Chiral auxiliaries Nazarov cyclization

Cross-conjugated dienones carrying a chiral auxiliary, suitable for Nazarov cyclization to provide chiral cyclopentenones, have been prepared from reaction of lithiated ethers 153/154 and 155" with A -alkenoylmorpholines. 

An early variant of the Nazarov cyclization119 employed an alkoxycarbonyl substituent and Lewis acid catalysis to facilitate the reaction. The cyclizations were described as temperamental", but did demonstrate the capability to facilitate the cyclization and control the site of the alkene in the cyclized product. For example, cyclization of the a,a -dienone 7 is promoted by the action of trimethylsilyl iodide to afford the /i-keto ester 8 in 48% yield. No studies in stereoinduction have been reported, but, given the recent advances in the design of chiral Lewis acids and the efficient chiral auxiliaries for the reactions of carboxylic acid esters, these substrates are potentially suitable candidates for such studies. 

As with many asymmetric processes, there are three ways to control absolute stereochemistry in the Nazarov cyclization Asymmetry transfer, the use of chiral auxiliaries, or asymmetric catalysis. It is important to realize, however, that there are two distinct processes operating that determine the stereochemistry of the product. To control the absolute stereochemistry of the p-carbon atom(s), it is necessary to control the sense of conrotation, clockwise or counterclockwise (torquoselectivity, see Section 3.4.3). To control the absolute stereochemistry of the a-carbon atom however, it is necessary to control the facial selectivity for enol protonation. 

Several groups have reported the use of chiral auxiliaries to control the stereochemical course of the Nazarov cyclization. In general, this strategy has proved effective, with the products isolated in good... 

Several reports gave account of the successful employment of chiral oxazolidinones as chiral auxiliaries. For example, they were used to direct, with a proper stereocontrol, the synthesis of modified amino acids (13BJ02009) and iso-fatty acids (13BJO1807) in one case, they were used to control a torquoselective Nazarov cyclization that yielded a precursor of the natural compound (+)-pauci lorol F (130L4118). 

Computational studies of oxazolidinone-directed Nazarov cyclization show that the chiral oxazolidinone auxiliaries provide control over the torquoselectivity of 4n electrocyclic ring closure and the regioselectivity of subsequent deprotonation (Scheme 177). °... 

SCHEME 19.31. Pyranose-derived chiral auxiliaries for asymmetric Nazarov cyclization. 

Banaag AR, Tius MA. Traceless chiral auxiliaries for the allene ether Nazarov cyclization. J. Org. Chem. 2008 73 8133-8141. 

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