Claisen rearrangements promoted

Lewis acid-mediated reactions can be classified into two groups (Fig. 4). In the first (type 1) the complex between substrate and Lewis-acid reagent produces the product. Claisen rearrangement promoted by a Lewis-acid catalyst is a typical example of this type. Some complexes formed between Lewis acids and substrates are, however, stable enough to react with a variety of reagents from outside the system to generate the product (type 2). The Diels-Alder reaction between Lewis acid-activated unsaturated carbonyl compounds and dienes is an example of type 2 reactions. 

The original tandem Claisen rearrangement promoted by Et2AlCl and 2-methyl-2-butene was utilized for synthesis of a new type of macrocyclic derivatives 186 from the corresponding macrocyclic polyethers 185 which were formed via 183 and 184 (equations 84 and 85). This very rapid reaction results in good yields of potential host molecules and supramolecular building blocks under mild conditions, instead of the thermal treatment. 

TableS. Claisen Rearrangements Promoted by Bulky Organoaluminum Reagents123...

A new method has been developed for the preparation of calixarene analogues from macrocyclic polyethers via intramolecular successive carbon-carbon bond formation in a tandem Claisen rearrangement, and a similar tandem Claisen rearrangement promoted by Et2AlCl and 2-methylbut-2-ene, has been used ° to synthesize macrocycles containing phenolic moieties from the corresponding macrocyclic polyether compounds (see Scheme 28). A number of furo[3,2-c 5,4-/]bis[l]benzopyran-3-ones have been synthesized regioselectively by the sequential... 

Like the Cope rearrangement, the Claisen rearrangement is sensitive to substituents on the reacting system. Cyano groups promote the rearrangement by a factor of 10 at positions 2 and 4 and have smaller effects at the other positions, as shown below. Data are also available for methoxy groups at positions 2, 4, 5, and 6. ... 

This reaction also is concerted and proceeds via a six-membered transition state, but here the species (59), corresponding to the ene-one intermediate (53a) in the aromatic Claisen rearrangement, is in fact the end-product. This is so because there is in (59) no energetic driving force, comparable to re-aromatisation in (53a— 52a), to promote its enolisation. 

Scheme 2.153. Yb(OTF)3-promoted domino ketene addition/acyl-Claisen rearrangement.

Simple aromatic aza-Claisen rearrangement without charge acceleration by addition of an acid required other activating factors to enable the reaction to be run at acceptable temperatures. The reduction of ring strain was found to serve as a useful promoter to induce aromatic aza-Claisen rearrangement [21]. 

An unusual [1,3]-rearrangement of aryl 2-halocyclohexenylmethyl ethers promoted by trifluoroacetic acid has been observed. Products due to a Claisen rearrangement were not formed and the proposed pathway for the process is outlined in Scheme 7. It has been shown that AICI3-mediated decomposition of A-phenoxybenzamide... 

The 3-aza-Claisen rearrangement concerning the rearrangement of aUyl vinyl amines, contrary to its Cope analogue, has not been used extensively to form carbon-carbon bonds, probably due to the high temperatures (>180°C) required for the uncatalysed variant and to the limited number of catalysts available for promoting the reaction at moderate temperatures (equation 4). 

Secondary aliphatic amines were found to give higher yields of thienothiophenes than did tertiary amines, which are weaker bases. A maximum ratio of thienothiophenes to thienothiopyrans of about 4 1 was achieved at 145° with diisopropylamine as cat yst and DMSO as solvent. Only thienothiopyrans were formed in DMF in the presence of the same catalyst The amines promote nucleophilic cyclization of Claisen rearrangement products into thienothiophenes. Since thienothiophenes are resistant to treatment with potassium t-butoxide in DMSO and thienothiopyrans form resinous products under these conditions, the method is a convenient route to pure thienothiophenes 35 and 42 in yields of up to 40%. ... 

Thermally promoted Claisen rearrangement of simple allyloxypyrimidines is difficult to effect, but is more common with quinazolines where it has been used to prepare allyl derivatives substituted in the carbocyclic ring < 1996HC(55) 1 >. An attempted amino-Claisen rearrangement of a 4-allylaminopyrimidine was unsuccessful <2005AJC368>. 

Thiochromans (1 R = H2) result from disproportionation of 2H- -benzothiopyrans (4) and also from thio-Claisen rearrangements of phenyl allyl sulfides. The first pathway was discovered by Tilak and Vaidya,24 who attempted to prepare one benzothiopyran (15) by cyclizing the /S-ketosulfide (14) in polyphosphoric acid (PPA), but obtained the thiochroman (16) and a benzothiopyrylium salt as in Eq. (5). This reaction involves25,26 an acid-promoted disproportionation... 

Why do Lewis acids promote Claisen reactions Suggest another method for accelerating aza- and thia-Claisen rearrangements. 

The opening move was the transformation of the known glucopyranoside 355 into exomethylene vinylpyranose 356. TIBAL-promoted Claisen rearrangement of 356 provided the cyclooctene derivative 357 almost quantitatively, which was then transformed to protected cyclooctanose 358 by methylation followed by hydroboration-oxidation. Installation of the hydroxymethyl function at C5 required three further operations oxidation of the Cs-hydroxyl, Tebbe methylenation, and hydroboration-oxidation. In the event, a mixture of epimeric... 

Thus, ketose 361 was first methylated and then subjected to a three step transformation including desilylation followed by iodination and hydride-promoted HI elimination. This furnished vinyl ketoside 362 whose treatment with excess of TIBAL ensured smooth Claisen rearrangement to afford cyclooctenic carbocycle 363 in excellent yield. 

The allyl vinyl ether needed for the Claisen rearrangement is an enol ether of an unsaturated aldehyde with an unsaturated alcohol. The two starting materials are themselves derived from a common precursor, making this a most efficient process Heating the enol ether promotes [3,3]-sigmatropic rearrangement propelled by the formation of a carbonyl group. 

Claisen rearrangement The Claisen rearrangement of highly substituted allyl vinyl ethers can proceed readily even when two vicinal quaternary centers are formed. Thus addition of an allylic alcohol (1) to an allenic sulfone (2) provides the allyl vinyl ether 3, whose anion rearranges at 50° to 4. Lithium dimsylate is the preferred base other counterions promote an undesirable side reaction.1... 

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