-NMR
(500 MHz, CDCl3): 0.08 (s, 1 MeSi); 0.14 (s, 1 MeSi); 0.90 (s, tBuSi); 0.98 (s, 1 Me); 0.99 (s, 1 Me); 2.18
(dABddd, 2JAB ˆ À14.3, 3J ˆ 4.4, 5J ˆ 1.8, 1.8, 1 H, CH2CꢀC); 2.46 (dABddd, 2JAB ˆ À14.3, 3J ˆ 6.5, 5J ˆ 2.2, 2.4,
2
1 H, CH2CꢀC); 3.53 (dd, 3J ˆ 4.3, 6.5, CHOSi); 4.239 (dABdd, JAB ˆ À2.2, 5J ˆ 2.2, 1.8, 1 H, CꢀCCH2OH);
5
4.244 (dABdd, 2JAB ˆ À2.2, J ˆ 2.4, 1.8, 1 H, CꢀCCH2OH); 4.97 (dABd, 2JAB ˆ À1.5, 3J ˆ 18.2, HcisÀCHˆCH);
4.98 (dABd, 2JAB ˆ À1.5, 3J ˆ 10.3, HtransÀCHˆCH); 5.86 (dd, 3J ˆ 10.3, 18.2, CH2ˆCH); OH signal missing.
13C-NMR (75 MHz, CDCl3): À 4.4; À 3.7; 18.3; 22.3; 24.2; 24.4; 25.4; 26.0; 42.6; 78.6; 79.8; 85.8; 112.2; 145.3.
Anal. calc. for C16H30O2Si (282.48): C 68.03, H 10.70; found: C 67.81, H 10.87.
4. rac-5-{[(tert-Butyl)dimethylsilyl]oxy}-6,6-dimethylocta-2,7-dien-1-ol (11). At 08, 10 (900 mg, 3.20 mmol)
was added to a suspension of LiAlH4 (450 mg, 12.8 mmol) in THF (70 ml). The mixture was heated to reflux for
12 h. After cooling to 08, AcOEt (1.5 ml), H2O (0.5 ml), 15% aq. NaOH soln. (0.5 ml), and H2O (0.5 ml) were
t
added sequentially. The mixture was filtered through Na2SO4, which was subsequently washed with BuOMe
(5 Â 20 ml). The combined filtrates were evaporated. FC (petroleum ether/tBuOMe 10 :1 ! 1:1) of the residue
furnished 11 (737 mg, 81%). Colorless oil. 1H-NMR (500 MHz, CDCl3): 0.02 (s, MeSi); 0.03 (s, MeSi); 0.91
(s, tBuSi); 0.99 (s, 2 Me); 1.65 (br. s, OH); 2.00 2.14 (m, 1 H, CH2CˆC); 2.29 2.33 (m, 1 H, CH2CˆC); 3.41
(dd, 3J ˆ 4.0, 6.7, CHOSi); 4.09 (br. s, CˆCCH2OH); 4.96 (dABd, 2JAB ˆ À1.5, 3J ˆ 17.1, HcisÀCHˆCH); 4.97
(dABd, 2JAB ˆ À1.5, 3J ˆ 11.3, HtransÀCHˆCH); 5.57 5.62 (m, CHˆCH); 5.68 5.73 (m, CHˆCH); 5.86
(dd, 3J ˆ 11.3, 17.1, CH2ˆCH). 13C-NMR (126 MHz, CDCl3): À 4.1; À 3.3; 18.3; 22.8; 24.6; 26.0; 36.9; 42.5;
63.8; 79.3; 111.6; 130.2; 131.7; 146.1. Anal. calc. for C16H32O2Si (284.51): C 67.55, H 11.35; found: C 67.46, H 11.61.
5. (2R,3R)-3-{(2R/S)-2-{[(tert-Butyl)dimethylsilyl]oxy}-3,3-dimethylpent-4-enyl}oxirane-2-methanol (12).
A soln. of (À)-diisopropyl tartrate (115 mg, 0.50 mol) and of titanium tetraisopropoxide (112 mg, 0.40 mmol) in
CH2Cl2 (20 ml) was stirred at À 308 for 30 min over 3-ä molecular sieves. A soln. of 11 (586 mg, 2.06 mmol) in
t
CH2Cl2 (2 ml) was added, and stirring was continued at À 308 for 10 min. A soln. of 7m BuOOH in CH2Cl2
(1.5 ml) was added, and the mixture was stored in a freezer at À 258 for 3 d. Aq. 10% tartaric acid (10 ml) was
added dropwise, and the mixture was allowed to reach r.t. and filtered over −Kieselgur×. The filtrate was
concentrated onto silica gel (3 g). FC (petroleum ether/ tBuOMe 1:1) furnished 12 (3 :2 diastereoisomer
mixture by NMR; 480 mg, 78%). Colorless oil. 1H-NMR (300 MHz, CDCl3): 0.03 (s, MeSi); 0.04 (s, MeSi); 0.86
(s, tBuSi); 0.92 (s, Me); 0.93 (s, Me); 1.31 1.55 (m, SiOCÀCH2); 1.63 (br. s, OH); 2.81 2.89 (m, CHOCH); 3.05
(m, CHOCH); 3.49 3.56 (m, CH2OH); 3.65 (m, CHOSi); 4.86 4.95 (m, CH2ˆCH); 5.84 (dd, 3J ˆ 10.2, 18.0,
CH2ˆCH). 13C-NMR (50 MHz, CDCl3): major (2R,2'S,3R)-diastereoisomer: À 4.0; 18.2; 21.6; 22.8; 26.0; 35.8;
42.0; 53.7; 60.0; 76.6; 111.8; 145.4; 1 C obscured; minor (2R,2'R,3R)-diastereoisomer: À 4.3; À 4.0; 18.2; 22.3;
24.6; 25.7; 36.7; 42.0; 54.2; 59.3; 112.0; 145.4; 2 C obscured. Anal. calc. for C16H32O3Si (300.21): C 63.95, H 10.73;
found (diastereoisomer mixture): C 63.94, H 10.94.
