Bicyclo heptenes, synthesis

The necessity for producing large amounts of synthetic prostaglandins and analogs provided the impetus for a number of improvements in the bicyclo[2.2.1]heptene approach. Especially important was the development of an enantioselective modification for the synthesis of chiral prostanoids without resolution (1975) and the invention of a chiral catalyst for the stereocontrolled conversion of 15-keto prostanoids to either 15(5)- or 15(7 )- alcohols. 

A modification of the bicyclo[2.2.1]heptene route to PC s was developed in which the omega chain was introduced at the end of the synthesis, for the purpose of facilitating the preparation of large numbers of omega-chain-differentiated PG analogs of either the first or second PG family. 

With the growing interest for the polynorbomene, photoresist polymer, and cyclic olefin copolymer, the synthesis norbornene or bicyclo[2,2,l]-2-heptene (NBN) has drawn significant attention because it is one of the most important precursor for these materials. Norbornene is produced by the reaction between ethylene and cyclopentadiene (CPD) via the Diels-Alder condensation process at elevated temperature and pressure [1,2]. 

Electrocyclic closure of butadiene units encased within cycloheptane rings has been used to obtain bicyclo[3.2.0]heptene systems (Scheme 5)12. For example, irradiation of eucarvone 21 led to the formation of adduct 22 in 52% yield via a disrotatory ring closure123. This adduct was used as a key intermediate in the synthesis of the pheromone grandisol, 23, which proceeded in 20% overall yield from 22. In their synthesis of a-lumicolchicine. Chapman and coworkers utilized a photochemically initiated four-electron disrotatory photocyclization of colchicine to produce /Murnicolchicine 24a and its /-isomer 24b in a 2 1 ratio12b. These adducts were then converted, in a second photochemical step, to the anti head-to-head dimer a-lumicolchicine 25. 

Bicyclo[2.2.1]hepten-7-one is a useful intermediate in the synthesis of a variety of norbornane derivatives. The present procedure involves a four-step synthesis from hexachlorocyclo-pentadiene with a 39% overall yield. The next best method3 involves a four-step synthesis from norbornadiene with a 15% overall yield. 

M. Green, J. A. K. Howard, J. L. Spencer, and F. G. A. Stone, Synthesis of Ethylene, Cyclo-octa- 1,5-diene, Bicyclo [2.2.1]heptene, and trans-Cyclo-octene Complexes of Palladium ) and Platinum(O) Crystal and Molecular Structure of Tris(bicyclo2.2.1]hepte-ne)platinum, J. Chem. Soc., Dalton Trans. 1977, 271-277. 

The range of cyclopropenes made by this route is not large and they are mostly simple alkylated cyclopropenes, but they do include a few not readily available in other ways most notably the bicyclo[4.1.0]heptenes 1 and the equivalent bicyclo[5.1.0]octenes. ° " The synthesis of the unstable 7,7-dimethylbicyclo[4.1.0]heptene (1) serves to illustrate an unusual side reaction sometimes encountered in the photolysis of 3/7-pyrazoles, namely formation of the valence tautomer The reaction is only observed at low temperatures and, as shown, the balance... 

The interest of the early synthetic and structural conundrums posed by camphor (40) (cf. Vol. 2, p. 149) are well illustrated in a profile of Julius Bredt. Three unusual bicyclo[2.2.1]heptenes, 772, have been characterized from lavender oil there is nothing spectacular about their synthesis, since they are... 

Reaction of several bicyclo[2,2,l]heptenes with phenyl(trichloromethyl)mer-cury reveals the fact that born-2-ene (281) (the synthesis of which has just appeared in Organic Syntheses ) is completely unreactive to this substance, because steric hindrance prevents the cxo-attack required by torsional strain. The labelled bornyl-isobornyl Grignard mixture (282) undergoes cis-exo eliminative transfer to phenyl isopropyl ketone, although to a lesser extent than in the norbornyl system, this probably being a reflection of the fact that the gem-dimethyl group reduces the energy difference between exo- and e/ido-transfer. ... 

The conversion of the bicyclo[2,2,l]heptene aldehydes (475) into PGp2a via the aldehyde (476) has previously required a number of protection and deprotection steps. An improved procedure for the conversion (475) - PGp2 in seven steps that avoids the need to prepare (476) or for protection has now been described. A new procedure for oxidative decarboxylation has been introduced that is of relevance in prostaglandin synthesis.Diels-Alder reaction between 5-cyclopentadienylmethyl methyl ether... 

A full report has been published on the chemistry of the highly functionalized bicyclo[3.2.0]heptene (90), reaction of which with diazoethane gives a mixture ica. 7 3) of the useful ring-expanded products (91) and (92). A synthesis of another potential precursor (93) of polycyclopentanoids has also been reported. ... 

The Claisen rearrangement of the orthoester of a bicyclo[2.2.1]heptene intermediate has been used in a synthesis and in a practical preparation of a 3-methylpenta-2,4-dienoate. ... 

Ramberg-Backlund reactions, discussed in more detail in Chapters 1 and 2, continue to be of great significance in the synthesis of strained alkenes. Bicyclo-[2,2,l]heptenes, [4,2,2]propellanes, 1,4-tetramethylene- and 1,4-penta-methylene-Dewar-benzene, and the ethylene ketal of hydrindane-3,6-dien-l-one have been prepared, utilizing this rearrangement as the final step. 2,5-Dialkyl-sulpholans have been converted, in synthetically useful yields (20— 67%), into 1,2-dialkyl-cyclobutenes upon reaction with Bu Li in THF followed by reduction with LiAlH4. This most interesting reaction has been applied to the preparation of a wide variety of fused benzocyclobutenes. ... 

Chao C-M, Beltrami D, Toullec PY, Michelet V (2009) Asymmetric Au(I)-catalyzed synthesis of bicyclo[4.1.0]heptene derivatives via a cycloisomerization process of... 

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