Synthesis of the FG fragment of the pectenotoxins

Article abstract of DOI:10.1055/s-2007-985600

The synthesis of the FG subunit of the pectenotoxins is reported herein. The synthesis hinges on the preparation of an appropriately functionalized acyclic precursor using a Z-selective Wittig reaction. Further elaboration using two sequential cyclization

Full text of DOI:10.1055/s-2007-985600

LETTER
2359
Synthesis of the FG Fragment of the Pectenotoxins
Synthesis of the
F
G
m
Fragment of the
P
a
ectenotoxin
n
s
da M. Heapy, Thomas W. Wagner, Margaret M. Brimble*
Department of Chemistry, The University of Auckland, 23 Symonds St., Auckland, New Zealand
Fax +64(9)3737422; E-mail: m.brimble@auckland.ac.nz.
Received 11 June 2007
To date, only one elegant total synthesis of the PTXs
(PTX-4 and PTX-8) has been completed by Evans et
al.13,14 The total synthesis involved a late stage assembly
of the FG unit of PTX-4 by attaching an F-ring fragment
Abstract: The synthesis of the FG subunit of the pectenotoxins is
reported herein. The synthesis hinges on the preparation of an
appropriately functionalized acyclic precursor using a Z-selective
Wittig reaction. Further elaboration using two sequential cycliza-
tion reactions furnished the tetrahydrofuran F ring and the tetra- that also contained the G-ring backbone to an ABCDE
hydropyran G ring, respectively.
portion of PTX using a Julia olefination. Subsequent
deprotection-induced cyclization to provide the G-ring
hemiacetal thus completed the synthesis of PTX-4. A syn-
thesis of an FG-ring fragment has previously been report-
ed from the laboratories of Murai et al.15,16 in which the
main backbone of the FG rings was prepared by reaction
of an anion generated from a chiral a-lithio tetrahydro-
furanyl ring, representing the F ring, with a five-carbon
aldehyde fragment. Studies toward the F ring have also
emanated from the work of Paquette et al.17,18 who
employed an elegant hydroxyl-directed hydrogenation of
a dihydrofuran to generate the desired chirality present in
the tetrahydrofuran F ring.
Key words: cyclization, Wittig reaction, epoxidation, shellfish
toxins, pectenotoxins
The pectenotoxins (PTXs) typified by pectenotoxin-2
(PTX-2, 1, Figure 1) are a family of structurally complex
polyether macrolides initially isolated in 1985 by
Yasumoto et al.1,2 from contaminated scallops (Patino-
pecten yessoensis) off the coast of Japan.
O
Me
O
O
A
B
C
O
We envisaged a modular approach to the preparation of
the PTXs in which several key fragments could be pre-
pared individually that would later be joined in a conver-
gent manner. The work reported herein on the synthesis of
the FG fragment of the pectenotoxins continues on from
the successful synthesis of the ABC ring of PTX-7 com-
pleted by this research group.19
O
O
Me
OH
O
OH
G
O
D
OH
Me
F
O
E
Me
Me
O
O
Me
Me
PTX-2 (1)
Figure 1 Pectenotoxin-2 (1)
Our retrosynthetic analysis of the key FG bicyclic frag-
ment 2 is depicted in Scheme 1. It was envisioned that in-
stallation of the tetrahydropyran G ring could be effected
by simultaneous deprotection of benzyl ether 3 followed
by 6-exo-trig cyclization of the resultant alcohol onto ke-
tone 3. The tetrahydrofuran F ring is then constructed via
5-exo-tet cyclization of masked g-hydroxy epoxide 4, it-
self obtained via stereocontrolled epoxidation of Z-olefin
5. Olefin 5 in turn is assembled via Z-selective Wittig
reaction of aldehyde 6 with phosphonium salt 7. The key
stereocenters in intermediates 6 and 7 are then established
by Sharpless asymmetric epoxidation and Sharpless
asymmetric dihydroxylation, respectively.
These marine biotoxins, mainly produced by the dino-
flagellate Dinophysis fortii,1 accumulate in the shellfish
that feed upon them and the toxins are then transferred to
humans upon consumption of the contaminated shellfish.