6. (2R,3R)-2-{(2R/S)-2-{[(tert-Butyl)dimethylsilyl]oxy}-3,3-dimethylpent-4-enyl}-3-{{[(tert-butyl)dime-
thylsilyl]oxy}methyl}oxirane (13). (tert-Butyl)chlorodimethylsilane (50% in hexane; 763 mg, 2.60 mmol) and
1H-imidazole (255 mg, 5.2 mmol) were added to a soln. of the alcohols 12 (380 mg, 1.30 mmol) in DMF (2 ml).
After stirring for 12 h, MeOH (1 ml) was added, and stirring was continued for 15 min. A pH 7 buffer soln.
t
t
(10 ml) and BuOMe (15 ml) were added, and the aq. layer was extracted with BuOMe (3 Â 10 ml). The
combined org. layer was washed with H2O (10 ml) and brine (2 Â 25 ml), dried (Na2SO4), and evaporated, and
the residue was subjected to FC (petroleum ether/tBuOMe/AcOEt 50 :1:1): 13 (diastereoisomer mixture;
423 mg, 78%). The diastereoisomers were separated by MPLC (petroleum ether/AcOEt 99 :1).
21
(2R,2'R,3R)-Isomer 13a: Less polar. ‰aŠ ˆ ‡12.9 (c ˆ 0.31, CHCl3). 1H-NMR (500 MHz, CDCl3): 0.07
D
(s, 1 MeSi); 0.08 (s, 1 MeSi); 0.10 (s, 1 MeSi); 0.12 (s, 1 MeSi); 0.91 (s, 1 tBuSi); 0.93 (s, 1 tBuSi); 0.98 (s, 1 Me);
0.99 (s, 1 Me); 1.56 (dABdd, 2JAB ˆ À14.45, 3J ˆ 3.29, 7.27, 1 H, CH2CHOSi); 1.70 (dABdd, 2JAB ˆ À14.53, 3J ˆ 4.27,
7.43, 1 H, CH2CHOSi); 2.83 (m, CHOCH); 2.99 (m, CHOCH); 3.61 (dd, 3J ˆ 3.47, 7.36, CHOSi); 3.65
(dABd, 2JAB ˆ À11.88, 3J ˆ 4.71, 1 H, CH2OSi); 3.80 (dABd, 2JAB ˆ À11.76, 3J ˆ 3.27, 1 H, CH2OSi); 4.96 4.99
(m, CH2ˆCH); 5.87 (dd, 3J ˆ 10.45, 17.87, CH2ˆCH).13C-NMR (126 MHz, CDCl3): À 5.3; À 3.9; À 3.8; 18.3;
22.7; 24.5; 25.9; 26.1; 36.2; 42.1; 53.9; 60.1; 63.4; 76.8; 111.8; 145.7. Anal. calc. for C22H46O3Si2 (414.78): C 63.71, H
11.17; found: C 63.97, H 10.93.
(2R,2'S,3R)-Isomer 13b: More polar. 1H-NMR (300 MHz, CDCl3): À 0.01 (s, 1 MeSi); 0.03 (s, 1 MeSi);
0.04 (s, 1 MeSi); 0.08 (s, 1 MeSi); 0.88 (s, 1 tBuSi); 0.90 (s, 1 tBuSi); 0.91 (s, 1 Me); 0.93 (s, 1 Me); 1.39 1.73

Helvetica Chimica Acta Vol. 87 (2004)
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(m, CH2CHOSi); 2.74 (m, CHOCH); 2.92 (m, CHOCH); 3.53 (dd, 3J ˆ 2.2, 9.7, CHOSi); 3.57 (dABd, 2JAB
ˆ
À11.8, 3J ˆ 4.6, 1 H, CH2OSi); 3.73 (dABd, 2JAB ˆ À11.8, 1 H, CH2OSi); 4.95 (d, 3J ˆ 12.0, HtransÀCHˆCH); 4.95
(d, 3J ˆ 16.3, HcisÀCHˆCH); 5.85 (dd, 3J ˆ 12.0, 16.3, CH2ˆCH). 13C-NMR (75 MHz, CDCl3): À 5.2; À 4.8; À
4.1; À 4.0; 18.1; 18.2; 21.7; 22.6; 24.4; 25.8; 26.0; 36.0; 41.9; 53.8; 63.3; 76.7; 111.6; 145.6.
