Oxocane 2,8-disubstituted

The Baeyer-Villiger oxidation can be used to convert large ring cyclic ketones to macrocyclic lactones, Lactones can be precursors of cyclic ethers. Chiral ketone (37) was oxidized to lactone (38) and subsequently stereoselectively converted to the c, r-2,8-disubstituted oxocane (39 Scheme 10). ... 

In the cyclization reactions of homoallylic ethers and higher homologs, alkoxymethyl radicals play a prominent role [26]. Substrates like 28 supply more useful carbon-centered radicals enjoying captodative stabilization, and trany-2,3-disubstituted tet-rahydropyrans were prepared stereoselectively with judicious modification of the double bond in the substrate [27] (Scheme 12). The same radical species from the substrate 30 was reported to give the oxocane 31 via the xanthate transfer %-endo cyclization, from which lauthisan (32) was obtained [28] (Scheme 13). 

The excision of the keto bridge present in tricyclo[5.3.1.1 ]dodecan-l 1-one taken from the work of Cha et al. on synthetic studies of taxol deserves special mention. Highly functionalized derivatives of bicyclo]5.3.1]undecane are obtained using the DIB/I2 system (Eq. 11) [38]. The fragmentation of a related derivative of oxabicyclo[3.3.1]nonan-9-one is used by the same authors as a key step in the synthesis of cK-2,8-disubstituted oxocanes (Eq. 12) [39]. 

Mono-substitution in all but the 5-positioh in oxocane results in a chiral center, accounting for the optical activity in many natural products. (Substitution at the 5-position for some conformations such as the crown or chair-chair would not give rise to a chiral center however, for some boat-chair and other less symmetric conformations, a chiral center could be generated. This issue appears not to have been specifically addressed in the literature.) The base-catalyzed isomerization of some 2,8-disubstituted oxocane derivatives has been studied. It has been found that the c -geometry is preferred over the trans-geometry <88TL4333). 

Tebbe reagent, Ti(Cp)2(/i-CH2, n-Cl)AI(CH3)2 reacts with 8-alkyl-2-oxocanones (30) to give the unstable 2-exo-methylenalated species (31). Reduction of (31) with borane-THF, followed by oxidation with hydrogen peroxide yields the 2,8-disubstituted oxocanes (32) (Scheme 2). The predominant product is the c/s-alcohol (32) favored by a ratio of ca. 10 1 over the trans-alcohol <86CC565>. This synthetic strategy was applied to the syntheses of both lauthisan and laurenan. 

Carling, R.W. and Holmes, A.B. (1986) A new synthetic method for the preparation of 2,8-disubstituted oxocane derivatives synthesis of lauthisan and laurenan. /. Chem. Soc. Chem. Commun., 565-567. 

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