Alkynes 2+2 -cycloaddition with ketenes

For thermally induced [2 + 2] cycloadditions, the concerted mechanism is operative only in particular cases, such as in the reactions between an alkene or alkyne and a ketene. The ketene can be generated directly in the reaction mixture from the appropriate acid chloride with triethylamine. The cycloaddition reaction is stereospecific and occurs exclusively in a cis fashion. Although the intermolecular cycloaddition with ketene itself proceeds in poor yields due to the propensity of the unsubstituted ketene to undergo dimerization, it is quite an efficient reaction with ketenes containing electron-withdrawing substituents. Usually, a-chloro ketenes are employed as reagents formed in situ from the corresponding a-chloro acid chlorides. Typical examples are represented in the preparation of cycloadducts such as 378 and 379 (Scheme 2.127). The latter cycloadduct, prepared in modest yield (ca. 20%),... 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Merlic demonstrated the direct, non-photochemical insertion of carbon monoxide from acylamino chromium carbene complexes 14 to afford a presumed chromium-complexed ketene 15 <00JA7398>. This presumed metal-complexed ketene leads to a munchnone 16 or munchnone complex which undergo dipolar cycloaddition with alkynes to yield the pyrroles 17 upon loss of carbon dioxide. 

Cycloaddition to alkynes, cyclobutenones. This ketene when formed in situ from CCI3COCI and Zn/Cu, reacts with alkynes to form 4,4-dichlorocyclobuten-ones,3 which can rearrange in part to 2,4-dichlorocyclobutenones.4 Both products are reduced to the same cyclobutenone by Zn(Cu) in HOAc/pyridine (4 1) or by zinc and acetic acid/TMEDA.5... 

As with the transition state of the [4+2]-addition of butadiene and ethene (Figure 15.8) both HOMO/LUMO interactions are stabilizing in the transition state of the [2+2]-addition of ketene to ethene (Figure 15.13). This explains why [2+2]-cycloadditions of ketenes to alkenes—and similarly to alkynes—can occur in one-step reactions while this is not so for the additions of alkenes to alkenes (Section 15.2.3). 

Dienophiles substituted with appropriate heteroatoms may offer a number of advantages such as (1) provide dienophilic equivalents of C-—C and moieties which do not undergo [4 + 2] cycloadditions to 1,3-dienes because of low (e.g. isolated alkenes, alkynes, allenes) or different reactivities (e.g. ketenes) (2) enhance or invert the regiochemistry of the Diels-Alder process (3) permit facile removal of the activating and/or regiocontrolling group after cycloaddition with or without introduction of further functionalities. The use of nitroalkenes as dienophiles demonstrates these issues most strikingly. 

Cycloadditions of ketenes with alkenes and alkynes constitute the most popular method for the synthesis of cyclobutanones and cyclobutenones. Unfoitunately, however, this process is truly general only for highly nucleophilic ketenophiles such as conjugated dienes and enol ethers. In general, unactivated alkenes and alkynes fail to react in good yield with either alkyl- or aryl-substituted ketenes, or with ketene itself To circumvent this limitation, dichloroketene is usually employed as a ketene equivalent, since this electrophilic ketene reacts well with many types of unactivated multiple bonds, and the resultant cycloadducts undergo facile dechlorination under mild conditions. ... 

The procedure described here illustrates a practical and convenient method for the generation of thio-substituted ketenes which participate in surprisingly facile cycloadditions with both activated and unactivated alkenes, alkynes, and imines to form four-membered carbocycles and heterocycles. As... 

In the presence of alkynes and PPhs, no ReCp 02( -RCsCR) complex is formed, as in the ReMeOs case. Cycloaddition of ketenes to (126) and (127) gives the Re species (128) and (129). No glycolates are formed in similar reactions with alkenes, in contrast to Tc analogs and OSO4,... 

Alkynyl complexes have been reported to undergo [2+2] and [2+4] cycloaddition reactions with ketenes Alkynes have been reacted with cyclopropylcarbene-chromium... 

The scope of the Diels-Alder cycloaddition in synthesis planning is extended by the fact that both terminal and internal alkynes (RC=CH, RC=CR) enter into [4 - - 2] cycloadditions with dienes in the presence of Co(0) catalysts. These cycloadditions result in cyclohexa-1,4-dienes arising from a formal Diels-Alder reaction [33, 34]. Finally, numerous synthetic equivalents for ketene to be used in [4 + 2] cycloadditions have been developed in the context of prostaglandin sjmtheses. Thus, a broad range of possibilities for achieving these cycloadditions is now available [35, 36, 37] (Scheme 6.13). 