7. (aR,2S,4R,6R)-4-{[(tert-Butyl)dimethylsilyl]oxy}-a-{{[(tert-butyl)dimethylsilyl]oxy}methyl}tetrahydro-
5,5-dimethyl-6-(prop-2-enyl)-2H-pyran-2-methanol (16). A stream of O3 in O2 was introduced at À 788 very
slowly into a soln. of 13a (19.9 mg, 48.1 mmol) in CH2Cl2/MeOH 1:3 (5 ml) until TLC indicated consumption of
the starting material. PPh3 (13.3 mg, 48.1 mmol) was added, and the mixture was stirred for 12 h at r.t. Petroleum
ether/tBuOMe 1:1 (15 ml) was added, and the precipitated PPh3ˆO was filtered over −Kieselgur×. The filtrate
was dried (MgSO4) and evaporated. The crude aldehyde was taken up under N2 in CH2Cl2 (5 ml) and
evaporated again. This step was repeated three times. The aldehyde was taken up once more in CH2Cl2 ( 5 ml)
and dried with 3-ä molecular sieves (0.5 g). Allyltrimethylsilane (50 ml, 0.3 mmol) was added, and the mixture
was cooled to À 788. A soln. of 2m TiCl4 in CH2Cl2 (2 drops) was added, and the mixture was stirred for 1 d at À
788. Upon slowly warming to À 508, TLC indicated the formation of a new product. A pH 7 buffer soln. (1 ml)
t
was added at À 508, and the mixture was allowed to reach r.t. The aq. layer was extracted with BuOMe (3 Â
5 ml), the combined org. layer washed with brine (2 Â 1 ml), dried (Na2SO4), and evaporated, and the residue
subjected to FC (petroleum ether/tBuOMe 20 :1 ! 10 :1): 16 (12.4 mg, 55%) containing 10% of an impurity.
Colorless oil. 1H-NMR (500 MHz, CDCl3): 0.08 (s, 2 MeSi); 0.09 (s, 2 MeSi); 0.90 (s, 2 tBuSi); 0.94 (s, 1 Me);
0.98 (s, 1 Me); 1.51 (br. s, OH); 1.65 1.74 (m, CH2CHˆCH2); 1.95 2.02 (m, 1 H, CH2CHOSi); 2.18 2.22
(m, 1 H, CH2CHOSi); 3.25 (dd, 3J ˆ 2.6, 10.8, CHOSi); 3.52 3.56 (m, 1 H, CH2OTBS); 3.61 (dd, 3J ˆ 4.0, 8.1,
CHOH); 3.76 (m, 1 H of CH2OTBS, 2 CHO); 5.05 (dd, 3J ˆ 12.1, 15.7, CHˆCH2); 5.78 5.86
(m, CHˆCH2).13C-NMR (75 MHz, CDCl3): À 5.4; À 5.0; À 4.3; 18.0; 18.3; 24.9; 25.8; 25.9; 30.5; 33.6; 38.4;
64.4; 70.0; 70.7; 73.0; 80.0; 128.8; 132.5; quat. C-atom not detected.
8. Benzyl d-Arabinoside. Acetyl chloride (5.0 ml, 70 mmol) was added to a soln. of d-(À)-arabinose (25.0 g,
167 mmol) in benzyl alcohol (125 ml), and the mixture was held at 508 for 1 d. After cooling, the mixture was
t
filtered, and the solid was taken up in BuOMe (30 ml). The mixture was suspended in toluene (400 ml),
tBuOMe (100 ml), CHCl3 (100 ml), and pyridine (10 ml), heated to 908, and filtered while hot. The product was
dried in vacuo: 27.0 g (67%) of solid material. On standing, the mother liquor deposited further 5.4 g. Total
19
D
1
yield: 32.4 g (81%). M.p. 169 1718 ([32]: 169 1718). ‰aŠ ˆ À217.6 (c ˆ 0.71, MeOH). H-NMR (300 MHz,
(D6)DMSO): 3.45 (dd, 3J ˆ 2.7, 11.8, HÀC(2)); 3.55 3.75 (m, HÀC(3), HÀC(4), 2 HÀC(5)); 4.52 (dAB, 2J ˆ
À12.3, HB of PhCH2); 4.59 4.79 (m, HA of PhCH2, HÀC(1), 3 OH); 7.19 7.35 (m, Ph). 13C-NMR (75 MHz,
(D6)DMSO): 63.5; 68.4; 68.6; 68.8; 69.3; 99.1; 127.5; 127.6; 128.3; 138.4. Anal. calc. for C12H16O5 (240.26): C
59.98, H 6.71; found: C 59.68, H 6.52.
