Bicyclo octanones synthesis

Bicyclic cyclotrigermanes, thermolysis, 3, 793 Bicyclic imidazoles, via intramolecular C-H functionalizations, 10, 138 Bicyclic siloxanes, rational synthesis, 3, 655 Bicycloctasilane dianion, preparation, 3, 466468 Bicyclo[5.3.0]decadiene, via [5+2]-cycloadditions, 10, 613 Bicyclo[5,3,0]-decanes, via Pauson-Khand reaction, 11, 361 Bicyclononasilane anions, preparation, 3, 466-468 Bicyclo[3.3.0]-octanones, via carbonylative carbocyclization, 11, 427... 

Interestingly, zirconacyclopentane 246 formed by the reaction of 1,6-heptadiene with the Zr complex has the firms ring junction mainly [108]. It should be noted that the preparation of the trans ring junction in the bicyclo[3.3.0]octane system by other means is difficult. Carbonylation of 246 affords trans-fuzed bicyclo[3.3.0]octanone 247 [109,111]. The diacetoxy compound 248 is obtained by oxidative cleavage of 246. Protonation affords the frans-dimethylcyclopentane skeleton. Similar reactions occur with 1,6-enynes, and Pauson Khand-type cyclopentenone synthesis is possible by carbonylation. 

The alkylation of acyclic imines with electrophilic alkenes such as acrylonitrile, methyl acrylate or phenyl vinyl sulphone is also sensitive to steric effects and again, as a consequence, only mono-alkylation occurs398. The regioselectivity of the reaction in methanol varied from 100% attack at the more substituted a-position to 70% attack at the less substituted a -position depending upon the steric inhibition manifested and the stabilization of the competing secondary enamine tautomers (vide infra) (Scheme 204). In contrast, the reaction of butanone and other methyl ketone imines with phenyl vinyl ketone occurs twice at the more substituted a-position but this is then followed by a double cyclization process (Scheme 205). Four carbon-carbon bonds are formed sequentially in this one-pot synthesis of the bicyclo[2.2.2]octanone 205 from acyclic precursors399,400. 

Tandem Oxidative Cydization of 4 to Afford 8. The utility of tandem cyclizations in which both addends are alkenes was demonstrated in the synthesis of bicyclo[3.2.1]octanone 8 (29, 36, 47). Oxidation of 4 with 2 equivalents of Mn(OAc)3 and 1 equivalent of Cu(OAc)2 in acetic acid afforded 86% of 8. Oxidation of 4 generated the a-keto radical 5 that underwent 6-endo cydization to afford tertiary radical 6. 5-Exo cydization of 5-hexenyl radical 6 provided primary radical 7 as a 2 1 mixture of exo and endo isomers. Oxidation of both stereoisomers of 7 by Cu(OAc)2 yielded alkene 8 and Cu(OAc), which was reoxidized to Cu(OAc)2 by the second equivalent of Mn(OAc)3. This process is therefore catalytic in Cu(OAc)2 but consumes 2 equivalents of Mn(OAc)3. Since this reaction proceeded selectively in very high yield, our initial goal was to make this reaction catalytic in Mn(OAc)3 by either electrochemical or chemical oxidative regeneration of Mn(ni) in the reaction mixture. 

Scheme 245 Enantioselective organocatalytic multicomponent synthesis of 2,6-diaza-bicyclo[2.2.2]octanones.

A number of transannular reactions have been applied in the synthesis of bicyclo[3,3,0]octanes from appropriately functionalized cyclo-octanes. Thus, treatment of the cyclo-octanone (111) with lithium in ammonia leads to the ketol (112), and reaction of the epoxide (113) with lithium diethylamide in ether-hexane gives largely (114). The base-catalysed rearrangement of (115) leads to the fused five-membered ring system (117) by way of the transient cyclo-octanone (116). °... 

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