Diastereoselective dihydroxylation and regioselective deoxygenation of dihydropyranones: A novel protocol for the stereoselective synthesis of C 1-C8 and C15-C21 subunits of (+)-discodermolide

Article abstract of DOI:10.1021/jo0492416

Diastereoselective dihydroxylation of dihydropyranones and subsequent regioselective α-deoxygenation provides 1,3-trans-β-hydroxy-6- lactones stereoselectively. This protocol has been applied for the synthesis of C₁-C₈ and C₁₅-C₂₁ subunits of (+)-discodermolide.

Full text of DOI:10.1021/jo0492416

Dia ster eoselective Dih yd r oxyla tion a n d Regioselective
Deoxygen a tion of Dih yd r op yr a n on es: A Novel P r otocol for th e
Ster eoselective Syn th esis of C1-C8 a n d C15-C21 Su bu n its of
(+)-Discod er m olid e
P. Veeraraghavan Ramachandran,* Bodhuri Prabhudas, J . Subash Chandra, and
M. Venkat Ram Reddy
Herbert C. Brown Center for Borane Research, 560 Oval Drive, Department of Chemistry,
Purdue University, West Lafayette, Indiana 47907-2084
chandran@purdue.edu
Received May 4, 2004
Diastereoselective dihydroxylation of dihydropyranones and subsequent regioselective R-deoxy-
genation provides 1,3-trans-â-hydroxy-δ-lactones stereoselectively. This protocol has been applied
for the synthesis of C1-C8 and C15-C21 subunits of (+)-discodermolide.
In tr od u ction
4a -d 4 (Figure 1). As expected, all of the homoallylic
alcohols 5a -l were obtained in excellent de and ee, which
upon treatment with acryloyl chloride and subsequent
ring-closing metathesis5 with Grubbs’s second-generation
ruthenium catalyst afforded the corresponding dihydro-
pyranones 7a -l (Scheme 1 and Table 1).
We observed that the dihydroxylation of the dihydro-
pyranones 7a -l under standard conditions using OsO4/
NMO is highly diastereoselective leading to the exclusive
formation of the trans isomers 8a -l. The relative ster-
eochemistry is with respect to the substituent at C-5
regardless of the stereochemistry at C-4 (Scheme 1). The
intermediate osmate ester formation takes place from the
side opposite to the substituent at C-5 due to the
favorable stereoelectronic factors.6 In fact, a similar kind
of diastereoselectivity has been reported by O’Doherty7
and also by Nicolaou2 during the synthesis of evernino-
micin. We then converted these diols into â-hydroxy-δ-
lactones regioselectively. Several biologically active mol-
ecules contain a â-hydroxy-δ-lactone moiety as an
important constituent8a-c or as a key pharmacophore.8d
The R-pyranone moiety is an important structural
feature found in many biologically active natural prod-
ucts.1 They also act as versatile synthetic intermediates
in organic synthesis.2 For the past few years, we have
been developing various R-pinene-based chiral allylbo-
ranes and applying them to the stereoselective synthesis
of R-pyranone-containing molecules.3 As a part of this
program we undertook a project involving the dihydroxy-
lation of dihydropyranones since this method would lead
to a simple synthesis of pyranose carbohydrate units. We
also envisaged that the dihydroxylated products should
provide â-hydroxy-δ-lactones upon selective deoxygen-
ation at the position R- to the carbonyl group. With these
goals in mind, we carried out a systematic examination
on the diastereoselectivity in dihydroxylation and regio-
selectivity in the deoxygenation of dihydropyranones. Our
interesting results are presented here.
Resu lts a n d Discu ssion
For the present study, we chose various C4- and C5-
substituted optically active dihydropyranones.3 Accord-
ingly R-pyrones 7a -l were prepared via allylboration
of aldehydes 1-3 with our R-pinene-based allylboranes
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10.1021/jo0492416 CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/05/2004
6294
J . Org. Chem. 2004, 69, 6294-6304

Regioselective Deoxygenation of Dihydropyranones
Laboratory synthesis seems to be the only feasible
alternative to obtain useful quantities of this cytotoxic
polyketide.
Several groups have reported the total synthesis of
10,14 and many other groups have reported the syntheses
of subunits of 10.15,16 Our retrosynthetic strategy for the
synthesis of discodermolide is outlined in Scheme 2.
Examination of the subunits 11 and 12 illustrates that
both of them contain 1,2-syn- and 1,2-anti-polypropionate
units and a 1,3-syn-diol unit. The presence of this
stereoregular array prompted us to develop a common
synthetic strategy for both of these subunits. We envis-
F IGURE 1. B-“Allyl”-diisopinocampheylboranes.
SCHEME 1a
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a
Key: (a) 4a -d , NaOH, H2O2; (b) CH2dCHCOCl, Py; (c)
Grubbs II generation catalyst; (d) OsO4, NMO; (e) (i) PhOC(S)Cl,
Py; (ii) Bu3SnH, AIBN.
Because of its proximity to the carbonyl group, R-hydroxyl
group at C-3 is more acidic and hence more reactive than
the â-hydroxyl group at C-4.9 Treatment of diols 8a -l
with 1 equiv of phenylchlorothionoformate selectively
transformed the R-hydroxyl group to the thionocarbonate,
which upon reaction with tributyltin hydride and AIBN
under Barton-McCombie conditions10 provided 1,3-trans-
â-hydroxy-δ-lactones 9a -l regioselectively (Scheme 1 and
Table 1).
We applied this methodology for the synthesis of C1-
C8 and C15-C21 subunits of (+)-discodermolide (10), a
complex natural product isolated by Gunasekara and co-
workers from deepwater Caribbean sponge Discodermia
dissolute.11 It exhibits excellent microtubule-stabilizing
capabilities with an IC50 value of <2.5 nM toward
paclitaxel (Taxol)12-resistant ovarian and colon cancer cell
lines.13a,b Collaborative efforts by Smith and Horwitz13c
reveal that a combination of discodermolide and Taxol
is 20-fold more active on the Taxol-dependent cell lines.
This highly encouraging biological profile makes 10 a
promising candidate for the synergistic cancer treatment
therapy13c and for clinical development as a chemothera-
peutic agent for Taxol-resistant breast, ovarian, colon,
and several other multidrug-resistant cancers. However,
the supply of this molecule from natural sources (0.002%
w/w from the frozen sponge) severely limits its potential.
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Trans. 1 1975, 1574. (b) Crich, D.; Quintero, L. Chem. Rev. 1989, 89,
1413.
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G. K. J . Org. Chem. 1990, 55, 4912. (b) Gunasekara, S. P.; Paul, G.
K.; Longley, R. E.; Isbrucker, R. A.; Pomponi, S. A. J . Nat. Prod. 2002,
65, 1643. (c) Gunasekara, S. P.; Longley, R. E.; Isbrucker, R. A. J . Nat
Prod. 2002, 65, 1830.
(12) Taxol is a registered trademark of the Bristol-Myers Squibb
Co.
(13) (a) terHaar, E.; Kowalski, R. J .; Hamel, E.; Lin, C. M.; Longley,
R. E.; Gunasekera, S. P.; Rosenkranz, H. S.; Day, B. W. Biochemistry
1996, 35, 243. (b) Kowalski, R. J .; Giannakakou, P.; Gunasekera, S.
P.; Longley, R. E.; Day, B. W.; Hamel, E. Mol. Pharm. 1997, 52, 613.
(c) Martello, L. A.; McDaid, H. M.; Regl, D. L.; Yang, C. P. H.; Meng,
D. F.; Pettus, T. R. R.; Kaufman, M. D.; Arimoto, H.; Danishefsky, S.
J .; Smith, A. B.; Horwitz, S. B. Clin. Cancer. Res. 2000, 6, 1978.
J . Org. Chem, Vol. 69, No. 19, 2004 6295

Ramachandran et al.
TABLE 1. P r ep a r a tion of Dih yd r op yr a n on es, Dih yd r oxyla cton es, a n d â-Hyd r oxyla cton es
dihydropyranone
R3
dihydroxylactone
â-hydroxylactone
no.
R1
R2
% yielda
deb
eeb
no.
% yield
no.
% yield
7a
7b
7c
7d
7e
7f
7g
7h
7i
C6H5
C6H5
C6H5
C6H5
C6F5
C6F5
C6F5
C6F5
C5H11
C5H11
C5H11
C5H11
H
H
Me
H
H
H
Me
H
H
H
H
Me
H
OMEM
H
Me
H
OMEM
H
Me
76
60
59
60
86
77
84
59
63
56
67
59
98
96
96
98
97
97
97
97
96
95
95
97
8a
8b
8c
8d
8e
8f
8g
8h
8i
72
75
78
86
80
80
85
75
81
79
88
87
9a
9b
9c
9d
9e
9f
9g
9h
9i
79
70
71
75
60
55
50
60
80
80
90
80
>98
>98
>98
>98
>98
>98
7j
7k
7l
>98
>98
>98
8j
8k
8l
9j
9k
9l
Me
H
H
OMEM
a
b
Combined yields for the two steps (conversion of 5a -l to 7a -l). de and ee on the basis of homoallylic alcohol 5.
SCHEME 2
SCHEME 3a
aged that diastereoselective 1,3-trans dihydroxylation of
dihydropyranones that can be readily prepared via a
tandem asymmetric “allyl”-boration and ring-closing me-
tathesis protocol, followed by a regioselective deoxygen-
ation of the more reactive R-hydroxyl group under
Barton-McCombie conditions,10 should furnish the â-hy-
droxy-δ-lactone with a 1,3-syn configuration. R-Methy-
lation of â-hydroxy-δ-lactone should take place in a trans
orientation to provide the 1,2-syn-polypropionate moiety.
a
Key: (a) (-)-Ipc2BAll; (b) TBSCl, Im, 80% overall; (c) O3, Me2S,
76%; (d) (E)-2-butene, n-BuLi, KOtBu, (+)-Ipc2BOMe, 82%; (e)
CH2dCHCOCl, NEt3, 85%; (f) Grubbs’ II generation catalyst, 96%;
(g) OsO4, NMO, 87%; (h) (i) PhOC(S)Cl, Py; (ii) Bu3SnH, AIBN,
93%; (i) LDA, HMPA, MeI, 78%; (j) TBSOTf, 2,6-lutidine, 92%;
(k) H2, Pd, 90%; (l) DMP, 93%.
the lactone 20. Cleavage of the benzyl group via hydro-
genolysis and oxidation of the resulting primary alcohol
using Dess-Martin periodinane18 provided the required
subunit 11 (Scheme 3).
The synthesis of subunit C1-C8 (11) was initiated with
the allylboration of benzyloxyacetaldehyde 13 with (-)-
diisopinocampheylallylborane.4a Silyl protection of the
resulting homoallylic alcohol 14 and ozonolysis of the
olefin afforded the aldehyde 15. Crotylboration of 15 with
(E)-B-crotyldiisopinocampheylborane4b,c furnished the ho-
moallylic alcohol 16.
The synthesis of C15-C21 segment 12 began with
the protection of commercially available hydroxy methyl
ester 21 as its silyl ether, followed by the reduction of
the ester to the alcohol 22. Oxidation of the alcohol to
the corresponding aldehyde and subsequent crotylbora-
tion with B-(Z)-crotyldiisopinocampheylborane furnished
the homoallylic alcohol 23 in >90% diastereoselectivity.
Acryloylation and ring-closing metathesis afforded the
dihydropyranone 24 in good yield. As expected, dihy-
droxylation using OsO4 and NMO provided the dihy-
droxylactone 25 as a single diastereomer. Regioselective
R-deoxygenation under Barton-McCombie conditions
yielded the â-hydroxy lactone 26. Treatment with LDA
Acryloylation, followed by ring-closing metathesis us-
ing Grubbs’s second-generation ruthenium catalyst,5
provided the dihydropyranone derivative 17. Dihydroxy-
lation under standard conditions with OsO4 and NMO
proved to be highly diastereoselective, and the diol 18
was obtained as a single diastereomer. Selective conver-
sion of the more reactive R-hydroxy group to the phenyl-
chlorothionoformate ester, followed by reduction with
Bu3SnH in the presence of AIBN, led to the regioselective
deoxygenation of the R-hydroxy group and yielded the
â-hydroxy-δ-lactone 19. The relative stereochemistry in
19 was confirmed by single-crystal X-ray analysis. The
hydroxy-directed methylation at the R- position provided
the anti product,17 and protection of the alcohol as its
silyl ether using TBS triflate and 2,6-lutidine afforded
(17) (a) Seebach, D.; Chow, H.-F.; J ackson, R. F. W.; Sutter, M. A.;
Thaisrivongs, S.; Zimmermann, J . Liebigs. Ann. Chem. 1986, 7, 1281.
(b) Tholander, J .; Carreira, E. M. Helv. Chem. Acta 2001, 84, 613.
(18) (a) Dess, D. B.; Martin, J . C. J . Org. Chem. 1983, 48, 4155. (b)
Dess, D. B.; Martin, J . C. J . Am. Chem. Soc. 1991, 13, 7277.
(19) Contribution no. 34 from the Herbert C. Brown Center for
Borane Research.