The resultant shellfish poisoning events not only have im-
plications for public health3 but also have economic con-
sequences on the global shellfish industry. The isolation
of the pectenotoxins has not been limited to Japan and
these shellfish toxins have now been isolated from many
major coastal regions.4–8 PTX-2 (1) exhibits potent cyto-
toxic effects against human colon, lung and breast
carcinomas9 and has since been found to induce its cyto-
toxic activity by binding to intracellular F actin.10,11
Further experiments have shown that this actin damage
triggers apoptosis through mitochondrial dysfunction in
p53-deficient tumour cells.12 The important antimitotic
activity reported for PTX-2 (1) has prompted considerable
synthetic activity in this area by several research groups.
The synthesis of aldehyde 6 (Scheme 2) began with
Horner–Wadsworth–Emmons reaction of known20
benzyl-protected aldehyde 8 with commercially available
triethyl phosphonoacetate. Use of potassium carbonate as
base21 in a biphasic solvent of diethyl ether and water
afforded E-conjugated ester 9 stereoselectively in 86%
yield. DIBAL-H reduction of the resultant ester to the cor-
responding allylic alcohol (DIBAL-H, CH2Cl2, –78 °C,
87%) followed by Sharpless asymmetric epoxidation22 us-
ing (L)-(+)-diethyl tartrate as the chiral catalyst proceeded
SYNLETT 2007, No. 15, pp 2359–2362
1
7
.0
9
.2
0
0
7
Advanced online publication: 22.08.2007
DOI: 10.1055/s-2007-985600; Art ID: D17807ST
© Georg Thieme Verlag Stuttgart · New York

2360
A. M. Heapy et al.
LETTER
smoothly {91%, [a]D23 –27.5 (c 2.00, CHCl3)} to provide
known epoxide 10 (> 86% ee).23 Opening of epoxide 10
with trimethylaluminium24 afforded enantiopure R,R-vic-
inal diol 11. Protection of diol 11 with TBSOTf and 2,6-
lutidine gave the bissilyl ether 12 in good yield (89%).
OPMB
TBDPSO
OMe
OPiv
Me
O
O
2
Selective deprotection of the primary TBS group in the
presence of the secondary25 was then undertaken using
HF–pyridine in THF with close monitoring of the reac-
tion. Only moderate yields were achieved for this step due
to the formation of the undesired diol species 11. Fortu-
nately, diol 11 and the unreacted starting material 12 were
able to be recycled resulting in an overall quantitative
yield of the desired monosilyl ether 13. Finally, Dess–
Martin periodinane oxidation26 of primary alcohol 13
furnished aldehyde 6 in excellent yield (96%).
OPMB
TBDPSO
Me
OPiv
BnO
O
O
3
Et
Et
TBDPSO
Me
O
O
BnO
O
The synthesis of phosphonium salt 7 (Scheme 3) com-
menced with reaction of known27 aldehyde 14 with trieth-
yl phosphonoacetate, using the aforementioned biphasic
conditions.21 Sharpless asymmetric dihydroxylation using
5 mol% (DHQD)2PHAL proceeded in 95% ee as deter-
mined by Mosher ester analysis28 of the resultant R,S-diol.
Diol 15 was transformed via a sequence of protection as a
p-methoxybenzylidene acetal followed by DIBAL-H re-
duction which effected reduction of the ester to a primary
alcohol and concomitant, regioselective acetal cleavage
affording PMB-protected alcohol 16. The terminal diol
was then protected as a diethyl acetal and the primary TB-
DPS group removed. After conversion of the resultant pri-
mary alcohol to iodide 17, conversion to phosphonium
salt 7 was effected by heating iodide 17 with triphen-
ylphosphine and Hünig’s base under reflux in acetonitrile.