Bicyclo[3,2,0]heptane Derivatives.— These are principally prepared by the [2 -I- 2] cycloaddition of a cyclopentene with another unsaturated unit. Typical combinations which have been routinely applied in syntheses are photochemical addition of a cyclopentene to an olefin or acetylene and thermal addition of a cyclopentadiene with an olefin, a keten, or an acetylene. In the last case, cycloaddition with an alkyne is complicated both by competition between [2 -h 2] and [2 + 4] modes of addition and by the possibility of a second addition of cyclopentadiene to the initially formed bicyclo[3,2,0]heptadiene. The results for diphenylacetylene and cyclopentadiene are shown in Scheme 31. 

Reactive Enophile in [4 + 2] Cycloadditions. Vinylketenes are not effective as dienes in Diels-Alder reactions because they undergo only [2 + 2] cycloaddition with alkenes, as predicted by frontier molecular orbital theory. However, silylketenes exhibit dramatically different properties from those found for most ketenes. (Trimethylsilyl)vinylketene (1) is a relatively stable isolable compound which does not enter into typical [2 + 2] cy do additions with electron-rich alkenes. Instead, (1) participates in Diels-Alder reactions with a variety of alkenic and alkynic dienophiles. The directing effect of the carhonyl group dominates in controlling the regiochemical course of cycloadditions using this diene. For example, reaction of (1) with methyl propiolate produced methyl 3-(trimethylsilyl)sahcylate with the expected regiochemical orientation. ProtodesUylation of this adduct with trifluoroacetic acid in chloroform (25 °C, 24 h) afforded methyl salicylate in 78% yield (eq 2). 

The inverse-electron-demand Diels-Alder reaction of 3,6-dichloro[l,2,4,5]tetrazine with alkenes and alkynes provides the synthesis of highly functionalized pyridazines. ° Also, the 4 + 2-cycloaddition reactions of the parent [l,2,4,5]tetrazine with donor-substituted alkynes, alkenes, donor-substituted and unsubstituted cycloalkenes, ketene acetals, and aminals have been investigated. ... 

In an analogous late-stage arylation approach, terminal alkyne 31 was envisioned as a versatile intermediate. Slow addition of 4-pentynoyl chloride to imine 3 and (n-Bu)3N at reflux (efficient condenser, 100°C, 12 h, 1 1 toluene heptane) afforded only trace amounts of 31. Reaction of 4-pentynoyl chloride with triethylamine in methylene chloride under preformed ketene conditions ( 78°C, 1 h), followed by addition of 3 and warming to — 10°C over 4 h, afforded a complex mixture of products. Since high-yield preparation of 31 remained elusive, access to internal alkynyl analogs (type 33) was accomplished by preassembly of the appropriate arylalkynyl acid substrate for the ketene-imine cycloaddition reaction (Scheme 13.9). 

Thermal and photochemical cycloaddition reactions of 27r-electron species represent an important synthetic approach to four-membered rings. The reactions summarized in this section include 2 + 2 cycloaddition reactions of thioketones, thioketenes, isothiocyanates, sulfenes and iminosulfenes with alkenes, allenes, ketenes, ketenimines and alkynes. 

Oxazin-4-ones and -thiazin-4-ones are well represented in the chemical literature. Thiazin-4-ones can be synthesized from 1,3-oxazinium salts by the action of hydrogen sulfide and potassium carbonate (81H(15)85l) and oxazin-4-ones are obtained by cycloadditions between isocyanates and ketenes (Scheme 73), or alkynes (Scheme 74), or between nitriles and acylketenes (Scheme 75). Similarly diketene is often used and affords oxazin-4-ones by its reactions with imidates and cyanamides (Scheme 76) (80H(14)1333>. 

Cycloaddition of a ketene complex with unsaturated bonds other than alkenes and alkynes is also possible. The ketene 312, formed from 311, adds to imine 313 to give the /1-lactam 314 under sunlight photolysis. The optically active /1-lactam 314 was prepared from the optically active carbene complex 311 with 99% ee, and converted to 315 [95]. Irradiation of carbene complex 316 generates ketene 317, which cyclizes to the o-hydroquinone derivative 318 [96],... 

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