Formal Danheiser annulation

The generally accepted mechanism of the classic Danheiser annulation involves three basic steps the Lewis acid-catalyzed electrophilic combination of the a, 0-unsaturated ketone with the silylallene, a 1,2-sp-silyl migration, and a final cyclization step. This mechanism was first proposed by Danheiser in the original publication of the annulation and has been generally accepted but has never been formally investigated. A more detailed account of the reaction pathway is shown below. Treatment of the a,y5-unsaturated ketone 1 with TiCU produces a titanium complex existing as two resonance-stablized cations 26 and 27. Attack of the 2,3-7c-bond of the... 

Two methods for accomplishing a formal [3 + 3] cycloadditions using the Danheiser annulation have been reported. Angle et al. reported that formation of dihydronaphthalene 99 was formed in 77% yield from the reaction of benzyl alcohol 97 with silylallene 98 in the presence of SnCU. Alternatively, the use of hydroxysubstituted benzyl alcohols provides the spirofused cyclopentene products. Treatment of hydroxybenzyl alcohol 100 with silylallene 98 in the presence of SnCU produces spirocyclopentene 101 in 76% yield. Depending on the nature of the substituents on the aryl ring, mixtures of dihydronaphthalenes and spirocyclopentenes may be obtained. 

Yadav et al. have reported using cyclopropanes as the electrophilic component in the Danheiser annulation leading to the formation of cyclohexene products.Treatment of cyclopropane 102 with Et2AlCl at 25 °C resulted in ring opening of the cyclopropane, which then underwent reaction with silylyallene 34 to afford cyclohexene 103, formally a [3 + 3] annulation product. 

The Danheiser annulation has been featured in the formal total synthesis of the natural products ( )-clavukerin (116) and ( )-isoclavukerin (117) reported by Schafer and coworkers. Cycloheptenone 118 was prepared in a three-step sequence from cycloheptadiene. Cycloheptenone 118 was then... 

H.J. Schafer et al. achieved the formal total synthesis of the trinorguaiane sesquiterpenes ( )-clavukerin and ( )-isoclavukerin by using the Danheiser cyciopentene annulation as the key step. Racemic 4-methylcyclohept-2-en-1-one was reacted with (trimethylsilyl)allene in the presence of 1.7 equivalents of TiCU in dichloromethane at -78 °C to afford a 1 1 mixture of the c/s-fused diastereomers, which were easily separated by HPLC. The diastereomers were then converted to key fragments of earlier total syntheses of the above mentioned natural products. 

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