Convergent synthesis of trans-fused oxane ring systems based on NiII/CrII-mediated cross-coupling reactions

Article abstract of DOI:10.1055/s-2001-11398

A general method for the convergent assembly of polyether structures has been developed based on a Ni^II/Cr^II-mediated cross-coupling reaction of alkenyl iodides with aldehydes. The present method allowed coupling to oxane rings via a

Full text of DOI:10.1055/s-2001-11398

LETTER
345
Convergent Synthesis of trans-Fused Oxane Ring Systems Based on NiII/CrII-
Mediated Cross-coupling Reactions
M. Teresa Díaz,a Ruby L. Pérez,a Elsa Rodríguez,b José L. Ravelo,b Julio D. Martín*a
a Instituto de Investigaciones Químicas, Américo Vespucio, s/n, Isla de la Cartuja, 41092 Seville, Spain
b Instituto de Bio-orgánica, Universidad de La Laguna, Carretera de la Esperanza, 2, 38206 La Laguna, Tenerife, Spain
Fax +34 954460565; E-mail: jdelgado@cica.es
Received 18 December 2000
Schemes 2 and 3 summarize the synthesis of the starting
Abstract: A general method for the convergent assembly of poly-
models, alkenyl iodide 27 (Scheme 2) and aldehyde 33
(Scheme 3). The synthesis of the allyl intermediate 18 be-
gan with 2-deoxyribose (11), which was converted into
olefin 12 by a Wittig reaction followed by sequential se-
lective protection involving 1,3-dioxacetalization and sil-
ylation. DIBAL-H reduction led to alcohol 12 (73% over-
all yield). Sharpless asymmetric epoxidation6 of 12 using
(-)-diethyl tartrate as the chiral auxiliary gave the epoxide
13 in 90% yield. Iodination of the tosyl derivative fol-
lowed by base treatment gave, after benzylation,7 com-
pound 16 (89% overall yield, three steps). Vinyl
fragmentation followed by oxidation of the resulting
hemiacetal gave the lactone 17 (61% yield). The equatori-
al C-glycosidation to give 18 was stereoselectively ac-
complished by addition of allylmagnesium bromide to the
lactone 17 followed by silane reduction.8 Compound 18
was alternatively synthesized via lactone 21 following a
protocol identical with that used for 17 to 18 conversion.
Lactone 21 was prepared from the D-glucopyranoside de-
rivative 209, with the free hydroxyl group being removed
under Barton 10 conditions. Vinyl fragmentation in 18 fol-
lowed by dibromoolefination of the resulting aldehyde11
gave the vinyl dibromide 23 which was converted to the
acetylene derivative 24 by further treatment with n-Buli.
Removal of the silyl group from 2412 then led to the alco-
hol 25 which was converted to the acetate 26.
Iodoboration13 of 26 gave the alkenyl iodide 27.14
ether structures has been developed based on a NiII/CrII-mediated
cross-coupling reaction of alkenyl iodides with aldehydes. The
present method allowed coupling to oxane rings via acetal cycliza-
tion and reductive etherification reactions.
Key words: coupling reactions, tetrahydropyrans, polyethers,
toxins
The reductive intramolecular coupling of hydroxy-ke-
tones in reactions with silane-Lewis acids (SI-LA) to gen-
erate oxane rings in C-linked oxacycles is affected by the
conformational preference of the hemiacetal intermedi-
ates.1 This finding implies that the convergent synthesis of
trans-fused polyethers may be conducted on driving ring
closure of hydroxy-ketones to oxane rings under thermo-
dynamic conditions. Recently, we have shown2 that SI-
LA-induced reductive cleavage of the anomeric center in
allyl spiroketals can be conducted chemo-, regio- and ste-
reoselectively to give C-linked oxacycles. As a part of a
larger project to synthesize trans-fused polyethers related
to ciguatoxin and congeners,3 both reductively conducted
possibilities are being considered4 (Scheme 1). In this
communication, we report on results related to the 5
1
cyclization approach based on very simple models. Our
synthetic plan began with the NiII/CrII-mediated coupling5
between fragments 9 and 10 followed by oxidation to the
, -unsaturated ketone 8. These reactions establish all the
requisite framework which should allow us to study se-
quentially the double SI-LA reductive process.
