Cycloadditions with alkynes

Chlorination of sodium cyanodithioformate gives 3,4-dichloro-5-cyanoisothiazole (227), probably via the isothiazolodithiine (226) (72AHC(l4)l). The thienoisothiazole (228) undergoes cycloaddition with alkynic esters to give adducts such as compound (229), which... 

Unactivated aziridines, such as 24, are not as reactive as their N-sulfonyl analogues. Nevertheless, in aqueous conditions they react with different nucleophiles, as Scheme 12.23 illustrates. Treatment with buffered azide at 50 °C gave 25 in 90% yield. Hydrazine proved potent even at room temperature and 26 was fonned in 95 % yield, while phenyltetrazole required heating at reflux in water. The resulting amines participated in dipolar cycloadditions with alkynes and condensations with P-diketones. 

By combining several click reactions, click chemistry allows for the rapid synthesis of useful new compounds of high complexity and combinatorial libraries. The 2-type reaction of the azide ion with a variety of epoxides to give azido alcohols has been exploited extensively in click chemistry. First of all, azido alcohols can be converted into amino alcohols upon reduction.70 On the other hand, aliphatic azides are quite stable toward a number of other standard organic synthesis conditions (orthogonality), but readily undergo 1,3-dipolar cycloaddition with alkynes. An example of the sequential reactions of... 

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. 

TABLE 2.41. INTRAMOLECULAR SILYL NITRONATE CYCLOADDITIONS WITH ALKYNES... 

ANR/versatile 1,2,4,5-tetrazine cycloaddition with alkynes Boger 1999A... 

The 1,2-dihydropyridine ring can also undergo [2 + 2] cycloaddition with alkynes (Scheme 58). 

An intramolecular double nitrile oxide cycloaddition with alkyne and olefin moieties was exploited in the synthesis of novel unsymmetrical hybrid spiro (isoxazole-isoxazoline) ligands 14 which were effective in promoting a Pd-catalyzed tandem cyclization <07TA919>. 

The reaction is successful only if the alkynes have EWGs attached and the thiophenes are substituted at least at C-2 and C-5 with electron-donating groups. The yields are much lower (5-15%) if the thiophene carries a C02Me group at C-2. Better yields of the aromatic products are obtained if a preformed thiophene 1-oxide is used in the cycloaddition (two examples are provided in Scheme 23). Benzo [ Jthiophene 1-oxides also undergo facile [4-1-2] cycloadditions with alkynes, the products being naphthalenes (Equation 48). 

Dithioles 480 undergo cycloaddition with alkynes, and subsequent rearrangement with loss of CI2 gives IH-thieno[2,3-f]thiopyran-7-thiones 481 and 4//-thieno[3,2-f]thiopyran-4-thiones 482 as an isomeric mixture (Scheme 80) <20050L791>. 

Methyl ylide 681, produced by thermal N2 extrusion of dihydrothiadiazole 680, undergoes 1,3-dipolar cycloaddition with alkynes to give dihydrothiophenes 682 (Scheme 101) <2002HCA451>. 

Using Ni(CO)4 as both reducing agent and cycloaddition mediator, o-diiodobenzene may be induced to serve as a benzyne equivalent in a cycloaddition with alkynes leading to indenones. Yields are consistently good and regioselectivity with terminal alkynes for the 2-substituted product excellent (equation... 

Nitrile oxides undergo efficient [3-1-2] cycloadditions with alkynes and alkenes to generate isoxazoles and 4,5-dihydroisoxazoles, respectively. With unsymmetrical dipolarophiles there exists the possibility of regioisomeric mixtures of products however, it is generally found that steric effects control the regioselectivity and the more encumbered end of the dipolarophile becomes attached to the oxygen of the nitrile oxide. Thus, terminal alkynes and alkenes afford almost exclusively 3,5-disubstituted isoxazoles and dihydroisoxazoles, respectively (Scheme 91). 

Oxazoles have also been used to generate azomethine ylides in intramolecular [3+2] cycloadditions with alkynes <2000JA5401 1 he nucleophilic attack of cyanide ion on the oxazolinium salt 75 led to the formation of azomethine... 

Substituted phenols are synthesized by the nickel(0)-catalyzed ring opening of cyclobutenones and subsequent [4+2]cycloaddition with alkynes [106]. 

The 2-pyrone 116 (Scheme 33), containing the weakly electron-donating carbamate group at C3, has been reported to undergo cycloadditions with alkynes in refluxing decalin or tetralin, providing aniline derivatives 118 upon elimination of CO2 and aromatization... 

Cycloadditions. Norbomene and norbomadiene undergo cycloaddition with alkynes from the exo-face. 2,6-Diisopropylphenyl isocyanide is provided as a ligand for the Re catalyst. ... 

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