6296 J . Org. Chem., Vol. 69, No. 19, 2004

Regioselective Deoxygenation of Dihydropyranones
SCHEME 4a
SCHEME 6a
a
Key: (a) PNBCl, Py, DMAP, 93%; (b) MEMCl, DIPEA, 56%;
(c) TESOTf, 2,6-lutidine, 97%; (d) K2CO3, MeOH, 83%; (e) I2, PPh3,
imidazole, 72%.
group to MEM ether (Scheme 6). However, treatment of
the hydroxy ester 31 with MEM chloride and Hunig’s
base resulted in the deprotection of the primary TBS
group and subsequent trans-acetalization furnished the
1,3-dioxane unit 32. Finally, protection of the secondary
alcohol in 31 as its triethylsilyl ether, which can be
selectively deprotected in the presence of a secondary
TBS group at C17 at a later stage of the synthesis,
followed by the hydrolysis of PNB group under basic
conditions led to the formation of the primary alcohol 33.
Iodination of 33 with I2 and PPh3 furnished the required
subunit 12 (Scheme 6).
a
Key: (a) TBSCl, Im, 90%; (b) BH3‚Me2S, MeOH, NEt3, 78%;
(c) DMP, 87%; (d) (Z)-2-butene, n-BuLi, KOtBu, (+)-Ipc2BOMe,
75%; (e) CH2dCHCOCl, DIEA, 79%; (f) Grubbs’ II generation
catalyst, 86%; (g) OsO4, NMO, 72%; (h) (i) PhOC(S)Cl, Py; (ii)
Bu3SnH, AIBN, 68%; (i) LDA, HMPA, MeI, 75%; (j) TBSOTf, 2,6-
di-tert-butyl-4-methylpyridine, 78%; (k) LiBH4, 76%; (l) I2, PPh3,
imidazole.
SCHEME 5
Con clu sion
In summary, we have developed a novel protocol for
the preparation of trans-â-hydroxy-δ-lactones via dia-
stereoselective dihydroxylation and regioselective deoxy-
genation of dihydropyranones. Application of this meth-
odology has been demonstrated by the synthesis two
subunits of potent anti cancer agent (+)-discodermolide.
The key steps in the synthesis involve the utilization of
inexpensive R-pinene-based chiral “allyl”-borane reagents
to introduce the initial chirality and ring-closing metath-
esis reaction to obtain R-pyranones. We believe that this
protocol will find further applications for the synthesis
of various other complex molecules.
and MeI,17 followed by silylation of the resulting R-me-
thylated alcohol with TBS triflate and 2,6-di-tert-butyl-
4-methylpyridine, afforded 27. Utilization of conventional
amines such as Hunig’s base and 2,6-lutidine resulted
in the â-elimination to afford the corresponding R-me-
thylated dihydropyranone. After establishing all of the
necessary chiral centers by reagent- and substrate-
controlled reactions, the lactone 27 was reduced with
LiBH4 to the acyclic diol 28 in good yield. Our initial
strategy was to selectively iodinate the primary alcohol
in 28 and then protect the secondary alcohol as the PMB
ether. However, the conversion of 28 to the primary
iodide posed some unexpected problems. Treatment of 28
with I2 and PPh3 in the presence of imidazole resulted
in a complex mixture of products as indicated by TLC
(Scheme 4).
Exp er im en ta l Section
P r ep a r a tion of (6S)-6-P h en yl-5,6-d ih yd r op yr a n -2-on e,
C
11H10O2, 7a . Acrylate 6a (8.0 g, 19.1 mmol) was refluxed in
toluene (200.0 mL) at 100 °C. Grubbs’ second-generation
catalyst (0.81 g, 0.95 mmol) was added and the solution
refluxed for 3 h. After completion of the reaction (TLC), solvent
was evaporated under vacuum and the crude product was
purified by column chromatography (silica gel, 3:2, hexane/
ethyl acetate) to obtain 7.2 g (96%) of the lactenone 7a : 1H
NMR (300 MHz, CDCl3) δ (ppm) 7.26-7.40 (m, 5H), 6.95-
6.99 (m, 1H), 6.12 (d, J ) 9.3 Hz, 1H), 5.45 (dd, J ) 6.4, 8.9
Hz, 1H), 2.62-2.64 (m, 2H); 13C NMR (75.5 MHz, CDCl3) δ
(ppm) 164.2, 145.4, 138.5, 128.7, 128.6, 126.1, 121.6, 79.3, 31.8.
(5S ,6R )-5-Me t h yl-6-p h e n yl-5,6-d ih yd r op yr a n -2-on e ,
C
12H12O2, 7b. Same procedure as for 7a : 1H NMR (300 MHz,
Conversion of the diol 28 as its di-PMB ether 29
followed by attempts to selectively deprotect the primary
PMB ether using 1.2 equiv of DDQ did not materialize
and resulted in the formation of 1,3-dioxane unit 30
(Scheme 5).
Selectively converting the primary alcohol in 28 to the
p-nitrobenzoate ester 31 and protection of the secondary
alcohol as its PMB ether under different conditions also
proved futile. This compelled us to change the protecting
CDCl3) δ (ppm) 7.30-7.42 (m, 5H), 7.10 (dd, J ) 6.2, 9.7 Hz,
1H), 6.08 (d, J ) 9.6 Hz, 1H), 5.59 (d, J ) 3.4 Hz, 1H), 2.59-
2.69 (m, 1H), 0.81 (d, J ) 7.1 Hz, 3H); 13C NMR (75.5 MHz,
CDCl3) δ (ppm) 164.5, 151.8, 137.0, 128.5, 128.0, 125.6, 120.0,
81.0, 34.8, 11.8.
(5R,6R)-5-Met h yl-6-p h en yl-5,6-d ih yd r op yr a n -2-on e,
C
12H12O2, 7c. Same procedure as for 7a : 1H NMR (300 MHz,
CDCl3) δ (ppm) 7.20-7.33 (m, 5H), 6.70 (dd, J ) 2.1, 9.7 Hz,
1H), 6.01 (dd, J ) 2.5, 9.8 Hz, 1H), 4.91 (d, J ) 10.6 Hz, 1H),
2.71-2.80 (m, 1H), 0.94 (d, J ) 7.3 Hz, 3H); 13C NMR (75.5
J . Org. Chem, Vol. 69, No. 19, 2004 6297

Ramachandran et al.
MHz, CDCl3) δ (ppm) 164.0, 151.5, 137.4, 129.0, 128.6, 127.5,
120.3, 86.0, 35.2, 15.8.
dissolved in acetone/water (4:1, 15 mL) at 0 °C. OsO4 (156 mg,
0.6 mmol) was added to the above solution and stirred for 6 h
at room temperature, the product was extracted with Et2O (3
× 20 mL) and washed, and the organic layers were concen-
trated under aspirator vacuum. The crude product was purified
by column chromatography (silica gel, hexane/ethyl acetate (1:
4)) to obtain 2.8 g (87%) of 8a : 1H NMR (300 MHz, CDCl3) δ
(ppm) 7.35-7.40 (m, 5H), 5.81 (dd, J ) 3.4, 12.0 Hz, 1H), 4.45
(m, 1H), 4.26 (d, J ) 2.4 Hz, 1H), 3.70 (bs, 1H), 3.10 (bs, 1H),
2.49 (ddd, J ) 3.5, 4.5, 14.9 Hz, 1H), 2.18 (t, J ) 13.4, 1H);
13C NMR (75.5 MHz, CDCl3) δ (ppm) 174.1, 138.7, 128.8, 128.7,
125.8, 79.4, 70.5, 66.3, 36.3; CI-MS 209 (M + H)+, 191 [(M +
H - H2O)+, 100], 173, 145; HRMS-CI 209.0817 (actual),
209.0814 (calcd).
(3S,4S,5S,6R)-3,4-Dih ydr oxy-5-m eth yl-6-ph en yltetr ah y-
d r op yr a n -2-on e, C12H14O4, 8b. Same procedure as for 8a : 1H
NMR (300 MHz, CDCl3) δ (ppm) 7.28-7.41 (m, 5H), 6.04 (d, J
) 3.2 Hz, 1H), 4.39 (d, J ) 3.1 Hz, 1H), 4.31 (t, J ) 3.5 Hz,
1H), 2.53-2.63 (m, 1H), 3.66 (bs, 1H), 3.31 (bs, 1H), 0.81 (d, J
) 7.4 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 174.7,
137.1, 128.5, 127.8, 125.1, 80.9, 71.4, 67.6, 39.1, 10.3; EI-MS
m/z 222 (M+), 176, 147, 134, 118, 107 (100), 91, 79, 70, 51;
CI-MS m/z 223 [(M + H)+, 100], 187, 119; HRMS-CI 222.0887
(actual), 222.0892 (calcd).
(5S,6S)-5-Met h oxyet h oxym et h oxy-6-p h en yl-5,6-d ih y-
d r op yr a n -2-on e, C15H18O5, 7d . Same procedure as for 7a :
1H NMR (300 MHz, CDCl3) δ (ppm) 7.32-7.46 (m, 5H), 7.12
(dd, J ) 5.8, 9.7 Hz, 1H), 6.24 (d, J ) 9.7 Hz, 1H), 5.49 (d, J
) 2.5 Hz, 1H), 4.49 (d, J ) 7.2 Hz, 1H), 4.27 (dd, J ) 2.8, 5.7
Hz, 1H), 4.09-4.18 (m, 1H), 3.46-3.51 (m, 1H), 3.26-3.38 (m,
5H), 3.10-3.16 (m, 1H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
143.3, 128.5, 128.3, 126.8, 123.5, 94.8, 81.2, 71.5, 67.6, 67.0,
59.0.
(6S)-6-P en tyl-5,6-dih ydr opyr an -2-on e, C10H16O2, 7e. Same
procedure as for 7a : 1H NMR (300 MHz, CDCl3) δ (ppm) 6.83
(ddd, J ) 3.1, 5.5, 9.7 Hz, 1H), 5.93 (ddd, J ) 1.2, 2.4, 9.7 Hz,
1H), 4.31-4.41 (m, 1H), 2.24-2.31 (m, 2H), 1.20-1.80 (m, 8H),
0.83 (t, J ) 6.7 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
164.6, 145.3, 121.3, 78.0, 34.8, 31.5, 29.4, 24.5, 22.5, 14.0.
(5R ,6S )-5-Me t h yl-6-p e n t yl-5,6-d ih yd r op yr a n -2-on e ,
C
11H18O2, 7g. Same procedure as for 7a : 1H NMR (300 MHz,
CDCl3) δ (ppm) 6.60 (dd, J ) 2.6, 9.7 Hz, 1H), 5.89 (dd, J )
2.4, 9.7 Hz, 1H), 3.98-4.08 (m, 1H), 2.38-2.48 (m, 1H), 1.21-
1.79 (m, 8H), 1.10 (d, J ) 7.3 Hz, 3H), 0.88 (t, J ) 6.6 Hz,
3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 164.4, 151.7, 120.0,
83.7, 33.1, 32.7, 31.6, 25.7, 24.4, 22.5, 16.5, 14.0.
(3S,4S,5R,6R)-3,4-Dih ydr oxy-5-m eth yl-6-ph en yltetr ah y-
d r op yr a n -2-on e, C12H14O4, 8c. Same procedure as for 8a : 1H
NMR (300 MHz, CDCl3) δ (ppm) 7.29-7.40 (m, 5H), 5.35 (d, J
) 10.8 Hz, 1H), 4.32-4.33 (m, 1H), 4.21 (bs, 1H), 3.64 (bs, 1H),
(5S,6S)-5-Met h oxyet h oxym et h oxy-6-p en t yl-5,6-d ih y-
d r op yr a n -2-on e, C14H24O5, 7h . Same procedure as for 7a :
1H NMR (300 MHz, CDCl3) δ (ppm) 7.04 (dd, J ) 5.4, 9.7 Hz,
1H), 6.09 (d, J ) 9.7 Hz, 1H), 4.79 (d, J ) 7.1 Hz, 1H), 4.31-
4.35 (m, 1H), 4.00-4.02 (m, 1H), 3.50-3.72 (m, 4H), 3.36 (s,
3H), 1.30-1.91 (m, 8H), 0.87 (t, J ) 6.8 Hz, 3H); 13C NMR
(75.5 MHz, CDCl3) δ (ppm) 163.6, 143.8, 123.3, 95.2, 80.2, 71.6,
67.4, 67.2, 59.1, 31.6, 30.0, 24.8, 22.5, 14.0.
2.94 (bs, 1H), 2.24-2.35 (m, 1H), 0.99 (d, J ) 6.9 Hz, 3H); 13
C
NMR (75.5 MHz, CDCl3) δ (ppm) 174.1, 137.4, 129.1, 128.7,
127.4, 85.4, 71.4, 71.0, 39.0, 13.6; EI-MS m/z 222 (M+), 118
[C9H10+, 100], 107, 91, 77; CI-MS m/z 223 (M + H)+, 205 (M +
H - H2O)+, 187 [(M + H - 2H2O)+, 100], 159, 119; HRMS-CI
222.0889 (actual), 222.0892 (calcd).
(6R )-6-P e n t a flu or op h e n yl-5,6-d ih yd r op yr a n -2-on e ,
C
11H5O2F 5, 7i. Same procedure as for 7a : 1H NMR (300 MHz,
(3S,4R,5S,6S)-3,4-Dih ydr oxy-5-m eth oxyeth oxym eth oxy-
6-p h en yltetr a h yd r op yr a n -2-on e, C15H20O7, 8d . Same pro-
cedure as for 8a : 1H NMR (300 MHz, CDCl3) δ (ppm) 7.30-
7.36 (m, 5H), 5.89 (bs, 1H), 4.61 (d, J ) 3.0 Hz, 1H), 4.47-
4.50 (m, 2H), 4.22-4.24 (m, 1H), 4.10 (d, J ) 7.1 Hz, 1H), 3.60
(bs, 1H), 3.33-3.42 (m, 1H), 3.26-3.31 (m, 6H), 2.95-3.01 (m,
1H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 174.2, 135.5, 128.4,
128.3, 126.5, 95.2, 80.9, 75.5, 71.5, 69.1, 68.0, 67.3, 59.0.
