Cyclopentenone imines

An intramolecular reaction of 1,5- and 1,6-enynes with isonitriles takes place in the presence of Ni(COD>2 (COD = 1,5-cyclooctadiene) and phosphines, giving bicyclic cyclopentenone imines (equation 5). Stereochemical characteristics in substituted systems appear to pardlel those in the intramolecular Pauson-Khand enynes with substituents in propargylic positions cyclize preferentially to products in which those substituents occupy exo positions relative to the newly created ring fusion. It is likely that these reactions proceed via similar mechanisms involving insertion into bonds of metallacycles, although the order of incorporation of the three two-electron systems into the precursor to the final product is open to question in the nickel system. 

Bicyclic cyclopentenones. Cyclization of the Pauson-Khand type from enynes is achievable with Ni(cod)j (12 examples, 38-85%). A bulky bis-ketimine ligand and a CO equivalent are present in the reaction medium. For the latter (i-Pr)3SiCN is adequate. The silyl cyanide is in equilibrium with the isocyanide. The primary products are the cyclopentenone imines, which undergo hydrolysis on workup. 

The Nef reaction can also be carried out with reducing agents. Aqueous titanium chloride reduces nitro compounds to imines, which are readily hydrolyzed to carbonyl compounds (Eq. 6.17).28 The Michael addition of nitroalkanes to enones followed by reaction with TiCl3 provides an excellent route to 1,4-diketones and hence to cyclopentenones. For example, cw-jasmone is readily obtained,28 as shown in Eq. 6.18. 

Davis et al. [88] described the asymmetric synthesis of a-substituted primary sulfonamides involving the diastereoselective a-alkylation of N-sulfonylcamphor-imine dianions, while Huart and Ghosez reported an enantioselective synthesis of bicyclic cyclopentenones via a stereoselective 1,4-addition of metallated enan-tiopure sulfonamides to cyclic enones [89]. 

The chiral organocopper compound (186) adds diastereoselectively to 2-methyl-2-cyclopentenone, allowing the preparation of optically active steroid CD-ring building blocks (Scheme 68).202-204 A related method was applied to a synthesis of the steroid skeleton via an intramolecular (transannular) Diels-Alder reaction of a macrocyclic precursor.203 Chiral acetone anion equivalents based on copper azaeno-lates derived from acetone imines were shown to add to cyclic enones with good selectivity (60-80% ee, after hydrolysis).206-208 Even better ee values are obtained with the mixed zincate prepared from (187) and dimethylzinc (Scheme 69). Other highly diastereoselective but synthetically less important 1,4-additions of chiral cuprates to prochiral enones were reported.209-210... 

Asymmetric Michael reactions have heen conducted with assistance of C2-symmetric malonamides derived from (5)-ptohne esters/ 2-Methyl-3,4,5,6-tetrahydropyridine and 2-cyclopentenone are condensed to afford a tricyclic alcohol. The reaction starts from Michael reaction of the endocychc enamine isomer and as the double bond shifts to the exo-cychc position an intramolecular aldol reaction follows. If the imine is hthiated, the initial Michael reaction (CuBr-catalyzed) then involves the exocyclic carbon. ... 

Acetonylation. - The reagent can be used for acetonylation of anions of esters, ketones, enamines, and imines. The methoxyallyl product is hydrolyzed by weak acids to 2-acetonyl derivatives. This process can be used to prepare substituted cyclopentenones (first example). 

A problem is that the Pauson-Khand reaction uses two equivalents of cobalt. More efficient versions, many of them catalytic, using other metals have been developed. These include carbonyl complexes of titanium, molybdenum, tungsten (Scheme 7.15), rhodium and ruthenium (Scheme 7.16). Rhodium, iridium and iron (Scheme 7.17) have also been used with two alkynes to give cyclopentadienones, often as complexes 7.59. A version of the Pauson-Khand reaction employing a nickel catalyst and an isonitrile in place of CO has been developed. The product is an imine, which can be hydrolysed to a cyclopentenone. 

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