Sigmatropic rearrangements pyridines

The formation of pyridine 210 appears to start with dimerization of aminobutenone 207 due to carbonyl-amino group interaction. Then the intermediate 208 undergoes [3,3]-sigmatropic rearrangement, whereupon dihydropyridine 209 eliminates ammonia. 

Dialkylaminobut-3-en-2-ones with acetylacetonimine and its analogs form only 2,6-dimethyl-3-substituted pyridines 221 (40—50°C, AcONa, AcOH, 5 h, 55%) (75DIS), seemingly via the intermediate 219 and its subsequent [3,3]-sigmatropic rearrangement to dihydropyiidine 220. 

As a continuation to the studies by Darwish and Braverman on the [2,3]-sigmatropic rearrangement of allylic sulfinates to sulfones, and in view of its remarkable facility and stereospecificity (see Chapter 13), Braverman and Stabinsky investigated the predictable analogous rearrangement of allylic sulfenates to sulfoxides, namely the reverse rearrangement of that attempted by Cope and coworkers . These authors initiated their studies by the preparation of the claimed allyl trichloromethanesulfenate using the method of Sosnovsky . This method involves the reaction between trichloro-methanesulfenyl chloride and allyl alcohol in ether at 0 °C, in the presence of pyridine (equation 6). 

It is known that 5-acyloxyoxazoles 132 rearrange to 4-acyl-5(4/l/)-oxazolones 133 in the presence of 4-(dimethylamino)pyridme or 4-(pyrrohdino)pyridine. Recently, an asymmetric variant of this nucleophUe-catalyzed rearrangement that employs a chiral derivative of 4-(pyrrolidino)pyridine has been described. This procedure allows the construction of quaternary stereocenters with high levels of enantioselectivity (Scheme 7.38). Representative examples of saturated 5(4//)-oxazolones prepared via sigmatropic rearrangements are shown in Table 7.16 (Fig. 7.18). 

The formation of pyrazolo[l,5-a]pyridines from diazocyclopentadienes was discussed in Section II,1,4,a The cyclopentanone 261 was converted to the corresponding reduced product 262 upon treatment with dipolarophiles, possibly involving [l,5]-sigmatropic rearrangement of the intermediate spiro adduct.212... 

Selective o/t/io-acylation and orrfio-formylation of 2-alkyl pyridines is possible by [2,3] sigmatropic rearrangement (Sommelet-Hauser) of a-pyrrolidinyl-2-alkylpyridine sulfonates (268), prepared by treating the parent base with cyanomethyl benzenesulfonate (76JOC2658). Acid hydrolysis of the rearranged product (269 R = H) yields 3-formyl-2-methylpyridine (270). Methylation of (269 R = H) using NaH-Mel and acid hydrolysis of the reaction mixture gives 3-acetyl-2-methylpyridine (270 R = Me). 

Heterocyclic nitrogen-derived ylids behaviors have been studied.373 For instance, pyridine derivatives lead exclusively to [2,3]-sigmatropic rearrangement (Sommelet-Hauser) products. 

Klunder nicely exploited the Sommelet-Hauser reaction to synthesize dipyridodiazepine derivatives, such as 84, whose structural analogues show potent inhibition of HIV-1 reverse transcriptase.42 The key step here involves a [2,3]-sigmatropic rearrangement across the pyridine ring. 

Harano and co-workers found that the cascade reaction of pyridine iV-oxides with allenes, after 1 1 cycloaddition and 1,5-sigmatropic rearrangement, added ketene in what they determined was a stepwise [2+2] cycloaddition <03CPB1068>. In some cases the addition of the ketene is stereoselective. 

The enantioselective total synthesis of the cyclooctanoid natural product (+)-epoxydictymene was accomplished in the laboratory of L.A. Paquette. The entire tricyclic framework was constructed by the application of a Claisen rerrangement via a chairlike transition state. The precursor for this / 3,37-sigmatropic rearrangement was obtained by treating a lactone precursor with the solution of the Tebbe reagent in the presence of pyridine. The corresponding enol ether was formed in almost quantitative yield, and immediately after isolation it was treated with triisobutylaluminum to effect the Claisen rearrangement. 

A general synthesis of 2-alkyl-3-acylpyridines is achieved from 2-substituted pyridines via a [2,3]-sigmatropic rearrangement of an intermediate a-cyanoamine... 

An interesting rearrangement has been observed in the reaction of pyridine JV-imines with triarylketeneimines an initial 1,3-dipolar cycloaddition is followed by a [l,5]-sigmatropic rearrangement with the subsequent loss of hydrogens, leading to the formation of lH-pyrrolo[3,2-h]pyridines 67 (Eq. 29).192... 

The thermal and acid-catalysed ring-contractions of l-acyl-l,2-diazepines to pyridine iV-imides and/or 2-(acylamino)pyridines is well known. Moore has now reported a new reaction path in the thermolysis of (84), leading to the 1,3-diazepine (85) in addition to a 6-benzamidopyridine. A stepwise conversion of (84) into (85) is favoured, assisted by electron release from oxygen, rather than a sigmatropic rearrangement " [cf. the formation of (65) described above]. 

Oxazoles readily participate in cycloaddition reactions as dienophiles and as dienes in Diels-Alder reactions, and suitably substituted oxazoles participate in sigmatropic rearrangements (e.g., aza-Claisen rearrangements). In particular, the Diels-Alder reaction of oxazoles is one of the most widely explored and synthetically useful reactions, and as such, it has been used extensively both in natural product syntheses and to convert oxazoles to other heterocyclic ring systems. For example, a partial list of heterocyclic systems readily accessible from oxazoles via Diels-Alder reactions or other cycloadditions include pyridines hydroxy-pyridines isoindoles pyridazines tetrahydronaphthyridines benzo[h]-l,6-naphthyridines benzopyrano[3,4-b]pyridines 2-substituted, 2,4-disubstituted,... 

Methyl 2-trifluoromethyl-2-siloxycyclopropanecarboxylate was found to undergo successive smooth deprotonation with lithium di-isopropyl amide and reaction with carbon disulfide and methyl iodide to afford a dihydrothiophene derivative most likely via ring-expansion of the anionic intermediate by a [1,3] sigmatropic rearrangement (14JOC4492).The dide-hydrothiophene derivative was then converted to the corresponding 5-trifluoromethylthiophene by treatment with phosphoryl chloride in refluxing pyridine. An example of this reaction is shown below. 

A synthesis of methyl a-D-sibirosaminide (23) has been reported (Scheme 3), which starts from a 3-C-methylaltropyranoside derivative, and Dyong and Schulte have described the synthesis of a closely related compound (24) from the 2-deoxy-3-ulose (25), which required introduction of the 2-hydroxy-group by means of a [2,3]-sigmatropic rearrangement (Scheme 4). The addition of HCN to the threo-analogue of (25) in the presence of pyridine afforded the kinetic cyanohydrin (axial attack) in 74% yield, whereas in the presence of sodium bicarbonate the thermodynamic product with the opposite configuration was obtained. The two products were isolated as their mesylates, which were... 

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