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Cyclobutylidenecyclopropane: New Synthesis and Use in 1,3‐Dipolar Cycloadditions − A Direct Route to Spirocyclopropane‐Annulated Azepinone Derivatives
Author(s) -
de Meijere Armin,
von Seebach Malte,
Kozhushkov Sergei I.,
Boese Roland,
Bläser Dieter,
Cicchi Stefano,
Dimoulas Tula,
Brandi Alberto
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200110)2001:20<3789::aid-ejoc3789>3.0.co;2-o
Subject(s) - chemistry , flash vacuum pyrolysis , regioselectivity , yield (engineering) , nitrone , ring (chemistry) , adduct , medicinal chemistry , stereochemistry , pyrolysis , cycloaddition , organic chemistry , catalysis , materials science , metallurgy
Cyclobutylidenecyclopropane ( 7 ) was prepared in multigram quantities by a new three‐step sequence starting from ethyl cyclobutanecarboxylate ( 4 ) (39% overall yield). 1,3‐Dipolar cycloadditions of phenyl‐ ( 9 ), pyridyl‐ ( 10 ), and the newly prepared (four steps, 43% overall yield) spirocyclic nitrone 11 onto 7 resulted in the regioselective formation of the corresponding adducts 15−17 , with the spirobutane moieties adjacent to the oxygen atom in the oxazolidine rings, in 52, 84, and 48% yields, respectively. Under flash vacuum pyrolysis conditions, the cycloadducts 15−17 underwent thermal rearrangement with opening of the four‐membered ring, to afford the spirocyclopropanated azepinones 21−23 in 32, 30, and 19% yields, respectively. In the case of 17 , the indolizidinone 25 was also isolated (13% yield). Mechanistically this rearrangement is interpreted in terms of a cyclobutylmethyl‐to‐penten‐5‐yl radical rearrangement.