Ketene-alkyne cycloaddition

R.L. Danheiser and co-workers generated a key vinylketene intermediate via tandem Wolff rearrangement-ketene-alkyne cycloaddition to utilize it in a photochemical aromatic annulation reaction Danheiser benzannulation) for the total synthesis of the phenalenone diterpene salvilenone. ... 

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). 

The intramolecular ketene-alkene cycloaddition has also been used to prepare highly substituted phenols. As originally formulated, a cyclobutenone such as 342 was converted to a phenol derivative (346). When 342 was heated in benzene, ketene 343 was formed. When done in the presence of an alkyne,281 an in situ [2+21-cycloaddition led to a new cyclobutenone (344) but under the reaction conditions, a four-electron electro-cyclic cleavage reaction occurred to give 345. This compound also reacted, via a six-electron electrocyclic... 

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

The common methods for the S5mthesis of p-lactams are cycloaddition reactions such as the Staudinger s ketene-imine cycloadditions, ester enolate-imine cycloadditions, alkyne-nitrone cycloadditions (Kinugasa reaction), alkene-isocyanate cycloadditions, and Torii s cyclocarbonylation of allyl halides with imines. Several cyclizahon reactions of p-amino esters, p-amino acids, p-hydroxamate esters, and a-diazocarbonyls have been developed for the formation of p-lactam ring. N,N-Disubstituted a-haloamides cyclize by C3-C4 bond formation leading to the formation of P-lactam ring. 

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... 

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. ... 

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 are obtained by cycloadditions between isocyanates and ketenes (Scheme 37). Routes to 1,3-oxazinium salts consist of 1,4-cycloadditions either between a,(3-unsaturated (3-chlorocarbonyl compounds and nitriles or between /V-acylimidoyl chlorides and alkynes. Tin(IV) chloride is an effective catalyst for both reactions (c/. Scheme 38). 

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],... 

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). 

Another possibility for the preparation of bicyclic systems such as III/47 from three-membered rings can be realized by a [2+2] cycloaddition of the cyclopropene, III/41, and an unsaturated molecule, III/46, such as alkene, alkyne, ketene, ketenimine, ketone, isocyanate, etc. A large number of examples of this reaction type have been reviewed recently [55]x). 

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%),... 

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