Cycloaddition of dichloroketene

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

The present procedure, based on the last method, is relatively simple and uses inexpensive starting materials. Step A exemplifies the 2 + 2 cycloaddition of dichloroketene to an olefin, " and the specific cycloadduct obtained has proved to be a useful intermediate in other syntheses. Step B has been the subject of several mechanistic studies, and its yield has been greatly improved by the isolation technique described above. This synthesis has also been extended to the preparation of various tropolone derivatives. " ... 

Dechlorination of 4,4-dichlorocyclobutenones.2 These products of [2 + 2] cycloaddition of dichloroketene with alkynes (9, 153) can be reduced satisfactorily and without isomerization by zinc dust in ethanol containing 5 equiv. each of acetic acid and a tertiary amine (preferably TMEDA). 

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with N-bromosuccinimide from cyclo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - The present procedure, based on the last method, is relatively simple and uses inexpensive starting materials. Step A exemplifies the 2 + 2 cycloaddition of dichloroketene to an olefin, " and the specific oycloadduot obtained has proved to be a useful intermediate in other syntheses. " Step B has been the subject of several mechanistic studies, " and its yield has been greatly improved by the isolation technique described above. This synthesis has also been extended to the preparation of various tropolone derivatives. - " ... 

Cycloadditions give better efficiency and stereocontrol for ring formation. A high regioselectivity (95 5) for the cycloaddition of dichloroketene to a cyclohexene en route to synthetic eriolanin [164] has been observed. It appears that the allylic methoxy group play a dominant role. Note that the proximal sp2-carbon is a donor by virtue of its 1,3-relationship with the oxygen function. 

The [2 + 2] cycloaddition of dichloroketene to an alkene is probably the most common non-photolytic method for cyclobutane synthesis (see Sections 1.3.1., 1.3.5. and 5.1.2.3.). The 2,2-dichlorocyclobutanones thus obtained readily undergo reductive dechlorination. Two... 

Cyclobntane. A few examples of cyclobutane derivatives have been described in the carbohydrate series. Formation of this type of ring involves a 2+2 cycloaddition. Relevant examples of cycloaddition of dichloroketene on glucals, explored by Redlich [195] and Lallemand [196,197], and significant transformations of the four-membered ring, such as ketone 165a, are given in Scheme 56. 

In an extension of this method, the cycloaddition of dichloroketene to the heterocyclic aminomethyleneketone (341) yields the dihydropyranone which is dehydrochlorinated with DBN to the fused pyran-2-one (Scheme 104) (78JHC181). Similar behaviour is shown by the benzologue of the enamine. 

An ab initio study of the 2 + 2-cycloadditions of allene to isocyanic acid and ketene to vinylimine found the reactions to be concerted and mostly asynchronous.28,29 The diastereoselective 2 + 2-cycloaddition of dichloroketene with a chiral enol ether (26) produced the cyclobutanone (27), which leads to a key intermediate (28) in (g) the total synthesis of the natural alkaloid (-)-Swainsonine (29) (Scheme 8).30 The... 

Fig. 14.22. Ring expansion of cyclobuta nones. The cydobutanones are accessible via [2+2]-cycloadditions of dichloroketene (for the mechanism, see Section 15.4).

Au-Yeung and Fleming have devised a new alternative synthesis of loganin (590) based upon allylsilane chemistry.438 The bicyclic ketone 586, obtained by cycloaddition of dichloroketene to trimethylsilylcyclopentadiene, was monodechlorina-ted, ring expanded with diazoethane, and again dehalogenated prior to equilibration... 

Cyclobutenediones. A general route to these diones involves the regiospecific cycloaddition of dichloroketene to the phenylthio enol ether (1) of a ketone. The adduct (2) on treatment with triethylamine eliminates (J MsSCI and rearranges to 3. Peracid oxidation of 3 results directly in a cyclobutenedione (4). 

Enantiospecific addition to chiral vinyl sulfoxides. The cycloaddition of dichloroketene (11, 169-17(1) to optically pure (R)- or (S)-l-cyclohexenyl tolyl sulfoxides (1) leads to optically pure y-butyrolactoncs (2) with complete cnantiospecificity at the two chiral centers. A third hiral ew-center is introduced in the addition of monochloroketene. 

The most recent formal asymmetric synthesis of (+)-anatoxin-a was achieved through a highly diastereoselective [2+2] cycloaddition of dichloroketene with a chiral enol ether(63 Scheme 7.15) in order to reach the general stracture of 2,5-disubstituted pyrrolidine (66) for generating the acyliminum ion and getting the required bicycle skeleton (67) (Muniz et al. 2005). 

I -CycloatUition, 22 222 2, 118 3, 87-88). Two reviews have been published recently on the 1,2-cycloaddition of dichloroketene to olefins and dienes. In general, the best yields of cyclobutanones are obtained when the dchydrochlorination of dichloroacetyl chloride with triethylamine is conducted between 30 and 50° in a hydrocarbon solvent containing an excess of the ketenophile. The following reactivity sequence has been observed in the behavior of various keienes with cyclopentene ... 

The cycloaddition of dichloroketene to trisubstituted olefins has been reported by Jeffs and Molina. Thus dichloroketene reacts with l-methylcyclohexene (I) to give... 

O-Pivaloyl-D-galactopyranosides were shown to be efficient stereodifferentiating tools [9]. Thus, the [2-1-2] cycloaddition of dichloroketene to chiral vinyl galactoside 27 afforded the cyclobutanone 28 with reasonable stereoselectivity (dr 4 1) [26] (Scheme 10.6). The resulting 2,2-dichlorocyclobutanones are reactive and often cannot be isolated in pure form. More stable cyclobutanols were isolated after reduction of the keto group [26]. 

Investigations by J. Oh showed that the cycloaddition of dichloroketene to glucal followed by Baeyer-Villiger oxidation afforded a bicyclic y-lactone, an a-D-C-glucoside, which was further transformed to a C1-methyl glucitol derivative. ... 

Subsequently, the absolute configuration of the natural lineatin was determined as (lR,4S,5R,7R)-77 by our second synthesis, as shown in Figure 4.16.35 The first step was the cycloaddition of dichloroketene to isoprene to construct a cyclobutane ring. The symmetrical cyclobutanone A was then converted to ( )-bicyclic lactone B. Enantiomer separation (optical resolution) of ( )-B was executed as follows. Reaction of ( )-B with the resolving agent C (derived from chrysanthemic acid) yielded a diastereomeric mixture... 

Cycloadditions of ketenes with olefins follows orbital symmetry requirements.2 Knoche3 has reported the cycloaddition of dichloroketene to butyne-2 (yield 12%). 

Tabic 1. 2,2-Dichlorocyclobutanoncs from the Cycloaddition of Dichloroketene to Chiral Propeny] Ethers... 

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