Methyl propiolate, addition

According to a recent report , high yields of 4-COOMe-substituted product can be obtained from methyl propiolate addition. 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Examples of photochemical methods of addition to acetylene derivatives are the addition of methyl disulfide to hexafluoro-2-butyne [7] (equation 8), of trifluaramethanethial to methyl propiolate [S] (equation 9), of methanethiol to trifluoromethylacetylene and hexafluoro-2-butyne [9] (equation 8), and of tri-methylsilane to tetrafluoropropyne [10. ... 

Similarly, methyl propiolate and methyl phenylpropiolate give the cyclazine (67) and its 2-phenyl derivative, respectively, as would be expected of reactions initiated through a Michael addition to the acetylenic ester. 

These amines gave, with methyl propiolate, products of Michael mono- and bis-addition. Adducts underwent further reaction leading to triazolo[4,5-/]quinolones 181, after retro Diels-Alder reaction and acetylene elimination to its methoxycar-... 

Phenylacetylene is apparently one of thee few actylenes so far reported which is able to react via the cis addition of Co—H. Methyl propiolate, ethyl... 

Figure 6.27. Conjugate addition of benzyl alcohol to methyl propiolate catalysed by a fluorous phosphine...

The crude enamine is dissolved in 450 ml. of ether, and the solution is transferred to a 1-1. three-necked flask equipped with a sealed stirrer, a 250-ml. dropping funnel, and a two-necked adapter fitted with a calcium chloride tube and a thermometer immersed in the solution. A solution of 71-76 g. (0.85-0.90 mole) (Note 5) of methyl propiolate (Caution Methyl propiolate is a severe lachrymator and should he handled only in the hood.) in 150 ml. of ether is added dropwise. During the addition the temperature of the mixture is maintained at 25-30° by periodic cooling of the reaction flask in a dry ice-acetone bath. When the addition is almost complete, a white solid begins to separate. The mixture is stirred at 25-30° for an additional hour, cooled to 0°, and filtered to remove the solid. This is dissolved in 700 ml. of 6% hydrochloric acid (Note 6), the acidic solution is warmed at 55-60° for 1 hour, and the mixture is cooled and extracted with two 100-ml. portions of ether. The ether is removed on a steam bath, and the residue of crude methyl 10-oxocyclodec-2-ene-l-carboxylate is dissolved in 300 ml. of methanol and hydrogenated over 5 g. of 5% palladium-on-alumina catalyst at 40 p.s.i. pressure and room temperature. 

Alkyne dipolarophiles such as methyl propiolate or DMAD reacted with ylides derived from [l,2,3]triazolo[l,5-tf]-pyridines, but the mechanism proposed involved a Michael addition and subsequent nucleophilic attack rather than a concerted [4+2] cycloaddition <1996T10519> (see Section 11.13.8). 

The two-fold Michael addition of nitroethane to methyl propiolate in the presence of potassium fluoride and the phase-transfer catalyst tetrabutylammonium chloride leads to the diester 432. Treatment of nitroethane with methyl propiolate under these conditions, followed by methyl vinyl ketone, leads to the mixed adduct 433460. 

Tandem addition-aldol reaction with methyl propiolate... 

Z, 6Z- 10 COOMe was produced by a short and stereospecific one-pot synthesis (Scheme 17) [25], via sequential addition of dipropyllithium cuprate 115 to two equivalents of acetylene, followed by Michael addition of the resulting conjugated dienyl cuprate 116 with methyl propiolate 117. The only sig-... 

As shown in Scheme 1, aliphatic phosphines such as P(n-Bu)3 catalyze the addition of alcohols (2) to methyl propiolate (3) [35]. The mechanism is believed to involve an initial addition of the phosphine to the C = C moiety to give a zwitterionic allenolate (I), which then deprotonates the alcohol, yielding a vinyl phosphonium salt (II). An alkoxide addition to give an enolate (III), followed by phosphine elimination gives the product 4 and regenerates the catalyst. Several experiments suggest that when alcohols are used in excess, the catalyst rests as the original phosphine [34]. 