(3S,4S,6S)-3,4-Dih yd r oxy-6-p en tyltetr a h yd r op yr a n -2-
on e, C10H1804, 8e. Same procedure as for 8a : 1H NMR (300
MHz, CDCl3) δ (ppm) 4.73-4.80 (m, 1H), 4.33 (m, 1H), 4.10
(m, 1H), 3.86 (bs, 1H), 3.20 (bs, 1H), 2.21 (dt, J ) 14.6, 3.5
Hz, 1H), 1.30-1.86 (m, 9H), 0.88 (t, J ) 6.6 Hz, 3H); 13C NMR
(75.5 MHz, CDCl3) δ (ppm) 174.4, 78.4, 70.6, 66.1, 35.6, 34.0,
31.5, 24.5, 22.5, 14.0; EI-MS m/z 139, 60 (100%), 57; CI-MS
203 [(M + H)+, 100], 157, 113; HRMS-CI 203.1285 (actual),
203.1283 (calcd).
(3S,4S,5S,6S)-3,4-Dih yd r oxy-5-m eth yl-6-p en tyltetr a h y-
d r op yr a n -2-on e, C11H20O4, 8f. Same procedure as for 8a : 1H
NMR (300 MHz, CDCl3) δ (ppm) 4.78-4.80 (m, 1H), 4.24 (d, J
) 3.4 Hz, 1H), 4.14 (t, J ) 3.4 Hz, 1H), 3.50 (bs, 1H), 2.20-
2.25 (m, 1H), 1.28-1.72 (m, 8H), 1.00 (d, J ) 7.4 Hz, 3H), 0.87
(t, J ) 6.3 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 174.9,
80.6, 71.6, 67.6, 36.4, 31.6(2 carbons), 25.1, 22.5, 14.0, 10.0;
EI-MS m/z 199 (M - OH)+, 60 [(C2H4O2)+, 100], 55; CI-MS
m/z 217 [(M + H)+, 100], 199 (M + H - H2O)+, 181, 153;
HRMS-CI 217.1440 (actual), 217.1440 (calcd).
(3S,4S,5R,6S)-3,4-Dih yd r oxy-5-m eth yl-6-p en tyltetr a h y-
d r op yr a n -2-on e, C11H20O4, 8g. Same procedure as for 8a : 1H
NMR (300 MHz, CDCl3) δ (ppm) 4.45 (ddd, J ) 2.8, 7.8, 10.5
Hz, 1H), 4.10 (d, J ) 3.0 Hz, 1H), 4.06 (m, 1H), 3.52 (bs, 1H),
2.74 (bs, 1H), 1.93-2.03 (m, 1H), 1.70-1.80 (m, 1H), 1.50-
1.63 (m, 2H), 1.25-1.43 (m, 5H), 1.14 (d, J ) 6.8 Hz, 3H), 0.90
(t, J ) 6.8 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 174.3,
83.5, 71.1, 71.1, 36.7, 33.0, 31.6, 24.1, 22.6, 14.2, 14.0; EI-MS
m/z 160, 60 [(C2H4O2)+, 100], 55; CI-MS m/z 217 [(M + H)+,
100], 199 (M + H - H2O)+, 181, 153; HRMS-CI 217.1445
(actual), 217.1440 (calcd).
CDCl3) δ (ppm) 6.99-7.05 (m, 1H), 6.17 (d, J ) 9.1 Hz, 1H),
5.81 (dd, J ) 3.8, 13.0 Hz, 1H), 3.01-3.11 (m, 1H), 2.47-2.57
(m, 1H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 162.7, 144.8,
121.4, 69.7, 28.6; [R]25 ) +118.6 (c 1.25, CHCl3); EI-MS m/z
264 (M+), 195, 194, 117, 68 [CH2CHdCHCO+, 100]; CI-MS m/z
265 [(M + H)+, 100], 81; HRMS-CI 264.0207 (actual), 264.0210
(calcd).
(5S,6R)-5-Meth yl-6-p en ta flu or op h en yl-5,6-d ih yd r op y-
r a n -2-on e, C12H7O2F 5, 7j. Same procedure as for 7a : 1H NMR
(300 MHz, CDCl3) δ (ppm) 7.06 (dd, J ) 6.1, 9.9 Hz, 1H), 6.10
(d, J ) 8.8 Hz, 1H), 5.93 (d, J ) 4.0 Hz, 1H), 2.61-2.68 (m,
1H), 1.13 (d, J ) 7.1 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ
(ppm) 162.7, 150.8, 119.9, 74.5, 33.9, 12.7; EI-MS m/z 195, 82
[C5H6O+, 100], 54; CI-MS m/z 279 [(M + H)+, 100]; HRMS-CI
279.0435 (actual), 279.0445 (calcd).
(5R,6R)-5-Meth yl-6-p en ta flu or op h en yl-5,6-d ih yd r op y-
r a n -2-on e, C12H7O2F 5, 7k . Same procedure as for 7a : 1H
NMR (300 MHz, CDCl3) δ (ppm) 6.79 (dd, J ) 1.9, 9.8 Hz,
1H), 6.12 (dd, J ) 2.6, 9.8 Hz, 1H), 5.40 (d, J ) 11.8 Hz, 1H),
3.12-3.24 (m, 1H), 1.07 (d, J ) 7.4 Hz, 3H); 13C NMR (75.5
MHz, CDCl3) δ (ppm) 162.6, 151.2, 120.3, 75.5, 32.7, 15.3; EI-
MS m/z 195, 82 [C5H6O+, 100], 54; CI-MS m/z 279 [(M + H)+,
100]; HRMS-CI 279.0435 (actual), 279.0445 (calcd).
(5S,6S)-5-Meth oxyeth oxym eth oxy-6-pen taflu or oph en yl-
5,6-d ih yd r op yr a n -2-on e, C15H13O5 F 5, 7l. Same procedure
as for 7a : 1H NMR (300 MHz, CDCl3) δ (ppm) 7.16 (dd, J )
5.5, 9.9 Hz, 1H), 6.27 (d, J ) 9.9 Hz, 1H), 5.90 (d, J ) 3.5 Hz,
1H), 4.72 (d, J ) 7.2 Hz, 1H), 4.52 (d, J ) 7.2 Hz, 1H), 4.26
(dd, J ) 3.6, 5.4 Hz, 1H), 3.60-3.66 (m, 1H), 3.42-3.46 (m,
2H), 3.52 (s, 3H), 3.31-3.38 (m, 1H); 13C NMR (75.5 MHz,
CDCl3) δ (ppm) 161.4, 142.9, 123.2, 94.9, 74.1, 71.3, 67.3, 66.7,
59.0; EI-MS m/z 323 (M - CH2OCH3), 263, 195, 89, 59 [CH3-
OCH2CH2+, 100]; CI-MS m/z 369 [(M + H)+, 100], 281, 263,
195, 172, 165, 105; HRMS-CI 369.0753 (actual), 369.0761
(calcd).
P r ep a r a tion of (3S,4S,6R)-3,4-Dih yd r oxy-6-p h en yltet-
r a h yd r op yr a n -2-on e, C11H12O4, 8a . NMO (1.4 g, 11.5 mmol)
was added to the dihydropyranone 7a (3.0 g, 7.7 mmol)
6298 J . Org. Chem., Vol. 69, No. 19, 2004

Regioselective Deoxygenation of Dihydropyranones
(3S,4R,5S,6S)-3,4-Dih ydr oxy-5-m eth oxyeth oxym eth oxy-
6-p en tyltetr a h yd r op yr a n -2-on e, C14H26O7, 8h . Same pro-
cedure as for 8a : 1H NMR (300 MHz, CDCl3) δ (ppm) 4.86 (d,
J ) 7.1 Hz, 1H), 4.77 (d, J ) 7.1 Hz, 1H), 4.70-4.75 (m, 1H),
4.42-4.44 (m, 2H), 3.93-3.96 (m, 1H), 3.66-3.75 (m, 3H), 3.56
(t, J ) 4.6 Hz, 2H), 3.39 (s, 3H), 3.33 (bs, 1H), 1.22-1.91 (m,
8H), 0.89 (t, J ) 6.6 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ
(ppm) 174.2, 96.2, 80.2, 75.4, 71.6, 68.7, 68.0 (2 carbons), 59.1,
31.6, 30.3, 25.0, 22.5, 14.0; EI-MS m/z 200, 89, 59 [(CH3OCH2-
CH2)+, 100]; CI-MS m/z 307 [(M + H)+, 100], 231, 89; HRMS-
CI 307.1753 (actual), 307.1757 (calcd).
(3S,4S,6R)-3,4-Dih yd r oxy-6-p en ta flu or op h en yltetr a h y-
d r op yr a n -2-on e, C11H7O4F 5, 8i. Same procedure as for 8a :
1H NMR (300 MHz, CDCl3) δ (ppm) 6.16 (dd, J ) 4.6, 11.9
Hz, 1H), 4.47-4.48 (m, 1H), 4.32 (d, J ) 2.7 Hz, 1H), 3.51 (bs,
1H), 2.87 (bs, 1H), 2.47-2.52 (m, 2H); 13C NMR (75.5 MHz,
CDCl3) δ (ppm) 172.6, 70.4, 69.8, 66.2, 33.0; 19F NMR (280
MHz, CDCl3) δ (ppm) -79.9, -89.2, -98.1; [R]25 ) -5.6 (c 0.5,
CH3OH); EI-MS m/z 223; CI-MS m/z 299 [(M + H)+, 100];
HRMS-CI 299.0342 (actual), 299.0343 (calcd).
(3S,4S,5S,6R)-3,4-Dih ydr oxy-5-m eth yl-6-pen taflu or oph e-
n yltetr a h yd r op yr a n -2-on e, C12H9O4F 5, 8j. Same procedure
as for 8a : 1H NMR (300 MHz, CDCl3) δ (ppm) 6.33 (d, J ) 3.8
Hz, 1H), 4.45 (d, J ) 3.0 Hz, 1H), 4.32 (t, J ) 3.4 Hz, 1H),
2.55 (dqu, J ) 3.8, 15.1 Hz, 1H), 3.40 (bs, 1H), 3.13 (bs, 1H),
1.12 (d, J ) 7.6 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
172.8, 74.6, 71.1, 67.4, 38.1, 11.0; EI-MS m/z 312 (M+), 197,
181, 76, 60 (100), 43; CI-MS m/z 313 [(M + H)+, 100], 267,
105; HRMS-CI 312.0421 (actual), 312.0421 (calcd).
(3S,4S,5R,6R)-3,4-Dih yd r oxy-5-m et h yl-6-p en t a flu or o-
p h en yltetr a h yd r op yr a n -2-on e, C12H9O4F 5, 8k . Same pro-
cedure as for 8a : 1H NMR (300 MHz, CDCl3) δ (ppm) 5.77 (d,
J ) 11.3 Hz, 1H), 4.33 (d, J ) 2.7 Hz, 1H), 4.20-4.24 (m, 1H),
3.50 (bs, 1H), 2.90 (bs, 1H); 2.53-2.64 (m, 1H), 1.09 (d, J )
7.2 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 172.7, 75.0,
71.1, 70.6, 36.5, 13.2; EI-MS m/z 312 (M+), 197, 181, 76, 60
(100%), 43; CI-MS m/z 313 [(M + H)+, 100], 267, 105; HRMS-
CI 312.0421 (actual), 312.0421 (calcd).
(3S,4R,5S,6S)-3,4-Dih ydr oxy-5-m eth oxyeth oxym eth oxy-
6-p en ta flu or op h en yl-tetr a h yd r op yr a n -2-on e, C15H15O7F 5,
8l. Same procedure as for 8a : 1H NMR (300 MHz, CDCl3) δ
(ppm) 6.22 (d, J ) 3.2 Hz, 1H), 4.70 (d, J ) 7.1 Hz, 2H), 4.55-
4.56 (m, 1H), 4.47 (d, J ) 7.2 Hz, 1H), 4.19-4.22 (m, 1H), 3.94
(bs, 1H), 3.78 (bs, 1H), 3.52-3.59 (m, 1H), 3.38-3.43 (m, 1H),
3.33 (s, 3H), 3.22-3.29 (m, 1H); 13C NMR (75.5 MHz, CDCl3)
δ (ppm) 172.4, 95.5, 75.0, 74.5, 71.3, 69.4, 67.9, 67.8, 59.1.
P r ep a r a tion of (4S, 6R)-4-Hyd r oxy-6-p h en yltetr a h y-
d r op yr a n -2-on e, C11H12O3, 9a . Diol 8a (2.0 g, 4.7 mmol) was
dissolved in 10.0 mL of CH2Cl2 and cooled to 0 °C. Phenyl-
chlorothionoformate (0.75 mL, 5.4 mmol) was added followed
by the addition of pyridine (0.76 mL, 9.4 mmol). After comple-
tion of the reaction as indicated by TLC, the reaction mixture
was worked up with ether and water. The crude thionoformate
ester was dissolved in benzene (50.0 mL) and refluxed at 85
°C. Tributyltin hydride (3.2 mL, 11.8 mmol) was added
followed by the addition of AIBN (77 mg, 0.47 mmol) and the
mixture refluxed for 5 h. The reaction mixture was concen-
trated under vacuum and purified by column chromatography
(silica gel, hexanes/ethyl acetate, 2:3) to obtain 1.8 g (93%) of
pure â-hydroxylactone 9a : 1H NMR (300 MHz, CDCl3) δ (ppm)
7.33-7.40 (m, 5H), 5.76 (dd, J ) 3.0, 11.0 Hz, 1H), 4.45 (qu, J
) 3.9 Hz, 1H), 2.86 (dd, J ) 4.9, 17.8 Hz, 1H), 2.74 (ddd, J )
1.6, 3.6, 17.7 Hz, 1H), 2.01-2.29 (m, 3H); 13C NMR (75.5 MHz,
CDCl3) δ (ppm) 170.1, 139.3, 128.7, 128.4, 125.9, 77.1, 62.8,
38.7, 38.4.
