1-Decalones synthesis

If the enone is part of a decalone system, i.e., a / - and an y-substituent are present, on reaction with lithiated areneacetonitriles in THF the exclusive formation of (Tv-substituted decalones is observedl26. The diastereoselectivity at the exocyclic stereogenic center is, however, poor. Applications in the synthesis of anthracyclines are given in the literature127,12S. 

Using 3-substituted cyclohexanones the /rans-diastereoselective synthesis of decalones and octahydro-1 //-indenones may be achieved 164 169. This method has been applied, for instance, in the synthesis of 19-norsteroids. In a related Michael addition the lithium enolate of (R)-5-trimethylsilyl-2-cyclohexenone reacts with methyl 2-propenoate selectively tram to the trimethylsilyl substituent. Subsequent intramolecular ring closure provides a single enantiomer of the bicyclo[2.2.2]octane170 (see also Section 1.5.2.4.4.). 

Dimethylcyclohexanone and 2-benzyl-2-methylcyclohex-anone have been prepared similarly in yields of 60% and 55%, respectively.2 The procedure has been extended to the synthesis of 9-methyl-, 9-w-butyl-, and 9-benzyl-l-decalone from the dianion of 2-formyl-l-decalone in yields of 55%, 48%, and 58%, respectively.2... 

However, as already stated [12] this is probably unnecessary, since in the basic medium in which the cyclisation takes place the rrans-decalone with no angular methyl group would be in equilibrium with the corresponding cii-decalone. Even in the less favoured case, the equilibrium would shift to the cis-isomer since this is the only isomer which can cyclise to twistanone. Should this be the case, then the stereochemical control in preparing the starting decalone would be unnecessary and the synthesis would be greatly simplified. 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

A 2-cyclohexenone derivative can be transformed into the corresponding epoxy tosyl-hydrazone by sequential treatment with peracid and tosylhydrazine. The elimination of nitrogen and p-toluenesulfinate and fragmentation after rearrangement to the 3-tosylazo allylic alcohol may occur under mild conditions. Carbonyl compounds with 5,6-triple bonds are formed in high yields (J. Schreiber, 1967 M. Tanabe, 1967). If one applies this reaction to a 9,10-epoxy-1-decalone, a ten-membered 5-cyclodecyn-l-one ring is formed (D. Felix, 1971). This product is an important intermediate in the perfume industry and has been used on a large scale. For this purpose Eschenmoser developed a synthesis in which the readily removed styrene was split off instead of a sulfmic acid. Thus a l-amino-2-phenylaziridine hydrazone was used instead of a tosylhydrazone (D. Felix, 1968). ... 

For the synthesis of an antibacterial clerodane 262, ozonolysis of a substituted optically pure (-)-2-decalone 261 with (57 ,97 ,1070-configuration was the starting step (Scheme 80) <1995J(P1)757>. 

Using methylene-triphenylphosphorane 205, in many cases carbonyl functions have been converted into exomethylene groups in cyclic terpene chemistry. This technique was used, among others in the preparation of (+)-steviol methyl ether 244), dihydro-5,6-norcaryophyllene 245), ( )-nootkatone 246 (-)-phyllodadene 247), and (+)-e-cadinene 248). In the synthesis of the latter the trans-decalin derivative 462 was formed from the cis-decalone 461 the epimerization of which proceeded via the enol form during the methylenation 248 (Scheme 80). 

The haloketal cyclization is most useful for synthesis of polycyclic systems. Thus (5) is converted into a < b-9-cyano-2-decalone (6), and (7) is converted into (8). The hydrin-dane (10) was prepared from (9). 

Shing, T. K. M., Lee, C. M., Lo, H. Y. Synthesis of the CD ring in taxol from (S)-(+)-carvone. Tetrahedron Lett. 2001,42, 8361-8363. Marchand, A. P., Kumar, V. S., Hariprakasha, H. K. Synthesis of novel cage oxaheterocycles. J. Org. Chem. 2001,66, 2072-2077. Demnitz, F. W. J., Philippini, C., Raphael, R. A. Unexpected Rearrangement in the Peroxytrifluoroacetic Acid-Mediated Baeyer-Villiger Oxidation of trans-3p-Hydroxy-4,4,10p-trimethyl-9-decalone Forming a 7-Oxabicyclo[2.2.1]heptane. Structure Proof and Total Synthesis of ( )-Farnesiferol-C. J. Org. Chem. 1995, 60, 5114-5120. 

A nice example of the foregoing stratagem is seen in equation (17) enone (6) undergoes copper(I)-catalyzed reaction with vinylmagnesium bromide from its less-hindered face to give an enolate that reacts with formaldehyde from the opposite face to provide decalone (7), an intermediate in the synthesis of insect antifeedants. Yoshida and coworkers have used this method for the stereospecific generation of tetrasubstituted thioamide enolates, which undergo remarkably stereoselective aldol reactions (equation 18). ° The stereochemistry of this process is discussed in Section 1.6.3.6. 

Regiosp>ecific synthesis of enol silyl ethers can also be achieved from enones either by reductive silylation or by 1,4-addition of the conjugated system. Thus, Li/NH reduction of the decalone (27) and silylation give the enol silyl ether (28). Similarly, addition of lithium dimethylcuprate to cyclohexenone followed by silylation gives the enol silyl ether (29). Trimethylsilyl cyanide (30) normally adds 1,2 to conjugated ketones (e.g. carvone, 31). However, in the presence of trialkylaluminum, 1,4-addition bdces place to give the enol silyl ether (32 Scheme 9). The same overall transformation can be accomplished by diethylaluminum cyanide and trimethylchlorosilane. ... 

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