LrgpV1, Main, Exploration, bibRecord, 000884

Total Synthesis of Laulimalide: Synthesis of the Northern and Southern Fragments

Identifieur interne : 000884 ( Main/Exploration ); précédent : 000883; suivant : 000885

Total Synthesis of Laulimalide: Synthesis of the Northern and Southern Fragments

Auteurs : Barry M. Trost [États-Unis] ; W. Michael Seganish ; Cheol K. Chung ; Dominique Amans

Source :

Chemistry – A European Journal [ 0947-6539 ] ; 2012-03-05.

RBID : ISTEX:A03AA1263ACCDF87A242126D348D42D3F5FD416C

English descriptors

KwdEn :
- Acetal, Acylpyrrole, Aldehyde, Aldol, Aldol products, Aldol reaction, Alkene, Alkyne, Angew, Bidentate, Bidentate phosphine, Bromide, Carbonate, Cdcl3, Chem, Column chromatography, Cyclization, Cycloisomerization, Cycloisomerization reaction, Dihydropyran, Dinuclear, Dinuclear zinc aldol reaction, Diol, Diyne, Diyne substrate, Epoxide, Ester, Ether, Flash column chromatography, Fragment, Gmbh, Hydroxyl, Hydroxyl group, Isomer, Kgaa, Laulimalide, Lett, Ligand, Lithium, Matsunaga, Mmol, Molecular sieves, Natural product, Northern fragment, Olefin, Optimization, Phosphine, Pyrrole, Reaction conditions, Reaction mixture, Retrosynthetic analysis, Room temperature, Selectivity, Shibasaki, Southern fragment, Sulfone, Tetrahedron, Tetrahedron lett, Total synthesis, Trost, Verlag, Verlag gmbh, Weinheim, Weinheim chem.
Teeft :
- Acetal, Acylpyrrole, Aldehyde, Aldol, Aldol products, Aldol reaction, Alkene, Alkyne, Angew, Bidentate, Bidentate phosphine, Bromide, Carbonate, Cdcl3, Chem, Column chromatography, Cyclization, Cycloisomerization, Cycloisomerization reaction, Dihydropyran, Dinuclear, Dinuclear zinc aldol reaction, Diol, Diyne, Diyne substrate, Epoxide, Ester, Ether, Flash column chromatography, Fragment, Gmbh, Hydroxyl, Hydroxyl group, Isomer, Kgaa, Laulimalide, Lett, Ligand, Lithium, Matsunaga, Mmol, Molecular sieves, Natural product, Northern fragment, Olefin, Optimization, Phosphine, Pyrrole, Reaction conditions, Reaction mixture, Retrosynthetic analysis, Room temperature, Selectivity, Shibasaki, Southern fragment, Sulfone, Tetrahedron, Tetrahedron lett, Total synthesis, Trost, Verlag, Verlag gmbh, Weinheim, Weinheim chem.

Abstract

The first stage in the development of a synthetic route for the total synthesis of laulimalide (1) is described. Our retrosynthetic analysis envisioned a novel macrocyclization route to the natural product by using a Ru‐catalyzed alkene–alkyne coupling. This would be preceded by an esterification of the C19 hydroxyl group, joining together two equally sized synthons, the northern fragment 7 and the southern fragment 8. Our first generation approach to the northern fragment entailed a key sequential Ru/Pd coupling sequence to assemble the dihydropyran. The key reactions proceeded smoothly, but the inability to achieve a key olefin migration led to the development of an alternative route based on an asymmetric dinuclear Zn‐catalyzed aldol reaction of a hydroxyl acylpyrrole. This key reaction led to the desired diol adduct 66 with excellent syn/anti selectivity (10:1), and allowed for the successful completion of the northern fragment 7. The key step for the synthesis of the southern fragment was a chemoselective Rh‐catalyzed cycloisomerization reaction to form the dihydropyran ring from a diyne precursor. This reaction proved to be selective for the formation of a six‐membered ring, over a seven. The use of an electron‐deficient bidentate phosphine allowed for the reaction to proceed with a reduced catalyst loading.

Url:

DOI: 10.1002/chem.201102898

Affiliations:

États-Unis

Le document en format XML

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<front><div type="abstract">The first stage in the development of a synthetic route for the total synthesis of laulimalide (1) is described. Our retrosynthetic analysis envisioned a novel macrocyclization route to the natural product by using a Ru‐catalyzed alkene–alkyne coupling. This would be preceded by an esterification of the C19 hydroxyl group, joining together two equally sized synthons, the northern fragment 7 and the southern fragment 8. Our first generation approach to the northern fragment entailed a key sequential Ru/Pd coupling sequence to assemble the dihydropyran. The key reactions proceeded smoothly, but the inability to achieve a key olefin migration led to the development of an alternative route based on an asymmetric dinuclear Zn‐catalyzed aldol reaction of a hydroxyl acylpyrrole. This key reaction led to the desired diol adduct 66 with excellent syn/anti selectivity (10:1), and allowed for the successful completion of the northern fragment 7. The key step for the synthesis of the southern fragment was a chemoselective Rh‐catalyzed cycloisomerization reaction to form the dihydropyran ring from a diyne precursor. This reaction proved to be selective for the formation of a six‐membered ring, over a seven. The use of an electron‐deficient bidentate phosphine allowed for the reaction to proceed with a reduced catalyst loading.</div>
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Total Synthesis of Laulimalide: Synthesis of the Northern and Southern Fragments

Total Synthesis of Laulimalide: Synthesis of the Northern and Southern Fragments

Source :

English descriptors

Abstract

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