2-Cyclopentadecanone synthesis

Synthesis of Optically Pure Chiral Lactones by Cyclopentadecanone Monooxygenase-catalyzed Baeyer-Villiger Oxidations... 

A cyclopentadecanone (V/74) and a ( )-muscone (V/70) synthesis were carried out by another method related to the reactions discussed in this Chapter. Scheme V/12 shows the thermal transformation of the cyclododecanone derivative, V/71, to V/74 [39], The proposed mechanism for this conversion presumably includes a [1.5] hydrogen shift, followed by a [3.3] sigmatropic rearrangement. 

There exists also a synthesis of cyclopentadecanone (VII/81) and ( )-mus-cone, based on a three-carbon annulation of cyclic ketones followed by the regioselective radical cleavage of the zero bridge of the so formed bicyclic system [44], The synthesis of cyclopentadecanone is summarized in Scheme VII/16. The cyclization of VII/78 to the bicyclic alcohol VII/79 proceeds best (94 % yield) with samarium diiodide in the presence of hexamethylphosphoric acid triamide and tetrahydrofuran [45], The oxidative cleavage of VII/79 to the ring expanded product VII/80, was performed by treatment with mercury(II)-oxide and iodine in benzene, followed by irradiation with a 100 Watt high pressure mercury arc. Tributyltinhydride made the de-iodination possible. 

Scheme VII/16. Synthesis of cyclopentadecanone (VII/81) by //-fission of the bicyclic zero bridge [44],...

Cheap and readily available cyclopentadecanone is alpha-brominated to (30) and ketalised with (29), and the resulting a-bromoketal (31) subjected to base induced elimination of HBr, giving (32). The key asymmetric step is now at hand. The Simmons-Smith cyclopropanation proceeds with very high facial selectivity, giving almost entirely the diastereomer of (33) shown. The result is rationalised on the basis of zinc chelation by the oxygens of the ketal. The synthesis is completed by acid hydrolysis of the ketal (the chiral diol may be recovered for reuse), reductive opening of the cyclopropane ring under Birch conditions, and re-oxidation of the alcohol back to the ketone. 

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