(M+), 188 (M - H2O), 178, 164, 117, 107 [(C6H5CH2O+, 100],
79, 58; CI-MS m/z 207 (M + H)+, 189 [(M + H - H2O)+, 100],
171, 119; HRMS-CI 206.0950 (actual), 206.0943 (calcd).
(4R,5R,6R)-4-H yd r oxy-5-m et h yl-6-p h en ylt et r a h yd r o-
p yr a n -2-on e, C12H14O3, 9c. Same procedure as for 9a : 1H
NMR (300 MHz, CDCl3) δ (ppm) 7.04-7.12 (m, 5H), 5.06 (d, J
) 10.7 Hz, 1H), 4.82 (bs, 1H), 3.81 (bs, 1H), 2.54-2.55 (m, 2H),
1.73-1.82 (m, 1H), 0.60 (d, J ) 6.7 Hz, 3H); 13C NMR (75.5
MHz, CDCl3) δ (ppm) 170.2, 138.6, 128.4, 128.3, 127.2, 83.0,
66.5, 39.8, 39.0, 13.4; EI-MS m/z 206 (M+), 188 (M - H2O),
178, 164, 117, 107 [(C6H5CH2O+, 100], 79, 58; CI-MS m/z 207
(M + H)+, 189 [(M + H - H2O)+, 100], 171, 119; HRMS-CI
206.0950 (actual), 206.0943 (calcd).
(4S ,6S )-4-H yd r oxy-6-p e n t ylt e t r a h yd r op yr a n -2-on e ,
C
10H18O3, 9e. Same procedure as for 9a : 1H NMR (300 MHz,
CDCl3) δ (ppm) 4.63-4.72 (m, 1H), 4.31-4.37 (m, 1H), 2.98
(bs, 1H), 2.68 (dd, J ) 17.9, 4.8 Hz, 1H), 2.59 (ddd, J ) 17.9,
3.8, 1.4 Hz, 1H), 1.92-1.99 (m, 1H), 1.23-1.73 (m, 9H), 0.87
(t, J ) 6.8 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 171.4,
76.3, 62.5, 38.6, 35.8, 35.5, 31.6, 24.6, 22.5, 14.0; EI-MS m/z
168 (M - H2O)+, 115 (100), 97, 73, 55; CI-MS m/z 187 [(M +
H)+, 100], 169 (M + H - H2O)+, 127; HRMS-CI 187.1335
(actual), 187.1334 (calcd).
(4R,5S,6S)-4-Hyd r oxy-5-m eth yl-6-p en tyltetr a h yd r op y-
r a n -2-on e, C11H2003, 9f. Same procedure as for 9a : 1H NMR
(300 MHz, CDCl3) δ (ppm) 4.70 (ddd, J ) 2.7, 4.7, 8.0 Hz, 1H),
4.01-4.05 (m, 1H), 2.78 (dd, J ) 5.4, 18.3 Hz, 1H), 2.53 (dd, J
) 3.1, 18.3 Hz, 1H), 2.52 (bs, 1H), 1.91-1.96 (m, 1H), 1.24-
1.78 (m, 8H), 0.92 (d, J ) 7.3 Hz, 3H), 0.89 (t, J ) 6.9 Hz,
3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 171.0, 78.3, 68.6,
37.3, 35.8, 31.8, 31.6, 25.2, 22.6, 14.0, 10.3; EI-MS m/z 182 (M
- H2O)+, 158, 129, 111, 87, 82, 71, 58 [(C4H10)+, 100]; CI-MS
m/z 201 [(M + H)+, 100], 183 (M + H - H2O)+, 141; HRMS-CI
201.1492 (actual), 201.1491 (calcd).
(4R,5R,6S)-4-Hyd r oxy-5-m eth yl-6-p en tyltetr a h yd r op y-
r a n -2-on e, C11H20O3, 9g. Same procedure as for 9a : 1H NMR
(300 MHz, CDCl3) δ (ppm) 4.38-4.44 (m, 1H), 4.05 (m, 1H),
2.59-2.74 (m, 3H), 1.65-1.79 (m, 2H), 1.48-1.59 (m, 2H),
1.24-1.41 (m, 5H), 1.05 (d, J ) 6.9 Hz, 3H), 0.88 (t, J ) 6.9
Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 170.9, 80.8, 67.7,
39.4, 36.8, 33.1, 31.7, 24.0, 22.5, 14.1, 13.7; EI-MS m/z 182 (M
- H2O)+, 158, 129, 111, 87, 82, 71, 58 [(C4H10)+, 100]; CI-MS
m/z 201 [(M + H)+, 100], 183 (M + H - H2O)+, 141; HRMS-CI
201.1492 (actual), 201.1491 (calcd).
(4R,5S,6S)-4-Hydr oxy-5-m eth oxyeth oxym eth oxy-6-pen -
tyltetr a h yd r op yr a n -2-on e, C14H26O6, 9h . Same procedure
as for 9a : 1H NMR (300 MHz, CDCl3) δ (ppm) 4.83 (d, J ) 7.1
Hz, 1H), 4.74 (d, J ) 7.1 Hz, 1H), 4.54 (ddd, J ) 2.4, 4.7, 7.6
Hz, 1H), 4.19-4.25 (m, 1H), 3.81 (ddd, J ) 3.2, 6.8, 9.9 Hz,
1H), 3.46-3.69 (m, 5H), 3.39 (s, 3H), 2.90 (dd, J ) 5.4, 17.2
Hz, 1H), 2.56 (dd, J ) 5.8, 17.1 Hz, 1H), 1.22-1.82 (m, 8H),
0.89 (t, J ) 6.7 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
170.5, 96.1, 78.2, 77.6, 71.6, 67.5, 66.9, 59.1, 35.6, 31.6, 30.3,
25.0, 22.5, 14.0.
(4S,6R)-4-Hyd r oxy-6-p en ta flu or op h en yltetr a h yd r op y-
r a n -2-on e, C11H7O3F 5, 9i. Same procedure as for 9a : 1H NMR
(300 MHz, CDCl3) δ(ppm) 6.16 (dd, J ) 4.8, 12.0 Hz, 1H), 4.47-
4.48 (m, 1H), 2.80-2.85 (m, 2H), 2.33-2.42 (m, 1H), 2.23-
2.44 (m, 1H), 2.1 (bs, 1H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
172.6, 70.4, 69.8, 66.2, 33.0; 19F NMR (280 MHz, CDCl3) δ
(ppm) -79.87, -89.20, -98.15; [R]25 ) -5.6 (c 0.5, CH3OH);
EI-MS m/z 223; CI-MS m/z 283 (M + H)+, 265 [(M + H -
H2O)+, 100].
(4R,5S,6R)-4-Hydr oxy-5-m eth yl-6-pen taflu or oph en yltet-
r a h yd r op yr a n -2-on e, C12H9O3F 5, 9j. Same procedure as for
9a : 1H NMR (300 MHz, CDCl3) δ (ppm) 6.19 (d, J ) 4.2 Hz,
1H), 4.11 (q, J ) 4.9 Hz, 1H), 3.00 (dd, J ) 5.0, 18.5 Hz, 1H),
2.66 (dd, J ) 4.4, 18.7 Hz, 2H), 2.21-2.27 (m, 1H), 1.01 (d, J
) 7.1 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 168.8,
73.3, 67.5, 38.8, 36.3, 11.2.
(4R,5S,6R)-4-H yd r oxy-5-m et h yl-6-p h en ylt et r a h yd r o-
p yr a n -2-on e, C12H14O3, 9b. Same procedure as for 9a : 1H
NMR (300 MHz, CDCl3) δ (ppm) 7.26-7.38 (m, 5H), 5.92 (m,
1H), 4.15-4.19 (m, 1H), 3.10 (bs, 1H), 2.92 (dd, J ) 5.2, 18.6
Hz, 1H), 2.65-2.72 (m, 1H), 2.18-2.25 (m, 1H), 0.71 (d, J )
7.4 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 170.9, 137.7,
128.4, 127.7, 125.5, 78.9, 68.2, 40.0, 35.7, 10.3; EI-MS m/z 206
(4R,5R,6R)-4-Hyd r oxy-5-m eth yl-6-p en ta flu or op h en yl-
tetr a h yd r op yr a n -2-on e, C12H9O3F 5, 9k . Same procedure as
J . Org. Chem, Vol. 69, No. 19, 2004 6299

Ramachandran et al.
for 9a : 1H NMR (300 MHz, CDCl3) δ (ppm) 5.79 (d, J ) 11.3
Hz, 1H), 4.21-4.24 (m, 1H), 2.86-2.88 (m, 2H), 2.37-2.48 (m,
1H), 2.12 (d, J ) 3.0 Hz, 1H), 1.00 (d, J ) 6.9 Hz, 3H).
6.9 Hz, 3H), 0.89 (s, 9H), 0.09 (s, 3H), 0.07 (s, 3H); 13C NMR
(75.5 MHz, CDCl3) δ (ppm) 140.7, 138.2, 128.4, 127.8, 127.7,
115.4, 73.7, 73.4, 71.4, 70.2, 44.3, 37.7, 25.9, 18.1, 15.8, -4.5,
-5.0; EI-MS m/z 201, 91 (100), 75, 55; CI-MS m/z 365 [(M +
H)+, 100], 347 [(M + H) - H2O]+; HRMS-CI 365.2510 (actual),
365.2512 (calcd).
P r epar ation of (S)-1-Ben zyloxypen t-4-en -2-ol, C12H16O2,
14. Aldehyde 13 (50.0 g, 333.3 mmol) dissolved in 200 mL of
CH2Cl2 was added to a stirred solution of (-)-B-allyldiisopi-
nocampheylborane (Ipc2BAll) (800 mL of 0.5 M solution in
Et2O-pentane) at -100 °C and maintained at that tempera-
ture for 2 h. The reaction was followed by 11B NMR spectros-
copy (δ 56). Upon completion, the mixture was oxidized with
160.0 mL of 3.0 M NaOH and 160.0 mL of 30% H2O2, stirred
for 4 h at room temperature, and extracted with Et2O. Alcohol
14 and isopinocampheol (byproduct) have a similar Rf, and
hence, it was not possible to purify the alcohol by column
chromatography. (The alcohol was injected on the HPLC and
the ee was found to be 96%.)
P r ep a r a tion of (2S)-1-Ben zyloxy-2-ter t-bu tyld im eth -
ylsilyloxyp en t-4-en e, C18H30O2Si, TBS-14. Crude alcohol 14
(30.0 g, 156.2 mmol) was dissolved in 1000 mL of dimethyl-
formamide. tert-Butyldimethylsilyl chloride (117.2 g, 781.2
mmol) and imidazole (79.7 g, 1171.9 mmol) were added at 25
°C, and the mixture was stirred for 8 h. After the completion
of the reaction as indicated by TLC, the reaction mixture was
worked up with ether and water. The organic layer was dried
over MgSO4, concentrated under aspirator vacuum, and puri-
fied by column chromatography (silica gel, hexanes/ethyl
acetate, 9:1) to obtain 42.9 g (80% overall) of pure silyl ether
TBS-14: 1H NMR (300 MHz, CDCl3) δ (ppm) 7.24-7.36 (m,
5H), 5.77-5.91 (m, 1H), 5.02-5.11 (m, 2H), 4.53 (s, 2H), 3.90
(qu, J ) 5.5 Hz, 1H), 3.41 (d, J ) 5.6 Hz, 2H), 2.32-2.42 (m,
1H), 2.19-2.29 (m, 1H), 0.90 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H);
13C NMR (75.5 MHz, CDCl3) δ (ppm) 138.5, 135.0, 128.4, 127.6,
127.5, 117.1, 74.3, 73.4, 71.2, 39.4, 25.9, 18.2, -4.4, -4.6.
P r ep a r a tion of (3S)-4-Ben zyloxy-3-ter t-bu tyld im eth -
ylsilyloxybu ta n a l, C17H28O3Si, 15. Olefin TBS-14 (31.9 g,
104.2 mmol) was dissolved in 200 mL of methanol and cooled
to -78 °C. Ozone gas was bubbled through the reaction
mixture until a persistent blue color was observed. The
resultant ozonide was quenched with methyl sulfide (38.2 mL,
521.0 mmol) and stirred for 1 h at room temperature. Methanol
was concentrated under vacuum and filtered over MgSO4. The
crude product was purified by column chromatography (silica
gel, hexanes/ethyl acetate, 7:3) to obtain 24.4 g (76%) of pure
aldehyde 15: 1H NMR (300 MHz, CDCl3) δ (ppm) 9.80 (m, 1H),
7.25-7.36 (m, 5H), 4.54 (s, 2H), 4.33-4.41 (m, 1H), 3.51 (dd,
J ) 5.1, 9.5 Hz, 1H), 3.40 (dd, J ) 6.2, 9.5 Hz, 1H), 2.67 (ddd,
J ) 2.1, 5.2, 15.9 Hz, 1H), 2.58 (ddd, J ) 2.7, 6.5, 15.9 Hz,
1H), 0.87 (s, 9H), 0.08 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ
(ppm) 201.5, 138.0, 128.4, 127.8, 127.1, 74.0, 73.4, 67.4, 49.0,
25.8, 18.1, -4.4, -4.9.