OPMB
4
Et
O
Et
OTBS
O
BnO
Me
H
OPMB
5
Et
Et
O
OTBS
O
O
I
Ph3P
BnO
OPMB
Me
6
7
Scheme 1 Retrosynthetic analysis of FG fragment 2
OH
TBDPSO
H
(i), (ii)
BnO
H
TBDPSO
OEt
BnO
OEt
(i)
O
8
9
O
14
OH
O
O
15
(iv)
BnO
OH
(ii), (iii)
OH
(v), (vi)
(vii)
(iii), (iv)
O
TBDPSO
OH
10
OR1
OPMB
16
BnO
OR2
Et
Et
Et
O
Et
Me
R2 = H
O
O
(viii)
O
11 R1 = H
I
Ph3P
I
(v)
12 R1 = TBS R2 = TBS
13 R1 = TBS R2 = H
OPMB
OPMB
(vi)
17
7
Scheme 3 Reagents and conditions: (i) (EtO)2P(O)CH2CO2Et,
K2CO3, Et2O, H2O, 0 °C to r.t., 86%; (ii) K3Fe(CN)6, (DHQD)2Phal,
MeSO2NH2, t-BuOH–H2O, K2CO3, OsO4, r.t., 2 h, then olefin, 0 °C
to r.t., 93%, 95% ee; (iii) MeOC6H4CH(OMe)2, CSA, PhH, r.t., 170
mbar, 76%; (iv) DIBAL-H, CH2Cl2, –78 °C, 77%; (v) 3,3-dimethoxy-
pentane, PTSA, PhH, r.t., 70%; (vi) TBAF, THF, r.t., 84%; (vii) imi-
dazole, PPh3, CH2Cl2, I2, r.t., 85%; (viii) PPh3, i-Pr2EtN, MeCN,
reflux, 60%.
OTBS
O
OTBS
BnO
H
BnO
OH
(vii)
Me
Me
6
13
Scheme 2 Reagents and conditions: (i) (EtO)2P(O)CH2CO2Et,
K2CO3, Et2O, H2O, O °C to r.t., 86%; (ii) DIBAL-H, CH2Cl2, –78 °C,
87%; (iii) Ti(i-OPr)4, (+)-DET, MS 4 Å, CH2Cl2, –20 °C, 30 min then
t-BuOOH, 91%; (iv) AlMe3, CH2Cl2, 0 °C to r.t., 66%; (v) TBSOTf,
2,6-lutidine, CH2Cl2, 0 °C, 89%; (vi) HF–pyridine, THF, 0 °C to r.t.,
quant.; (vii) Dess–Martin periodinane, pyridine, THF, r.t., 96%.
With both coupling partners 6 and 7 in hand, attention
next turned to the union of these fragments via a Z-selec-
tive Wittig reaction (Scheme 4). The key Wittig reaction
proceeded smoothly in good yield (93%) using n-BuLi to
Synlett 2007, No. 15, 2359–2362 © Thieme Stuttgart · New York

LETTER
Synthesis of the FG Fragment of the Pectenotoxins
2361
Et
Et
Et
OR
O
(v)
Et
OTBS
O
O
BnO
(i)
(ii), (iii)
O
6
7
BnO
O
Me
OPMB
18
Me
OPMB
19 R = H
(iv)
4
R = TBDPS
OPMB
OPMB
OPMB
TBDPSO
Me
TBDPSO
Me
TBDPSO
Me
OMe
O
OPiv
(viii), (ix)
(vi), (vii)
O
OH
BnO
OPiv
BnO
O
O
OH
20
O
2
3
Scheme 4 Reagents and conditions: (i) n-BuLi, HMPA, THF, –78 °C, 93%; (ii) TBAF, THF, r.t., 81%; (iii) MCPBA, CH2Cl2, 0 °C, 99%,
>95% de; (iv) TBDPSCl, imidazole, CH2Cl2, r.t., 85%; (v) 50% aq TFA, CH2Cl2, r.t., 53%; (vi) PivCl, pyridine, CH2Cl2, –5 °C, 97%;
(vii) Dess–Martin periodinane, pyridine, CH2Cl2, r.t., 99%; (viii) Raney nickel, EtOH, H2, r.t.; (ix) CSA, CH(OMe)3, MeOH, r.t., 70%, 2 steps.
generate the ylide and 7% HMPA as a lithium ion seques-
tering agent.29,30 The use of KHMDS as base, with and
without HMPA additive, also gave the desired product but
in lower yield (45% and 72%, respectively). The Z-stereo-
chemistry of olefin 18 was confirmed by the magnitude of
the vinylic coupling constant, J5,6 = 9.8 Hz. The undesired
E-olefin was not observed in the crude 1H NMR spectrum.
