Bicyclo octenone

Another example of suprafacial migration with inversion is the rearrangement of bicyclo octenone to give again a ketone and reported by J.A. Berson (1972). 

Intramolecular Pauson-Khand reactions to prepare [3.3.0]-bicyclo-octenones from several 1,6-enynes (eq. 2.11) were reported to occur efficiently in sc C02 using a Co2(CO)8 catalyst (Jeong et ah, 1997). The reactions proceed very well regardless of the substitution pattern of... 

Ikegami and his co-workers route to coriolin starts as far back as cyclo octa-1,3-diene, which is first elaborated to the bicyclo-octenone (66). The third ring in this multi-stage sequence is synthesized by an intramolecular aldol condensation [i.e. (67) - (68)]. 

Intramolecular Friedel-Crafts acylations of olefins also give cycHc a,P-unsaturated cycHc ketones. Cyclopropane fused bicyclo[5.3.0]octenones, thus obtained, were used in the preparation of the marine sesquiterpenes, africanol [53823-07-7] and dactjlol [58542-75-9] (174). 

Ogasawara and coworkers have also published a complete series of threefold anionic domino reactions, all of which are based on an initial retro-aldol process. For instance, starting from chiral bicyclo[3.2.1]octenone 2-437, a formal total synthesis of (-)-morphine (2-445) [233] has been successfully performed (Scheme 2.103) [234]. Transformation of 2-437 into the substrate 2-488, necessary for the domino reaction, was achieved in seven linear steps. The domino process was then initiated by simply refluxing a solution of 2-438 in benzene in the presence of ethy-... 

Another synthesis using in situ-prepared o-benzoquinones has been reported by Liao and coworkers [45]. These authors observed that oxidation of 2-methoxy-phenols 7-92 with DAIB in the presence of unsaturated alcohols 7-93 furnish transient o-benzoquinone monoacetal intermediates, which easily undergo an intramolecular Diels-Alder reaction to provide bicyclo[2.2.2]octenones 7-94 with high regio- and stereoselectivity, as well as in acceptable yields (Scheme 7.25). 

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. 

As indicated in Scheme 57, the formation of the secondary bicyclo[3.3.0]octenone product is thought to occur via an in situ transannular closure of the initially formed cyclooctadienone 185. In some cases, cycloctenediones and the [5 + 2]-cycloadducts are observed as minor products (Equations (33) and (34)). 

Scheme 33. Enzyme-initiated domino reaction to give bicyclo[2.2.2]octenones 164 and 165...

Jeong described desymmetrization of dienynes, such as iV-propargyl-jY-(penta-l,4-dien-3-yl) tosylamides, by the asymmetric Ir(i)-based PK-type reaction. The corresponding vinyl-substituted bicyclo[3,3,0]-octenones were obtained with high diastereoselectivity and enantioselectivity (Equation (36)). ... 

Selectivity for the cyclopentenone formation is improved by an intramolecular version. For example, 1,6-hepta-diyne (256, X = CH2) reacts in benzene with 2molarequiv. of Bu Me2SiH to give two bicyclo[3.3.0]octenones, 257 and 258, in 14% and 63% yield, respectively, at 95 °G under GO (20 atm) pressure.When benzene is replaced by acetonitrile, 258 becomes a sole product (60% yield). On the other hand, the reaction at 25 °G gives normal silylformylation product 259 as a major component (59%) with the concomitant formation of 258 (20%) (Scheme 12). ... 

More complicated results are observed in the reaction of 4,4-dimethyl-l,6-heptadiyn-3-ol 269 with Bu Me2SiH, giving a mtKture of 270 and 271 (Equation (44)). Discrimination of the two acetylenic moieties in 269 is hard at the silylrhodation, and thus a complex mixture of regioisomers and diastereomers results. In any event, use of rhodium species as a catalyst is essential for smooth construction of bicyclo[3.3.0]-octenone frameworks. 

