Cycloaddition acetylene

M 10. Krafft, M.E. Regiocontrol in the Intermolecular Cobalt-Catalyzed Olefin-Acetylene Cycloaddition J. Am. Chem. Soc. 1988,110, 968-970... 

An expeditious route to hydroxy butenolides, found in several natural products, also uses a 5-alkoxyoxazole-acetylene cycloaddition. Reaction of 8 with ethyl... 

Figure 9 New inhibitors of CAII are genraated using the enzyme itself as a template for irrevrasible (a) thiol alkylation and (b) azide-acetylene cycloaddition. Exemplary hit compounds and their potencies are shown on the right...

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

CycIoa.ddltlons. Cyclobutene adducts are formed from the reaction of acetylenic derivatives and maleic anhydride through a 2 + 2 cycloaddition (48). The reaction is photochemicaHy cataly2ed (see Photochemical technology). 

Polymerization by Gycloaddition. Bisimides and oligoimides capped with reactive unsaturations such as maleimide, acetylene, and xylylene groups, can be chain-extended by a cycloaddition reaction with proper bisdienes. 

Doubt (75ZN(B)822) has been cast on a number of claims for the formation of 2-azetin-4-ones from cycloaddition of activated isocyanates to acetylenes (70TL119). The simple 2-azetin-4-one (246) was not isolated or even detected directly at -50 °C in the photofragmentation of compound (245), but indirect evidence for its formation was the isolation of adducts (248 X = MeO, MeNH) in the presence of methanol or methylamine (75TL1335). The most convincing evidence for an isolable 2-azetin-4-one involves treatment of the... 

Fluoroalkyl acetylenes are powerful enophiles and Diels-Alder dienophiles but also can give good yields of cyclobutenes in their cycloadditions [115,116,117] (equations 48 and 49)... 

The above cycloaddition process consists of two separate [3-1-2] cycloaddition steps and represents a 1,3-2,4 addition of a multiple bond system to a hetero-1,3-diene [7S7]. The structure ot the azomethine imine intermediate has been proved unequivocally by X-ray analysis [195] Ethylene [194], acetylene [/iS2] . many alkyl- and aryl- as well sgemmal dialkyl- and diaryl-substituted alkenes [196,197, 198, 199], dienes [200], and alkynes [182, 201], certain cyclic alkenes [198, 199,... 

A more conventional cycloaddition occurs with activated acetylenes, however, the intermediate cyclobutene adducts undergo rearrangement to give insertion of two carbon atoms into the enamine chain (55). Thus the enamine (16) reacted with methyl propiolate to give the dienamino ester (73), presumably via the cycloaddition product (65a). 

Terminal alkynes with no electron-withdrawing group next to the acetylenic linkage when treated with enamines merely add across the double bonds of the enamines (9i). But electrophilic alkynes (those with an electron-withdrawing group next to the acetylenic linkage) undergo cycloaddition reactions with enamines. 

Al-Heterocycles, formation from olefins and acetylenes in a metallocomplex-catalyzed cycloaddition reaction and further transformations 98IZV816. 

The addition of 1,3-dipoles to alka-l,3-diynes has been studied in less detail than that to conjugated alkadienes and alkenynes (80UK1801). Conjugated diynes get involved in [2- -3]cycloaddition at the unsubstituted acetylene bond. 

A synthesis of 2-alkyl-2,3-dihydro-y-pyrones (187) from methoxybutenyne and aldehydes has been described (83TL4551). The condensation of lithiomethoxy-butenyne (184) with aldehydes at -78°C leads to the secondary alcohols 185, which form the dihydropyrones 187 via hydration of the acetylenic bond and hydrolysis of the methoxyethenyl group to the ketoenol 186 (0°C, p-TSA, THF, H2O or 30% HCIO4, 20 min) folowed by intramolecular cycloaddition. 

Analogously to ynamines and o, /3-acetylenic ketones, 4-aminobut-3-yn-2-ones react with 1,3-dipoles (68HCA443 73HCA2427 92KGS867). The reaction of 4-dimethylaminobut-3-yn-2-one with diphenylketene follows a route of [2-1-21-cycloaddition (30°C, THF, 1 h) to give 2-acetyl-3-dimethylamino-4,4-diphenyl-cyclobut-2-en-l-one (377) in 15% yield. With ethyl azidoformate (30°C, THF, 3 h), the tiiazole 378 is formed in 82% yield, whereas with phenyl isocyanate, the quinoline 379 is the product (by a [2- -4] scheme) in 70% yield (68HCA443). 

A mechanism for this reaction has been proposed [75], The first key intermediate in the reaction is the copper(I) acetylide 42. The additional ligand may be solvent or H2O. The acetylene moiety in 42 is activated for a 1,3-dipolar cycloaddition with the nitrone to give intermediate 43, with introduction of chirality in the product. A possible route to ris/traws-41 might be via intermediate 44. Finally, the cis isomer is isomerized into the thermally more stable trans-41. It should be mentioned that the mechanism outlined in Scheme 6.32 was originally proposed for a racemic version of the reaction to which water was added. 

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