Deprotection of the secondary TBS ether 1831 gave the
corresponding allylic alcohol in good yield although long
reaction times were required (TBAF, THF, 5 h, r.t., 81%).
Substrate-directed epoxidation32,33 of the resultant allylic
alcohol using MCPBA afforded epoxy alcohol 19 as the
sole diastereomer which was then reprotected as a TBDPS
ether.
Acknowledgment
A. Heapy acknowledges the award of a Bright Future Top Achiever
Doctoral Scholarship from the New Zealand Tertiary Education
Commission.
References and Notes
(1) Yasumoto, T.; Murata, M.; Oshima, Y.; Sano, M.;
Matsumoto, G. K.; Clardy, J. Tetrahedron 1985, 41, 1019.
(2) Sasaki, K.; Wright, J. L. C.; Yasumoto, T. J. Org. Chem.
1998, 63, 2475.
(3) Burgess, V.; Shaw, G. Environ. Int. 2001, 27, 275.
(4) Wilkins, A. L.; Rehmann, N.; Torgersen, T.; Rundberget, T.;
Keogh, M.; Petersen, D.; Hess, P.; Rise, F.; Miles, C. O.
J. Agric. Food Chem. 2006, 54, 5672.
(5) Suzuki, T.; Walter, J. A.; LeBlanc, P.; MacKinnon, S.;
Miles, C. O.; Wilkins, A. L.; Munday, R.; Beuzenberg, V.;
MacKenzie, A. L.; Jensen, D. J.; Cooney, J. M.; Quilliam,
M. A. Chem. Res. Toxicol. 2006, 19, 310.
(6) Miles, C. O.; Wilkins, A. L.; Hawkes, A. D.; Jensen, D. J.;
Selwood, A. I.; Beuzenberg, V.; MacKenzie, A. L.; Cooney,
J. M.; Holland, P. T. Toxicon 2006, 48, 152.
(7) Madigan, T. L.; Lee, K. G.; Padula, D. J.; McNabb, P.;
Pointon, A. M. Harmful Algae 2006, 5, 119.
(8) Kuuppo, P.; Uronen, P.; Petermann, A.; Tamminen, T.;
Graneli, E. Limnol. Oceanogr. 2006, 51, 2300.
(9) Jung, J. H.; Sim, C. J.; Lee, C. O. J. Nat. Prod. 1995, 58,
1722.
(10) Leira, F.; Cabado, A. G.; Vieytes, M. R.; Roman, Y.;
Alfonso, A.; Botana, L. M.; Yasumoto, T.; Malaguti, C.;
Rossini, G. P. Biochem. Pharmacol. 2002, 63, 1979.
(11) Spector, I.; Braet, F.; Shochet, N. R.; Bubb, M. R. Microsc.
Res. Tech. 1999, 47, 18.
(12) Chae, H. D.; Choi, T. S.; Kim, B. M.; Jung, J. H.; Bang, Y.
J.; Shin, D. Y. Oncogene 2005, 24, 4813.
(13) Evans, D. A.; Rajapakse, H. A.; Chiu, A.; Stenkamp, D.
Angew. Chem. Int. Ed. 2002, 41, 4573.
Cyclization to form the tetrahydrofuran F ring was accom-
plished by deprotection of the diethyl acetal protecting
group using 50% aqueous TFA in dichloromethane to un-
mask the g-hydroxyepoxide thus facilitating the 5-exo-tet
cyclization to afford tetrahydrofuran 20.34 Attempts to in-
duce this desired deprotection–cyclization sequence using
CSA and PPTS led to the formation of complex mixtures
with none of the desired tetrahydrofuran moiety being
formed. Selective pivaloyl protection of the primary
alcohol over the resultant secondary alcohol was achieved
in 97% yield using pivaloyl chloride and pyridine as base
in dichloromethane at –5 °C. Dess–Martin periodinane
oxidation26 of the remaining secondary alcohol proceeded
in high yield (99%) thus providing the appropriately func-
tionalized acyclic framework for the final cyclization step.