9. Benzyl 3,4-O-Isopropylidene-d-arabinoside (18). Dimethoxypropane (12.0 g, 116 mmol) and TsOH
(5 mg) were added to a soln. of benzyl d-arabinoside (13.9 g, 57.8 mmol) in acetone (200 ml). After stirring for
40 h, 25% aq. ammonia (0.3 ml) was added, and the soln. was evaporated. The residue was taken up in CH2Cl2
(150 ml), the soln. washed with sat. aq. NaHCO3 soln. (100 ml), dried (Na2SO4), and evaporated, and the
19
residue dried at 2 ¥ 10À2 mbar: 16.2 g of a sirup, which slowly solidified on standing. ‰aŠ ˆ À171.2 (c ˆ 1.07,
D
CHCl3). 1H-NMR (300 MHz, CDCl3): 1.27 (s, 3 H, Me2CO2); 1.45 (s, 3 H, Me2CO2); 2.79 (br. s, OH); 3.67 3.75
(m, HÀC(2)); 3.86 (dAB, 2JAB ˆ À13.3, 1 HÀC(5)); 3.91 (dABd, 2JAB ˆ À13.3, 3J ˆ 1.9, 1 HÀC(5)); 4.11
(m, HÀC(3), HÀC(4)); 4.47 (dAB, 2JAB ˆ À16.1, 1 H, PhCH2); 4.65 (dAB
,
2JAB ˆ À16.4, 1 H, PhCH2); 4.85
(d, 3J ˆ 3.6, HÀC(1)); 7.19 7.30 (m, Ph). 13C-NMR (75 MHz, CDCl3): 25.8; 27.7; 59.6; 69.6; 69.9; 72.8; 75.8;
97.0; 110.0; 127.8; 128.3; 137.2. Anal. calc. for C15H20O5 (280.32): C 64.27, H 7.19; found: C 64.24, H 7.28.
10. Benzyl 3,4-O-Isopropylidene-2-O-[(phenylthio)carbonyl]-d-arabinoside. S-Phenyl carbonochlorido-
thioate (8.0 ml, 58 mmol) was added slowly to a soln. of 18 (16.2 g, 57.8 mmol) in pyridine (36 ml) and MeCN
(120 ml). The dark red mixture was stirred for 1 h at r.t. N-Hydroxysuccinimide (35 mg) was added, and stirring
was continued for 5 h. tBuOMe (100 ml) and H2O (50 ml) were added. The aq. layer was extracted with tBuOMe
(3 Â 100 ml), the combined org. layer washed with brine (100 ml), dried (Na2SO4), and evaporated, and the
18
residue subjected to FC (petroleum ether/tBuOMe 10 :1): product (19.4 g, 81%). Light yellow oil. ‰aŠ ˆ À182.7
D
(c ˆ 1.06, CHCl3). 1H-NMR (300 MHz, CDCl3): 1.41 (s, 3 H, Me2CO2); 1.60 (s, 3 H, Me2CO2); 4.09 (br.
s, 2 HÀC(5)); 4.34 (dt, 3J ˆ 5.5, HÀC(4)); 4.58 (dd, 3J ˆ 2.6, 5.5, HÀC(3)); 4.60 (dAB, 2JAB ˆ À12.4, 1 H,
PhCH2); 4.79 (dAB, 2JAB ˆ À12.4, 1 H, PhCH2); 5.27 (d, 3J ˆ 3.5, HÀC(1)); 5.46 (dd, 3J ˆ 3.5, 8.1, HÀC(2)); 7.08
7.41 (m, 2 Ph). 13C-NMR (75 MHz, CDCl3): 26.4; 28.0; 59.0; 69.6; 72.6; 73.7; 81.2; 94.2; 109.6; 121.8; 126.6;
127.6; 128.0; 128.5; 129.4; 137.0; 153.4; 194.8. Anal. calc. for C22H24O6S (416.49): C 63.45, H 5.81; found: C 63.34,
H 5.81.

1224
Helvetica Chimica Acta Vol. 87 (2004)
11. Benzyl 2-Deoxy-3,4-O-isopropylidene-d-erythro-pentopyranoside (19). Tributylstannane (8.50 ml,
32.2 mmol) was added to a soln. of the thiocarbonate described in Exper. 10 (11.2 g, 26.9 mmol) in toluene
(350 ml). The soln. was heated to 808, and a soln. of azobis[isobutyronitrile] (400 mg) in toluene (40 ml) was
added at a rate of 4 ml/min via a syringe pump. After 10 h stirring (TLC monitoring), further azobis[isobutyro-
nitrile] (100 mg) in toluene (20 ml) was added at a rate of 10 ml/min. Then, the mixture was evaporated and the
residue subjected to FC (petroleum ether/tBuOMe 1 :0 ! 10: 1): crude 19 (5.42 g, 76%) and starting material
(2.02 g, 18%). Bulb-to-bulb distillation of 19 at 1 ¥ 10À2 mbar (bath of 1008) gave a colorless solid. To remove
traces of S-contaminants, the product was dissolved in EtOH (15 ml) and stirred with Raney-Ni (ca. 500 mg).
The mixture was filtered over −Kieselgur×, the filtrate evaporated, the residue taken up in tBuOMe (50 ml), and
20
D
the soln. dried (MgSO4) and evaporated: pure 19 (4.31 g, 65%). M.p. 43 448. ‰aŠ ˆ À117.8 (c ˆ 4.75, CHCl3).
