Norbomadiene synthesis

Synthesis. The unsymmetrical norbomadiene substituted pz (34) (Scheme 7) (34%) (36), was prepared by a mixed cyclization of benzonorbomadiene phthalonitrile (32) (93) with a sevenfold excess of dipropylmaleonitrile (33) (28) (Scheme 7). 

This method is applicable to the efficient synthesis of 2,5-norbomadiene, which can be obtained in low yield by anodic decarboxylation of 5-norbomene-2,3-dicarboxylic acid (equation 43)47. 

The Homo Diels-Alder Reaction of Norbomadiene with Acetylenes. [2 + 2+2] Cycloadditions of dienes such as norbomadiene with the double bonds in 1,4-position are called homo Diels-Alder reactions. Using an in situ catalyst (consisting of Co(acac)3-Et2AlCl-bis(diphenylphosphino)ethane) the products obtained with monosubstituted acetylenes, such as phenyl, i-propyl-, n-butyl-, t-butyl-, and trimethylsilylacetylene, are 4-substituted deltacyclenes. - In the formation of the polycyclic deltacyclene skeleton, six new stereo centers are generated in one step. Thus enantiocontrol by using optically active phosphine ligands as cocatalysts allows the synthesis of optically active cycloadducts, as shown for the reaction of norbomadiene with phenylacetylene to give 4-phenyldeltacyclene (eq 1). 

Oda et al. have reported a ternary coupling involving norbomadiene, a vinyltin and a vinyl iodide (Scheme 4-25), which is proposed as a model for leukotriene synthesis [71]. 

Osmium tetraoxide has also been used in the oxidation of bicyclic and polycyclic dienes. Thus, oxidation of norbomadiene (26) in a stoichiometric reaction was found to yield the exo-cis diol exclusively. On the other hand, in the NMO catalytic system a mixture of the exo-cis and endo-cis products was reported. However, by use of the NMO catalytic procedure for the substituted norbomadiene 27, the exc-diol was formed exclusively at the sterically crowded unsubstituted double bond and this product was utilized in the synthesis of pentalenolactone. Somewhat surprisingly, oxidation of hexamethyl Dewar benzene (28) exclusively gave the endo-cis diol as sole product. The tricyclic compound 29 gave the usual c/s-diol oxidation product of one of the double bonds. ... 

The synthesis of a mixed double cycloadduct 16 is possible by either allowing 11 to react with LitBu in the presence of norbomadiene or by reaction of 13 with Li/Bu and anthracene (Scheme 6). 

Only limited data are available for the kinetics of oxo synthesis with the water-soluble catalyst HRh(CO)(TPPTS)3. The hydroformylation of 1-octene was studied in a two-phase system in presence of ethanol as a co-solvent to enhance the solubility of the olefin in the aqueous phase [115]. A rate expression was developed which was nearly identical to that of the homogeneous system, the exception being a slight correction for low hydrogen partial pressures. The lack of data is obvious and surprising at this time, when the Ruhrchemie/ Rhone-Pou-lenc process has been in operation for more than ten years [116]. Other kinetic studies on rhodium-catalyzed hydroformylation have been published, too. They involve rhodium catalysts such as [Rh(nbd)Cl]2 (nbd = norbomadiene) [117] or [Rh(SBu )(CO)P(OMe)3]2 [118], or phosphites as ligands [119, 120]. 

A particularly useful synthesis of cyclopentanones involves the coupling of an alkene, an alkyne and carbon monoxide in the presence of dicobalt octacarbonyl (equation 17). The reaction proceeds via an al-kyne-cobalt complex (7) and with relatively unreactive alkenes such as cyclopentene it is preferable to synthesize the complex in a separate step. With highly strained alkenes such as norbomadiene, how-... 

The cycloaddition between cyclopentadiene and Bu3SnC=CCHO can be catalysed by a chiral Lewis acid to give the norbomadiene with 80% ee, and then reactions at the stannyl group can lead to the synthesis of other chiral bicycloheptadienes 74... 

The incorporation of sulphonyl groups does not inhibit the cyclization process as demonstrated by Gleiter and Ohlbach, who have reported the efficient synthesis of the quadricyclane 252 by irradiation of the norbomadiene derivatives 253. A study has also been made of the sulphonyl-substituted norbomadiene derivatives 254 ... 

Norbomadiene may be carbonylated essentially under the conditions of Reppe s acrylic ester synthesis. Cycloheptenecarboboxylates (XVIII)... 

Numerous synthetic applications of the inteimolecular Pauson-Khand reaction have been reported. Pauson has reported a number of very direct tqrplications of cycloadditions of ethylene in the synthesis of prostanoids and jasmone analogs (e.g. equations 15 and 16). - This is a reliable entry to 2-sub-stituted cyclopentenones. The suitability of cyclopentene and dihydrofuran as substrates has permitted the extension of this work to the preparation of still further varieties of prostaglandin analogs (e.g. equations 27 and 51). Simple 4,5-disubstituted 2-cyclopentenones are not as directly accessible, but may be prepared from the cycloaddition products of norbomadiene (equation 45). A sequence of conjugate addition followed by retro-Diels-Alder reaction affords the product (Scheme 5). Dihydrofuran cycloadditions have been used by Billington in the syntheses of the antibiotic methylenomycin B (Scheme 6), as well as cyclomethylenomycin A (synthetic precursor to the antibiotic methylenomycin A), cyclosarko-mycin (precursor to the antitumor agent sarkomycin) ° and the iridoid Jq>anese hop ether. ... 

The Prins reaction with formaldehyde is a well-known route to prostaglandins using bicyclic lactone 3 as a precursor. One synthesis of this lactone14 started this sequence with a Prins reaction. Treatment of norbomadiene with paraformaldehyde in the presence of formic acid produced a mixture of epimeric diformates in 67% yield which were transformed in several steps into lactone 3. A second synthesis starts with the unsaturated bicyclic lactone which undergoes attack by the oxonium ion both regio- and stereoselectively from the less hindered face of the double bond, trims Addition of the nucleophilic acetate generates the lactone 3 as the bisacetate derivative15. 

---