Transition-Metal Catalysis of the Michael Reaction of 1,3-Dicarbonyl Compounds and Acceptor-Activated Alkenes

Tetrahedron report number 230

Synthetic Connections to the aromatic directed metalation reaction. Radical-induced cyclization to substituted benzofurans, benzopyrans, and furopyridines

Macroexpansion methodology : Medium ring synthesis based on an eight unit ring expansion process

Publisher Summary The Claisen rearrangement of heteroaromatic allyl ethers shows many similarities to the rearrangement of simple benzenoid aromatic allyl ethers. Mechanistically, the reactions are for the most part genuine [3,3]-sigmatropic rearrangements, although the presence of nitrogen in the aromatic ring does allow alternative pathways to operate, and hence more than one product may be formed. However, these alternative products are usually easily rationalized on mechanistic grounds. One other difference between the Claisen rearrangement of heteroaromatic ally1 ethers (or thioethers) and their benzene counterparts is that the rearrangement product is often more stable in the one form than as the hydroxy (or mercapto) heteroaromatic compound. The Claisen rearrangement has been widely used in the synthesis of natural heterocyclic products. Although much of this work has been in the coumarin series, there are now several alkaloid syntheses in which the Claisen rearrangement features as a key step. Indications are that the Claisen rearrangement continues to hold an important role in organic chemistry.

Claisen rearrangements in heteroaromatic systems

The Cope Rearrangement, a Reaction for Repeatable Ring Expansions - Starting with the unsaturated beta-ketoesters of type I, a vinyl group is introduced into the beta-position by 1,4-addition of vinyl magnesium chloride to give II (Scheme 3). Treatment of the beta-ketoester II with phenyl vinyl sulfoxide in the presence of sodium hydride yields the sulfides III, which on thermolysis lead to the alpha,beta-divinyl ketoesters of type IV via elimination of sulfinic acid (Scheme 3). The Cope-System IV undergoes rearrangement to V, which is again an unsaturated beta-ketoester. The latter is suitable for a further ring expansion sequence. These reaction steps were carried out with the nine-, twelve- and fifteen-membered ketoesters 32, 33 and 34, as well as with the open-chain compound 35 (Table 1). With the cyclohexane derivative 31, ring expansion could not be achieved with the described sequence.

Die Cope‐Umlagerung als Prinzip einer repetierbaren Ringerweiterung

Claisen Rearrangement of 2-Propinyl (3-Pyridyl) and Allyl (3-Pyridyl) Ethers1



2-Propinyl (3-pyridyl) ether (1), synthesized from the corresponding 3-pyridinol, was heated in DMF or decane at 208° in a sealed tube. In this way the furopyridines 2 and 3 were formed, and furthermore the pyranopyridine 4 if decane was used as solvent (Scheme 1). The same reactions took place with (2-methyl-3-pyridyl) 2-propinyl ether (14). In DMF only 15, and in decane 16 as well as 15 were formed (Scheme 3). The rearrangement of the pyridine derivative 17, which is substituted in both O-positions to the ether moiety, gave in both DMF and decane the diastereoisomeric tetracyclic compounds 18 and 19. The same kind of reaction took place with 25 (Scheme 4).



In the thermolysis of the allyl 3-pyridyl ether (27) cyclization was observed, too. The isolated product has the structure of the dihydrofuropyridine 28 (Scheme 6). The substituted allyl 3-pyridyl ether 30 reacted in the same way to the dihydrofuropyridine 31 (Scheme 6).

Jens Bruhn

Papers

Die Cope‐Umlagerung als Prinzip einer repetierbaren Ringerweiterung

Claisen-Umlagerung von 2-Propinyl-(3-pyridyl)-und Allyl-(3-pyridyl)äthern†

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