Debenzylation was achieved in the presence of the PMB
group35 using freshly prepared Raney nickel36,37 in ethanol
under an atmosphere of hydrogen. The resultant hemiace-
tal was obtained cleanly as a single isomer38,39 that was
immediately converted to the corresponding methyl acetal
2 to facilitate purification (CSA, MeOH, trimethyl ortho-
formate, 2 h, r.t., 70%, 2 steps).
(14) Evans, D. A.; Rajapakse, H. A.; Stenkamp, D. Angew. Chem.
Int. Ed. 2002, 41, 4569.
(15) Amano, S.; Fujiwara, K.; Murai, A. Synlett 1997, 1300.
(16) Fujiwara, K.; Kobayashi, M.; Yamamoto, F.; Aki, Y.;
Kawamura, M.; Awakura, D.; Amano, S.; Okano, A.; Murai,
A.; Kawai, H. E.; Suzuki, T. Tetrahedron Lett. 2005, 46,
5067.
In summary, a convergent synthesis of the FG fragment of
the pectenotoxins has been successfully achieved in prep-
aration for union with the previously prepared ABC frag-
ment. Synthetic studies towards the D and E rings are
under way.
(17) Peng, X. W.; Bondar, D.; Paquette, L. A. Tetrahedron 2004,
60, 9589.
Synlett 2007, No. 15, 2359–2362 © Thieme Stuttgart · New York

2362
A. M. Heapy et al.
LETTER
(18) Paquette, L. A.; Peng, X. W.; Bondar, D. Org. Lett. 2002, 4,
937.
(19) Halim, R.; Brimble, M. A.; Merten, J. Org. Biomol. Chem.
2006, 4, 1387.
(20) Mans, D. M.; Pearson, W. H. Org. Lett. 2004, 6, 3305.
(21) Cordero, F. M.; Pisaneschi, F.; Gensini, M.; Goti, A.;
Brandi, A. Eur. J. Org. Chem. 2002, 1941.
(22) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102,
5974.
(23) Hirai, Y.; Chintani, M.; Yamazaki, T.; Momose, T. Chem.
Lett. 1989, 1449.
(24) Suzuki, T.; Saimoto, H.; Tomioka, H.; Oshima, K.; Nozaki,
H. Tetrahedron Lett. 1982, 23, 3597.
(25) Crouch, R. D. Tetrahedron 2004, 60, 5833.
(26) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(27) Caprio, V.; Brimble, M. A.; Furkert, D. P. Tetrahedron
2001, 57, 4023.
(28) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969,
34, 2543.
(34) Selected Spectral Data
Compound 20: [a]D –6.9 (c 1.75, CHCl3). HRMS: m/z calcd
for C42H55O7Si: 699.3717; found: 699.3721 [MH+]. IR:
nmax = 3469, 3069, 2930, 2856, 1612, 1513, 1247, 1110 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.99 (3 H, d, J = 6.85 Hz,
CH3), 1.08 (9 H, s, Ph2t-BuSi), 1.41–1.61 (2 H, m, H-4),
1.65–1.69 (2 H, dd, J = 11.5, 4.0 Hz, H-3¢), 1.50–1.72 (1 H,
m, H-3), 2.20–2.27 (1 H, br, C-1¢¢-OH), 2.66 (1 H, d, J = 8.0
Hz, C-1-OH), 3.15–3.34 (2 H, m, H-5), 3.34–3.42 (1 H, m,
H-1), 3.56–3.72 (3 H, m, H-1¢¢, H-2), 3.80 (3 H, s, OMe),