Scheme 1
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346
M. T. Díaz et al.
LETTER
Scheme 2 Preparation of intermediate 27. Reagents and conditions: (a) i, 1.2 equiv of Ph3PCHCO2Me, THF, 80ºC, 5 h, 99%; ii, 1.5 equiv of
Me2C(OMe)2, CSA cat., CH2Cl2, 40ºC, 12 h, 93%, iii, 1.4 equiv of TBSOTf, 2.0 equiv of Et3N, CH2Cl2, 0-25ºC, 1 h, 98%; iv, 2.5 equiv of
DIBAL-H, Et2O, 0-25ºC, 5 h, 81%. (b) 0.3 equiv of Ti (O-i-Pr)4, 0.2 equiv of (-)-diethyl tartrate, 3.0 equiv of t-BuOOH (5-6 N in decane), 4
Å MS, CH2Cl2, -20ºC, 24 h, 90%. (c) 1.1 equiv of TsCl, 0.05 equiv of 4-DMAP, 2.0 equiv of Et3N, CH2Cl2, 0-25ºC, 3 h, 98%. (d) 2.3 equiv
of NaI, 2.0 equiv of NaHCO3, butanone, 60ºC, 2 h, 97%. (e) i, 2.0 equiv of t-BuLi, Et2O, -78ºC, 30 min, 94%; ii, 1.1 equiv of BnBr, 1.1 equiv
of NaH, (n-Bu)4NI cat., THF, 0-25ºC, 12 h, 93%. (f) i, 3.0 equiv of NMO, OsO4 cat., THF-H2O-acetone (1:1:1), 25ºC, 12 h, 91%; ii, H2, Pd
(C) 5% cat., EtOAc, 12 h, 99%; iii, 1.5 equiv of (n-Bu)4 NIO4, CH2Cl2, 0-25ºC; iv, 3.0 equiv of PCC, 0.3 equiv of NaOAc, 3 Å MS, CH2Cl2,
25ºC, 12 h, 80%. (g) i, 1.2 equiv of allylmagnesium bromide, THF, -78ºC, 1 h; ii, 1.5 equiv of Et3SiH, 1.5 equiv of TMSOTf, CH2Cl2, -78ºC,
5 h, 68%. (h) i, 1.6 equiv of NaH, 3.3 equiv of CS2, 1.8 equiv of MeI, imidazole cat., THF, 0-20ºC, 1 h; ii, 1.5 equiv of Bu3SnH, AIBN cat.,
toluene, 110ºC, 36 h, 87% (two steps); iii, 0.1 equiv of AcOH, 0.5 equiv of HCl 1N, 60ºC, 48 h, 69%; iv, 3.0 equiv of (COCl)2, 9.0 equiv of
DMSO, 15.0 equiv of Et3N, CH2Cl2, -78-0ºC, 2 h, 70%. (i) i, 1.1 equiv of allylmagnesium bromide, THF, -78ºC, 1 h; ii, 1.5 equiv of Et3SiH,
1.5 equiv of BF3·Et2O, CH2Cl2, 0ºC, 2 h, 64% (two steps). (j) i, Na, NH3 liq, THF, -60ºC, 2 h, 100%; ii, 1.5 equiv of 2,2-dimethoxypropane,
POCl3 cat., DMF, 20ºC, 12 h, 60%; iii, 1.2 equiv of t-BuMe2SiCl, 2.5 equiv of imidazole, CH2Cl2, 20ºC, 48 h, 96%. (k) i, 1.5 equiv of 4-me-
thylmorpholine N-oxide, OsO4 cat., H2O: THF (1:1), 20ºC, 12 h; ii, 1.5 equiv of NaIO4, MeOH: H2O (8:1), 0ºC, 90% (two steps); iii, 4.0 equiv
of Ph3P, 2.0 equiv of CBr4, 5.0 equiv of Et3N, CH2Cl2, hexane, 0ºC, 3 h, 97%. (l) 1.0 equiv of n-BuLi, THF, -78ºC, 2 h, 65%. (m) 1.3 equiv of
n-BuLi, THF, 0ºC, 2 h, 98%. (n) 1.5 equiv of Ac2O, 2.5 equiv of Et3N, DMAP cat., CH2Cl2, 20ºC, 2 h, 89%. (o) i, 1.2 equiv of B-I-9-BBN (1.0
M in hexane), n-pentane, -20-20ºC, 8 h, then 0.02 equiv of AcOH, 0ºC, 30 min, then NaOH, H2O2 35%, 0ºC, 30 min; ii, 1.5 equiv of 2,2-
dimethoxypropane, POCl3 cat., CH2Cl2, 20ºC, 12 h; iii, 1.5 equiv of Ac2O, 2.5 equiv of Et3N, DMAP catalyst, CH2Cl2, 20ºC, 1 h, 53% (three
steps).