Scheme 1 Phosphine-catalyzed addition of alcohols (2) to methyl propiolate (3)...

The 7-azaquadricyclane (77), like its precursor (12), shows evidence in the NMR spectrum of restricted rotation about the N-CO bond. All the 7-heteroquadricyclanes, 76-79, are thermolabile, and they rearrange very readily to the corresponding azepines (80) or oxepin (81). (In another instance the 7-oxabicyclo[4.1.0] valence-bond tautomer was obtained instead. ) In appropriate conditions the addition of acetylenic esters (methyl propiolate and dimethyl acetylene-dicarboxylate) competes successfully with the isomerization and gives the ca o-tricyclic adducts 82 or 83. " °... 

The reactions of anhydro 2-aryl-3-hydroxythiazolo[2,3-a]phthalizinium hydroxides (171) with methyl propiolate (87EUP226196 88EUP294599), dimethyl acetylenedicarboxylate (85JOC1677), or fumaronitrile (85JOC1677) gave 4//-pyrido[2,l-a]phthalazin-4-ones (173) via cycloadducts 171. When methyl vinyl ketone was reacted with 171 (R = H), in addition to 9% of 4//-pyrido[2,l-a]phthalazin-4-one (173, R = H, R = COMe), a cycloadduct was also isolated (85JOC1677). 

The meso-ionic l,3>2-oxathiazol-5-ones (169) show an interesting range of reactions with nucleophiles including ammonia, primary amines, and aqueous alkali. They also react with l,3-dipolarophiles, including dimethyl acetylenedicarboxylate and methyl propiolate, yielding isothiazoles (171) and carbon dioxide. 1,3-Dipolar cycloaddition reactions with alkenes such as styrene, dimethyl maleate, and methyl cinnamate also lead to isothiazoles (171) directly. BicycUc intermediates (cf. 136) were not isolable these cycloaddition reactions with alkenes giving isothiazoles involve an additional dehydrogenation step. 

Mercaptoacetone reacts with methyl propiolate to give a 1 1 adduct, which then cyclizes to a substituted thiophene. Similar addition reactions of mercaptans with acetylenic acids have also been reported by Owen and Sultanbawa. ... 

Acyloxyacrylates are conveniently prepared through the catalyzed addition of carboxylic acids to propiolic esters. Thus, the addition of acetic acid (iron salt) to methyl propiolate yields methyl 3-acetoxyacrylate. Similar additions have been observed with benzoic acid to give the corresponding acrylic esters. 

Coppola et al. (81) extensively studied the dipolar cycloaddition of methyl propiolate with unsymmetrical miinchnones. In addition to their own results (Table 10.3), these investigators summarized much previous data on these cycloadditions. In the authors words No single criterion can successfully be used to correlate the experimental observations regarding the regioselectivity in milnch-none cycloaddition reactions. Steric and electronic effects must be considered in... 

Michael Reaction. 5(47/)-Oxazolones undergo base-catalyzed conjugate addition to activated unsaturated compounds to afford the corresponding C-4 Michael adducts. For example, base-catalyzed addition of a 4-monosubstituted-5(4//)-oxazolone 157 to methyl propiolate yields a mixture of diastereomeric methyl 3-(5-oxo-2-phenyl-2-oxazolin-4-yl)acrylates 158. Hydrolytic ring opening of 158 and subsequent oxidation with lead tetraacetate affords 3-acylacrylates 160... 

The intermediates which are assumed to be involved in the Knorr cyclization can also be prepared by addition of a-amino ketones to electrophilic alkynes (equation 77). This methodology has found use primarily with dimethyl acetylenedicarboxylate to form pyrrole-2,3-dicarboxylate esters (equation 77), but methyl propiolate is also reactive (68T1567,69T527, 64JA107, 62JOC3346). 

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