2,9-Dioxabicyclo nonane synthesis

An interesting multicomponent domino free radical reaction in which five new bonds are formed in one operation has recently been applied in the total synthesis ofyingzhaosu A by Bachi and coworkers. Thus, a 2,3-dioxabicyclo[3.3.1]nonane system reacts with phenylthiol and 2 equiv. of molecular oxygen in the presence of AIBN, which under irradiation with UV light led to a diastereomeric mixture of en-doperoxide-hydroperoxides [127]. 

More recently, Bachi and coworkers extended and adapted the TOCO reaction to the synthesis of 2,3-dioxabicyclo[3.3.1]nonane derivatives hke 228 (Scheme 52) ° ° . As detailed in Scheme 53a, the bridged bicyclic hydroperoxide-endoperoxides hke 229 are obtained, from (S )-limonene (227), in a 4-component one-operation free-radical domino reaction in which 5 new bonds are sequentially formed. Particular experimental conditions are required in order to reduce the formation of by-products 230 and (PhS)2, and to favor the critical 6-exo-ring closure of peroxy-radical 231 to carbon-centered radical 232206 chemoselective reduction of bridged bicyclic hydroperoxide-endoperoxides... 

As in the case of the 1,2-dioxins, the 1,2-dithiins exist in various states of saturation, oxidation, and benzoannelation (cf. Scheme 1, 17-27) and they have been studied in detail both theoretically and experimentally. Not only were the conformations of the ring and attached substituents investigated, but the valence isomerism of 1,2-dithiin by both NMR and high-level ab initio molecular orbital (MO) calculations and the dithiol/disulfide equilibrium by MP2 calculations were also examined. The latter equilibrium has been applied successfully as a luminescent molecular switch (cf. Section 8.10.2.1). Finally, as a very interesting 1,2-dithiin derivative, the synthesis, structure, and reactivity of the (-l-)-camphor-derived analog 25 and its sulfoxide 26 and sulfone 27 have been reported. Both the synthesis and the antimalarial activity of the 2,3-dioxabicyclo[3.3.1]nonane pharmacophore 28, which contains the 1,2-dioxane moiety, have been reviewed recently <2006BML2991>. 

A synthesis of the 2,3-dioxabicyclo[3.3.1]nonane system 24, which is present in the antimalarial yingzhaosu, involves an initial thiol-limonene co-oxygenation reaction followed by reduction of a hydroperoxide by PPh3 and a sulfenyl —> sulfonyl oxidation <02T2449>. 

A very short asymmetric synthesis of an insect attractant, (lS,35,5f )-l,3-dimethyl-2,9-dioxabicyclo[3.3.1]nonane, has been realized with high enantio- and diastereo-selectivity by means of an (5)-3f-mediated aldol reaction strategy (Eq. 52) [43c]. This compound is a host-specific substance for the ambrosia beetle that infests the bark of the Norway spruce. 

A Concise Approach to (-)-Tirandamycin A (2) and (+)-Tirandamycic Acid (3). Tirandamycin A (2) is a representative member of a novel class of naturally-occurring antibiotics that are characterized by the presence of an enolized 3-dienoyl tetramic acid moiety coupled with the unusual dioxabicyclo[3.3.1]nonane ring system. In addition to its antimicrobial activity, 2 inhibits bacterial DNA-directed RNA polymerase, and it interferes with oxidative phosphorylation. Early synthetic work in this area focused upon the preparation of (+)-tirandamycic acid (3), " which is a degradation product of tirandamycin A (2). The first major achievement in this area was Ireland s synthesis of 3 from D-glucose, but more recently 2 has also been prepared by total synthesisOur own investigations in this area culminated in a facile, asymmetric synthesis of 26, which played a pivotal role in Ireland s synthesis of 2 and Schlessinger s synthesis of 3. ... 

Scheme 17 Synthesis of l-hydroxy-8-aza-2,3-dioxabicyclo[4.3.0]nonan-9-ones...

Demole, E., and C. Demole A Chemical Study of Burley Tobacco Flavour Nicotiana tabacum L.). VII. Identification and Synthesis of Twelve Irregular Terpenoids Related to Solanone Including 7,8-Dioxabicyclo[3.2.1] octane and 4,9-Dioxabicyclo[3.3.1]nonane Derivatives Helv. Chim. Acta 58, 1867 (1975). 

Kamata, M., Ohta, M., Komatsu, K., Kim, H.-S., and Wataya, Y., Synthesis, Fe(Il)-induced degradation and antimalarial activities of l,5-diaryl-6,7-dioxabicyclo(3.2.2]nonanes direct evidence for nucleophihc 0-l,2-aryl shifts. Tetrahedron Lett., 43, 2063, 2002. 

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