1H-NMR (300 MHz, CDCl3): 1.33 (s, 3 H, Me2CO2); 1.49 (s, 3 H, Me2CO2); 1.85 (dABdd, 2J ˆ À14.7, 3J ˆ 4.6, 6.1,
1 HÀC(2)); 2.16 (dABt, 2J ˆ À14.7, 3J ˆ 4.9, 1 HÀC(2)); 3.75 (dABd, 2J ˆ À12.9, 3J ˆ 2.4, 1 HÀC(5)); 3.89
(dABd, 2J ˆ À12.9, 3J ˆ 2.9, 1 HÀC(5)); 4.13 (dt, 3J ˆ 2.7, 3J ˆ 6.6, 1 HÀC(4)); 4.42 4.47 (m, HÀC(3)); 4.49
(dAB, 2JAB ˆ À11.9, 1 H, PhCH2); 4.76 (dAB, 2JAB ˆ À11.9, 1 H, PhCH2); 4.96 (dd, 3J ˆ 4.5, 6.0, HÀC(1)); 7.24
7.33 (m, Ph). 13C-NMR (75 MHz, CDCl3): 25.4; 27.2; 31.5; 61.3; 69.2; 69.9; 72.0; 95.7; 108.5; 127.6; 127.7; 128.4;
137.9. Anal. calc. for C15H20O4 (246.32): C 68.16, H 7.63; found: C 68.00, H 7.54.
12. 2-Deoxy-3,4-O-isopropyliden-d-erythro-pentopyranose (20). Pd(OH)2 (Pearlman catalyst, ca. 10 mg)
was added to a soln. of 19 (407 mg, 1.77 mmol) in THF (30 ml). The soln. was stirred for 12 h under H2. The
mixture was filtered over −Kieselgur×, and the filtrate was evaporated: 20 (anomeric mixture; 308 mg, 100%).
19
Colorless oil. ‰aŠ ˆ À22.4 (c ˆ 1.36, CHCl3; [43]: À 18.5 (c ˆ 4.2, CHCl3)). 1H-NMR (300 MHz, CDCl3): a-d-
D
anomer: 1.25 (s, 3 H, Me2CO2); 1.40 (s, 3 H, Me2CO2); 1.68 (dABdd, 2JAB ˆ À14.7, 3J ˆ 4.2, 7.5, 2 HÀC(2)); 2.05
2.18 (m, HÀC(3), HÀC(4)); 2.48 (q, J ˆ 6.8, 2 HÀC(5)); 4.53 (br. s, OH); 5.12 (dd, 3J ˆ 4.5, 7.1, HÀC(1)); b-d-
anomer (selected signals): 1.23 (s, 3 H, Me2CO2); 1.44 (s, 3 H, Me2CO2); 1.86 2.01 (m, 2 HÀC(5)); 4.89 (t, J ˆ
4.7, HÀC(1)). 13C-NMR (75 MHz, CDCl3): a-d-anomer: 25.2; 27.1; 32.1; 61.8; 70.6; 71.4; 90.7; 108.6; b-d-
anomer: 25.5; 27.8; 33.2; 60.8; 70.4; 71.8; 91.5; 109.2. Anal. calc. for C8H14O4 (174.20): C 55.16, H 8.10; found: C
55.07, H 8.38.
13. (aR,4S,5R)-a-[(2E)-1,1-Dimethylbut-2-enyl]-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-ethanol
(22). A soln. of 20 (411 mg, 2.36 mmol), (4R,5R)-2-[(1R)-1,3-dimethylbut-2-enyl)-4,5-dicyclohexyl-1,3,2-
dioxaborolane [29] (21; 977 mg, 3.07 mmol), and pyridin-2-ol (22 mg, 0.23 mmol) in CH2Cl2 (1 ml) was
pressurized for 7 d to 8 9 kbar. GC analysis indicated a 75% conversion. The mixture was subjected to FC
(silica gel, petroleum ether/tBuOMe 1 :0 ! 0 :1). Excess reagent 21 (302 mg) eluted with the nonpolar solvent.
The product was eluted with the polar fractions which were taken up in CH2Cl2 (5 ml), after evaporation.
Triethanolamine (ˆ2,2',2''-nitrilotris[ethanol]; 0.5 g) was added, and the mixture was stirred for 2 h. Silica gel
was added, and the mixture was evaporated. FC (petroleum ether/tBuOMe 2 :1) furnished 22 (single
19
diastereoisomer; 408 mg, 67%). Colorless oil. ‰aŠ ˆ ‡39.5 (c ˆ 0.98, CHCl3). 1H-NMR (500 MHz, C6D6): 1.16
D
(s, 1 Me); 1.17 (s, 1 Me); 1.21 (s, 3 H, Me2CO2); 1.31 (s, 3 H, Me2CO2); 1.54 (dABddd, 2JAB ˆ À14.20, 3J ˆ 9.85,
4
4
3
10.27, J ˆ À0.16, 1 H, CH2(b)); 1.66 (dd, 3J ˆ 6.32, J ˆ À1.59, MeCHˆCH); 1.71 (dABddd, 2JAB ˆ À14.20, J ˆ
1.61, 3.96, 4J ˆ À0.13, 1 H, CH2(b)); 3.17 (br. s, 1 OH); 3.39 (br. s, 1 OH); 3.43 (ddd, 3J ˆ 1.61, 10.27, 4J ˆ À0.23,
HÀC(a)); 3.61 3.65 (m, CH2OH); 4.20 (m, HÀC(5)); 4.36 (dddd, 3J ˆ 3.96, 3J ˆ 6.08, 9.85, 4J ˆ À0.23,
HÀC(4)); 5.44 (dABq, 3J ˆ 6.32, JAB ˆ 15.57, MeCHˆCH); 5.62 (dABq, 3JAB ˆ 15.57, 4J ˆ À1.59, MeCHˆCH).