P r ep a r a tion of (2S,4S,5R)-1-Ben zyloxy-2-ter t-bu tyld i-
m eth ylsilyloxy-5-m eth yl-6-h ep ten -4-ol, C21H36O3Si, 16.
Potassium tert-butoxide (56.7 mL, 1.0 M solution, 56.7 mmol)
was dissolved in 100 mL THF at -78 °C, and trans-2-butene
(12.0 mL, 128.9 mmol) was added. n-Butyllithium (22.7 mL,
2.5 M solution, 56.7 mmol) was added and the mixture stirred
for 20 min at -45 °C. The reaction mixture was cooled to -78
°C, (+)-B-methoxydiisopinocampheylborane [(+)-Ipc2BOMe]
(22.0 g, 69.6 mmol) dissolved in 50.0 mL of THF was added,
and the mixture was stirred for 1 h. Aldehyde 15 (15.9 g, 51.6
mmol) was dissolved in 20.0 mL of THF precooled to -78 °C,
and the reaction mixture was transferred via cannula at -78
°C and stirred for 3 h. The reaction mixture was oxidized with
27.8 mL of 3 M NaOH and 27.7 mL 30% H2O2 and stirred
overnight. The reaction mixture was worked up with ether and
water. The organic layer was dried over MgSO4, concentrated
under vacuum, and purified by column chromatography (silica
gel, 3:2, hexane/ethyl ether) to obtain 15.4 g (82%) of pure
alcohol 16. 1H NMR (300 MHz, CDCl3) δ (ppm) 7.26-7.36 (m,
5H), 5.75-5.88 (m, 1H), 5.04-5.10 (m, 2H), 4.48-4.58 (m, 2H),
4.11-4.18 (m, 1H), 3.70-3.76 (m, 1H), 3.40-3.50 (m, 2H), 3.00
(bs, 1H), 2.16-2.23 (m, 1H), 1.57-1.74 (m, 2H), 1.03 (d, J )
P r ep a r a tion of (1S,3S)-1-((1R)-1-Meth yl-2-p r op en yl)-
4-ben zyloxy-3-ter t-b u t yld im et h ylsilyloxybu t yl P r op -2-
en oa te, C24H38O4Si, Acr -16. Alcohol 16 (10.0 g, 27.5 mmol)
was dissolved in CH2Cl2 (60.0 mL) and cooled to 0 °C. Acryloyl
chloride (3.4 mL, 41.2 mmol) and triethylamine (9.6 mL, 68.7
mmol) were added at 0 °C and the mixture stirred for 1 h at
room temperature. After completion of the reaction as indi-
cated by TLC, the reaction mixture was filtered over magne-
sium sulfate pad and purified by column chromatography
(silica gel, 9:1, hexane/ethyl acetate) to obtain 9.8 g (85%) of
pure acrylate ester Acr -16: 1H NMR (300 MHz, CDCl3) δ
(ppm) 7.24-7.36 (m, 5H), 6.38 (dd, J ) 1.6, 17.3 Hz, 1H), 6.11
(dd, J ) 10.3, 17.3 Hz, 1H), 5.70-5.82 (m, 2H), 5.04-5.15, (m,
3H), 4.51 (s, 2H), 3.81-3.89 (m, 1H), 3.41 (dd, J ) 5.3, 9.6 Hz,
1H), 3.33 (dd, J ) 5.7, 9.6 Hz, 1H), 2.51-2.60 (m, 1H), 1.82
(ddd, J ) 3.0, 9.7, 14.5 Hz, 1H), 1.62 (ddd, J ) 2.6, 9.0, 14.5
Hz, 1H), 1.10 (d, J ) 6.9 Hz, 3H), 0.88 (s, 9H), 0.03 (s, 3H),
0.01 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 165.8, 139.4,
138.3, 130.4, 129.0, 128.4, 127.7, 127.6, 115.6, 75.0, 74.2, 73.3,
68.5, 41.5, 36.1, 26.0, 18.1, 14.8, -4.1, -5.0; EI-MS m/z 289,
91 [(C6H5CH2)+, 100], 73, 55; CI-MS m/z 419 [(M + H)+, 100],
347 [(M + H) - (CH2dCHCOOH)]+, 287, 255, 215, 201; HRMS-
CI 419.2607 (actual), 419.2618 (calcd).
P r ep a r a tion of (5R,6S)-(6-((2S)-3-ben zyloxy-2-ter t-bu -
t yld im e t h ylsilyloxyp r op yl)-6-m e t h yld ih yd r op yr a n -2-
on e, C22H34O4Si, 17. Acrylate Acr -16 (8.0 g, 19.1 mmol) was
refluxed in toluene (200.0 mL) at 120 °C. Grubbs’ second-
generation catalyst (0.81 g, 0.95 mmol) was added and the
mixture refluxed for 3 h. After completion of the reaction
(TLC), solvent was evaporated under vacuum and the crude
product was purified by column chromatography (silica gel,
3:2, hexane/ethyl acetate) to obtain 7.2 g (96%) of the lactenone
17: 1H NMR (300 MHz, CDCl3) δ (ppm) 7.26-7.34 (m, 5H),
6.64 (dd, J ) 2.4, 9.8 Hz, 1H), 5.95 (dd, J ) 2.4, 9.8 Hz, 1H),
4.53 (s, 2H), 4.20-4.30 (m, 2H), 3.44 (dd, J ) 4.9, 9.8 Hz, 1H),
3.38 (dd, J ) 5.4, 9.8 Hz, 1H), 2.42-2.47 (m, 1H), 1.61-1.92
(m, 2H), 1.12 (d, J ) 7.4 Hz, 3H), 0.86 (s, 9H), 0.08 (s, 3H),
0.07 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 163.9, 151.8,
138.3, 128.4, 127.7, 127.6, 120.2, 80.0, 74.8, 73.3, 66.8, 38.2,
33.8, 25.9, 18.1, 16.5, -4.2, -4.9; EI-MS m/z 333 (M -
C(CH3)3)+, 91 [(C6H5CH2)+, 100], 73, 57; CI-MS m/z 391 [(M +
H)+, 100]; HRMS-CI 391.2304 (actual), 391.2305 (calcd).
P r ep a r a tion of (3S,4S,5R,6S)-(6-((2S)-3-ben zyloxy-2-
ter t-bu tyld im eth ylsilyloxyp r op yl)-3,4-d ih yd r oxy-6-m eth -
yltetr a h yd r op yr a n -2-on e, C22H36O6Si, 18. NMO (1.4 g, 11.5
mmol) was added to the dihydropyranone 17 (3.0 g, 7.7 mmol)
dissolved in acetone/water (4:1, 15 mL) at 0 °C. OsO4 (156 mg,
0.6 mmol) was added to the above solution and stirred for 6 h
at room temperature, the product was extracted with Et2O (3
× 20 mL) and washed, and the organic layers were concen-
trated under aspirator vacuum. The crude product was purified
by column chromatography (silica gel, hexane/ethyl acetate (1:
4)) to obtain 2.8 g (87%) of 18: 1H NMR (300 MHz, CDCl3) δ
(ppm) 7.26-7.38 (m, 5H), 4.60-4.67 (m, 1H), 4.54 (s, 2H),
4.15-4.21 (m, 1H), 4.07 (d, J ) 9.3 Hz, 2H), 3.33-3.52 (m,
3H), 2.73 (s, 1H), 1.91-1.96 (m, 1H), 1.78 (t, J ) 6.2 Hz, 2H),
1.14 (d, J ) 6.9 Hz, 3H), 0.88 (s, 9H), 0.10 (s, 3H), 0.07 (s,
3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 173.7, 138.3, 128.4,
127.7, 127.6, 79.9, 74.8, 73.3, 71.2, 71.0, 67.0, 39.0, 37.4, 25.9,
18.1, 14.2, -4.3, -4.9; EI-MS m/z 275, 91 [(C6H5CH2)+, 100],
81, 69, 57; CI-MS m/z 425 [(M + H)+, 100], 407 [(M + H) -
H2O]+; HRMS-CI 425.2351 (actual), 425.2359 (calcd).
P r ep a r a tion of (4S,5R,6S)-(6-((2S)-3-Ben zyloxy-2-ter t-
bu tyldim eth ylsilyloxypr opyl)-4-h ydr oxy-6-m eth yltetr ah y-
d r op yr a n -2-on e, C22H36O5Si, 19. Diol 18 (2.0 g, 4.7 mmol)
was dissolved in 10.0 mL of CH2Cl2 and cooled to 0 °C.
6300 J . Org. Chem., Vol. 69, No. 19, 2004

Regioselective Deoxygenation of Dihydropyranones
Phenylchlorothionoformate (0.75 mL, 5.4 mmol) was added
followed by the addition of pyridine (0.76 mL, 9.4 mmol). After
completion of the reaction as indicated by TLC, the reaction
mixture was worked up with ether and water. The crude
thionoformate ester was dissolved in benzene (50.0 mL) and
refluxed at 85 °C. Tributyltin hydride (3.2 mL, 11.8 mmol) was
added followed by addition of AIBN (77 mg, 0.47 mmol) and
refluxed for 5 h. The reaction mixture was concentrated under
vacuum and purified by column chromatography (silica gel,
hexanes/ethyl acetate, 2:3) to obtain 1.8 g (93%) of pure
â-hydroxylactone 19: 1H NMR (300 MHz, CDCl3) δ (ppm)
7.26-7.35 (m, 5H), 4.53 (s, 2H), 4.61 (dt, J ) 2.5, 10.3 Hz,
1H), 4.65 (m, 3H), 4.19-4.27 (m, 1H), 4.03-4.07 (m, 1H), 3.44
(dd, J ) 5.0, 9.7 Hz, 1H), 3.38 (dd, J ) 5.4, 9.8 Hz, 1H), 2.58-
2.73 (m, 2H), 2.45 (bs, 1H), 1.66-1.82 (m, 3H), 1.05 (d, J )
6.8 Hz, 3H), 0.88 (s, 9H), 0.10 (s, 3H), 0.07 (s, 3H); 13C NMR
(75.5 MHz, CDCl3) δ (ppm) 170.2, 138.3, 128.4, 127.7, 127.6,
127.5, 77.2, 75.0, 73.3, 67.6, 67.0, 39.4, 38.9, 37.6, 26.0, 18.1,
13.8, -4.2, -4.8; EI-MS m/z 351 (M - C(CH3)3)+, 91 [(C6H5-
CH2)+, 100], 81, 69, 57; CI-MS m/z 409 [(M + H)+, 100], 391
[(M + H) - H2O]+, 107, 91 (C6H5CH2)+, 81, 69; HRMS-CI
409.2415 (actual), 409.2410 (calcd).
117, 91 [(C6H5CH2)+, 100], 73; CI-MS m/z 537 [(M + H)+, 100];
HRMS-CI 537.3429 (actual), 537.3432 (calcd).
P r ep a r a tion of (3R,4S,5R,6S)-(6-((2S)-2-ter t-Bu tyld i-
m eth ylsilyloxy-3-h yd r oxyp r op yl)-4-ter t-bu tyld im eth ylsi-
lyloxy-3,6-d im eth yltetr a h yd r op yr a n -2-on e, C22H46O5Si2,
OH-20. Benzyl ether 20 (0.5 g, 0.93 mmol) was dissolved in
ethyl acetate (2.0 mL). 0.1 g (10%, 0.09 mmol) of 10%
palladium over charcoal was added, and hydrogen gas was
bubbled through the reaction mixture for 6 h. The reaction
mixture was filtered over silica gel and purified by column
chromatography (silica gel, hexanes/ethyl acetate, (3:1)) to
obtain 0.37 g (90%) of pure alcohol OH-20: 1H NMR (300 MHz,
CDCl3) δ (ppm) 4.46 (t, J ) 9.93 Hz, 1H), 4.13-4.20 (m, 1H),
3.62-3.68 (m, 2H), 3.44 (dd, J ) 2.6, 11.2 Hz, 1H), 2.64 (dq, J
) 2.6, 7.6 Hz, 1H), 1.79-2.01 (m, 3H), 1.49-1.58 (m, 1H), 1.26
(d, J ) 7.5 Hz, 3H), 0.98 (d, J ) 6.5 Hz, 3H), 0.88-0.89 (m,
18H), 0.11 (m, 6H), 0.07 (s, 3H), 0.06 (s, 3H); 13C NMR (75.5
MHz, CDCl3) δ (ppm) 173.7, 77.4, 74.7, 68.1, 67.1, 44.1, 38.4,
34.4, 25.9, 25.7, 18.0 (two carbons), 16.5, 14.1, -4.5, -4.6, -4.8,
+
-4.9; EI-MS m/z 415 (M - CH2OH)+, 217, 115, 73 [(SiCH3)3
,
100]; CI-MS m/z 447 [(M + H)+, 100], 429 [(M + H) - H2O]+;
HRMS-CI 447.2971 (actual), 447.2962 (calcd).
