Cycloalkanones, ring annulation

SCHEME 16. Ring annulation of cycloalkanones due to Uthiated 3,3-dichloropropene... 

In 1980 we noticed that a samarium Barbier reaction between n-butyl iodide and 2-octanone which needed 8 h at 65 °C could be run in 3 h at room temperature in the presence of a catalytic amount (2 mol%) of ferric chloride [15]. This experiment was inspired by the known catalytic effect of the Fe3+ ion on the Ln2+/Ln3+ conversion [146]. The beneficial influence of the Fe(III) derivative in reactions mediated by Sml2 has been used by several authors in various processes. Thus, Molander et al. described a general procedure for five- and six-mem-bered ring annulation starting from 2-(oo-iodoalkyl) cycloalkanones [ 147]. 

In the first method, a dialkylzinc reagent bearing an acetal moiety at the d-posi-tion is used (Scheme 7.25(b)). The catalytic 1,4-addition is followed by acetal hydrolysis and aldol cyclization of the 4-substituted cycloalkanone, affording 6,6- (92), 6,7-, (93) and 6,8- (94) annulated ring systems with high enantioselectivities (>96% ees) [80]. In addition, dimethyl-substituted decalone 95, with a structure frequently found in natural products, is readily obtained in enantiomerically pure form. 

The 4-(chloromethyl)isoxazole 13, which is readily accessible from 3,5-dimethyloxazole, serves as a C4-building-block in annulations to cycloalkanones (isoxazole annelation according to Stork). The primary step is alkylation leading to product 14, a masked triketone. On hydrogenation, the isoxazole ring is reductively opened and cyclization via the enaminone 15 leads to the enamine 16. On treatment with sodium hydroxide, this is converted into the bicycloenone 17 by hydrolysis, acid fission of the y dicarbonyl system and an intramolecular aldol condensation (analogous to a Robinson annu-lation) ... 

Robinson annulation is a reaction sequence consisting of a Michael addition of a cycloalkanone a-carbanion to an a,[3-unsaturated ketone derivative, followed by al-dol condensation to form the final product, a 2-cyclohexenone ring fused to the... 

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