3
13C-NMR (50 MHz, CDCl3): 18.2; 22.7; 24.0; 25.5; 28.1; 30.3; 40.3; 61.6; 77.3; 78.0; 78.4; 108.6; 123.1; 137.7. Anal.
calc. for C14H26O4 (258.36): C 65.09, H 10.14; found: C 65.33, H 10.33.
14. (aR,4S,5R)-5-[(Benzyloxy)methyl]-a-[(2E)-1,1-dimethylbut-2-enyl]-2,2-dimethyl-1,3-dioxolan-4-eth-
anol. Benzyl bromide (385 ml, 3.22 mmol) and 80% NaH in white oil (92 mg, 3.06 mmol) were added to a
soln. of 22 (832 mg, 3.22 mmol) in DMF/THF 1:1 (10 ml). After stirring for 10 h, pH 7 buffer soln. (2 ml) and
t
tBuOMe (5 ml) were added. The aq. layer was extracted with BuOMe (3 Â 25 ml) and the combined org. layer
washed with H2O ( 2Â 10 ml) and brine (2 Â 5 ml), dried (Na2SO4), and evaporated. FC (petroleum ether/
19
tBuOMe 5 :1 ! 1 :2) furnished the benzyl ether (853 mg, 76%) and 22 (70 mg, 8%). ‰aŠ ˆ ‡3.71 (c ˆ 1.12,
D
CHCl3). 1H-NMR (300 MHz, CDCl3): 0.97 (s, 2 Me); 1.33 (s, 3 H, Me2CO2); 1.39 (s, 3 H, Me2CO2); 1.65 (d, 3J ˆ
3
3
4.7, MeCHˆCH); 1.73 (dABdd, 2JAB ˆ À14.4, J ˆ 1.4, 3.2, 1 H, CH2(b)); 1.78 (dABdd, 2JAB ˆ À14.4, J ˆ 1.5, 2.9,
1 H, CH2(b)); 3.21 (d, 3J ˆ 1.6, OH); 3.44 3.53 (m, HÀC(a), BnOCH2); 4.25 4.37 (m, HÀC(4), HÀC(5));
4.49 (dAB, 2JAB ˆ À12.0, 1 H, PhCH2); 4.55 (dAB, 2JAB ˆ À12.0, 1 H, PhCH2); 5.33 5.47 (m, MeCHˆCH); 7.28
7.38 (m, Ph). 13C-NMR (75 MHz, CDCl3): 18.2; 22.5; 24.0; 25.5; 28.0; 30.7; 40.3; 68.9; 73.5; 76.4; 78.1; 78.6;
108.6; 122.7; 127.7; 128.4; 137.8; 138.1. Anal. calc. for C21H32O4 (348.48): C 72.38, H 9.26; found: C 72.47, H 9.46.
15. [(4R,5S)-4-[(Benzyloxy)methyl]-5-{(2R,4E)-2-{[(tert-butyl)dimethylsilyl]oxy}-3,3-dimethylhex-4-en-
yl}-2,2-dimethyl-1,3-dioxolane (24). At 08, 2,6-lutidine (ˆ2,6-dimethylpyridine; 105 ml, 0.86 mmol) and (tert-

Helvetica Chimica Acta Vol. 87 (2004)
1225
butyl)dimethylsilyl trifluoromethanesulfonate (160 ml, 0.60 mmol) were added to a soln. of the alcohol prepared
in Exper. 14 (150 mg, 0.43 mmol) in CH2Cl2 (3 ml). After stirring for 2 h, MeOH (1 ml) was added. Stirring was
continued for 15 min, and silica gel (ca. 1 g) was added. The mixture was evaporated and the residue subjected to
19
FC (petroleum ether/tBuOMe 30 :1): 24 (184 mg, 93%). Colorless oil. ‰aŠ ˆ ‡4.48 (c ˆ 1.19, CHCl3). 1H-NMR
D
(300 MHz, CDCl3): 0.03 (s, 1 MeSi); 0.05 (s, 1 MeSi); 0.89 (s, tBuSi); 0.90 (s, 1 Me); 0.91 (s, 1 Me); 1.30 (s, 3 H,
Me2CO2); 1.40 (s, 3 H, Me2CO2); 1.51 1.61 (m, 1 H, CH2CHOSi); 1.58 (d, 3J ˆ 5.6, MeCHˆCH); 1.79 1.89
(m, 1 H, CH2CHOSi); 3.33 3.46 (m, CH2CHOSi, BnOCH2); 4.14 4.28 (m, HÀC(4), HÀC(5)); 4.52
(dAB, 2JAB ˆ À12.1, 1 H, PhCH2); 4.54 (dAB, 2JAB ˆ À12.1, 1 H, PhCH2); 5.25 5.40 (m, MeCHˆCH); 7.26 7.33
(m, Ph). 13C-NMR (75 MHz, CDCl3): À 4.1; À 3.7; 18.3; 18.4; 22.1; 25.2; 25.5; 26.1; 28.1; 33.6; 41.6; 69.3; 73.4;
75.2; 76.1; 76.6; 107.5; 121.8; 127.7; 127.7; 128.3; 138.0; 138.9. Anal. calc. for C27H46O4Si (462.74): C 70.08, H
10.02; found: C 69.84, H 9.75.
