Silicon Tether-Aided Coupling Metathesis:  Application to the Synthesis of Attenol A

Abstract

A new synthesis of attenol A is described. Key features of this work include a crucial silicon tether-aided coupling metathesis step and the use of iodoetherification as an efficient protection method for 1,5-ene-ols. [reaction: see text]

Temporary Silicon–Tethered Ring–Closing Metathesis Reactions in Natural Product Synthesis

“…Additional studies by the same group utilized a similar sequence for the construction of the spiro [5,4]ketal present in attenol A (Scheme 8.6) [23]. The unsymmetrical bis-alkoxysilane 23 was prepared from the epimeric allylic alcohol 21 and the secondary alcohol 22 as a mixture of diastereoisomers.…”

Functionalized organolithium compounds in total synthesis

“…55 The above-mentioned b-elimination of generated b-oxido alkyllithiums can also be synthetically useful as shown in Scheme 21, where b-oxygenated organolithium 115, generated by treatment of the corresponding iodomethylpyran with n-butyllithium, suffers ring opening to give alcohol 116 which can be transformed, after deprotection of the p-methoxybenzyl group using dichlorodicyanoquinone (DDQ), into attenol A (117) a metabolite of the Chinese bivalve Pinna attenuata with moderate cytotoxicity against P388 cells. 56 3.2. b-Functionalized sp 2 -hybridized organolithiums 1-Lithio-2-alkoxyethenes, generally obtained from the corresponding brominated precursors by alkyllithium-promoted bromine/lithium exchange at low temperature, can be considered as acetaldehyde enolates, the Z-isomer showing much higher thermal stability than its corresponding E counterpart. 57 A recent example of their use in total synthesis is shown in Scheme 22, where (Z)-1-lithio-2-ethoxyethene (119) is employed in the Cr(CO) 3 -promoted dearomatization which takes place in benzaldehyde/Dvalinol-derived complex 118.…”

A Centennial Methodology for the Preparation of Heterocyclic Compounds: The Intramolecular Coiodination of Alkenes with Internal Oxygenated Nucleophiles

“…A recent preparation of attenol A, a naturally spiroketal which exhibits moderate cytotoxity against P388 cells, was published by a French group [50]. One step of the synthesis is the intramolecular coiodination of the 5-alkene-1-ol (26) to produce a tetrahydropyran derivative (Scheme 14).…”