Annulation regiocontrolled

The synthetic strategies depicted in the Scheme 1 provide an overall view of the scope and potential of Jl-heteroaromatic annulation protocol to yield benzoheterocycles with full regiocontrol on all the four positions of the newly formed benzene ring. 

This sequence initiated by the nucleophilic cyclopropyl conjunctive reagent 9 allows facile annulation concommitant with regiocontrolled further structural elaboration as outlined in Eq. 8429). With the electrophilic conjunctive cyclopropyl reagent 58, this [3 + 2] annulation onto a vinyl organometallic (Eq. 85) has the availability of the... 

The temporary functionalization of cyclic or acyclic alkenes with a phenylsulfonyl group, followed by [4 -t- 2] cycloadditions of 1,3-bis-oxygenated dienes, opens a regiocontrolled route to annulated or 5-substituted cyclohexenones (Scheme 18). ... 

Danheiser, R. L., Carini, D. J., Basak, A. (Trimethylsilyl)cyclopentene annulation a regiocontrolled approach to the synthesis of five-membered rings. J. Am. Chem. Soc. 1981, 103, 1604-1606. 

Studies directed at a synthesis of the morphine alkaloids. Regiocontrol in Robinson-type annulations of 2-(hydroxymethyl)-4-oxo-3-piperidinecarboxylic acid. gamma.-lactones Schultz, Arthur G. Shannon, Paul J. 

The stereochemical requirements for the synthesis were fulfilled starting from enantiomerically pure alkynes 16, whereas the regiocontrol was achieved, when necessary (the [4-1-1] annulation can afford mixtures of quinoline derivatives, see Scheme 6), using ort/ o-(trimethylsilyl)-substituted arylisonitriles 15 (Scheme 7). In conclusion, the authors set up an asymmetric, regioselective, and widely applicable protocol that allowed the synthesis of more than fifty different compounds, proving once more the broad scope and functional-group tolerance of radical reactions. 

Regiocontrol for the Robinson annotation is an important factor that can infiuence a synthetic route because there are two a-carbons to the keto group to be considered. Consequently, techniques for regiocontrol have been developed. Under either the basic or acidic standard annulation conditions deprotonation occurs under thermodynamic control at the higher substituted carbon and hence forms an angular substitution at the fused side of the end-product. An exception to this is steric hindrance where alkylation occurs at the least substituted a-carbon, as shown in the synthesis of 9. ... 

In the past 70 years different variations have immerged for the Robinson annulation reaction to rectify its weaknesses such as polymerization tendencies for the parent vinyl ketone imder standard reaction conditions, multiple alkylation products, regiocontrol, and stereocontrol. 

A (trimethylsilyl)cyclopentene annulation method has been developed that leads to a regiocontrolled approach to the synthesis of five-membered rings/ Thus, it was shown that (trimethylsilyl)allenes could be persuaded to react at -78 C with unsaturated carbonyl compounds in the presence of titanium tetrachloride (Scheme 16). The methodology is presently being applied to polyquin-ane natural product synthesis. 

Synthesis of Furans and Isoxazoles. Electrophilic species of the general form Y=X+ serve as heteroallenophiles, combining with allenylsilanes in a regiocontrolled [3 + 2] annulation method. As illustrated in the mechanism shown in eq 13, addition of the heteroallenophUe at C-3 of the allenylsilane produces a vinyl cation stabilized by hyperconjugative interaction with the adjacent carbon-silicon tr-bond. A 1,2-trialkylsilyl shift then occurs to generate an isomeric vinyl cation, which is intercepted by nucleophilic X. Elimination of H" furnishes the aromatic heterocycle. 

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