For the synthesis of aldehyde 33 (Scheme 3), diol 2815 was
selectively protected involving 1,3-benzylidene ketaliza-
tion followed by DIBAL-H reduction to give 30. Tosyl-
ation and displacement of the tosyl group with cyanide
provided 32 which was further reduced to the aldehyde 33
(62% overall yield).
The completion of the synthesis is shown in Scheme 4.
The NiII/CrII-mediated coupling5 of 27 with 33 proceeded
smoothly to yield the two expected allylic alcohols, which
were oxidized to the , -unsaturated ketone 34.16 Subse-
quent ozonolysis led to diketone 35. Base-induced hydro-
lysis of diketone 35 gave hemiacetal 37. Debenzylation of
35 gave hemiacetal 36. Hemiacetals 36 and 37 were inde-
pendently converted to the common bis-hemiacetal 38.
Scheme 3 Preparation of aldehyde 33. Reagents and conditions:
(a) 1.5 equiv of PhCH(OMe)2, 0.01 equiv of CSA, DMF, 50ºC, 3 h,
85%. (b) 3.0 equiv of DIBAL-H, CH2Cl2, 0ºC, 24 h, 97%. (c) 1.2
equiv of TsCl, 0.05 equiv of 4-DMAP, 1.5 equiv of Et3N, CH2Cl2,
25ºC, 24 h, 100%. (d) 3.0 equiv of KCN, DMSO, 60ºC, 24 h, 87%.
(e) 1.5 equiv of DIBAL-H, Et2O, 20ºC, 12 h, 86%.
O-Methylation of bis-hemiacetal 38 under the base condi-
tions reported by Mori1j gave the methyl diacetal 39,
which was doubly reduced by SI-LA treatment to the tet-
racyclic diol 40, further protected as its dibenzyl ether de-
rivative 41.1j
Synlett 2001, No. 3, 345–348 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Convergent Synthesis of trans-Fused Oxane Ring Systems
347
Tetrahedron Lett. 2000, 41, 507-508. (i) Matsuo, G.; Hinou,
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(3) (a) Murata, M.; Legrand, A.-M.; Ishibashi, Y.; Yasumoto, T.
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(4) For previous studies by our group, see: Brouard, I.; Hanxing,
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(5) For a recent review, see: Fürstner, A. Chem. Rev. 1999, 99,
991-1045.
(6) Katsuki, T.; Sharpless, K.B. J. Am. Chem. Soc. 1980, 102,
5974-5976.
(7) Under base conditions the silyl group is quantitatively
transferred to the allylic alkoxide.
(8) Zheng, W.; De Mattei, J.; Wu, J.-P.; Duan, J.J.-W.; Cook, L.
R.; Oinuma, H.; Kishi, Y. J. Am. Chem. Soc. 1996, 118, 7946-
7968.
