DABCO cycloadditions

Maximally unsaturated azepines feature during the period under review. Cyclisation of the P,y-unsaturated aldehyde (1) by treatment with trifluoroacetic acid, followed by treatment with base (DABCO or DMAP) affords 2//-azepine <95AG(E)I469>. The compound itself is difficult to isolate but it is remarkably stable in solution, no trace of the thermodynamically favoured 3/f-azepine being observed after 48h at room temperature. In addition, the bicyclic adduct (2) is formed, probably arising from [2 + 4] cycloaddition of isobutene formed in situ and the intermediate immonium ion (3). 

The methylene blue-sensitized photochemical addition of singlet 02 to 5-alkoxyoxazoles in the presence of DABCO gives high yields of 1,2,4-dioxazolines (131) via a 1,2-addition of oxygen (Scheme 50). The DABCO is believed to inhibit the more commonly observed 1,4-cycloaddition pathway (77S572). 

Summary The reaction of trichlorosilane with DABCO provides the anion SiCb, which can be used instead of SiCh in cycloaddition reactions. In the presence of the 1,4-diaza-l,3-butadienes la-g, the five membered rings 2a-g are found. 2b was characterized by an X-ray structure determination. 

Dabco-based ionic liquids have been recently used, together other basic and neutral ILs, in the copper(i)-catalyzed azide-alkyne click reaction (Scheme 4.3). The model cycloaddition of a sugar azide with a sugar acetylene has been carried out in ten ILs. With one exception, in all investigated ILs the reaction afforded exclusively the 1,4-disubstituted triazole, namely a triazole-linked C-dis-accharide, in high yields. 

Isoxazolidines is another class of heterocycles that are very useful in medicinal chemistry. DABCO has been used for the synthesis of these compounds by using activated nitrocompounds in the presence of dipolar-ophiles. Pyrazolines could also be obtained by means of DABCO in the [3 + 2] cycloaddition reaction of ethyl diazoacetate with various activated olefins, under solvent-free conditions. ... 

More recently, allenes, acetylenes and activated dienes have been added as olefin equivalents, leading to products of more eomplex skeletons. Though the first report on allenic compounds involved in a MBH reaction dates back to the DABCO-catalyzed and butyllithium-promoted aldol condensation of allenic ester with aldehydes reported by Tsuboi et there are very few reports of MBH reactions involving allenoates because they easily undergo cycloaddition reactions under different Lewis bases. For instance, five-membered pyrrolidine... 

In the mid-1980s, Hoffman and co-workers described a simple synthesis of racemic mikanecic acid via in situ Diels-Alder dimerization of the diene generated from t-butyl 2-bromomethylbut-2-enoate. " The first example of a Diels-Alder reaction of a MBH adduct was the dimerization of 2-hydroxy-alkyle-nones" and the previously mentioned addition to anthracene. The appKcation of the MBH adducts as hetero dienes or precursors of dienes, and dienophiles for the Diels-Alder cycloaddition reactions was then initiated and expanded by the group of Hoffman. In a series of reports, Hofftnan and co-workers have described the in situ Diels-Alder dimerization of various dienes (157), generated via stereoselective dehydration with MsCl-DABCO-DMAP of the corresponding MBH adducts The elimination of water from MBH adducts always resulted... 

The enantioselective Lewis-acid-promoted 2 -t- 2-cycloaddition of trifluoropyruvate with various alkynes produced stable oxetene derivatives for use in the synthesis of pharmaceuticals and agrochemicals. l,4-diazabicyclo[2.2.2]octane (DABCO)-catalysed 2- -2-cycloaddition of allenoates and trifluoromethylketones produced 2-alkyleneoxetanes in good yields and with good diastereo-selectivities dr > 20 1). A cinchona alkaloid (20) catalysed the 2- -2-cycloaddition between tV-sulfonylimines and alkyl 2,3-butadienoates to form / -configured 2,4-disubstituted azetidines in high yields and with high enantioselectivities. ... 

Basic conditions and a nucleophilic base such as PPh3 or DABCO were required to perform the sequence SN2/[2 -I- 2]-cycloaddition displayed in Seheme 5.52 [135]. The allenyl ester 149 reacts with allylamine 150, leading to diastereomerically pure bicycles 151. 

Phosphine-catalyzed one-pot isomerization and [3+2] cycloaddition of 3-butynoates with electron-deficient olefins affords highly functionalized cyclopentenes in good yields and selectivities of up to 99% (Scheme 6.9). Isomerization of 3-butynoates to allenoates takes place initially, and it is notable that, when the reaction is carried out with DABCO or tributyl phosphine also, isomerization takes place, but not the cycloaddition [11]. 

To the best of our knowledge, no examples of direct cycloadditions for nitronic acids 6a leading to isoxazole derivatives have been reported before 2005 [61]. This was the state of the art when we observed that, upon addition of l,4-diazabicyclo[2.2.2]octane (DABCO), chloroform solutions of ethyl nitroacetate, in the presence of dipolarophiles, produced isoxazoline derivatives [62]. Preliminary investigations leading to this result were based on the assumption that water elimination is not reversible therefore, the production of isoxazole derivatives should be possible, in principle, without the need for dehydrating agents. 

Nitroacetic ester on treatment in chloroform with a base (e.g., DABCO, 0.1 equiv) is converted into the salt, evidenced in the H-NMR spectram [62]. In view of the role of H-bonding for the success of the condensation, it is reasonable to assume the two ions to be H-bonded, in this solvent. This salt 26 (Scheme 8.11) or possibly its protonated form 27 (nitronic acid) undergoes either dehydration to nitrile oxide 1, followed by cycloaddition to dipolarophile (path A), or cycloaddition followed by dehydration (path B) to afford the same isoxazo-line 28. With electron-poor dipolarophiles, a third possibility (path C) leads to the addition product 29 (Scheme 8.11). 

A set of Diels-Alder reactions of fused pyran-2-ones with ethyl vinyl ether (an appropriate synthetic equivalent of acetylene) gave fused carbocyclic systems. DABCO was used as a catalyst for the elimination of ethanol under microwave irradiation (Juranovic et al., 2012). The Diels-Alder cycloaddition reaction in 3-nitro-l-(p-toluenesulfonyl)indole with dienes under microwave irradiation in solvent-free conditions gave carbazole derivatives after elimination of the nitro group and in situ aromatization (Victoria et al., 2009). 

A notable example of an intramolecular Diels-Alder cycloaddition reaction is found in Kishi s synthetic investigations that culminated in the total synthesis of pinnatoxin A (66, Scheme 17.12) [49]. The intriguing Diels-Alder macrocyclization was initiated when mesylate 64 was treated with DABCO and Et3N to form the corresponding diene. The cycloaddition that ensued gave 65, and subsequent deprotection and intramolecular imine formation completed the synthesis of pinnatoxin A (66), a shellfish toxin and Ca -channel activator. 

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