16. (bR,4S,5R)-5-[(Benzyloxy)methyl]-b-{[(tert-butyl)dimethylsilyl]oxy}-a,a,2,2-tetramethyl-1,3-dioxo-
lane-4-butanal (25). At À 788, a stream of O3 in O2 was introduced very gently into a soln. of 24 (198 mg,
0.43 mmol) in CH2Cl2/MeOH 1:3 (10 ml) until TLC indicated consumption of the starting material (less than
1 min!). PPh3 (161 mg, 0.62 mmol) was added and the mixture was allowed to reach r.t. over 12 h. The mixture
was evaporated and the residue subjected to FC (petroleum ether/tBuOMe 10 :1): 25 (154 mg, 80%). Colorless
21
oil. ‰aŠ ˆ À9.3 (c ˆ 0.57, CHCl3). 1H-NMR (300 MHz, CDCl3): 0.15 (s, 1 MeSi); 0.16 (s, 1 MeSi); 0.80
D
t
(s, 1 Me); 1.01 (s, 1 Me, BuSi); 1.15 (s, 1 Me); 1.37 (s, 1 Me); 1.47 1.60 (m, CH2(d)); 3.45 (m, BnOCH2); 3.72
(dd, 3J ˆ 2.6, 3J ˆ 11.9, HÀC(b)); 3.86 3.94 (m, HÀC(3), HÀC(4)); 4.32 (dAB, 2JAB ˆ À12.1, 1 H, PhCH2); 4.36
(dAB, 2JAB ˆ À12.1, 1 H, PhCH2); 7.06 7.28 (m, Ph); 9.52 (s, CHO). 13C-NMR (75 MHz, CDCl3): À 4.3; À 4.2;
16.8; 18.5; 18.6; 19.5; 25.8; 26.1; 30.0; 48.9; 70.0; 71.9; 73.1; 73.5; 74.8; 98.7; 127.7; 127.8; 128.5; 138.9; 205.4. Anal.
calc. for C25H42O5Si (450.69): C 66.63, H 9.39; found: C 66.41, H 9.27.
17. {{(1S,3R,5S,7R)-7-[(Benzyloxy)methyl]-4,4-dimethyl-6,8-dioxabicyclo[3.2.1]oct-3-yl}oxy}(tert-butyl)-
dimethylsilane (26). TsOH ¥ H2O (15 mg) and H2O (0.1 ml) were added to a soln. of 25 (286 mg, 0.64 mmol)
in benzene (50 ml). The mixture was placed in a distillation apparatus and heated until liquid distilled over at
798 (ca. 45 min). The residue was cooled to r.t., K2CO3 (0.5 g), silica gel (ca. 1 g), and Et3N (2 drops) were
added, and the mixture was evaporated. FC (petroleum ether/tBuOMe 5 :1) furnished 26 (250 mg, 100%).
23
D
1
Colorless oil. ‰aŠ ˆ À68.9 (c ˆ 0.78, CHCl3). H-NMR (500 MHz, C6D6): À 0.01 (s, 1 MeSi); 0.02 (s 1 MeSi);
0.99 (s, tBuSi); 1.05 (s, 1 Me); 1.06 (s, 1 Me); 1.59 (dABdd, 2J ˆ À13.9, 3J ˆ 1.50, 6.46, 1 HÀC(2)); 1.77
(dABdd, 2J ˆ À14.1, 3J ˆ 11.5, 4.63, 1 HÀC(2)); 3.46 (dd, 2J ˆ À9.99, 3J ˆ 7.02, 1 H, BnOCH2); 3.70 (dd, 2J ˆ
À9.11, 3J ˆ 6.11, 1 H, BnOCH2); 3.89 (dd, 3J ˆ 6.34, 10.57, HÀC(3)); 4.21 (dt, 3J ˆ 1.72, 3J ˆ 4.31, HÀC(1)); 4.29
(td, 3J ˆ 6.68, 4.0, HÀC(7)); 4.37 (dAB, 2JAB ˆ À12.36, 1 H, PhCH2); 4.43 (dAB, 2JAB ˆ À12.36, 1 H, PhCH2); 5.14
(s, HÀC(5)); 7.20 7.29 (m, Ph). 13C-NMR (75 MHz, C6D6): À 4.8; À 4.0; 18.2; 18.3; 23.3; 26.0; 32.8; 41.4; 67.8;
71.4; 73.5; 74.7; 77.7; 108.9; 127.9; 128.7; 128.8; 138.5. Anal. calc. for C22H36O4Si (392.61): C 67.30, H 9.24; found:
C 67.11, H 9.40.
18. (1S,3R,5S,7R)-3-{[(tert-Butyl)dimethylsilyl]oxy}-4,4-dimethyl-6,8-dioxabicyclo[3.2.1]octane-7-meth-
anol (27). Pd(OH)2 (Pearlman catalyst; ca. 10 mg ) was added to a soln. of 26 (207 mg, 0.53 mmol) in THF
(20 ml). The soln. was stirred for 12 h under H2. The mixture was filtered over −Kieselgur×, the filtrate
evaporated, and the residue subjected to FC (petroleum ether/tBuOMe 1:1): 27 (158 mg, 99%). Colorless solid.