Scheme 4 Synthesis of compound 41.1j Reagents and conditions:
(a) i, 4.0 equiv of CrCl2, 0.1 equiv of NiCl2, DMSO, 20ºC, 12 h, 86%;
ii, 3.0 equiv of oxalyl chloride, 9.0 equiv of DMSO, 15.0 equiv of
Et3N, CH2Cl2, -78°C, 2 h, 96%. (b) O3, CH2Cl2, -78ºC, 20 min, then
3.0 equiv of Ph3P, 20°C, 1 h, 56-60%. (c) 1.1 equiv of K2CO3, Me-
OH, 20ºC, 2 h, 79%. (d) H2, Pd-C 10% cat., EtOAc, 20ºC, 2 h, 55-
63%. (e) 2.5 equiv of NaH, 5.0 equiv of MeI, DMF, 0ºC, 6 h, 62%.
(f) 10.0 equiv of Et3SiH, 4.0 equiv of TMSOTf, CH2Cl2, 0ºC, 3 h,
66%. (g) 2.5 equiv of BnBr, 2.5 equiv of NaH, n-Bu4NI (cat.), THF-
DMF (3:1), 25ºC, 3 h, 76%.
(9) Koto, S.; Takebe, Y.; Zen, S. Bull. Chem. Soc. Jpn. 1972, 45,
291-293.
(10) Barton, D. H. R.; Mc Combie, S.W. J. Chem. Soc., Perkin
Trans. 1 1975, 1574-1585. For a review on this subject, for
example, see: Hartwig, W. Tetrahedron 1983, 39, 2609-2645.
(11) Corey, E. J.; Fuch, P. L. Tetrahedron Lett. 1972, 3769-3772.
(12) When iodoboration is conducted on acetylene 24 the expected
alkenyl iodide is obtained although in very poor yield (5-
10%).
(13) Hara, S.; Dojo, H.; Takinami, S.; Suzuki, A. Tetrahedron Lett.
1983, 24, 731-734.
The present strategy will be extended for synthesizing
polycyclic marine toxins, which will be reported in due
course.
(14) Data for selected compounds included in Scheme 2: 17:
colorless foam. [ ]27D +14.5 (c 4.93, CHCl3). 1H NMR (400
MHz, CDCl3) 4.53 (1H, dd, J = 7.7, 7.7 Hz, H-5), 4.46 (1H,
ddd, J = 3.6, 7.6, 8.4 Hz, H-3), 4.20 (1H, ddd, J = 5.3, 6.9, 8.4
Hz, H-2), 4.11 (1H, dd, J = 6.9, 8.7 Hz, H-1), 3.77 (1H, dd,
J = 5.3, 8.7 Hz, H-1), 2.44 (1H, ddd, J = 3.6, 7.7, 13.1 Hz, H-
4), 2.25 (1H, ddd, J = 7.6, 7.6, 13.1 Hz, H-4), 1.45 (3H, s),
1.34 (3H, s), 0,91 (9H, s), 0.16 (3H, s), 0.14 (3H, s). 13C NMR
(100 MHz, CDCl3) 175.4 (Cq, C6), 110.2 (Cq), 77.1 (CH, C3),
76.2 (CH, C2), 67.8 (CH, C5), 66.2 (CH2, C1), 33.1 (CH2, C4),
26.3 (CH3), 25.7 (CH3), 24.6 (CH3), 18.2 (Cq), -4.8 (CH3), -5.3
(CH3). IR (KBr): max 1790 cm-1. Anal. calcd for C15H28O5Si:
Acknowledgement
This work was supported in part by grants-in-aid from MEC (Spain,
PB97-1123) and the Ramón Areces Foundation. M.T.D. thanks the
MEC of Spain for a post-doctoral fellowship. R.L.P.M. thanks
AECI of Spain for a fellowship.
