Annelation processes

The annelation process in the Robinson reaction can also be carried out in a stepwise mode, so the alcohols from the aldol condensation step are often obtained (e.g., Scheme 5.17).63... 

The Bose group s prolific applications of the microwave-assisted ketene-imine annelation process suggest that research laboratories everywhere should be able to justify acquisition of microwave equipment to accelerate research programs via the rapid preparation of a variety of new structures. In a process development setting, the microwave technique should find application in the rapid evaluation and optimization of process parameters, such as solvent, reaction concentration (and neat reactions), temperature, time, pressure, the structure of catalyzing bases/acids, rates of addition, and so on. 

Because of the discovery of a growing number of naturally occurring substances of biological importance that contain the five-membered ring moiety 178), the synthesis of cyclopentanoid compounds is a subject of present interest. Indeed, among the various approaches recently investigated, the thermal vinylcyclopropane-cyclopentene rearrangement of readily available 1-siloxy-l-vinylcyclopropanes (vide supra, Sect. 4.1.5) constitutes an efficient three-carbon annelation process 179). 

The thermal C3 -> 5 ring expansion of 1-siloxy-l-vinylcyclopropanes occurs either from the Z or from the E isomers. It leads to cyclopentanone silyl enol ethers that are able to undergo either further regiospecific alkylation into 2,3-disubstituted cyclopenta-nones 145.209,213 dehydrosilylation into cyclopentenones The overall process constitutes an efficient three-carbon annelation process (equation 129). 

The reaction of allenylsilanes with electron deficient ir-systems constitutes a powerful and general method for the tegio- and stereo-selective preparation of substituted cyclopentenes. As first reported, (trimethylsilyl)allenes function as three-carbon nucleophiles in TiCU-promoted (trimethylsilyl)cyclopen-tene annelations (Scheme 31). The annelation process involves the polarization of an a,p-unsaturated carbonyl compound by TUTU to generate an alkoxyallylic cation. Regiospecific electnqrhilic substitution of this cation at C-3 of the allenylsilane produces a silicon-stablizied vinyl cation. A 1,2-shift of the tri-... 

A new annelation process involving photochemical cycloaddition of a-formyl ketones to symmetrical alkenes has provided alternative synthetic routes (Scheme 37) to valerane (385) and isovalerane (386) (cf. Vol. 5, p. 78 Vol. 6, p. 87). 

Similar behavior with the simpler 1,5-diketone (65) has been documented by Marshall and Schaeffer. As shown in equation (12()), diketone (65) cyclizes to octalone (66) under basic conditions and to the bicyclo[3.3.1]nonenone (67) under acidic conditions. The regiochemistry of ring closure in this system is sensitive to the exact reaction conditions. For example, diketone (65), an intermediate in the acid-mediated Robinson annelation process, cyclizes to octalone (66 equation 121). In this example, it is... 

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). 

Plenary Lecture The use of kinetically generated unstable enolate ions in the regiospecific formation of carbon-carbon bonds. Special applications to annelation processes. 

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