P r ep a r a tion of (3R,4S,5R,6S)-(6-((2S)-3-Ben zyloxy-2-
ter t-bu tyld im eth ylsilyloxyp r op yl)-4-h yd r oxy-3,6-d im eth -
yltetr a h yd r op yr a n -2-on e, C23H38O5Si, Me-19. A solution of
lithium diisopropylamide (LDA) in hexanes (3.5 mL, 1.7 M
solution, 6.0 mmol) was cooled to -60 °C, and a solution of
the hydroxylactone 19 (1.0 g, 2.45 mmol) and hexamethylphos-
phoramide (3.0 mL, 0.017 mmol) in THF was added dropwise
over 40 min and stirred at -60 °C for 2 h. The reaction mixture
was cooled to -78 °C, n-butyllithium (1.9 mL, 2.5M solution,
4.9 mmol) was added dropwise over 30 min, and the mixture
was stirred for 45 min at -78 °C. Iodomethane (0.92 mL, 14.7
mmol) was added in one portion and stirred for 16 h. The
reaction mixture was quenched with water and worked up
with ether. The organic layer was dried over MgSO4, concen-
trated under aspirator vacuum, and purified by column
chromatography (silica gel, 3:2, hexane/ethyl acetate) to obtain
0.81 g (78%) of the R-methyl-â-hydroxylactone Me-19: 1H
NMR (300 MHz, CDCl3) δ (ppm) 7.26-7.35 (m, 5H), 4.49-
4.57 (m, 3H), 4.17-4.24 (m, 1H), 3.72 (t, J ) 4.0 Hz, 1H), 3.43
(dd, J ) 5.0, 9.7 Hz, 1H), 3.37 (dd, J ) 5.3, 9.7 Hz, 1H), 2.62
(dq, J ) 4.4, 7.3 Hz, 1H), 2.22 (bs, 1H), 1.81-1.94 (m, 1H),
1.65-1.77 (m, 2H), 1.30 (d, J ) 7.3 Hz, 3H), 1.03 (d, J ) 6.9
Hz, 3H), 0.88 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H); 13C NMR (75.5
MHz, CDCl3) δ (ppm) 174.0, 138.3, 128.4, 127.7, 127.6, 76.6,
75.0, 73.3, 73.2, 67.1, 43.3, 38.6, 36.0, 25.9, 18.1, 15.6, 12.6,
-4.3, -4.9; EI-MS m/z 365 (M - C(CH3)3)+, 91 [(C6H5CH2)+,
100], 81, 69, 57; CI-MS m/z 423 [(M + H)+, 100], 405 [(M + H)
- H2O]+; HRMS-CI 423.2561 (actual), 423.2567 (calcd).
P r ep a r a tion of (3R,4S,5R,6S)-(6-((2S)-3-Ben zyloxy-2-
ter t-bu tyld im eth ylsilyloxyp r op yl)-4-ter t-bu tyld im eth yl-
silyloxy-3,6-d im eth yltetr a h yd r op yr a n -2-on e, C29H52O5-
Si2, 20. Alcohol Me-19 (0.5 g, 1.2 mmol) was dissolved in
CH2Cl2 (2.0 mL) and cooled to -78 °C. tert-Butyldimethyl-
silyltrifluoromethanesulfonate (0.33 mL, 1.42 mmol) was
added dropwise followed by the addition of 2,6-lutidine (0.21
mL, 1.8 mmol) and the mixture stirred for 2 h at -78 °C. The
reaction mixture was worked up with ether and water. The
organic layer was dried (MgSO4) and concentrated under
vacuum to obtain the crude silyl ether 20, which was purified
by column chromatography (silica gel, hexanes/ethyl acetate
(5:1)) to obtain 0.59 g (92%) of 20: 1H NMR (300 MHz, CDCl3)
δ (ppm) 7.26-7.34 (m, 5H), 4.49-4.57 (m, 3H), 4.21-4.28 (m,
1H), 3.66 (m, 1H), 3.42 (dd, J ) 4.9, 9.7 Hz, 1H), δ 3.36 (dd, J
) 5.4, 9.8 Hz, 1H), 2.64 (dq, J ) 2.6, 7.6 Hz, 1H), 1.63-1.90
(m, 3H), 1.26 (d, J ) 7.6 Hz, 3H), 0.99 (d, J ) 6.8 Hz, 3H),
0.87-0.89 (m, 18H), 0.06-0.09 (m, 12H); 13C NMR (75.5 MHz,
CDCl3) δ (ppm) 173.7, 138.4, 128.4, 127.7, 127.6, 77.1, 75.0,
74.8, 73.3, 66.9, 44.1, 39.1, 34.6, 26.0, 25.8, 18.1, 18.0, 16.5,
14.1, -4.3, -4.5, -4.8, -4.9; EI-MS m/z 479 (M - C(CH3)3)+,
P r ep a r a t ion of (3R,4S,5R,6S)-6-((2S)-2-ter t-Bu t yld i-
m et h ylsilyloxy-3-oxop r op yl)-4-ter t-b u t yld im et h ylsilyl-
oxy-3,6-d im eth yltetr a h yd r op yr a n -2-on e, C22H44O5Si2, 11.
Dess-Martin periodinane (285 mg, 0.67 mmol) was suspended
in 1 mL of CH2Cl2, and alcohol OH-20 (0.2 g, 0.45 mmol) was
added at 25 °C. The reaction mixture was stirred for 2 h and
filtered over a sodium sulfate pad. The crude product was
concentrated under vacuum and purified by column chroma-
tography (silica gel, hexanes/ethyl acetate, (4:1)) to obtain 185
mg (93%) of pure aldehyde 11: 1H NMR (300 MHz, CDCl3) δ
(ppm) 9.66 (d, J ) 0.8 Hz, 1H), 4.54 (dd, J ) 2.4, 10.3 Hz,
1H), 4.44-4.49 (m, 1H), 3.67 (t, J ) 2.3 Hz, 1H), 2.66 (dq, J )
2.5, 7.7 Hz, 1H), 1.71-1.98 (m, 3H), 1.27 (d, J ) 7.6 Hz, 3H),
0.98 (d, J ) 6.8 Hz, 3H), 0.92 (s, 9H), 0.89 (s, 9H), 0.13 (s,
3H), 0.11 (s, 3H), 0.08 (s, 3H), 0.06 (s, 3H); 13C NMR (75.5
MHz, CDCl3) δ (ppm) 203.4, 173.2, 76.1, 74.7, 73.7, 42.2, 36.2,
34.2, 25.8, 25.7, 18.1, 18.0, 16.6, 14.1, -4.5, -4.6, -4.8, -5.1;
EI-MS m/z 415, 159, 115, 73 [(SiCH3)3+, 100]; CI-MS 445 [(M
+ H)+, 100], 313, 217, 133; HRMS-CI 445.2804 (actual),
445.2806 (calcd).
P r ep a r a tion of Meth yl (2S)-3-ter t-Bu tyld im eth ylsilyl-
oxy-2-m eth ylp r op ion a te, C11H24O3Si, TBS-21. Alcohol 21
(50.0 g, 423.7 mmol) was dissolved in 800 mL of dimethylfor-
mamide. tert-Butyldimethylsilyl chloride (69.9 g, 466.1 mmol)
and imidazole (43.2 g, 635.6 mmol) were added at 0 °C, and
the mixture was stirred for 3 h. After completion of the reaction
as indicated by TLC, the reaction mixture was worked up with
ether and water. The organic layer was dried over MgSO4 and
concentrated under aspirator vacuum to obtain 88.5 g (90%)
of silyl ether TBS-21, which was used for the next step without
further purification: 1H NMR (300 MHz, CDCl3) δ (ppm) 3.76
(dd, J ) 6.86, 9.66 Hz, 1H), 3.60-3.85 (m, 4H), 2.57-2.69 (m,
1H), 1.12 (d, J ) 7.1 Hz, 3H), 0.85 (s, 9H), 0.02 (s, 6H); 13C
NMR (75.5 MHz, CDCl3) δ (ppm) 175.5, 65.3, 51.5, 42.5, 25.8,
18.2, 13.5, -5.5.
P r ep a r a t ion of (2R)-3-ter t-Bu t yld im et h ylsilyloxy-2-
m eth yl-1-p r op a n ol, C10H24O2Si, 22. Silyl ether TBS-21 (70.0
g, 301.7 mmol) was dissolved in 600 mL of diethyl ether,
borane-methyl sulfide (50.9 mL, 10 M solution, 509.9 mmol)
was added at 0 °C, and the mixture was stirred overnight at
room temperature. The excess borane methyl sulfide was
quenched with triethylamine and methanol (1:5, 200.0 mL).
The reaction mixture was worked up with ether and water.
The organic layer was dried over MgSO4 and evaporated under
aspirator vacuum to obtain 48.0 g (78%) of alcohol 22, which
was used for the next step without further purification: 1H
NMR (300 MHz, CDCl3) δ (ppm) 3.66-3.70 (m, 1H), 3.48-
3.59 (m, 3H), 3.02 (bs, 1H), 1.86-1.94 (m, 1H), 0.9 (s, 9H), 0.84
J . Org. Chem, Vol. 69, No. 19, 2004 6301

Ramachandran et al.
(d, J ) 8.7 Hz, 3H), 0.08 (s, 6H); 13C NMR (75.5 MHz, CDCl3)
δ (ppm) 68.4, 67.9, 37.2, 25.9, 18.2, 13.1, -5.5, -5.6.
J ) 5.0, 9.8 Hz, 1H), 3.72 (dd, J ) 2.8, 9.7 Hz, 1H), 2.36-2.45
(m, 1H), 1.90-1.99 (m, 1H), 1.03 (d, J ) 7.0 Hz, 3H), 0.96 (d,
J ) 6.9 Hz, 3H), 0.87 (s, 9H), 0.04 (s, 6H); 13C NMR (75.5 MHz,
CDCl3) δ (ppm) 164.7, 152.0, 120.0, 80.1, 63.5, 36.4, 30.1, 25.9,
18.3, 12.6, 10.8, -5.4; EI-MS m/z 227 (M - C4H9)+, 145, 75
[(CH3)2SiOH+, 100], 59; CI-MS m/z 285 [(M + H)+, 100], 271,
153, 69; HRMS-CI 285.1889 (actual), 285.1886 (calcd).
P r ep a r a t ion of (2S)-3-ter t-Bu t yld im et h ylsilyloxy-2-
m eth yl-1-p r op a n a l, C10H22O2Si, Ald -22. Dess-Martin pe-
riodinane (197.5 g, 465.7 mmol) was suspended in 100 mL of
CH2Cl2, and alcohol 22 (50.0 g, 245.1 mmol) was added at 0
°C. The reaction mixture was stirred for 1 h and filtered over
a sodium sulfate pad to obtain 43.1 g (87%) of aldehyde Ald -
22, which was used for the next step without further purifica-
tion: 1H NMR (300 MHz, CDCl3) δ (ppm) 9.71 (s, 1H), 3.74-
3.86 (m, 2H), 2.48-2.52 (m, 1H), 1.05 (d, J ) 7.0 Hz, 3H), 0.85
(s, 9H), 0.02 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
204.7, 63.4, 48.8, 25.8, 18.2, 10.2, -5.6.
P r ep a r a t ion of (2S,3R,4S)-1-ter t-Bu t yld im et h ysilyl-
oxy-2,4-d im eth yl-5-h exen -3-ol, C14H30O2Si, 23. Potassium
tert-butoxide (237.6 mL, 1.0 M solution, 237.6 mmol) was
dissolved in 200 mL THF at -78 °C, and cis-2-butene (38.3
mL, 396.0 mmol) was added. n-Butyllithium (95.0 mL, 2.5 M
solution, 237.6 mmol) was added and the mixture stirred for
20 min at -45 °C. The reaction mixture was cooled to -78 °C,
and (+)-B-methoxydiisopinocampheylborane [(+)-Ipc2BOMe]
(112.7 g, 356.4 mmol) dissolved in 100.0 mL of THF was added
and stirred for 1 h. Aldehyde Ald -22 (40.0 g, 198.0 mmol) was
dissolved in 20.0 mL of THF precooled to -78 °C and
transferred to the reaction mixture via a cannula at -78 °C
and the mixture stirred for 3 h. The reaction mixture was
oxidized with 142.6 mL of 3 M NaOH and 142.6 mL of 30%
H2O2 and stirred overnight. The reaction mixture was worked
up with ether and water. The organic layer was dried over
MgSO4, concentrated under vacuum, and purified by column
chromatography (silica gel, 19:1 hexane/ethyl ether) to obtain
38.3 g (75%) of pure alcohol 23: 1H NMR (300 MHz, CDCl3) δ
(ppm) 5.81-5.93 (m, 1H), 4.97-5.09 (m, 2H), 3.82-3.88 (m,
1H), 4.04-4.12 (m, 2H), 3.35-3.45 (bs, 1H), 2.29-2.31 (m, 1H),
1.74-1.83 (m, 1H), 1.06 (d, J ) 5.4 Hz, 3H), 0.84-0.96 (m,
12H), 0.08 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 142.5,
113.9, 79.6, 68.0, 41.3, 36.7, 25.9, 18.2, 14.1, 13.5, -5.5, -5.6;
EI-MS m/z 203 (M - C4H7)+, 145, 109, 75 [(CH3)2SiOH+, 100],
55, 43; CI-MS m/z 259 (M + H), 241 (M + H - H2O)+, 145,
127, 109 (100), 89.