C, 56.93; H, 8.93. Found C, 56.94, H, 8.87. 27: Oil. [ ]20
References and Notes
D
-28.5 (c 1.4, CHCl3). 1H NMR (500 MHz, CDCl3) 6.06 (1H,
brs, H-9), 5.74 (1H, brs, H-9), 4.69 (1H, ddd, J = 4.8, 9.8, 11.0
Hz, H-5), 3.88 (1H, dd, J = 5.2, 10.8 Hz, H-1), 3.65 (1H, dd,
J = 10.8, 10.8 Hz, H-1), 3.62 (1H, ddd, J = 3.5, 8.8, 9.8 Hz, H-
6), 3.59 (1H, ddd, J = 4.2, 9.4, 9.8 Hz, H-3), 3.21 (1H, ddd,
J = 5.2, 9.4, 10.8 Hz, H-2), 2.61 (1H, brdd, J = 3.5, 15.1 Hz,
H-7), 2.44 (1H, brdd, J = 8.8, 15.1 Hz, H-7), 2.35 (1H, ddd,
J = 4.2, 4.8, 11.4 Hz, H-4), 2.04 (3H, s), 1.56 (1H, ddd,
(1) For convergent synthesis of fused polytetrahydropyran
systems via reductive hydroxy-ketone coupling, see: (a)
Alvarez, E.; Pérez, R.; Rodríguez, R. M.; Martín, J. D. J. Org.
Chem. 1996, 61, 3003-3016. (b) Nicolau, K. C.; Postema, M.
H. D.; Claiborne, C. F. J. Am. Chem. Soc. 1996, 118, 1565-
1566. (c) Sasaki, M.; Fuwa, H.; Inoue, M.; Tachibana, K.
Tetrahedron Lett. 1998, 39, 9027-9030. (d) Fujiwara, K.;
Saka, K.; Takaoka, D.; Murai, A. Synlett 1999, 1037-1040. (e)
Takemoto, Y.; Furose, S.-I.; Hayase, H.; Echigo, T.; Iwata, C.;
Tanaka, T.; Ibuka, T.; J. C. S., Chem. Commun. 1999, 2515-
2516. (f) Sasaki, M.; Fuwa, H.; Ishikawa, M.; Tachibana, K.
Org. Lett. 1999, 1, 1075-1077. (g) Sasaki, M.; Noguchi, K.;
Fuwa, H.; Tachibana, K. Tetrahedron Lett. 2000, 41, 1425-
1428. (h) Fujiwara, K.; Morishita, H.; Saka, K.; Murai, A.
J = 11.4, 11.4, 11.4 Hz, H-4), 1.45 (3H, s), 1.37 (3H, s). 13
C
NMR (125 MHz, CDCl3) 169.9 (Cq), 128.1 (CH2, C9), 105.6
(Cq, C8), 99.3 (Cq), 77.9 (CH, C6), 74.4 (CH, C2), 70.0 (CH,
C5), 68.4 (CH, C3), 62.6 (CH2, C1), 47.4 (CH2, C7), 35.3 (CH2,
C4), 29.1 (CH3), 21.1 (CH3), 19.1 (CH3). HRMS calcd for the
deacetylated derivative C12H19IO4, m/z M+ 354.03281. Found,
354.03317.
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M. T. Díaz et al.
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(15) Nicolaou, K. C.; Hwang, C.-K.; Marron, B. E.; De Frees, S.
A.; Couladouros, E. A.; Abe, Y.; Carrol, P. J.; Snyder, J. P. J.
Am. Chem. Soc. 1990, 112, 3040-3054.