28
M.p. 64 678. ‰aŠ ˆ À76.9 (c ˆ 0.54, CHCl3). 1H-NMR (300 MHz, C6D6): 0.04 (s, 1 MeSi); 0.14 (s, 1 MeSi); 0.97
D
(s, tBuSi); 1.03 (s, 1 Me); 1.04 (s, 1 Me); 1.41 (br. s, OH); 1.54 (dABdd, 2J ˆ À13.9, 3J ˆ 1.3, 6.6, 1 HÀC(2)); 1.70
(dABdd, 2J ˆ À14.0, 3J ˆ 4.0, 10.0, 1 HÀC(2)); 3.46 (dABd, 2J ˆ À11.3, 3J ˆ 5.9, 1 H, CH2OH); 3.72 (dABd, 2J ˆ
À11.3, 3J ˆ 6.9, 1 H, CH2OH); 3.91 (dd, 3J ˆ 6.5, 10.5, HÀC(3)); 3.95 (m, HÀC(7)); 4.07 (dt, 3J ˆ 1.7, 4.1,
HÀC(1)); 5.10 (s, HÀC(5)). 13C-NMR (75 MHz, C6D6): À 4.8; À 3.9; 18.2; 18.4; 23.4; 26.0; 32.9; 41.4; 60.9;
71.5; 74.4; 79.7; 109.0. Anal. calc. for C15H30O4Si (302.49): C 59.56, H 10.00; found: C 59.38, H 10.15.
19. {(1S,3R,5S,7S)-3-{[(tert-Butyl)dimethylsilyl]oxy}-4,4-dimethyl-6,8-dioxabicyclo[3.2.1]oct-7-yl}carb-
amic Acid 2-(Trimethylsilyl)ethyl Ester (30). RuCl3 ¥ 3 H2O (15 mg, 0.06 mmol) was added to a soln. of
dipotassium peroxodisulfate (728 mg, 2.70 mmol) in 0.117m aq. KOH (100 ml, 11.7 mmol). After stirring for
30 min, a soln. of 27 (180 mg, 0.60 mmol) in tBuOH (30 ml) was added. After stirring for 2 h, sat. aq. Na2S2O3
soln. (8 ml) was added followed by solid NaH2PO4 until the pH reached 5 6. The aq. layer was extracted with
tBuOMe (2 Â 100 ml). The pH value was again adjusted by addition of NaH2PO4 soln., and the mixture was once
t
more extracted with BuOMe (2 Â 100 ml). The combined org. layer was washed with brine (2 Â 20 ml), dried
(Na2SO4) and evaporated. Remaining tBuOH was removed by addition of hexane (10 ml) and distillation of the
solvent. This was repeated twice. The residue, the crude carboxylic acid 28, was dried at 2 ¥ 10À2 mbar.
To a suspension of crude 28 in petroleum ether (20 ml), Et3N (108 ml, 715 mmol) and diphenylphosphoryl
azide (154 ml, 715 mmol) were added at 08. The mixture was allowed to reach r.t. over 12 h. After filtration over

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Helvetica Chimica Acta Vol. 87 (2004)
−Kieselgur× and evaporation, the residue was taken up in benzene (20 ml) and heated to reflux for 1 h. The
solvent was evaporated. To an aliquot of the resulting crude isocyanate 29 (76 mg, 0.244 mmol) in THF (20 ml),
2-(trimethylsilyl)ethanol (72 ml, 0.5 mmol) was added, and the soln. was heated for 10 h under reflux. The soln.
was evaporated and the residue subjected to FC (petroleum ether/tBuOMe 7:1): 30 (59 mg, 56%). Colorless oil.
21
‰aŠ ˆ À62.3 (c ˆ 0.41, CHCl3). 1H-NMR (400 MHz, (D6)acetone; double set of signals due to amide rotamers):
D
t
0.06 0.12 (m, 3 H, MeSi); 0.86 (s, 3 H, Me); 0.89 (s, 3 H, Me); 0.92 (s, 18 H, BuSi); 0.94 (s, 3 H, Me); 0.95
(s, 3 H, Me); 0.99 1.04 (m, 4 H, Me3SiCH2); 1.65 1.82 (m, 2 H, CH2); 2.00 (m, 2 H, CH2); 3.82 (dd, J ˆ 6.1,
10.4, 1 H, CHO); 4.08 (dd, J ˆ 6.4, 10.6, 1 H, CHO); 4.16 4.20 (m, 4 H, CHO); 4.27 (m, 1 H, CHO); 4.36
(m, 1 H, CHO); 4.89 (s, 1 H, OCHO); 5.01 (s, 1 H, OCHO); 5.38 (dd, 3J ˆ 4.0, 7.5, 1 H, NCHO); 5.43 (br. d, 3J ˆ
9.5, 1 H, NCHO); 6.48 (br. s, 1 H, NH); 6.68 (br. s, 1 H, NH). 13C-NMR (126 MHz, (D8)toluene; 348 K; double
set of signals due to amide rotamers): À 5.4; À 5.2; À 4.6; À 4.5; À 2.0; 18.0; 18.1; 18.2; 18.3; 23.3; 23.4; 26.1;
32.1; 34.5; 41.4; 41.5; 63.3; 63.7; 70.9; 71.8; 73.6; 78.7; 82.2; 82.9; 108.9; 109.4; 155.5; even in (D6)DMSO, a
double set of signals was observed up to 373 K. Anal. calc. for C20H41NO5Si2 (431.72): C 55.64, H 9.57, N 3.24;
found: C 55.64, H 9.30, N 3.42.
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Received November 26, 2003