Dichloroketene 4+2 cycloaddition reactions

Cycloaddition Reactions. Dichloroketene, A-sulfonyl-imines, diazomethane, and aroylketenes add to (1) to provide good yields of a cyclobutenone, 2-azetines, a pyrazole, and 4-pyrones, respectively. Cooligomerization of three molecules of (1) with one molecule of carbon dioxide proceeds in the presence of Ni catalyst, giving a 2-p5Tone derivative in 90% yield. ... 

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). 

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. - " ... 

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... 

A [2+2] cycloaddition reaction of l-[azet-l(277)-yl]-2,3-dimethylpropan-l-one 596 to dichloroketene leading to cycloadduct 597 has been described <2006TL6377>. An immediate reduction of the ketone group in the unstable cycloadduct afforded cyclobutanol-fused azetidine 598 (Scheme 78). 

Although the earliest syntheses of the Corey lactone, using a cyclopentadienyl-thallium species, were not very attractive, it was soon found that the lactone could be usefully generated by a Baeyer-Villiger reaction on a bicycloheptenone.8 In turn, this derives from an easy [2 + 2] cycloaddition reaction between dichloroketene and cyclopentadiene (Scheme 30.2).9 Additionally, an intermediate of the lactone could be resolved by way of the a-methylbenzylamine salt of its opened hydroxyacid, bringing the resolution step earlier in the synthesis than previously.10... 

The Staudinger ketene cycloaddition was utilized as the key reaction in the synthesis of a number of bakkane natural products in the laboratory of A.E. Greene. Dichloroketene was generated in situ from trichloroacetyl chloride by zinc-copper alloy in the presence of phosphorous oxychloride. The [2+2] cycloaddition between dichloroketene and 1,6-dimethylcyclohexene gave the product in high yield and excellent regio- and diastereoselectivity. The cycloadduct was successfully converted to (+)-bakkenolide A. 

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... 

Camphorsulfonyl chlorides 45 readily form amides by reaction with amines. On reduction of the carbonyl group, alcohols, e.g., 46 and 47, are obtained which are extremely useful auxiliaries for many purposes. Thus, esters are formed with carboxylic acids which may then undergo enolate reactions (SectionsD.1.1.1.3.2., D.l.5.2.1., D.3. and D.7.1.) or act as dienophiles and dipolar-ophiles (Sections D.l.6.1.1.1.2.2.1. and D.l.6.1.2.1.). Enol ethers of these auxiliaries give [2 + 2] cycloadditions with dichloroketene (Section D.l.6.1.3.), while carbamate derivatives have been used in acyliminium reactions (Section D.l.4.5.). Generally, steric hindrance in the sulfonamide group improves the stereoselectivity of the reactions and, therefore, the amides with diisopropylamine and dicyclohexylamine are used as auxiliaries both enantiomers of the dicyclohexyl derivative are commercially available. 

DicWoroketene is particularly reactive, and reductive dechlorination of the product with zinc and acetic acid allows access to the cyclobutanone from formal addition of ketene itself. Thus, cycloaddition of dichloroketene with cyclopentadiene, followed by dechlorination and Baeyer-Villiger oxidation gave the lactone 173, a usehil precursor to various oxygenated cyclopentane products (3.117). Intramolecular cycloaddition reactions of ketenes can allow the formation of bicyclic and polycyclic products using otherwise unstable ketene intermediates. ... 

Another useful method for the preparation of tropolone utilises the cycloaddition reaction of dichloroketene with cyclopentadicne to give a bicyclo[3.2.0]heptenone derivative which can be transformed into tropolone [251,252]... 

The chemo-,46 regio-, and stereoselective [2+2]-cycloaddition of dichloroketene to olefins is a versatile reaction that gives access to a wide variety of synthetically useful... 

