DANHEISER Annulation

OAKIN Oxidation 84 DAKIN WEST Acylation 84 DANHEISER Annulation 85 DANISHEFSKY Sitytoxydenes 66 DARAPSKI Ammoacid synthesis 87 DARZENS-NENITZESCU Acylation 87 DAR2fENS Epoxide synthesis 88 DAVIDSON Oxazola synthesa 89 OELEPINEAMehydeoxidalion 89 DAVIS Oxidizing reagent 90 Decker 127... 

Other references related to the Danheiser annulation are cited in the literature. 

The Danheiser annulation, in its classic form, is the Lewis acid-catalyzed reaction of an a,yff-unsaturated ketone 1 with a trimethylsilylallene 2 to form a silyl cyclopentene 3. More broadly, the Danheiser annulation ecompasses reactions of silylallenes 4 with electrophilic double bonds to form cyclic products 5, usually under Lewis acid catalysis. The Danheiser annulation should not be confused with other annulation processes developed by Danheiser, such as Danheiser s aromatic annulation and the Stork-Danheiser alkylation. ... 

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... 

The original application of the Danheiser cyclization was for the preparation of cyclopentenes employing a, -unsaturated ketones as the electophilic component of the annulation process. A variety of a, y9-unsaturated ketones with various alkyl substitution patterns readily participate in the Danheiser annulation. ... 

The Danheiser annulation has also been reported to be useful for the preparation of substituted azulene products." For example, treatment of silylallene 58 with tropylium cation 59 at 23 °C produces intermediate cyclopentene dihydroazulene 60, which is not isolated but rather undergoes in situ dehydrogenation with a second equivalent of tropylium cation 59 to provide azulene 61. The use of the tert-butyldimethylsilyl group as opposed to the trimethylsilyl group is necessary since the trimethylsilyl group tends to undergo premature desilylation rather than cyclization to the azulene. Substitution at the 3-position of the allene was also found to significantly... 

The use of other electrophiles in the Danheiser annulation for the formation of cyclopentenes is relatively unexplored. Ynones have been reported to imdergo cycloaddition, although examples are limited. Thus treatment of butynone 64 with silyl allene 47 under the usual conditions delivered cyclopentadiene 65 in 53% yield. Danheiser has reported that nitroalkenes do not provide annulation products furnishing instead acyclic alkynes. For example, treatment of nitroalkene 66 with silylallene 34 under standard conditions gives alkyne 67 rather than the cyclopentene 68. afi-Unsaturated aldehydes have been reported to be problematic, failing to provide isolable cyclopentene products. Treatment of methacrolein (69) with silylallene 34 under the standard conditions produced only a complex mixture of unidentified products. 

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. 

Two reports of enantioselective Danheiser annulations have appeared in the literature. Evans et al. have reported the annulation of ethyl glyoxylate (104) to form dihydrofuran products in good to excellent enantioselectivity using a chiral scandium catalyst. For example, reaction of ethyl glyoxylate (104) with tert-butyldiphenylsilylallene 105 in the presence of the chiral scandium catalyst 106 led to dihydrofuran 107 in 91% yield and 92% ee. As... 

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... 

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