3.88 (1 H, m, H-5¢), 4.06–4.10 (2 H, m, H-4¢, H-2¢) 4.22 (1
H, d, J = 11.5 Hz, CH2Ar), 4.35–4.41 (2 H, m, CH2Ar), 4.44
(1 H, d, J = 11.5 Hz, CH2Ar), 6.85–6.88 (2 H, m, ArH), 7.16–
7.37 (13 H, m, ArH), 7.66–7.69 (4 H, m, ArH). 13C NMR (75
MHz, CDCl3): d = 15.4 (CH3, CHCH3), 19.6 (C, Ph2t-BuSi),
27.2 (3 × CH3, Ph2t-BuSi), 32.5 (CH2, C-4), 33.9 (CH2, C-
3¢), 34.7 (CH, C-3), 55.3 (CH3, OMe), 62.0 (CH2, C-1¢¢),
68.6 (CH2, C-5), 71.1 (CH2, CH2Ar), 72.0 (CH, C-1), 72.9
(CH2, CH2Ar), 76.5 (CH, C-2), 79.2 (CH, C-4¢), 79.8 (CH,
C-2¢), 81.5 (CH, C-5¢), 113.9 (CH, Ar), 127.5 (C, Ar), 127.5
(C, Ar), 127.6 (C, Ar), 128.3 (CH, Ar), 129.0 (CH, Ar),
129.8 (CH, Ar), 129.8 (CH, Ar), 133.6 (C, Ar), 133.7 (C,
Ar), 136.0 (CH, Ar), 136.1 (CH, Ar), 138.4 (C, Ar), 159.3
(C, Ar). MS–FAB: m/z (%) = 699 (0.2) [MH+], 199 (10), 197
(8), 137 (14), 136 (13), 135 (9), 122 (10), 121 (100), 91 (27).
(35) Horita, K.; Yoshioka, T.; Tanaka, T.; Oikawa, Y.;
Yonemitsu, O. Tetrahedron 1986, 42, 3021.
(29) Reich, H. J.; Kulicke, K. J. J. Am. Chem. Soc. 1996, 118,
273.
(30) Paterson, I.; Chen, D. Y. K.; Coster, M. J.; Acena, J. L.;
Bach, J.; Wallace, D. J. Org. Biomol. Chem. 2005, 3, 2431.
(31) Selected Spectral Data
Compound 18: [a]D +7.2 (c 7.20, CHCl3). HRMS: m/z calcd
for C37H57O6Si: 625.3924; found: 625.3919 [M – H]+. IR:
nmax = 3433, 2929, 2856, 1613, 1514, 1463, 1249, 1083, 835,
775 cm–1. 1H NMR (300 MHz, CDCl3): d = 0.01 (3 H, s,
Me2t-BuSi), 0.03 (3 H, s, Me2t-BuSi), 0.85–0.94 (18 H, m,
Me2t-BuSi, CH3, H-2¢¢), 1.25–1.30 (1 H, m, H-2), 1.61–1.71
(5 H, m, H-1¢¢, H-3), 1.82–1.94 (1 H, m, H-2), 2.10–2.30 (2
H, m, H-7), 3.45–3.50 (3 H, m, H-1, H-8), 3.60–3.67 (1 H,
m, H-5¢), 3.80 (3 H, s, OMe), 3.94–4.00 (1 H, m, H-5¢), 4.17–
4.20 (2 H, m, H-4, H-4¢), 4.49–4.71 (4 H, m, CH2Ar), 5.40–
5.54 (2 H, m, H-5, H-6), 6.86–6.89 (2 H, m, ArH), 7.26–7.35
(7 H, m, ArH). 13C NMR (75 MHz, CDCl3): d = –4.8 (CH3,
Me2t-BuSi), –4.2 (CH3, Me2t-BuSi), 8.1 (CH3, C-2¢¢), 8.3
(CH3, C-2¢¢), 15.4 (CH3, Me), 18.1 (C, Me2t-BuSi), 25.8
(CH3, Me2t-BuSi), 29.2 (CH2, C-7), 29.6 (2 × CH2, C-1¢¢),
31.6 (CH2, C-2), 37.3 (CH, C-3), 55.2 (CH3, OMe), 66.4
(CH2, C-5¢), 68.9 (CH2, C-1), 72.6 (CH2Ar), 72.8 (CH2Ar),
72.6 (CH, C-4), 78.5 (CH, C-4¢), 79.1 (CH, C-8), 113.2 (C,
C-2¢), 113.7 (CH, ArH), 125.4 (CH, C5 or C6), 127.4 (CH,
ArH), 127.6 (CH, ArH), 128.3 (CH, ArH), 129.4 (CH, ArH),
130.7 (C, Ar), 134.0 (CH, C5 or C6), 138.7 (C, Ar), 159.2
(C, Ar). MS–FAB: m/z (%) = 627 (0.1) [MH+], 625 (0.2),
598 (0.2), 495 (0.2), 211 (3), 137 (3), 121 (100), 91 (25)
[CH2Ph], 73 (16).