Nevertheless, in some cases the [2+2]-cycloaddition reaction under ultrasonic irradiation does not proceed or the yield is low. Different zinc powders were tested for the [2+2]-cycloaddition of dichloroketene with 1-methyl-l-cyclohexene. In line with the results of Takai et who reported the importance of catalytic amouts of lead on zinc reactions, we observed that zinc dust free of lead impurities was indeed poorly reactive, affording only ca. 10% of the cycloadduct. However, the reactions carried out under the same conditions, but with zinc powders containing lead as an impurity (from Union Mini re, Belgium), gave the cycloaddition product in 65-75% yield. The addition of a catalytic amount (0.5 mol%) of PbCl2 afforded highly reproducible results (80% yield after distillation). 

Shenone et al. have reported numerous examples of [4 + 2] cycloadditions of dichloroketene with N,N-disubstituted vinyl ketones 99 to afford 5-lactones or 2-pyrone 100 derivatives (Scheme 33) (1979JHC93, 1978JHC181). The synthetic usefulness of this less frequently observed, 1,4-addition reaction of a ketene has been well estabHshed for the synthesis... 

Dichloroketene can be reacted with N,N-disubstituted 2-aminomethy-lene-cyclopentanones 101a, -cyclohexanones 101b, -cycloheptanones 101c, and -cyclooctanones lOld to afford the 1,4-cycloaddition products, N,N-disubstituted 3,3-dichloro-4-amino-5,6-poly-methylene-3,4-dihydro-u-pyrones 102 (Scheme 34) (1972JHC1071). Diphenylketene and ketene also can undergo this 1,4-cycloaddition reaction (1967MFC1518). 

The first total synthesis of trihydroxydecipiadiene (45), a member of the structurally unique decipiene diterpenes, has been reported. A route involving cycloaddition of dichloroketen and reductive dehalogenation led to (42) which was found to undergo a stereospecific aldol reaction to give (43) under carefully controlled conditions. As expected, catalytic hydrogen was stereospecific giving the desired isomer (44), which in turn was converted to (45) in several steps. 

Vinyl sulfilimines 359 react with dichloroketene via a [3+2] cycloaddition reaction to give Q -dichloro-y-butyrolactams 360 . ... 

Various chiral cyclobutanone derivatives have been prepared by cycloaddition of dichloroketene to the glycal (1), as shown in Scheme 1. A number of other reactions of (2) and (3) were also reported, including Baeyer-Villiger oxidations to y-lactones.. S... 

Greene and co-workers used a dichloroketene/enol ether cycloaddition and a Beckmann ring expansion as key reactions en route to (+)-preussin [76]. 

Unlike ordinary alkenes, ketenes do 2 + 2 cycloadditions with themselves—the dimerisation above—and with other alkenes.1 Reaction of dichloroketene with cyclobutadiene 11 to give the... 

Ketene Cycloadditions. As we saw earlier [see (Section 6.3.2.8) pages 211 and 212], ketenes undergo cycloadditions to double bonds 6.118 (repeated below) to give cyclobutanones. In practice, the reaction is faster and cleaner when the ketene has electron-withdrawing groups on it, as in dichloroketene, and when the alkene is relatively electron-rich, as in cyclopentadiene. The product from this pair of reagents is the cyclobutanone 6.249. 

S.2 Cycloadditions Involving Ketenes We next present two examples of cycloadditions involving ketenes that invoke a bifurcating PES. The cycloaddition of ketene with cy clopentadiene had long been thought to simply give the formal [2-1-2] product, such as the reaction of cyclopentadiene 67 with dichloroketene 68... 

Examples of the application of this chemistry to the preparation of cyclobutanones, cyclobutenones, and P-lactams are presented in the Table. The mesityl thiol ester has proven to be particularly effective in reactions with less ketenophilic alkenes, although with the more reactive ketenophiles nearly identical results are obtained using either the mesityl a-diazo thiol ester or the more readily available thiophenyl ester. In the case of readily available ketenophiles, the reaction is best conducted using excess alkene, alkyne, or imine, but in other cases the cycloaddition can be carried out with excess diazo thiol ester. The efficiency of the reaction with unactivated alkenes is especially notable, and compares favorably with results obtained previously employing dichloroketene. For example, addition of dichloroketene to methylenecyclohexane is reported to proceed in 55% yield," while up to 81% of the desired [2-1-2] cycloadduct is produced in the reaction of (mesitylthio)ketene with this olefin under our conditions. 

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