1107602-24-3Relevant academic research and scientific papers
The combination of diallylboration and ring-closing metathesis in the synthesis of spiro-β-amino alcohols and (±)-cephalotaxine
Kuznetsov, Nikolai Yu.,Kolomnikova, Galina D.,Khrustalev, Victor N.,Golovanov, Denis G.,Bubnov, Yuri N.
, p. 5647 - 5655 (2008)
A convenient and practical methodology for the preparation of various spiro-β-amino alcohols has been elaborated. The approach involves allylboration and ring-closing methathesis to prepare spirobicyclic compounds and their subsequent modification to spiro-β-amino alcohols containing four- to six-membered azacycles. N-Boc-protected azaspirocyclic olefins reacted with NBS in solvent under reflux to give tricyclic bromocyclocarbamates. The structure of one of the bromides was established by single-crystal X-ray analysis. The dehydrobromination of the tricyclic bromides with tBuOK produced olefins in good yields, which underwent allylic-type rearrangement in the presence of MgBr2Et2O. Alkaline hydrolysis of the rearranged carbamates led to diastereomerically pure spiro-β-amino alcohols. The structure of the dimethyl-substituted amino alcohol was proved by single-crystal X-ray analysis. rac-(5R*,6S*)-1-Azaspiro[4.4]non-7- en-6-ol was used in the formal synthesis of cephalotaxine. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
Construction of mononitrogen heterocycles with a combined system of 1-azaspiro[4.n]alkene and 3-benzazocine fragments through the intramolecular eight-membered Heck cyclization
Kuznetsov,Khrustalev,Bubnov
scheme or table, p. 1393 - 1399 (2011/04/16)
Amides, obtained from 1-azaspiro[4.n]alkenes (n = 3, 4, 5) and 2-(6-bromo-1,3-benzo-dioxol-5-yl)acetyl chloride, upon heating with a Herrmann-Beller palladium catalyst undergo intramolecular cyclization by the Heck reaction to form pentacyclic compounds (up to 94% yield) including an 1-azaspiro[4.n]alkene (n = 4, 5) fragment and a new eight-membered 3-benzazocine ring. The structure of the thus obtained pentacycles with the 1-azaspiro[4.4]non-7-ene fragment is isomeric to the structure of the main core of alkaloid cephalotaxine. In the case of 1-azaspiro[4.5]dec-2-ene derivative, the reaction is accompanied by the reduction of bromo amide, with the yield of the cyclization product being 34%. The starting 1-azaspiro-[4.n]alkenes (n = 3, 4, 5) were synthesized by the reductive diallylboration of 3-chloropropion- itrile or the corresponding lactams (piperidin-2-one, (2S)-2-hydroxymethyl-and 5,5-di-methylpyrrolidin-2-one) with subsequent intramolecular metathesis upon the action of Grubbs catalyst.