10.7 Hz, H-2), 3.17 (1H, ddd, J = 4.2, 7.0, 9.8 Hz, H-11), 2.84
(1H, J = 9.8, 13.5 Hz, H-10), 2.67 (1H, dd, J = 5.0, 13.5 Hz,
H-10), 2.39 (1H, brddd, J = 4.4, 5.0, 11.2 Hz, H-4), 2.31 (1H,
brdd, J = 2.0, 15.0 Hz, H-13), 2.10-2.03 (1H, m, H-7), 2.04
(3H, s), 1.77 (1H, brdd, J = 8.0, 15.0 Hz, H-13), 1.78-1.70
(2H, m, 2 H-14), 1.47 (1H, ddd, J = 11.2, 12.0, 12.0 Hz, H-
(16) Data for selected compounds included in Scheme 4: , -
Unsaturated ketone 34: Oil. [ ]20D +0.02 (c 0.55, CHCl3).1H
NMR (500 MHz, CDCl3) 7.32-7.26 (5H, m, H), 5.98 (1H,
s, CH), 5.78 (1H, s, CH), 4.62 (1H, d, J = 11.7 Hz, CH),
4.58 (1H, ddd, J = 4.9, 9.8, 9.8 Hz, H-5), 4.39 (1H, d, J = 11.7
Hz, CH), 3.82 (1H, brd, J = 11.5 Hz, H-15), 3.79 (1H, dd,
J = 5.2, 10.8 Hz, H-1), 3.71 (1H, ddd, J = 3.0, 8.9, 8.9 Hz, H-
11), 3.58 (1H, dd, J = 10.8, 10.8 Hz, H-1), 3.56 (1H, ddd,
J = 4.1, 9.4, 11.6 Hz, H-3), 3.48 (1H, ddd, J = 3.0, 9.8, 9.3 Hz,
H-6), 3.35 (1H, ddd, J = 2.7, 11.5, 11.7 Hz, H-15), 3.14 (1H,
ddd, J = 5.2, 9.4, 10.8 Hz, H-2), 3.09 (1H, dd, J = 3.0, 15.8 Hz,
H-10), 3.08 (1H, ddd, J = 5.0, 8.9, 9.3 Hz, H-12), 2.75 (1H, dd,
J = 8.9, 15.8 Hz, H-10), 2.66 (1H, brdd, J = 2.2, 14.7 Hz, H-
7), 2.32 (1H, ddd, J = 4.5, 4.5, 11.3 Hz, H-4), 2.28 (1H, brd,
J = 12.4 Hz, H-13), 2.18 (1H, dd, J = 8.9, 14.7 Hz, H-7), 2.03
(3H, s), 1.70-1.65 (1H, m, H-14), 1.63-1.56 (1H, m, H-14),
1.47 (1H, ddd, J = 11.3, 11.3, 11.3 Hz, H-4), 1.43 (3H, s),
1.44-1.38 (1H, m, H-13), 1.36 (3H, s). 13C NMR (125 MHz,
CDCl3) 199.6 (Cq, C9), 170.1 (Cq), 144.8 (Cq, C8), 138.4
(Cq), 128.4 (CH), 127.8 (CH), 127.7 (CH), 126.6 (CH2), 99.2
(Cq), 77.6 (CH, C6), 77.6 (CH, C11), 76.8 (CH, C2), 74.1 (CH,
C12), 70.8 (CH, C5), 70.4 (CH2), 68.5 (CH, C3), 67.8 (CH2,
C15), 62.6 (CH2, C1), 40.9 (CH2, C10), 35.2 (CH2, C4), 33.4
(CH2, C7), 29.7 (CH2, C13), 29.1 (CH3), 25.3 (CH2, C14), 21.1
(CH3), 19.1 (CH3). HRMS, calcd for C28H38O8 m/z M+
4), 1.46 (3H, s), 1.40-1.36 (1H, m, H-7), 1.37 (3H, s). 13
C
NMR (125 MHz, CDCl3) 201.5 (Cq, C9), 169.7 (Cq), 99.5
(Cq), 97.2 (Cq, C8), 78.1 (CH, C11), 77.7 (CH, C6), 74.8 (CH,
C2), 69.8 (CH, C5), 69.6 (CH, C12), 68.1 (CH, C3), 67.7 (CH2,
C15), 62.3 (CH2, C1), 42.3 (CH2, C10), 35.2 (CH2, C13), 35.0