P r ep a r a t ion of (3S,4S,5S,6S)-6-((1S)-2-ter t-Bu t yld i-
m et h ylsilyloxy-1-m et h ylet h yl)-3,4-d ih yd r oxy-5-m et h yl-
tetr a h yd r op yr a n -2-on e, C15H30O5Si, 25. NMO (0.8 g, 13.8
mmol) was added to the dihydropyranone 24 (1.9 g, 6.9 mmol)
dissolved in acetone/water (4:1, 15 mL) at 0 °C. OsO4 (0.18 g,
0.7 mmol) was added to the above solution and stirred for 6 h
at room temperature, and the product was extracted with Et2O
(3 × 10 mL), washed with saturated solution of sodium sulfite,
and dried over MgSO4. The solvent was removed under
aspirator vacuum. The crude product was purified by column
chromatography (silica gel, hexane/ethyl acetate (3:2)) to
obtain 1.6 g (72%) of 25: 1H NMR (300 MHz, CDCl3) δ (ppm)
4.64 (dd, J ) 2.7, 10.8 Hz, 1H), 4.21 (d, J ) 3.5 Hz, 1H), 4.14
(t, J ) 3.7 Hz, 1H), 3.77 (dd, J ) 2.9, 9.7 Hz, 1H), 3.63 (dd, J
) 6.0, 9.8 Hz, 1H), 2.27-2.34 (m, 1H), 1.85-1.94 (m, 1H), 1.02
(d, J ) 7.3 Hz, 3H), 0.92 (d, J ) 6.8 Hz, 3H), 0.87 (s, 9H), 0.03
(s, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 174.6, 80.6, 71.4,
67.6, 64.2, 36.7, 34.5, 25.9, 18.3, 12.6, 9.7, -5.40; EI-MS m/z
285, 243, 215, 199, 143, 75 [(CH3)2SiOH+, 100], 55, 43; CI-MS
m/z 319 [(M + H)+, 100], 301, 261, 187; HRMS-CI 319.1941
(actual), 319.1941 (calcd).
P r ep a r a tion of (4S,5S,6S)-6-((1S)-2-ter t-Bu tyld im eth -
ylsilyloxy-1-m et h ylet h yl)-4-h yd r oxy-5-m et h ylt et r a h y-
d r op yr a n -2-on e, C15H30O4Si, 26. Diol 25 (1.5 g, 4.7 mmol)
was dissolved in 10.0 mL of CH2Cl2 and cooled to 0 °C.
Phenylchlorothionoformate (0.71 mL, 5.2 mmol) was added
followed by the addition of pyridine (0.83 mL, 10.24 mmol).
After completion of the reaction as indicated by TLC, the
reaction mixture was worked up with ether and water. The
crude thionoformate ester was dissolved in benzene (10.0 mL)
and refluxed at 80 °C. Tributyltin hydride (5.06 mL, 18.8
mmol) was added followed by the addition of AIBN (0.08 g,
0.5 mmol) and refluxed for 5 h. The reaction mixture was
concentrated under vacuum and purified by column chroma-
tography (silica gel, hexanes/ethyl acetate, 4:1) to obtain 0.96
g (67% overall) of pure â-hydroxylactone 26: 1H NMR (300
MHz, CDCl3) δ (ppm) 4.57 (dd, J ) 2.3, 10.6 Hz, 1H), 4.04 (dt,
J ) 2.9, 5.7 Hz, 1H), 3.76 (dd, J ) 3.1, 9.7 Hz, 1H) 3.70 (dd, J
) 5.4, 9.7 Hz, 1H), 2.77 (dd, J ) 5.6, 18.1 Hz, 1H), 2.51 (dd, J
) 3.0, 18.1 Hz, 1H), 1.98-2.07 (m, 1H), 1.83-1.95 (m, 1H),
P r ep a r a tion of (1R,2S)-1-((1S)-2-ter t-Bu tyld im eth ylsi-
lyloxy-1-m eth yleth yl)-2-m eth yl-3-bu ten yl P r op -2-en oa te,
C
17H32O3Si, Acr -23. Alcohol 23 (4.0 g, 15.5 mmol) was
dissolved in CH2Cl2 (30.0 mL) and cooled to -15 °C. Acryloyl
chloride (10.1 mL, 124.0 mmol) and diisopropylethylamine
(43.1 mL, 248.0 mmol) were added at -15 °C and the mixture
stirred for 1 h at room temperature. After completion of the
reaction as indicated by TLC, the reaction mixture was filtered
over a magnesium sulfate pad and then purified by column
chromatography (silica gel, 19:1, hexane/ethyl acetate) to
obtain 3.8 g (79%) of pure acrylate ester Acr -23: 1H NMR (300
MHz, CDCl3) δ (ppm) 6.38 (dd, J ) 1.4, 17.3 Hz, 1H), 6.11
(dd, J ) 10.3, 17.3 Hz, 1H), 5.70-5.83 (m, 2H), 5.00-5.09 (m,
2H), 4.91 (t, J ) 6.3 Hz, 1H), 3.66 (dd, J ) 4.4, 9.5 Hz, 1H),
3.37 (dd, J ) 7.8, 9.7 Hz, 1H), 2.54-2.62 (m, 1H), 1.97-2.07
(m, 1H), 0.99 (d, J ) 6.9 Hz, 3H), 0.95 (d, J ) 6.7 Hz, 3H),
0.88 (s, 9H), 0.02 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
165.9, 140.6, 130.5, 128.6, 115.0, 78.1, 64.2, 39.3, 37.6, 26.0,
18.3, 14.4, 14.3, -5.4; EI-MS m/z 257 (M - C4H9)+, 227, 129
(100), 109, 89, 75, 55; CI-MS m/z 313 [(M + H)+, 100], 241,
181, 127, 109; HRMS-CI 313.2193 (actual), 313.2199 (calcd).
P r ep a r a tion of (5S,6R)-6-((1S)-2-ter t-Bu tyld im eth ylsi-
lyloxy-1-m e t h yle t h yl)-5-m e t h yl-5,6-d ih yd r op yr a n -2-
on e, C15H28O3Si, 24. Acrylate Acr -23 (2.5 g, 8.0 mmol) was
refluxed in toluene (80.0 mL). Grubbs’ second-generation
catalyst (0.7 g, 0.8 mmol) was added and the mixture refluxed
for 3 h. After completion of the reaction (TLC), solvent was
evaporated under vacuum and the crude product was purified
by column chromatography (silica gel, 2:3, hexane/ethyl ace-
tate) to obtain 2.0 g (86%) of the dihydropyranone 24: 1H NMR
(300 MHz, CDCl3) δ (ppm) 6.99 (dd, J ) 6.5, 9.6 Hz, 1H), 5.96
(d, J ) 9.6 Hz, 1H), 4.25 (dd, J ) 3.0, 10.6 Hz, 1H), 3.83 (dd,
0.94, (d, J ) 7.8 Hz, 3H), 0.88-0.90 (m, 12H), 0.03 (s, 6H); 13
C
NMR (75.5 MHz, CDCl3) δ (ppm) 170.8, 78.2, 68.7, 64.0, 36.7,
35.7, 35.3, 25.9, 18.3, 12.7, 10.0, -5.3, -5.4; EI-MS m/z 245
(M - C4H9)+, 227, 203, 185, 153, 145, 115, 83, 75 [(CH3)2SiOH+,
100], 55, 43; CI-MS m/z 303 [(M + H)+, 100], 285 (M +
H-H2O)+, 245, 227, 171, 153, 133, 113; HRMS-CI 303.1999
(actual) 303.1992 (calcd).
P r ep a r a t ion of (3R,4S,5S,6S)-6-((1S)-2-ter t-Bu t yld i-
m et h ylsilyloxy-1-m et h ylet h yl)-4-h yd r oxy-3,5-d im et h yl-
tetr a h yd r op yr a n -2-on e, C16H32O4Si, Me-26. A solution of
LDA in hexanes (4.3 mL, 1.7 M solution, 7.3 mmol) was cooled
to -60 °C, a solution of the hydroxylactone 26 (1.0 g, 3.3 mmol)
and hexamethylphosphoramide (4.0 mL, 22.3 mmol) in THF
was added dropwise over 40 min, and the mixture was stirred
at -60 °C for 2 h. The reaction mixture was cooled to -78 °C,
and n-butyllithium (2.8 mL, 2.5M solution, 6.9 mmol) was
added dropwise over 30 min and stirred for 45 min at -78 °C.
Iodomethane (1.2 mL, 19.8 mmol) was added in one portion
and stirred for 16 h. The reaction mixture was quenched with
water and worked up with ether. The organic layer was dried
over MgSO4, concentrated under aspirator vacuum, and puri-
fied by column chromatography (silica gel, 1:3, hexane/ethyl
acetate) to obtain 0.8 g (75%) of the R-methyl-â-hydroxylactone
Me-26: 1H NMR (300 MHz, CDCl3) δ (ppm) 4.40 (d, J ) 10.2
Hz, 1H), 3.74 (dd, J ) 4.8, 9.8 Hz, 1H), 3.66 (dd, J ) 2.5, 9.6
6302 J . Org. Chem., Vol. 69, No. 19, 2004

Regioselective Deoxygenation of Dihydropyranones
Hz, 1H), 3.36 (d, J ) 5.8 Hz, 1H), 2.72 (bs, 1H), 2.50 (qu, J )
6.8, 1H), 1.99-2.07 (m, 1H), 1.83-1.90 (m, 1H), 1.30 (d, J )
6.9, 3H), 0.93 (d, J ) 6.9 Hz, 3H), 0.90 (d, J ) 7.7 Hz, 3H),
0.86 (s, 9H), 0.02 (s, 3H), 0.01 (s, 3H); 13C NMR (75.5 MHz,
CDCl3) δ (ppm) 174.6, 78.1, 77.5, 63.9, 41.9, 39.3, 36.1, 25.9,
18.3, 13.9, 12.7, 11.9, -5.4, -5.5; EI-MS m/z 259 (M - C4H9)+,
203, 185, 167, 145, 115, 75 [(CH3)2SiOH+, 100], 55, 43; CI-MS
317 (M + H)+, 299 (M + H - H2O)+, 259, 185, 167; HRMS-CI
317.2158 (actual), 317.2148 (calcd).
P r ep a r a t ion of (3R,4S,5R,6S)-6-((1S)-2-ter t-Bu t yld i-
m et h ylsilyloxy-1-m et h ylet h yl)-4-ter t-b u t yld im et h ylsi-
lyloxy-3,5-d im eth yltetr a h yd r op yr a n -2-on e, C22H46O4Si2,
27. Alcohol Me-26 (0.5 g, 1.6 mmol) was dissolved in CH2Cl2
(3.0 mL) and cooled to -78 °C. tert-Butyldimethyl silyltrifluo-
romethanesulfonate (0.4 mL, 1.7 mmol) was added dropwise
followed by the addition of 2,6-di-tert-butyl-4-methylpyridine
(0.6 g, 3.2 mmol) and stirred for 1 h at -78 °C. The reaction
mixture was filtered with ether over silica gel and purified by
column chromatography (silica gel, hexanes/ethyl acetate, 5:1)
to obtain 0.54 g (78%) of 27: 1H NMR (300 MHz, CDCl3) δ
(ppm) 4.44 (d, J ) 10.5 Hz, 1H), 3.76 (dd, J ) 4.6, 9.6 Hz,
1H), 3.67 (dd, J ) 2.8, 9.7 Hz, 1H), 3.32 (d, J ) 5.9 Hz, 1H),
2.47 (qu, J ) 6.7 Hz, 1H), 1.82-1.96 (m, 2H), 1.27 (d, J ) 6.9
Hz, 3H), 0.91 (d, J ) 7.1 Hz, 3H), 0.89 (s, 9H), 0.88 (s, 9H),
0.84 (d, J ) 7.4 Hz, 3H), 0.08 (s, 3H), 0.07 (s, 3H), 0.03 (s,
6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 174.6, 78.5, 77.2,
63.9, 43.0, 39.4, 36.2, 25.9, 25.7, 18.3, 17.8, 14.6, 12.7, 11.0,
-4.4, -4.7, -5.4, -5.5; EI-MS m/z 373 (M - C4H9)+, 115, 89,
73 [(CH3)3Si+, 100], 57, 47; CI-MS 431 (M + H)+, 133, 81, 69;
HRMS-CI 431.3000 (actual), 431.3013 (calcd).
7.42 (d, J ) 8.8 Hz, 2H), 6.88 (d, J ) 8.5 Hz, 2H), 5.44 (s, 1H),
3.80 (s, 3H), 3.50-3.84 (m, 6H), 1.70-1.94 (m, 3H), 1.08 (d, J
) 6.6 Hz, 3H), 0.86-0.97 (m, 24H), 0.03-0.08 (m, 12H); 13C
NMR (75.5 MHz, CDCl3) δ (ppm) 132.1, 127.2, 113.5, 101.3,
84.0, 81.2, 64.3, 64.2, 55.3, 36.8, 36.6, 26.0, 25.9, 18.4, 18.2,
14.5, 12.1, 6.3, -5.3, -5.4, -5.5, -5.6.
P r ep a r a t ion of (2S,3R,4R,5S,6S)-3,7-Bis(ter t-b u t yld i-
m eth ylsilyloxy)-5-h yd r oxy-2,4,6-tr im eth ylh ep tyl-p-n itr o-
ben zoa te, C29H53NO7Si2, 31. Diol 28 (0.2 g, 0.5 mmol) was
dissolved in CH2Cl2 (1.0 mL). 4-Nitrobenzoyl chloride (0.1 g,
0.6 mmol), pyridine (1.0 mL, 1.0 mmol), and catalytic amounts
of DMAP (5 mg, 0.04 mmol) were added at 25 °C and the
mixture stirred for 3 h at room temperature. After completion
of the reaction as indicated by TLC, the reaction mixture was
filtered over magnesium sulfate pad and purified by column
chromatography (silica gel, 19:1, hexane/ethyl acetate) to
1
obtain 271 mg (93%) of pure acrylate ester 31: H NMR (300
MHz, CDCl3) δ (ppm) 8.26 (d, J ) 9.0, 2H), 8.22 (d, J ) 9.0
Hz, 2H), 4.32 (dd, J ) 7.1, 10.5 Hz, 1H), 4.22 (dd, J ) 7.8,
10.6 Hz, 1H), 3.96 (d, J ) 8.1 Hz, 1H), 3.89 (bs, 1H), 3.77 (dd,
J ) 3.9, 10.0 Hz, 1H), 3.53-3.60 (m, 2H), 2.36-2.43 (m, 1H),
1.70-1.85 (m, 2H), 0.85-0.99 (m, 24H), 0.74 (d, J ) 6.9 Hz,
3H), 0.06-0.09 (m, 12H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
164.7, 150.5, 136.0, 130.7, 123.6, 77.0, 73.8, 69.9, 69.1, 39.0,
37.7, 35.1, 26.3, 25.9, 18.6, 18.1, 12.9, 10.3, 9.9, -3.3, -3.9,
-5.5, -5.6; EI-MS m/z 364, 185, 150, 145, 135, 115, 75 [(CH3)2-
SiOH+, 100], 69, 57; CI-MS m/z 584 (M + H)+, 452 (M + H -
HOSi(CH3)2)+, 422 [100], 417; HRMS-CI 584.3442 (actual),
584.3439 (calcd).