In sharp contrast to 1,6-diyne 256, which gives a five-membered ring with two vo-methylene bonds and then bicyclo[3.3.0]-octenones, 1,6-enyne 273 (X = G(G02Me)2) gives five-membered product 274 (X = G(G02Me)2) as a sole product under similar conditions (Equation (46)). ... 

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]. 

Highly strained substrates can be transformed into even more strained isomers by ODPM rearrangement. This has been shown by Murata et al. for the synthesis of a valence isomer of azulene [45]. Albeit the photochemical reaction yielded only 20-25% of the bicyclo[1.1.0]butane derivative 15, the synthesis of the precursor cyclobutene (14) is straight-forward from the bicyclo[3.3.0]octenone 13 (Sch. 18). This substrate has obviously a diverse reactivity pattern when directly excited, however, triplet sensitization reduces these competitive pathways because alkene excitation is excluded. Also benzo-annulated azulene valence isomers were generated by this approach [46]. 

The photolyses of conformationally fixed 3,y-unsaturated ketones can also be performed in constrained media. This was described for the ODPM rearrangement of bicyclo[2.2.1]heptenone and bicyclo[2.2.2]octenone in MY zeolites [47]. It is remarkable that direct irradiation of the guest-incorporated thallium-Y (TIY) zeolites at 254 nm resulted in higher yields of ODPM products than the triplet-sensitized solution photolyses (Sch. 19). This indicates that the triplet carbonyl species are generated more efficiently in the supercages of the zeolites presumably because of the presence of heavy... 

If rapid bond formation at the stage of the Norrish I fragments competes with decarbonylation, 1,2-acyl shift products are formed as the major components from direct photolysis. In case of the cyclobuteno-annulated bicyclo[2.2.2]octenone 21, 1,2-acyl shift results in the cyclo-butanone 22, whereas ODPM rearrangement (photolysis in acetone) results in the cyclobuteno-diquinane 23 in 44% yield (Sch. 21) [49]. 

This concept has been applied for the synthesis of the structurally complex and highly oxyfunctionalized triquinane (—)-coriolin (Sch. 31) [61]. Two carbonyl groups, both in the right position for 1,2-acyl shift were present in the trimethyl-functionalized bicyclo[2.2.2]octenone 58. With a site-selectivity of 85% the expected regioisomeric tricyclic dione 59 was formed as a mixture of epimers (Sch. 31). Subsequent transformations involving the annulations of the third five-membered ring as well as epoxidation and hydroxylation steps led to the desired natural product... 

Moreto and coworkers have made improvements to the Chiusoli reaction, the Ni(CO)4-mediated carbonylation cyclization of allyl halides and alkynes, by conducting it in methanol403. It has subsequently been applied in the synthesis of methylenomycin B, in an intramolecular sense to provide bicyclo[3.3.0]octenones, and in intermolecular cases to form both fused bicyclic cyclopentenones and spirocyclopentenones (equations 203 and 204)403-405. 

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 convenient generation of bicyclo[2.2.2]octenones through the use of ortho-quinol derivatives in Diels-Alder reactions recently inspired Wood and co-workers in their studies toward the total synthesis of CP-263,114 (110) [148]. They relied on the Wessely-Yates tandem oxidative acetoxylation/intramolecular Diels-Alder sequence to build bicyclo[2.2.2]octenones such as 114 en route to advanced isotwistane intermediates such as 111b, which could eventually be fragmented to furnish the carbocyclic core of 110 (i.e. 111a —> 110, Figure 29) [149-153],... 

Photochemical transformations of bicyclo[2.2.2]octenones derived from Diels-Alder reaction of spiroepoxycyclohexa-2,4-dienones 116 have been exploited by Singh s group in their synthetic studies towards triquinane 119 and oxa-triquinane 121, protoilludane 120, and oxa-sterpurane 122 frameworks (Figure 30) [120, 154]. Spiroepoxycyclohexa-2,4-... 

---