Cycloadditions bicyclo octenone

Recognizing that intermediates in the [5 + 2]-reaction of VCPs and 7r-systems could be trapped with other components, Wender and co-workers reported a three-component [5 + 2 + l]-cycloaddition involving VCPs, alkynes, and CO that provide efficient access to densely functionalized bicyclo[3.3.0]octenones via a cyclooctadienone intermediate (Scheme 55).129 This reaction converts three commercially available materials to bicyclic products and creates two stereocenters and four C-C bonds. 

The normally sluggish Diels-Alder cycloaddition between cyclohexa-1,3-diene and various enones and enals can be activated by precoordination of the diene to a jt-basic molybdenum complex TpMo(NO)MeIm(//-cyclohexadiene)].134 The 4-1-2-cycloaddition of cyclohexa-2,4-dienones with electron-deficient 2n -dienophiles produced bridged bicyclo[2.2.2]octenones. Triplet-sensitized irradiation of these bridged bicyclooctenones produced bicyclo[3.3.0]octanoids, whereas direct irradiation yielded bicyclo[4.2.0]octanes.135... 

Recently, the reaction of masked ortho-benzoquinone [92] with C60 was tested [93]. The [4+2] cycloaddition reaction of such electron-deficient dienes with fullerenes resulted in the formation of highly functionalized bicyclo [2.2.2] octenone-fused fullerenes. The reactants were generated in situ by the oxidation of the readily available 2-methoxy phenols with hypervalent iodine agents. For the several different masked ortho-benzoquinones that were tested, it was found that the yield of the cycloadducts depends on the nature of the starting materials and the reaction conditions. Other Diels-Alder reactions of such electron-deficient dienes with electron-poor fullerenes involved tropones [94], 1,3-butadienes substituted with electron-withdrawing groups [95], and 2-pyrone [96]. 

Another early success of the (TpRe(CO)(MeIm) fragment was the promotion of Diels-Alder cycloaddition reactions with benzene and anisole. Complex 101 [TpRe(CO)(MeIm)( 2-benzene)] undergoes an endo-selective Diels-Alder reaction with N-methylmaleimide to afford the bound bicyclo[2.2.2]octadiene complex 102 in 65 % yield (Scheme 12) [40]. Oxidation of 102 yields the bicyclo[2.2.2]octadiene 103 and/or the bicyclo[2.2.2]octenone 104 depending upon the choice of oxidation conditions. 

The (1S,5R)-2-oxabicydo-octenone (see Fig. 5) is formed with 96% ee from one ketone enantiomer of racemic bicyclo[3.2.0]hept-2-en-6-one, which is synthesized in a cycloaddition reaction from cyclopentadiene and dichloroacetylchloride with subsequent Zn-reduction. The key limitation to the biocatalytic Baeyer-Villiger process is product inhibition [26]. In order to overcome product inhibition problems, in situ product removal was required. 

This bicyclo[3.3.0]octenone preparation has been employed in numerous natural product syntheses. Scheme 5-4 shows an early adaption of one of the cycloadditions shown in Eq. (53) toward the synthesis of the linearly fused triquinane system in coriolin. The substitutional and stereochemical characteristics built in by the Pauson-Khand process lend themselves to a very efficient approach [120]. Angularly fused triquinanes have also been prepared by closing the third ring onto a bicyclic Pauson-Khand product [121]. 

MOBs reactive with cyclohexa-2,4-dienones undergo Diels-Alder cycloadditions with [60]fullerene to produce hitherto unknown, stable, and highly functionalized bicyclo-[2.2.2]-octenone derivatives. In light of the mild conditions and considerable generality, these reactions are certainly noteworthy... 

Cycloaddition. In 2002, a three-component [5+2+1] cycloaddition of vinyl-cyclopropane 199 (VCP), alkynes 200, and carbon monoxide using [Rh(CO)2Cl]2 as catalyst was reported by Wender and co-workers (162). The process initially leads to an eight-membered ring 201, which upon hydrolytic workup yields bicyclo[3.3.0] octenone products 202 in good to excellent yields (Scheme 90). The process was found to be more efficient with the use of carbonyl-activated alkynes. NMR and x-ray studies of products indicated that CO insertion occurred... 

A formal [5+2] cycloaddition starts from cyclohexenones and propargyl acetates (Scheme 5-181) (see also 2.4). In this case, bicyclo[3.2.1]octenones were produced in good yield and good overall stereoselectivity. 

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