Dimethyl acetylenedicarboxylate ketone derivations

Ylides forming from the thermolysis of compound 59 (R1, R2 = Me, R3 = Ar, R4 = OMe) reacted also with dimethyl acetylenedicarboxylate (DMAD) or diethyl azodicarboxylate (DEAD) <2003TL5029> in the presence of aldehydes, quinones <2001TL2043>, or ketones <20020L2821, 20000L3501> to give 2,5-dihydrofuran derivatives, for example, 67 (Rs = Me, Et). 

Condensation of cyclic enaminoamides (246) with dimethyl acetylene-dicarboxylate gives 2-azepinone derivatives (247) (85AJC1847). Similarly, immonium salts (248) when treated with bases give enamines, which subsequently react with dimethyl acetylenedicarboxylate or unsaturated ketones and give azepines (81AP787). The reaction of primary enaminonitriles with dimethyl acetylenedicarboxylate proceeds in a similar fashion (84CPB2596). Another route to azepines has been described (95JHC57) (Scheme 51). 

Substituted 4,5-dihydroazepines 281 can be prepared in high yield by a rhodium-mediated hetero-[5 + 21-cycloaddition of the cyclopropyl imines derived from ketones 279 on reaction with the primary amines 280, with dimethyl acetylenedicarboxylate (Scheme 146) <2002JA15154>. 

Diazo compounds have also been used as precursors in the preparation of pyrazoles and indazoles. The copper-promoted cycloaddition reaction of lithium acetylides 18 with diazocarbonyl compounds 19 provided a direct and efficient approach to the synthesis of pyrazoles 20 <07AG(I)3242>. A facile, efficient, and general method for the synthesis of 1-arylated indazoles 22 and A-unsubstituted indazoles 23 by the 1,3-dipolar cycloaddition of benzynes, generated from 21, with diazomethane derivatives has been reported <07AG(I)3323>. Reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate <07S3371>. 

Reaction with enamines and related substances. Brannock el al. found that the enamines derived from acyclic aldehydes and ketones react with dimethyl acetylene-dicarboxylate to give products derived by rearrangement of cyclobutenes initially formed by 1,2-cycloaddition. Thus, N,N-dimethylisobutcnylamine (1) reacts with dimethyl acetylenedicarboxylate in refluxing ether to give dimethyl 2-dimethylamino-methylenc-3-isopropylidencsuceinate (2) in 49 % yield. 

Dithiobenzoates PhCS2R (R = allyl, propargyl, or benzyl) add to dimethyl acetylenedicarboxylate to form the dithioles (288) with migration of the group R. Piperidine catalyses the addition of acetylenic ketones Ar COC=CAr to 4-methylbenzene-l,2-dithiol to give the benzodithioles (289). The reaction of the acetal BrCH2CH(OEt)2 with ethanedithiol yields a mixture of the bis(dithiolan) (291) and derivatives of dithian, which are formed, respectively, from the cations (290) and (292). ... 

Iwasawa et al. developed a tungsten-mediated benzannulation reaction (Scheme 15.15). On treatment of o-ethynylphenyl ketones 11 with 3 equiv of preformed W(C0)5(THF), followed by the addition of electron-rich alkenes 8, such as enam-ines and enol ethers, the corresponding naphthalenes 19 were produced together with W(CO)6 [26]. Ohe, Miki, and co-workers prepared pyranyUdene-metal complexes from conjugated enyne-carbonyl compounds using Mo, W, and Cr complexes, which were treated with dimethyl acetylenedicarboxylate to give benzene derivatives [27]. 

In 1999, Hashimoto and coworkers demonstrated the first successM examples of the intermolecular cycloadditions of carbonyl ylides derived from a-diazo ketones with dimethyl acetylenedicarboxylate (DMDA) using fV-benzene-fitsed phthaloyl-(5)-valine-derived Rh catalyst, Rh2(5-BTPV)4 with high enantioselectivity (up to 92% ee) (Scheme 7.21) [57]. 

Several new examples of the reactivity of thioamides towards compounds containing activated carbon-carbon double or triple bonds have appeared. Thus little-known thiazine derivatives have been synthesized by treatment of primary thioamides with a -unsaturated ketones pyridine-2-thiones afforded, on treatment wi a-bromo-a 3-unsaturated acids or acetylenedicarboxylic acid, dihydrothiazolo[3,2-a]pyridinium salts, whereas die vinyl sulphides (263) were the products obtained in their reactions with propiolic or phenylpropiolic acid a Diels-Alder adduct was produced by the reaction of the thioamide (264) with dimethyl acetylenedicarboxylate. NN -Disubstituted phenylpropiolamidines (265),... 

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