Cyclohexene derivatives synthesis

Cyclopentene-l-carboxaldehydes are obtained from cyclohexene precursors by the sequence cyclohexene - cyclohexane-1,2-diol -> open-chain dialdehyde - cyclopentane aldol. The main advantage of this ring contraction procedure is, that the regio-and stereoselectivity of the Diels-Alder synthesis of cyclohexene derivatives can be transferred to cyclopentane synthesis (G. Stork, 1953 G. BUchi, 1968). 

Diels-Alder reaction (Section 10.12) Conjugate addition of an alkene to a conjugated diene to give a cyclohexene derivative. Diels-Alder reactions are extremely useful in synthesis. 

Treatment of 51 with an excess of sodium benzoate in DMF resulted in substitution and elimination, to yield the cyclohexene derivative (228, 36%). The yield was low, but 228 was later shown to be a useful compound for synthesis of carba-oligosaccharides. <9-Deacylation of228 and successive benzylidenation and acetylation gave the alkene 229, which was oxidized with a peroxy acid to give a single epoxide (230) in 60% yield. Treatment of 230 with sodium azide and ammonium chloride in aqueous 2-methoxyeth-anol gave the azide (231,55%) as the major product this was converted into a hydroxyvalidamine derivative in the usual manner. On the other hand, an elimination reaction of the methanesulfonate of 231 with DBU in toluene gave the protected precursor (232, 87%) of 203. 

Neier and coworkers have used a domino Diels-Alder/Ireland-Claisen process for the synthesis of (rac)-juvabione 4-46 and (rac)-epijuvabione [15]. Since neither the Diels-Alder reaction of the acetal 4-44 and methyl acrylate nor the sigmatropic rearrangement seemed to be stereoselective, these authors obtained the cyclohexene derivative 4-45 as a mixture of three diastereomers (Scheme 4.9). 

Dimethyldioxirane has also been used as the epoxidizing agent in a key step in the synthesis of A-norsteroids69,70. The reaction occurs in dichloromethane-acetone and is highly regio- and stereoselective as shown in equation 9. Dioxiranes may also be generated in situ, by reaction of potassium monoperoxysulfate (sold commercially as OXONE) and cyclohexanones. In this case, cyclohexene derivatives may be smoothly epoxidized in 40-100% yields (equation 10)71. 

Elwesine. The starting material for a synthesis [83] of elwesine (320) [84] (Scheme 48), the 0-protected cyclohexene derivative 321, itself obtained from 4-benzyloxycyclo-hexanone, was converted into a 1 4 diastereomeric mixture of bromohydrins 322 and 323 with N-bromosuccinimide and thence by dehydration to a mixture of a-allyl bromide 324 and the p isomer325. 

Another strategy for the synthesis of lycorine commenced with the Diels-Alder reaction of l-methylenedioxyphenyl-2-nitroethylene with butadiene to provide the cyclohexene derivative 85, which on reaction with MCPBA gave 86 together with the diastereomeric epoxide (1 1) (Scheme 6) (112). Hydrogena-... 

Polyhydroxylated cyclohexene derivatives such as conduritol A-F (7-12) are important secondary messengers eliciting a wide range of biological responses and have also been widely used as starting materials for advanced organic synthesis (4). RCM opens a particularly concise entry into this class of compounds, not least because of the ready availability of the required cyclization precursors from abundant monosaccharides (5,6). 

The versatility of the 1,4-disubstituted cyclohexene derivatives as synthesis intermediates, with emphasis on stereo control, was demonstrated by substitution procedures. Direct Sn2 with malonate anion proceeds selectively for Cl with inversion, and Pd°-catalyzed substitution also proceeds selectively at Cl, but with retention. A second substitution, Pd°-catalyzed, using dimethylamine in this case, leads to replacement of the acetate with retention (Scheme 24). ... 

Coupling of amino cyclohexene derivative 100 with 6-bromopiperonylic acid (101) provides amide 102, which is a key intermediate for the synthesis of phenanthridone alkaloid lycoricidine (103).39... 

A number of cyclohexene derivatives can be cleaved thermally to an olefin and a diene, preferably by passage in the vapor phase over red-hot metal wires. This is the reverse of the Diels-Alder diene synthesis. The oldest example is the formation of isoprene from dipentene described by Harries and Gottlob 96... 

A method for synthesis of chiral cyclohexene derivatives from 4-substituted cyclohexyl halides involves derivatization to the Grignard reagent, reaction with menthyl... 

From the petroleum ether extract of the fresh roots of A. flabellata, a cyclohexene derivative, alflabene (112) was isolated and identified on the basis of its spectral properties and by synthesis [73]. The same compound was also isolated from the rhizomes of Zingiber cassumunar. 

A synthesis of the alkaloid narseronine 53 that highlights yet another novel mode of cyclisation of arylated cyclohexenes derived from compound 67 is shown Scheme 9 (White et al., unpublished work [45]). Thus, nitrile 73 (generated from precursor 67 during the course of our synthesis of the lycorine degradation product 79 as shown in Scheme 6) was reduced with dihydrogen in the presence of Raney-cobalt and the resulting primary amine was then protected as the corresponding... 

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