Isotwistane

The convenient generation of bicyclo[2.2.2]octenones through the use of ortho-quinol derivatives in Diels-Alder reactions recently inspired Wood and co-workers in their studies toward the total synthesis of CP-263,114 (110) [148]. They relied on the Wessely-Yates tandem oxidative acetoxylation/intramolecular Diels-Alder sequence to build bicyclo[2.2.2]octenones such as 114 en route to advanced isotwistane intermediates such as 111b, which could eventually be fragmented to furnish the carbocyclic core of 110 (i.e. 111a —> 110, Figure 29) [149-153],... 

Corey EJ, Pearce HL (1979) Total Synthesis of Picrotoxinin. J Am Chem Soc 101 5842 Niwa H, Wakamatsu K, Hida T, Niiyama K, Kigoshi H, Yamada M, Nagase H, Suzuki M, Yamada K (1984) Stereocontrolled Total Synthesis of (—)-Picrotoxinin and (-i)-Coriamyrtin via a Common Isotwistane Intermediate. J Am Chem Soc 106 4547 Miyashita M, Suzuki T, Yoshikoshi A (1989) Selective Total Synthesis of (—)-Picrotoxinin and (—)-Picrotin. J Am Chem Soc 111 3728... 

In the laboratory of J.L. Wood, an expeditious approach to the densely functionalized isotwistane core of CP-263,114 was developed. For the proposed radical cyclization, an exo-methylene group was installed on a five-membered lactone ring. It was discovered that both the formation of the lactone ring and the Eschenmoser methenylation could be conducted in a one-pot operation by simply treating the a-acetoxy ketone with excess amounts of LiTMP and then with Eschenmoser s salt. 

Restriction among the great number of possible dihetero-tricyclodecanes to such with a carbocyclic 8-membered ring (cyclooctane) as basic skeleton, which is crosswise bridged by two heteroatoms, and restriction to 5-, 6- and 7-membered heterocyclic rings, isomeric dihetero-tricyclodecanes of the following five different stmctural types are possible 2,6-dihetero-adamantane (G 7 ) 2,7-dihetero-isotwistane (G 2,7-dihetero-twistane (G S) 2,8-dihetero-homotwistbrendane (G 4) and 2,6-dihetero-tricyclo[3.3.2.0 Jdecane (G 5) . 

The first synthesis of a tricyclo[4.3.1.0 ]decane, namely of pure carbocyclic iso-twistane [G 2 X(2) = CHj, Y(7) = CHj ], was reported by Vogt S in 1968. Almost at the same time 2,7-dihetero-isotwistanes (G 2) and/or derivatives thereof became available. Today a variety of such compounds are known ... 

Heating a solution of the syn-exo-diepoxide 74 in 0.5N HCl yielded 61% of N(6)-phenylsulfonyl4 8 -dihydroxy-2 -oxa-6-aza-adamantane (76) as the sole tricyclic compound, which was also characterized as its diacetate 49. Analogous treatment of the anti-epoxide 75 led to a mixture of adamantane-diol 76 (48%) and the isomeric N(7)-phenylsulfonyl-4 l0 -dihydroxy-2-oxa-7-aza-isotwistane (77) (22%). Both diols were also converted to the corresponding diacetates 49 and 78 K... 

Syntheses of various 2,7-dihetero-isotwistanes by bridging suitable bicyclononanes were successful applying one or several of the pathways F-M. Ring closures occurred either by nucleophilic attack at a double bond (in G 15, G 16 and G 7 7), at a carbonyl carbon (in G 20) and at an epoxide ring (in G 21 and G 22) or by substitution of a leaving group (in G 75 and G 79). 

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