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DOI: 10.1055/s-2008-1078170
A Cross-Metathesis Approach to the Synthesis of Key Precursor of the Macrolide Core of Rhizoxin D [¹]
Publication History
Publication Date:
10 September 2008 (online)
Abstract
The synthesis of key precursor 5 of the macrolide core of rhizoxin D has been achieved by cross metathesis between two olefinic fragments 6 and 7. Both the olefinic fragments are easily synthesized in a diastereoselective manner from the common precursor 1-benzyloxy-2-methylhex-5-ene-3-ol (8).
Keywords
rhizoxin D - Keck allylation - Crimmins aldol - Takai olefination - cross metathesis
DRL Publication No. 691.
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References and Notes
DRL Publication No. 691.
17
Crystal Data for
Fragment 17
C40H50O4Si1, M = 622.92,
monoclinic, space group P2
1
, a = 14.79
(2) Å, b = 9.29
(1) Å, c = 15.09
(2) Å, β = 102.33 (2)˚, V = 2026 (4) ų, Z = 2, D
c = 1.021
g cm-³, reflections collected = 20735,
unique reflections = 4637, [R
int = 0.0682],
final R indices [I > 2σ(I)]: R
1 = 0.065, wR
2 = 0.114,
CCDC-662327 contains the supplementary crystallographic data for
this letter. These data can be obtained free of charge from The
Cambridge Crystallo-graphic Data Centre via www.ccdc.cam.ac.uk./data_request/cif.
Spectral Data
for 6
[α]D
²³ -21.6
(c 0.5, CHCl3). IR (neat):
2918, 1722, 1614, 1514 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 0.92 (d,
3 H, J = 6.8
Hz), 1.72 (ddd, 1 H, J = 14.0,
10.4, 3.6 Hz), 1.77 (d, 3 H, J = 1.2
Hz), 1.89 (ddd, 1 H, J = 12.0,
9.6, 2.4 Hz), 2.14 (ddd, 1 H, J = 11.6,
6.4, 4.8 Hz), 3.29 (dd, 1 H, J = 9.2,
6.4 Hz), 3.46 (dd, 1 H, J = 10.0,
6.4 Hz), 3.78 (s, 3 H), 3.82 (dd, 1 H, J = 9.2,
4.0 Hz), 4.11 (d, 1 H, J = 10.8,
Hz), 4.30 (d, 1 H, J = 10.8
Hz), 4.46 (m, 2 H), 5.29 (ddd, 1 H, J = 7.2,
4.8, 2.4 Hz), 5.79 (dd, 1 H, J = 10.4,
1.6 Hz), 6.05 (dd, 1 H, J = 17.2,
10.4 Hz), 6.20 (s, 1 H), 6.34 (dd, 1 H, J = 17.2,
1.2 Hz), 6.83 (d, 2 H, J = 8.8
Hz), 7.22 (d, 2 H, J = 8.4
Hz), 7.28 (m, 5 H). ¹³C NMR (50 MHz,
CDCl3): δ = 13.0, 19.1, 35.7, 37.3,
55.2, 70.3, 71.9, 72.6, 72.9, 79.2, 80.0, 113.8, 127.4, 127.5, 128.3,
129.4, 129.6, 130.0, 130.5, 138.4, 148.0, 159.1, 165.5. ESI-HRMS: m/z calcd for C27H33IO5Na [M + Na]+:
587.1270; found: 587.1277.
Synthetic Procedure
and Spectroscopic Data of 5
A mixture of a solution
of 6 (0.035 g, 0.06 mmol) and 7 (0.024 g, 0.123 mmol) in DCE (0.3 mL)
was treated with Grubbs second-generation catalyst (5.25 mg, 0.0056
mmol) and the dark purple solution stirred at reflux temperature
for 48 h. The reaction mixture was then loaded directly on top of a
wet column packed with SiO2 and purified by flash chromatography
(EtOAc-hexane, 1:3) to afford the product 5 (0.036
g, 80%) as light brown oil; [α]D
²³ -22.0
(c 0.1, CHCl3). IR (neat):
3468, 2924, 1712, 1414, 1247 cm-¹. ¹H NMR
(400 MHz, CDCl3): δ = 0.92 (d, 3 H, J = 6.8 Hz),
0.97 (d, 3 H, J = 7.2
Hz), 1.42 (m, 1 H), 1.72 (m, 1 H), 1.77 (s, 3 H), 1.88 (m, 2 H),
2.18 (m, 6 H), 2.71 (dd, 1 H, J = 12.0,
2.0 Hz), 3.30 (dd, 1 H, J = 9.2,
6.4 Hz), 3.45 (dd, 1 H, J = 9.6, 6.4
Hz), 3.62 (dd, 1 H, J = 10.4,
5.2 Hz), 3.71 (dd, 1 H, J = 10.8,
7.6 Hz), 3.78 (s, 3 H), 3.82 (dd, 1 H, J = 8.8,
4.4 Hz), 4.12 (m, 2 H), 4.30 (d, 1 H, J = 10.8),
4.57 (s, 2 H), 5.26 (ddd, 1 H, J = 7.2,
4.8, 2.8 Hz), 5.81 (d, 1 H, J = 15.6
Hz), 6.20 (s, 1 H), 6.79 (m, 1 H), 6.83 (d, 2 H, J = 8.4
Hz), 7.21 (d, 2 H, J = 8.8
Hz), 7.38 (m, 5 H). ¹³C NMR (50 MHz, CDCl3): δ = 10.4,
12.4, 19.0, 30.9, 32.0, 35.4, 35.9, 37.2, 38.5, 39.6, 55.1, 63.9,
70.2, 71.9, 72.6, 72.8, 79.3, 80.0, 80.2, 113.7, 123.9, 127.4, 128.2,
129.2, 129.5, 129.9, 138.3, 144.5, 147.8, 159.0, 165.4, 170.9. ESI-HRMS: m/z calcd for C36H47IO8Na [M + Na]+:
757.2213; found: 757.2210.