Bicyclo octenone synthesis

Bicyclo[2.2.2]octenediones 299 synthesis of 1220, 1222 Bicyclo[2.2.2]octenones, synthesis of 1327 BINAP 701... 

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). 

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]. 

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. 

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],... 

This reagent is used as a Lewis acid catalyst for the intramolecular addition of diazo ketones to alkenes [130], The direct synthesis of bicyclo[3.2.1]octenones from the appropriate diazoketones using BF3 Et20 (Eq. 76) is superior to the copper-catalyzed thermal decomposition of the diazo ketone to a cyclopropyl ketone and subsequent acid-catalyzed cleavage [131]. 

The conversion of a bicyclo[2.2.1]octenone derivative to the corresponding bicyclo[3.3.0]octenone, a common intermediate in the total synthesis of several iridoid monoterpenes, was achieved by N.C. Chang et al. The target was obtained by sequential application of the Corey-Chaykovsky epoxidation, Demjanov rearrangement and a photochemical [1,3]-acyl shift. 

SCHEME 171. Synthesis of bicyclo[2.2.2]octenones via Wessely oxidation of phenols... 

A synthesis of allamcin (415, R = H) by Parkes and Pattenden also starts with the bicyclo[3.3.0]octenone 413. Spiroannulation of the P-oxy-y-butyrolactone ring was carried out by initially introducing a formyl group and constructing the ring on this, then taking advantage of the difference in nucleo-philicity of one of the double bonds in 418 to hydroxylate it, then oxidative... 

The tricyclic compound 75, a derivative of the fungal metabolite stepurane, was obtained by irradiation of the bicyclo[2.2.2]octenone 76, obtained in good yield from 77 in a bve-step synthesis (Scheme 6.28).628 The reaction proceeds by a 4-jt-electron suprafacial sigmatropic 1,3-acyl shift. 

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]. 

Photochemical oxa-di-jt-methane rearrangement of bicyclo[3.2.1]octa-noid scaffolds affords multifunctional, donor-acceptor cyclopropanes (34). Application of this reaction to bicyclo[2.2.2]octenones has been used as a key step in the total synthesis the hirsutane-type sesquiterpenes (-)-connatusin A (35), (+)-connatusin B (36), and the marine sesquiterpenoid 2-isocyanoallopupukeanane (37). ... 

Irradiation of 5-benzoylbicyclo[2.2.2]octenone oximes (41) in the presence of triethylamine affords the corresponding bicyclo[3.2.1]octane derivatives via an electron transfer pathway. The synthesis of 2-vinylcyclo-propanecarbaldehydes, precursors of cyclopropane components present in pyrethroids, has been achieved by using the oxa-di-71-methane... 

Peddinti also reported a simple and efficient one-pot synthesis of benzoxazolic bicyclo[2.2.2]octenones 29-31 by subjecting 2-methoxy-substituted phenolic aldimines of type 26 to a similar treatment with DIB in the presence of the same kind of dienophiles 24, or furans, in MeOH [47], This clever domino reaction starts with a DIB-mediated oxidative cychzation of the phenolic aldimines into the phenolic benzoxazoles 27, which are then converted, with a second equivalent of DIB, into the MOBs 28 that are finally trapped with excess of dienophile to furnish selectively the expected [4+2] cycloadducts 29-31 (Fig. 11) [47]. 

In another full report, details are given of the preparation of (95a) by an intramolecular Wadsworth-Emmons reaction of the phosphonate (94) this method constitutes a key step in a synthesis of 6a-carbaprostaglandin 12. A related Wittig reaction using a phosphonium salt derived from a chiral phosphine has been used to obtain (96) in high optical purity. Bicyclo-A -octenone... 

Yates, P. and Stevens, K.E., Bicyclopentanoid sesquiterpenes. The synthesis of cedranoid sesquiterpenes via the photorearrangement of bicyclo[ 2.2.2]octenones. Tetrahedron, yj, 4401,1981. 

Singh, V.K., Deota, RT., and Bedekar, A.V., Studies in the synthesis of polycyclopentanoids synthesis, oxa-di-7i-methane rearrangement of annulated bicyclo[2.2.2]octenones and cyclopropane ring cleavage of tetracyclo[6.3.0.0. > 0 > ]undecenones,/. Chem. Soc., Perkin Trans. 1, 903,1992. 

---