(CH2, C4), 29.0 (CH2, CH3), 29.0 (CH2, C7), 25.2 (CH2, C14),
21.0 (CH3), 19.0 (CH3). HRMS, calcd for C20H30O9 m/z M+
414.18898. Found, m/z 414.18778. 37: 1H NMR (500 MHz,
CDCl3) 7.35-7.26 (5H, m, H), 4.61 (1H, d, J = 11.4 Hz,
CH), 4.46 (1H, d, J = 11.4 Hz, CH), 4.10 (1H, ddd, J = 4.4,
9.5, 11.8 Hz, H-5), 3.88 (1H, dd, J = 5.1, 10.7 Hz, H-1), 3.88
(1H, dd, J = 5.1, 10.7 Hz, H-15), 3.69-3.64 (1H, m, H-3), 3.68
(1H, dd, J = 10.5, 10.7 Hz, H-1), 3.63 (1H, ddd, J = 5.0, 5.4,
10.1 Hz, H-11), 3.36-3.26 (3H, m, H-6, H-12, H-15), 3.20
(1H, ddd, J = 5.2, 10.0, 10.5 Hz, H-2), 2.85 (1H, dd, J = 12.3,
12.5 Hz, H-7), 2.70 (1H, dd, J = 5.1, 13.5 Hz, H-7), 2.47 (1H,
dd, J = 5.0, 15.1 Hz, H-10), 2.26 (1H, brddd, J = 4.1, 4.1, 11.4
Hz, H-13), 2.24 (1H, brd, J = 11.8 Hz, H-4), 1.86 (1H, dd,
J = 5.0, 15.1 Hz, H-10), 1.70-1.60 (2H, m, 2 H-14), 1.56
(1H, ddd, J = 11.4, 11.4, 11.8 Hz, H-4), 1.53 (1H, brs, C9-OH),
1.48 (3H, s), 1.43-1.34 (1H, m, H-13), 1.39 (3H, s). 13C NMR
(125 MHz, CDCl3) 200.9 (Cq, C8), 137.6 (Cq), 128.5 (CH),
128.1 (CH), 99.4 (Cq), 96.7, (Cq, C9), 77.9 (CH, C11), 77.7
(CH, C6), 77.0 (CH, C12), 73.6 (CH, C2), 70.7 (CH2), 69.4
(CH, C3), 68.1 (CH, C5), 68.0 (CH2, C15), 62.6 (CH2, C1), 41.9
(CH2, C7), 36.7 (CH2, C10), 35.0 (CH2, C4), 29.2 (CH3), 29.0
(CH2, C13), 25.1 (CH2, C14), 19.1 (CH3). 39: 1H NMR (500
MHz, CDCl3) 3.90 (1H, brd, J = 11.0 Hz, H-15), 3.87 (1H,
dd, J = 5.1, 10.8 Hz, H-1), 3.67 (1H, dd, J = 10.8, 10.8 Hz, H-
1), 3.63 (1H, ddd, J = 4.1, 11.0, 11.2 Hz, H-3), 3.49 (1H, ddd,
J = 4.0, 9.2, 11.2 Hz, H-5), 3.38 (1H, ddd, J = 5.0, 11.0, 13.0
Hz, H-12), 3.36-3.33 (1H, m, H-15), 3.29 (1H, ddd, J = 5.2,
11.2, 11.7 Hz, H-6), 3.26 (6H, s, 2 CH3O), 3.20 (1H, ddd,
J = 5.1, 10.8, 11.0 Hz, H-2), 3.14 (1H, ddd, J = 5.0, 9.5, 11.0
Hz, H-11), 2.19-2.13 (3H, m, H-4, H-7, H-10), 1.96 (1H, dd,
J = 11.7, 11.7 Hz, H-7), 1.96-1.93 (1H, m, H-13), 1.93 (1H,
dd, J = 11.0, 11.0 Hz, H-10), 1.75-1.70 (2H, m, 2 H-14),
1.64 (1H, ddd, J = 11.2, 11.2, 11.2 Hz, H-4), 1.56-1.52 (1H,
m, H-13), 1.46 (3H, s, CH3), 1.39 (3H, s, CH3).). 13C NMR
(125 MHz, CDCl3) 99.3 (Cq), 98.6 (Cq, C8), 98.4 (Cq, C9),
