Annelation, Robinson method

Amplification. See Chirality amplification Anhydrides, ring opening, 331 Anionic polymerization methyl sorbate, 174 trityl acrylate, 181 Annelation, Robinson method, 336 Antibiotics, 8, 44, 80 Antibodies, 12... 

Epoxy-5,5-dimethylcyclohexanone allowed to react 2 hrs. at 25 with 1.25 equivalents cyclopropyldiphenylsulfonium fluoroborate and 2 equivalents KOH in dimethyl sulfoxide -> diepoxide (Y 96%) dissolved in pentane and washed with aq. 1 M fluoroboric acid epoxycyclobutanone deriv. (Y ca. 100%) (startg. m. f. 101). - This sequence can be used as part of an annelation process complimentary to the normal Robinson method. F. e., rearrangement also with oxalic acid, s. B. M. Trost and M. J. Bogdanowicz, Am. Soc. 94, Mil (1972) lactone annelation cf. Tetrah. Let. 1973, 923 Am. Soc. 95, 5321 (1973) replacement of carbonyl oxygen by 2 functionalized carbon substituents cf. Am. Soc. 95, 2038, 7862 (1973). 

The Robinson annelation reaction has classically been employed for the building up of the six-membered ring components of the steroid nucleus (18). In the original method, the enolate is treated with the methiodide of )9-diethylaminoethyl methyl... 

Select one compound from (37) - (40) for synthesis by each of the methods of this chapter Robinson annelation, Diels-Alder reaction, total reduction of aromatics, and Birch reduction. 

The utilization of the Robinson annellation method for the synthesis of cory-nanthe-type alkaloids has been thoroughly investigated by Kametani and coworkers (149-152). The tetracyclic ring system was efficiently formed via the Michael addition of dimethyl 3-methoxyallylidenemalonate (247) to the enamine derived from 3,4-dihydro-1 -methyl-(3-carboline (150). Alkylation of 248, followed by hydrolysis and decarboxylation, resulted in a mixture of stereosiomeric enamides 250 and 251. Hydrogenation of 250 afforded two lactams in a ratio of 2 1 in favor of the pseudo stereoisomer 253 over the normal isomer 252. On the other hand, catalytic reduction of 251 gave 254 as the sole product in nearly quantitative yield. Deprotection of 254, followed by lithium aluminum hydride reduction, yielded ( )-corynantheidol (255) with alio relative configuration of stereo centers at C-3, C-15 and C-20. Similar transformations of 252 and 253 lead to ( )-dihydrocorynantheol and ( )-hirsutinol (238), respectively, from which the latter is identical with ( )-3-epidihydrocorynantheol (149-151.). 

This asymmetric phase-transfer method has been applied to enantio-selective Robinson annelation as shown in Scheme 14 (41). First, alkylation of a 1-indanone derivative with the Wichtetie reagent as a methyl vinyl ketone equivalent in the presence of p-CF3BCNB gives the S-alkylation product in 92% ee and 99% yield. With 1 -(p-trifluoro-methylbenzyl)cinchonidinium bromide, a pseudo-enantiomeric diaste-reomer of p-CF3BCNB, as catalyst, the -alkylation product is obtained in 78% ee and 99% yield. These products are readily convertible to the... 

The isoxazole annelation reaction2,3 is a general method for fusing a new cyclohexanone ring onto an existing system and is complementary to the well-known Robinson annelation.4 It has several major advantages ... 

The present procedure is illustrative of the general method which finds its utility largely in the construction of more complex polycyclic systems. The specific compound herein synthesized can be made more conveniently by standard Robinson annelation techniques.8... 

The cyclohexenone 13 was needed for a synthesis of the boll weevil hormone grandisol. Disconnection with Robinson annelation (chapter 21) in mind gives the rather unstable looking enone 15. No doubt a Mannich method could be used (16 R = NR2) but any leaving group X in 16 will do. 

In 1973, Wiesner, Vlahov, and Muzika reported (176) a relatively simple annelation procedure for the construction of ring A as an alternative to the Robinson annelation method. 

In Chapter 28 you met the Robinson annelation as a method of making cyclohexenones. The product of the elimination step contains a double bond, but there is no question about its geometry because in a six-membered ring only a cis double bond can exist—a trans one would be far too strained. 

Retrosynthetic analysis of six-membered ringformation almost always boils down to a Diels-Alder reaction176) or a Robinson annelation 177) (or variations thereof) as the crucial C—C bond forming step. Both methods have in common that more than one carbon—carbon bond is formed in a one pot reaction which allows a rapid and efficient construction of complex organic molecules from rather simple building blocks. No such general tool exists for the formation of carbocyclic five-membered rings. 

Ketone (8) was an intermediate in a synthesis of the boll weevil hormone grandisol (7). This cyclohexenone is a Robinson annelation product disconnection by the method of Chapter 21 leads back to the available aldehyde (9) and the curious enone (10). 

The synthesis can be completed either by activating aldehyde (9) as an enamine and eliminating to give (10) before combining the two in a Robinson annelation (synthesis 2), or by the lazy man s method of simply using no control at all —with good results in this case (synthesis 3). 

Further disconnection of (24) by 1,3-dicarbonyl methods (Chapter 19) gives aldehyde ester (25) as starting material. The aldehyde group will certainly need protection here and probably also during the Robinson annelation so available dichloracetic acid is used. 

An elegant synthesis of Warburganal (12) from the ketone (2) was reported by Kende and Blacklock [8] as depicted in Tig (1)". The ketone (2), prepared [3] by Robinson annelation of the 2-methyl-1,3-cyclohexanedione with ethyl vinyl ketone, on ketalization afforded (3) which was converted to the trans-decalone (4) by the reductive methylation procedure of Stork [9]. Wolff-Kishner reduction of (4) produced the ketal (5), which without purification was hydrolyzed with acid to obtain the trans-decalone (6) [10] in excellent yield. The present method for the synthesis of the decalone (6) appears more efficient and convenient than the methods previously reported [11,12], considering the overall yield and the stereoselectivity. 

Trost has reported on a process where the normally electropositive /3-carbon of a Michael acceptor becomes effectively electronegative, functioning as the unit (44) application of this method (Scheme 108) provides a useful annelation procedure complementary to the well-known Robinson approach. 

Robinson and Related Annelations.—Since Robinson described his celebrated annelation reaction some forty years ago, it has remained one of the most widely used methods for six-ring synthesis. There have been several variants and modifications of the first described procedure, and this year two excellent reviews of the reaction and its variants have appeared (see Review Section). 

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