Siloxydiene asymmetric Diels-Alder reaction

Several groups exploited the power of the intermolecular Diels-Alder reaction early in their syntheses for the formation of substituted cyclohexenes. In his synthesis of platencin, Nicolaou used a Danishefsky-like diene in an asymmetric Diels-Alder reaction for the synthesis of a chiral cylohexenone. Kanai and Shibasaki developed a catalytic asymmetric Diels-Alder reaction promoted by barium isopropoxide for the first step in their synthesis of Tamiflu. Danishefsky constructed the cyclohexene ring in paecilomycine A by employing a highly e t/o-selective Diels-Alder reaction of siloxydiene 115 and enyne dienophile 116 to yield target 117. ... 

Shibasaki et al. also developed a chiral baiium-catalyzed asymmetric Diels—Alder reaction of a siloxydiene with fumarate for the synthesis of an optically active Tamiflu precursor [104] for a review of asymmetric Diels—Alder reactions, see [105]. Metal exchange from silicon to barium occurred via activatitm by CsF to form an activated chiral diene, which reacted with fumarate with high enantioselectivity (Scheme 11). 

The asymmetric total synthesis of the natural enantiomer (—)-nakadomarin A was completed by Nishida et al. in 2004 (Scheme 8.12) [82]. Diels-Alder reaction between siloxydiene 173 and chiral dienophile 172 (prepared from L-serine in 10 steps [83]) gave the highly functionalized key intermediate hydroisoquinoline 174, which was subjected to Luche reduction, cyclization, and HCl treatment to furnish the tricyclic intermediate 175. Compound 175 was converted to 177 via ozonolysis cleavage of ring B followed by recyclization of the unstable bisaldehyde to a five-membered ring by aldol condensation. The Z-olefin 178 was obtained from Wittig reaction of 177, and was further converted to furan 180 via peroxide 179. The... 

Danishefsky and co-workers pioneered the use of chiral lanthanide complexes as catalysts in organic reactions. They found out that Eu(hfc)3, which is used as an NMR shift reagent, promoted hetero Diels-Alder reactions [30] of aldehydes with siloxydienes and induced enantiomeric enrichment (Sch. 1) [31]. Suitable substituents on the dienes were introduced to improve the extent of asymmetric induction. The best result was obtained in the reaction of benzaldehyde with l-methoxy-2-methyl-3-(trimethyl-siloxy)- , 3-butadiene using 1 mol % Eu(hfc)3 the enantiomerie excess was, however, moderate (58%). The authors maintained that the major advantage of lanthanide catalysis lay in the survival of otherwise labile systems used as adducts. 

Since Danishefsky demonstrated that activated dienes, such as siloxydiene (commonly referred to as Danishefsky s diene) react with a wide spectrum of aldehydes to afford 5,6-dihydro-y-pyrones in 1982 [l],the hetero-Diels-Alder reaction has attracted a great deal of attention over the last two decades [2,3]. The use of asymmetric catalysis in these reactions is overwhelmingly associated with heterodienophiles. Especially, the cyclocondensations of activated dienes with aldehydes or their derivatives are of particular importance, providing a multitude of opportunities for the highly efficient regio- and stereoselective construe-... 

The cycloadditions of aldehydes with chiral siloxydienes, bearing the chiral substituent at the 1-position, proceed with moderate selectivities in the presence of Eu(fod)3 or Eu(hfc)3 at low temperature. Asymmetric thermal hetero Diels-Alder reaction of triketones with 2-methyl-l-(l-phenylalkoxy)-1,3-butadienes bearing the chiral alcohols 16 or 17 (Chapter 6) as auxiliaries lead highly selective to the cycloadducts. ... 

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