76.2 (CH, C6), 76.2 (CH, C11), 75.2 (CH, C2) 70.7, (CH, C12),
69.8 (CH, C3), 69.1 (CH, C5), 68.3 (CH2, C15), 62.7 (CH2, C1),
47.3 (CH3, CH3O), 47.2 (CH3, CH3O), 34.7 (CH2, C4), 29.5
(CH2, C7), 29.3 (CH2, C10), 29.2 (CH3), 28.8 (CH2, C13), 25.9
(CH2, C14), 19.1 (CH3). HRMS, calcd for C20H32O8, m/z M+
400.20968. Found, m/z 400.20963.
502.25667. Found, m/z 502.25632. Diketone 35: Oil. [ ]20
D
-8.9 (c 0.59, CHCl3) 1H NMR (500 MHz, CDCl3) 7.32-7.23
(5H, m, H), 4.55 (1H, ddd, J = 4.4, 9.3, 11.2 Hz, H-5), 4.54
(1H, d, J = 11.5 Hz, CH), 4.33 (1H, d, J = 11.5 Hz, CH),
3.86 (1H, ddd, J = 3.3, 9.3, 9.3 Hz, H-6), 3.80 (1H, brdd,
J = 4.5, 11.4 Hz, H-15), 3.76 (1H, dd, J = 5.3, 10.8 Hz, H-1),
3.68 (1H, ddd, J = 5.6, 7.8, 8.8 Hz, H-11), 3.58-3.52 (2H, m,
H-1, H-3), 3.32 (1H, ddd, J = 2.7, 11.7, 11.7 Hz, H-15), 3.15
(1H, ddd, J = 5.0, 10.0, 10.0 Hz, H-2), 3.11 (1H, ddd, J = 4.4,
9.3, 10.6 Hz, H-12), 3.02 (1H, dd, J = 5.5, 15.3 Hz, H-10),
2.90 (1H, dd, J = 7.7, 15.3 Hz, H-10), 2.78 (1H, dd, J = 8.9,
16.7 Hz, H-7), 2.62 (1H, dd, J = 3.4, 16.7 Hz, H-7), 2.36 (1H,
ddd, J = 4.4, 4.4, 11.2 Hz, H-4), 2.24 (1H, brdd, J = 3.0, 12.2
Hz, H-13), 1.98 (3H, s), 1.68-1.62 (1H, m, H-14), 1.60-1.57
(1H, m, H-14), 1.47 (1H, ddd, J = 11.2, 11.2, 11.2 Hz, H-4),
1.46 (3H, s), 1.37-1.34 (1H, m, H-13), 1.35 (3H, s). 13C NMR
(125 MHz, CDCl3) 196.7 (Cq, C8), 196.5 (Cq, C9), 137.9
(Cq), 128.5 (CH), 128.4 (CH), 127.9 (CH), 127.8 (CH), 99.3
(Cq), 77.4 (CH, C12), 77.3 (CH, C11), 75.1 (CH, C6), 74.4 (CH,
C2), 70.5 (CH, C5), 70.4 (CH2), 68.3 (CH, C3), 67.8 (CH2, C15),
62.4 (CH2, C1), 40.1 (CH2, C10), 38.5 (CH2, C7), 35.1 (CH2,
C4), 29.1 (CH3), 29.0 (CH2, C13), 25.2 (CH2, C14), 21.0 (CH3),
19.1 (CH3). HRMS calcd for C27H36O9 m/z 504.23561. 36:
Colorless foam [ ]20D -22.5 (c, 0.32, CHCl3). 1H NMR (500
MHz, CDCl3) 4.82 (1H, ddd, J = 4.4, 10.7, 11.2 Hz, H-5),
3.95-3.88 (3H, m, H-6, H-12, H-15), 3.84 (1H, dd, J = 5.2,
10.7 Hz, H-1), 3.67-3.60 (2H, m, H-1, H-3), 3.35 (1H, ddd,
J = 3.3, 11.0, 11.0 Hz, H-15), 3.22 (1H, ddd, J = 4.8, 10.7,
Article Identifier:
1437-2096,E;2001,0,03,0345,0348,ftx,en;L21200ST.pdf
Synlett 2001, No. 3, 345–348 ISSN 0936-5214 © Thieme Stuttgart · New York