(36) Adkins, H.; Billica, H. R. J. Am. Chem. Soc. 1948, 70, 695.
(37) Billica, H. R.; Adkins, H. Org. Synth. 1949, 29, 24.
(38) Selected Spectral Data
Compound 2: [a]D –6.0 (c 0.2, CHCl3). HRMS: m/z calcd for
C41H55O8Si: 703.3666; found: 703.3670 [M – H]+. IR: nmax
=
2932, 1729, 1613, 1514, 1428, 1248, 1170, 1093, 821, 703
cm–1. 1H NMR (300 MHz, CDCl3): d = 1.03–1.16 (20 H, m,
Ph2t-BuSi, H-3¢), 1.21 (3 H, d, J = 7.2 Hz, C-4-CH3), 1.34–
1.40 (1 H, m, H-5), 1.64–1.76 (1 H, m, H-5), 1.99–2.09 (1 H,
m, H-4), 3.39 (3 H, s, C-2-OMe), 3.42–3.47 (2 H, m, H-6),
3.61 (1 H, d, J = 5.0 Hz, H-3), 3.73–3.77 (1 H, m, H-4¢), 3.80
(3 H, OMe, OPMB), 3.93–3.98 (1 H, m, H-5¢), 4.03–4.07 (1
H, m, CH2, OPMB), 4.10–4.21 (2 H, m, H-1¢¢), 4.23–4.27 (1
H, m, CH2, OPMB), 4.41 (1 H, t, J = 7.5 Hz, H-2¢), 6.82–6.86
(2 H, m, ArH), 7.09–7.12 (2 H, m, ArH), 7.30–7.42 (6 H, m,
ArH), 7.65–7.76 (4 H, m, ArH). 13C NMR (75 MHz, CDCl3):
d = 14.1 (CHCH3), 19.7 (C, Ph2t-BuSi), 27.1 (CH3, t-Bu),
27.1 (CH3, t-Bu), 27.2 (CH3, t-Bu), 30.4 (CH2, C-5), 31.6
(CH, C-4), 32.6 (CH2, C-3¢), 50.4 (CH3, C-2-OMe), 55.3
(OCH3, OPMB), 56.4 (CH2, C-6), 63.0 (CH2, C-1¢¢), 70.4
(CH2, OPMB), 73.0 (CH, C-3), 78.2 (CH, C-4’), 79.8 (CH,
C-5¢), 80.0 (CH, C-2¢), 100.6 (C, C-2), 113.8 (CH, OPMB),
127.4 (CH, Ar), 127.5 (CH, Ar), 128.8 (CH, Ar), 129.5 (CH,
Ar), 129.6 (CH, Ar), 130.3 (C, Ar), 133.8 (C, Ar), 134.1 (C,
Ar), 136.2 (CH, Ar), 136.2 (CH, Ar), 159.1 (C, OPMB),
178.2 (C=O). MS–FAB: m/z (%) = 703 (0.1) [M – H]+, 673
(2), 647 (0.2), 617 (2), 597 (2), 383 (18), 239 (7), 197 (7),
121 (100), 89 (18).
(32) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993,
93, 1307.
(33) Adam, W.; Wirth, T. Acc. Chem. Res. 1999, 32, 703.
(39) The stereochemistry at C2 in 2 was assumed to be that in
which the OMe group adopts an axial position due to
stabilization by the anomeric effect.
Synlett 2007, No. 15, 2359–2362 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.