Cycloadditions 4-dimethylaminopyridine

For example, the reaction of nitroalkanes with di-tert-butyl dicarbonate, (B0C)20, and 4-dimethylaminopyridine (DMAP) as catalysts in the presence of dipolarophiles at room temperature affords cycloadducts in improved yields compared with the Mukaiyama-Hosino method.58 The conversion of Eq. 6.32 gives a 90% yield by this procedure, whereas the conventional method using PhNCO gives a 79% yield of the same product. An additional advantage of this new method is that the use of (B0C)20 allows the reaction to be carried out with substrates that contain NH or OH groups without prior protection. The cycloaddition leads directly to protected N- or (9-Boc products (see Eq. 6.33). 

One obvious synthetic route to isoxazoles and dihydroisoxazoles is by [3+2] cycloadditions of nitrile oxides with alkynes and alkenes, respectively. In the example elaborated by Giacomelli and coworkers shown in Scheme 6.206, nitroalkanes were converted in situ to nitrile oxides with 1.25 equivalents of the reagent 4-(4,6-di-methoxy[l,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and 10 mol% of N,N-dimethylaminopyridine (DMAP) as catalyst [373], In the presence of an alkene or alkyne dipolarophile (5.0 equivalents), the generated nitrile oxide 1,3-dipoles undergo cycloaddition with the double or triple bond, respectively, thereby furnishing 4,5-dihydroisoxazoles or isoxazoles. For these reactions, open-vessel microwave conditions were chosen and full conversion with very high isolated yields of products was achieved within 3 min at 80 °C. The reactions could also be carried out utilizing a resin-bound alkyne [373]. For a related example, see [477]. 

Dipolar cycloaddition of nitrile oxides to olefins and acetylenes is among the most widely exploited synthetic routes towards isoxazoles and isoxazolines. It is well-known that microwave irradiation in cycloaddition reactions considerably reduces reaction times. Indeed, the use of dielectric heating (microwave-heated reactions were performed in a flask with a reflux condenser mounted outside the apparatus) allowed for a remarkable reduction of the cycloaddition reaction time from 6-12 hours to merely 3 minutes [69]. Simple aqueous workup provided the target isoxazoles and isoxazolines. The requisite nitrile oxides for the cycloaddition reaction were generated in situ from the corresponding nitroalkanes, 4-(4,6-dimethoxy [1,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and 4-dimethylaminopyridine (DMAP) (Scheme 22). 

The [2 + 4] cycloadditions of a,/l-unsaturated carbonyl compounds and nitriles to 4,4-bis(trifluoromethyl)-substituted hetero-1,3-dienes give heterocyclic compounds. The [4 + 2] cycloaddition of hetero-1,3-diene to methylvinylketone is highly selective when the process is conducted in the presence of equimolar amounts of 4-dimethylaminopyridine. 

A literature survey of nitrile oxide [3+2] cycloaddition reactions with MW activation for the period 2002-2005 reveals that only a limited number of examples have been reported. Among these examples, nitroalkenes are converted in situ into nitrile oxides using 4-(4,6-dimethoxy[l,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and 4-N,N-dimethylaminopyridine (DMAP) (Scheme 11.27) [38]. The generated 1,3-dipoles undergo cycloaddition to alkene 103 or alkyne 106 dipo-larophiles (5 equiv.), to furnish 4,5-dihydroisoxazoles 104 or isoxazoles 107, respectively. Open-vessel conditions were used and full conversions with very high yields of products were achieved within 3 min at 80 °C. 

Type of reaction C-S and C-C bond formation Reaction conditions Dichloromethane, room temperature Synthetic strategy One-pot two-component [3+2]-cycloaddition Catalyst 4-Dimethylaminopyridine (DMAP)... 

A review of organocatalytic asymmetric 2-1-2- and 4 -1- 2-cycloaddition reactions of ketenes has been published. The domino 1,4-dipolar addition and the Diels-Alder reaction of in situ generated Huisgen 1,4-dipoles (4), from dimethyl acetylenedicarboxy-late (DMAD) and 4-dimethylaminopyridine to 3-phenylacyhdeneoxindole (5), formed complex dispirooxindole-fused heterocyclic compounds (6) (Scheme 2). A multicat-alytic one-pot Diels-Alder/benzoin reaction sequence has been developed for the synthesis of complex tetrahydrocarbazoles possessing four stereogenic centres. ... 

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