P r ep a r a tion of (2S,3R,4R)-3-(ter t-Bu tyld im eth ylsilyl-
oxy)-2-m eth yl-4-((4S,5S)-5-m eth yl-1,3-d ioxa n -4-yl)p en tyl
p-Nitr oben zoa te, C24H39NO7Si, 32. Alcohol 31 (0.2 g, 0.34
mmol)) was dissolved in CH2Cl2 and MEM chloride (0.05 mL,
0.41 mmol) and N,N-diisopropylethylamine (0.08 mL, 0.51
mmol) and the mixture stirred for 2 h. The reaction mixture
was worked up with dilute acid, and the combined organic
layers were dried, concentrated under vacuum, and purified
by column chromatography (silica gel, hexanes/ethyl acetate,
P r ep a r a t ion of (2S,3R,4R,5S,6S)-3,7-Bis(ter t-b u t yld i-
m eth ylsilyloxy)-2,4,6-tr im eth ylh ep ta n e-1,5-d iol, C22H50
-
O4Si2, 28. Silyl ether 27 (0.4 g, 0.9 mmol) was dissolved in
THF (2.0 mL) and cooled to 0 °C. LiBH4 (30 mg, 1.4 mmol)
was added and the mixture stirred for 2 h. After completion
of the reaction, the reaction mixture was quenched with water
and worked up with ether. The organic layer was dried,
concentrated under vacuum, and purified by column chroma-
tography (silica gel, hexanes/ethyl acetate, 1:4) to obtain 0.25
g (65%) of pure diol 28: 1H NMR (300 MHz, CDCl3) δ (ppm)
3.82-3.86 (m, 1H), 3.75 (dd, J ) 3.9, 9.8 Hz, 1H), 3.45-3.65
(m, 4H), 2.04-2.11 (m, 1H), 1.68-1.86 (m, 2H), 0.95 (d, J )
6.9 Hz, 3H), 0.91 (s, 9H), 0.90 (s, 9H), 0.86 (d, J ) 7.1 Hz,
3H), 0.76 (d, J ) 7.1 Hz, 3H), 0.09 (s, 6H), 0.08 (s, 6H); 13C
NMR (75.5 MHz, CDCl3) δ (ppm) 77.3, 75.2, 69.6, 66.3, 39.0,
38.6, 37.6, 26.2, 25.9, 18.5, 18.2, 13.1, 11.3, 9.8, -3.7, -3.8,
-5.5, -5.6; EI-MS m/z 377 (M - C4H9)+, 203, 145, 89, 75
[(CH3)2SiOH+, 100], 57; CI-MS m/z 435 [(M + H)+ 100], 303
(M + H - HOSi(CH3)2)+, 203, 153, 133, 83, 69; HRMS-CI
435.3327 (actual), 435.3326 (calcd).
P r ep a r a t ion of (2S,3S,4R,5R,6S)-1,5-Bis(ter t-b u t yld i-
m et h ylsilyloxy)-3,7-b is(p -m et h oxyb en zyloxy)-2,4,6-t r i-
m eth ylh ep ta n e, C36H62O6Si2, 29. Diol 28 (0.2 g, 0.5 mmol)
was dissolved in 2 mL of THF/DMF (10:1) and added slowly
to a precooled suspension of NaH (58 mg, 1.2 mmol) in 2 mL
of THF at 0 °C. After the mixture was stirred for 2 h at 0 °C,
p-methoxybenzyl bromide (0.4 g, 1.8 mmol) was added and the
mixture stirred for 12 h. After completion of the reaction (TLC),
the mixture was worked up with ether and water. The organic
layer was dried over MgSO4 and concentrated under vacuum
and purified by column chromatography (silica gel, hexanes/
ethyl acetate, 2:3) to obtain 0.26 g (81%) of 29.
1
5:1) to yield 91 mg (56%) of 32: H NMR (300 MHz, CDCl3) δ
(ppm) 8.30 (d, J ) 8.9 Hz, 2H), 8.19 (d, J ) 8.9 Hz, 2H), 4.95
(d, J ) 5.8 Hz, 1H), 4.56 (d, J ) 6.0 Hz, 1H), 4.31 (dd, J ) 6.8,
10.7 Hz, 1H), 4.18 (dd, J ) 8.4,10.6 Hz, 1H), 3.97 (dd, J ) 4.5,
11.1 Hz, 1H), 3.86 (dd, J ) 1.2, 7.5 Hz, 1H), 3.19-3.30 (m,
2H), 2.25-2.32 (m, 1H), 1.96-2.08 (m, 1H), 1.82-1.92 (m, 1H),
0.93-1.00 (m, 15H), 0.69 (d, J ) 6.6 Hz, 3H), 0.09 (s, 3H),
0.07 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 164.6, 150.6,
135.8, 130.6, 123.7, 93.7, 82.8, 77.3, 73.0, 72.9, 69.0, 37.6, 34.9,
31.5, 26.2, 18.5, 12.3, 10.7, 10.2, -3.5, -4.0; EI-MS m/z 436,
394 [100], 185, 73; CI-MS m/z 482 (M + H)+, 350 [(M + H) -
HOSi(CH3)3]+, 320; HRMS-CI 482.2576 (actual), 482.2574
(calcd).
P r ep a r a t ion of (2S,3R,4R,5S,6S)-3,7-Bis(ter t-b u t yld i-
m eth ylsilyloxy)-5-tr ieth ylsilyloxy-2,4,6-tr im eth ylh ep tyl
p-Nitr oben zoa te, C35H67NO7Si3, TES-31. Alcohol 31 (0.2 g,
0.34 mmol) was dissolved in CH2Cl2 (1.0 mL) and cooled to
-78 °C. Triethylsilyltrifluoromethanesulfonate (0.09 mL, 0.41
mmol) was added dropwise followed by the addition of 2,6-
lutidine (0.08 mL, 0.68 mmol) and the mixture stirred for h
at -78 °C. The reaction mixture was worked up with ether
and water. The organic layer was dried (MgSO4) and concen-
trated under vacuum to obtain the crude silyl ether, which
was purified by column chromatography (silica gel, hexanes/
ethyl acetate, (5:1)) to obtain 229 mg (97%) of TES-31: 1H
NMR (300 MHz, CDCl3) δ (ppm) 8.29 (d, J ) 9.0 Hz, 2H), 8.21
(d, J ) 9.0 Hz, 2H), 4.32 (dd, J ) 7.6, 10.9 Hz, 1H), 4.25 (dd,
J ) 7.1, 10.7 Hz, 1H), 3.74 (dd, J ) 1.7, 8.0 Hz, 1H), 3.66 (dd,
J ) 2.8, 5.5 Hz, 1H), 3.62 (dd, J ) 5.5, 9.8 Hz, 1H), 3.43 (dd,
J ) 6.5, 9.8 Hz, 1H), 2.22-2.29 (m, 1H), 1.78-1.89 (m, 2H),
0.88-0.99 (m, 36H), 0.58 (q, J ) 8.2 Hz, 6H), 0.09 (s, 3H), 0.08
(s, 3H), 0.04 (s, 3H), 0.03 (s, 3H); 13C NMR (75.5 MHz, CDCl3)
δ (ppm) 164.7, 150.5, 135.8, 130.7, 123.6, 74.2, 73.4, 69.3, 65.1,
40.9, 38.7, 36.6, 26.3, 25.9, 18.6, 18.3, 14.3, 12.0, 10.5, 7.2, 5.7,
P r ep a r a tion of (4R,5S,6S)-4,6-Bis((1S)-2-ter t-bu tyld i-
m eth ylsilyloxy-1-m eth yleth yl)-2-p-m eth oxyph en yl-5-m eth -
yl-1,3-d ioxa n e, C30H56O5Si2, 30. Ether 29 (0.2 g, 0.3 mmol)
was dissolved in 1 mL of CH2Cl2/water (20:1) mixture and
cooled to 0 °C. DDQ (77 mg, 0.34 mmol) was added and the
mixture stirred for 5 min. The reaction mixture was filtered
over silica gel and washed with CH2Cl2. The organic layer was
dried, concentrated under vacuum, and purified by column
chromatography (silica gel, hexanes: ethyl acetate, 4:1) to
obtain 117 mg (69%) of 30: 1H NMR (300 MHz, CDCl3) δ (ppm)
J . Org. Chem, Vol. 69, No. 19, 2004 6303

Ramachandran et al.
-3.1, -3.9, -5.3, -5.4; EI-MS m/z 224, 185, 115, 89, 73 [(CH3)3-
Si+, 100], 59, 47; CI-MS m/z 698 (M + H)+, 434, 399, 185 (100),
135; HRMS-CI 698.4302 (actual), 698.4304 (calcd).
completion of the reaction as indicated by TLC, the reaction
mixture was worked up with ether and water. The organic
layers were dried, concentrated under vacuum, and purified
by column chromatography (silica gel, hexanes/ethyl acetate,
50:1) to afford 85 mg (72%) of 12: 1H NMR (300 MHz, CDCl3)
δ (ppm) 3.57-3.66 (m, 3H), 3.40 (dd, J ) 6.8, 9.8 Hz, 1H), 3.26
(dd, J ) 5.1, 9.5 Hz, 1H), 3.05-3.11 (m, 1H), 2.03-2.05 (m,
1H), 1.73-1.84 (m, 2H), 0.82-1.00 (m, 36H), 0.64 (q, J ) 7.9
Hz, 6H), 0.08 (s, 6H), 0.04 (s, 6H); 13C NMR (75.5 MHz, CDCl3)
δ (ppm) 76.0, 74.5, 65.0, 40.9, 40.6, 39.2, 26.2, 26.0, 18.6, 18.4,
14.5, 14.2, 14.1, 11.9, 7.2, 5.7, -3.4 (2 carbons), -5.2, -5.3;
ESI-MS 681 (Na adduct), 658.7, 624.9, 608.9, 582.8, 567, 554
[100], 544; HRMS-ESI 681.3023 (actual), 681.3028 (calcd).
P r ep a r a t ion of (2S,3R,4R,5S,6S)-3,7-Bis(ter t-b u t yld i-
m et h ylsilyloxy)-2,4,6-t r im et h yl-5-t r iet h ylsilyloxyh ep -
ta n -1-ol, C28H64O4Si3, 33. K2CO3 (78 mg, 0.57 mmol) was
added to the ester TES-31 (0.2 g, 0.28 mmol) dissolved in 1
mL of methanol and stirred for 1 h. Solvent was removed
under aspirator vacuum, extracted with ether, washed with
water, dried (MgSO4), and purified by silica gel column
chromatography to obtain 127 mg (83%) of alcohol 33: 1H
NMR (300 MHz, CDCl3) δ (ppm) 3.72 (dd, J ) 2.4, 6.4 Hz,
1H), 3.67 (dd, J ) 5.1, 9.9 Hz, 1H), 3.49-3.61 (m, 2H), 3.39
(dd, J ) 7.0, 9.8 Hz, 1H), 1.80-1.96 (m, 2H), 1.71-1.73 (m,
1H), 1.57 (bs, 1H), 0.84-1.00 (m, 36H), 0.63 (q, J ) 8.0 Hz,
6H), 0.04-0.08 (m, 12H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
75.3, 74.0, 66.3, 65.0, 40.2, 39.8, 38.4, 26.2, 26.0, 18.5, 18.4,
15.0, 11.8, 11.2, 7.2, 5.7, -3.4, -3.9, -5.3, -5.4; CI-MS m/z
549 (M + H)+, 417, 317, 285, 259, 203 [100]; HRMS-CI
549.4188 (actual), 549.4191 (calcd).
Ack n ow led gm en t. Financial assistance from the
Herbert C. Brown Center for Borane Research19 and
Aldrich Chemical Co. are gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental and
spectral data along with 1H and 13C NMR spectra for various
compounds and an X-ray structure of compound 19. This
material is available free of charge via the Internet at
http://pubs.acs.org.
P r ep a r a t ion of (2S,3S,4R,5S,6R)-1,5-Bis(ter t-b u t yld i-
m e t h ylsilyloxy)-7-iod o-2,4,6-t r im e t h yl-3-t r ie t h ylsilyl-
oxyh ep ta n e, C28H63IO3Si2, 12. Alcohol 33 (0.1 g, 0.18 mmol)
was dissolved in CH2Cl2. Iodine (81 mg, 0.32 mmol), triph-
enylphosphine (83 mg, 0.32 mmol), and imidazole (40 mg, 0.59
mmol) were added, and the mixture was stirred for 6 h. After
J O0492416
6304 J . Org. Chem., Vol. 69, No. 19, 2004