Annelation regiospecific

Hauser has used repetitive annelations of this type tor synthesis of linear aromatic systems. This methodology provides a simple regiospecific route to the tetracyclic system of the antibiotic anthracyclinones. For this purpose 5-ethoxy-2(5Ff)-furanone (2) is used as the Michael acceptor in the first annelation of the anion of 1. After methylation, 3 is obtained in 65% yield. It is then converted into 4, for a second annelation with cyclohexenone or a derivative (5). The reaction results in a tetracyclic hydronaphthacene 6. 

Cyclopentenone annelation, The isomeric adducts 1 of 2-methylcyclohexanone and propargyi alcohol both cyclize regiospecifically to the hydrindanone 2 (70%... 

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). 

Regiospecific cyclopentenone annelations vinylsilane-terminated annelations... 

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-... 

Regiospecific cyclopemenone annelations vinyisiiane-terminated anneiations... 

The enol triflate comes from regiospecific reduction of the enone (chapter 3) which can be made by a Robinson annelation. 

Azides have been used widely in synthetic approaches to azepines, diazepines, and their annelated derivatives. Two new cyclizations extend the range of azide reactions available. The first of these offers a new route to clavicipitic acid and its analogues (Scheme 6). The key step is a regiospecific intramolecular cycloaddition of the azide group to the neighbouring 24... 

Schreiber et al. have been able to apply their enediyne intramolecular Diels-Alder approach to the synthesis of dynemicin model systems [268-270], culminating in the total synthesis of di- and tri-O-methyl dynemicin A methyl esters 388 and 389 (Scheme 7-78) [271], derivatives of the natural product itself. Highlights of this synthetic approach include (a) intramolecular lactonization and concomitant Diels-Alder cyclization (380- 381) (b) allylic hydroxylation followed by an allylic diazene rearrangement in order to regiospecifically isomerize a double bond (381 - 382) (c) a-hydroxylation of the lactone 381 and subsequent conversion to the P-ketoester 383 (d) annelation of the anthraquinone unit (383- 384- 385- 386) (e) mild base-induced P-elimination of the N-protecting group of 386 to give the free amine 387 and (f) a final oxidation to complete the anthraquinone (387 - 388). 

Substituted tropones may also react with bifunctional nucleophiles to give annelated products, for example amidines give cyclo-heptatrieno-imidazoles [204,205], Reaction is regiospecific, as the following examples show [204] ... 

The reactions of sterically encumbered allenylsilanes of structure type (66) with iV-acyliminium ions generated by the titanium tetrachloride promot reaction of ethoxypyirolidinone produced the nitrogen heterocycle (70), as depicted in Figure 13. In this reaction it is likely the lactam product is generated by a pathway similar to that involved in the [3 + 2] cyclopentene annelation. Thus, a regiospecific electro-... 

The related Trost cyclobutanone annelation procedure, in which 1-lithiophenyl cyclopropyl sulphide is condensed with a cyclic ketone and the product rearranged with an acid catalyst, can be controlled to give considerable stereoselectivity and regiospecificity. Application to the methyladamantanone (321) permits specific syntheses of the two ketones (322a) and (322b) to be accomplished, and these have been used in the first experimental verification of the Front Octant Rule. ... 

The diene (9) undergoes Diels-Alder reactions readily and is, therefore, a useful synthon for a-phenylthiocycloalkanones the observed regiospecificity of the Diels-Alder annelations is due to the influence of the phenylthio-group. " ... 

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

Oxa- and Thia-diazines.—Intramolecular cyclodehydration of phenylglyoxalic acid benzohydrazide [PhC0NHN=C(Ph)C02H] with dicyclohexylcarbodi-imide in THF, or with a mixture of trifluoroacetic acid and trifluoroacetic anhydride, yields 2,5-diphenyl-6-oxo-l,3,4-oxadiazine (359), a synthetically useful diaza-diene. For example, with ynamines, regiospecific cyclo-addition of the nucleophilic /S-carbon of the ynamine with the electrophilic C-2 of the oxazinone yields adduct (360) and hence, by loss of nitrogen, the a-pyrone (361). The annelated a -pyrone (362), from benzyne and the oxadiazinone (359), is itself a diene, and reacts further with the dienophile to give ultimately 9,10-diphenyl-anthracene. 

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