Cycloaddition precursor cyclopentenes

The synthesis of new 11-deoxyprostaglandin analogs with a cyclopentane fragment in the oo-chain, prostanoid 418, has been accomplished by a reaction sequence involving nitrile oxide generation from the nitromethyl derivative of 2-(oo-carbomethoxyhexyl)-2-cyclopenten-l-one, its 1,3-cycloaddition to cyclopenten-l-one and reductive transformations of these cycloadducts (459). Diastereoisomers of a new prostanoid precursor 419 with a 4,5,6,6a-tetrahydro-3aH-cyclopent[d isoxazole fragment in the oo-chain have been synthesized. Reduction of 419 gives novel 11-deoxyprostanoids with modified a- and oo-chains (460). 

Highly alkylated l-chloro-2-(trimethylsilyl)cyclopentenes 44, which are of interest as possible cyclopentyne precursors, were prepared by reacting 3-chloro-3-methyl-l-(trimethylsilyl)but-l-yne (45) with 1,1-dialkylated or 1,1,2-trialkylated ethylenes in the presence of titanium tetrachloride35. Because of the low S/v 1 reactivity of 45, the yields of the products were moderate. The stepwise [3 + 2]-cycloaddition mechanism discussed above was proven by the isolation of the intermediate acyclic adduct (in 74% yield) when 45 and isobutene were reacted in the presence of BCI3. Under these conditions, the intermediate 46 could be trapped by Cl since BCI4 is more nucleophilic than TiC.15 (equation 16). 

A total synthesis of the sesquiterpene ( )-illudin C 420 has been described. The tricyclic ring system of the natural product is readily quickly assembled from cyclopropane and cyclopentene precursors via a novel oxime dianion coupling reaction and a subsequent intramolecular nitrile oxide—olefin cycloaddition (463). 

Butyn-2-one undergoes tandem [3+2] cycloadditions of allyltriisopropylsilane to give a bicyclo[3.3.0]octane as a mixture of three possible diastereomers in a good yield (Scheme 10.169) [468]. The use of a reduced amount of the allylsilane forms a silylated cyclopentene as a minor product. This indicates that the 1 1 cycloadduct is the precursor of the bicyclic product. In contrast, the ZnL or Me2AlCl-promoted reaction of 3-butyn-2-one with an isocyclic allyltrimethylsilane affords a [2+2] adduct wifhout [3+2] adducts [448a, 469] (vide infra). 

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 Diels-Alder reaction of these chiral dioxinones with cyclopentadiene has provided a highly stereoselective route to carbocyclic C-nucleoside precursors (27) (Scheme 11) <89CPB2615>. The [2 + 2] cycloaddition of the same menthone-derived dioxinone with cyclopentene has also been observed <87CPB3539>. 

When carbene 21 is generated from the diazo precursor photochemically in solution, it reacts with added alcohols by 0,H insertion (equation 55), in contrast to the gas-phase copyrolysis where the silene intermediate is trapped . Similarly, photolysis of 20 in the presence of 2,3-dimethylbutadiene gives mainly vinylcyclopropane 184, while after copyrolysis of 20 and the same diene one finds that most of the vinylcyclopropane rearranged to the cyclopentene, together with the [4-1-2] cycloaddition product of diene and silene 22 °. Furthermore carbene 21, generated photochemically or thermally (at 117-148 °C) in solution, undergoes [1 4-2] cycloaddition to alkynes to give cyclopropenes 185. 

The first models for asymmetric induction in [2 + 2] cycloadditions are ketimines derived from precursors such as (25), which react with both cyclic and acyclic alkenes to give adducts with high enantiomeric excesses. Full details have been reported on the regio- and stereo-specificity of the addition of dichloroketene to 1-substituted cyclohexenes. Methyl (phenylthiomethyl)-ketene (26) provides a further example of a ketene which, after cycloaddition to cyclopentadiene, undergoes facile opening of the cyclobutane that is thus formed to provide vicinally substituted cyclopentene derivatives. ... 

---