Dipolarophiles methyl propiolate

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 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. 

Confirmation was provided by the observation that the species produced by the photolysis of two different carbene sources (88 and 89) in acetonitrile and by photolysis of the azirine 92 all had the same strong absorption band at 390 nm and all reacted with acrylonitrile at the same rate (fc=4.6 x 10 Af s" ). Rate constants were also measured for its reaction with a range of substituted alkenes, methanol and ferf-butanol. Laser flash photolysis work on the photolysis of 9-diazothioxan-threne in acetonitrile also produced a new band attributed the nitrile ylide 87 (47). The first alkyl-substituted example, acetonitrilio methylide (95), was produced in a similar way by the photolysis of diazomethane or diazirine in acetonitrile (20,21). This species showed a strong absorption at 280 nm and was trapped with a variety of electron-deficient olefinic and acetylenic dipolarophiles to give the expected cycloadducts (e.g., 96 and 97) in high yields. When diazomethane was used as the precursor, the reaction was carried out at —40 °C to minimize the rate of its cycloaddition to the dipolarophile. In the reactions with unsymmetrical dipolarophiles such as acrylonitrile, methyl acrylate, or methyl propiolate, the ratio of regioisomers was found to be 1 1. 

Doyle et al. (39) expanded the rhodium-catalyzed generation of isomiinchnones from diazoacetacetamides and subsequent trapping with dipolarophiles (38). As shown in Scheme 10.12, in the case of diazoacetoacetyl urea (79) the derived isomtinchnone 80 reacts with methyl propiolate to give a 2 1 mixture of cycloadducts 81. The resulting regiochemistry is successfully rationalized using frontier molecular orbital (FMO) theory as being isomiinchnone-HOMO controlled. This result represents one of the few reactions in which the cycloadducts from isomiinchnones and alkynes are stable. 

Dumitrascu and co-workers (52) transformed 4-halosydnones into 5-halopyr-azoles by cycloaddition with DMAD and methyl propiolate followed by retro-Diels-Alder loss of CO2. Turnbull and co-workers (194) reported that the cycloadditions of 3-phenylsydnone with DMAD and diethyl acetylenedicarboxylate to form pyrazoles can be achieved in supercritical carbon dioxide. Nan ya et al. (195) studied this sydnone in its reaction with 2-methylbenzoquinone to afford the expected isomeric indazole-4,7-diones. Interestingly, Sasaki et al. (196) found that 3-phenylsydnone effects the conversion of l,4-dihydronaphthalene-l,4-imines to isoindoles, presumably by consecutive loss of carbon dioxide and A-phenylpyrazole from the primary cycloadduct. Ranganathan et al. (197-199) studied dipolar cycloadditions with the sydnone 298 derived from A-nitrosoproline (Scheme 10.43). Both acetylenic and olefinic dipolarophiles react with 298. In... 

Avalos and co-workers (220-228) extensively investigated the 1,3-dipolar cycloaddition chemistry of 2-aminothioisomiinchnones with both acetylenic and olefinic dipolarophiles. For example, sugar derivatives of the mesoionic imi-dazo[2,l-Z7]thiazolium-3-olate system react regioselectively with a variety of acetylenic dipolarophiles [DMAD, diethyl azodicarboxylate (DEAD), methyl propiolate, ethyl phenylpropiolate] to give the corresponding imidazo[l,2-a]pyr-idin-4-ones (e.g., 323) following sulfur extrusion from the not isolable cycloadducts (220). Similarly, these thioisomtinchnones react with diethyl azodicarboxylate and arylisocyanates in the expected fashion (221), and also with aryl aldehydes to form episulfides (222). 

The 4-phospha-1,3-butadiene 77/80 serves as an effective synthon for the unknown H-substituted nitrile ylide 79 in [3 + 2]-cycloaddition reactions with a range of electron-poor dipolarophiles (e.g., reaction with DMAD gave 78 in 80% yield). Similar yields were also obtained using methyl propiolate, azodicaboxylic esters, ethyl acrylate, and acrylonitrile (39). The reactant was generated under very mild conditions from 75 as shown below. 

Compounds 332a, b possess an azomethine imine structure and should undergo cycloaddition reactions.4208 Although dimerization of 332b has not been observed,335 dipolarophiles yield cycloadducts 444 and Michael adducts 445.420a The structure of the product obtained from methyl propiolate, an unsymmetrical acetylene, has been studied by NMR and shown to be 446.420b... 

The 2,5-disubstituted tetrazoles 131 readily lose N2 upon pyrolysis to give the nitrile imines 132, which can be trapped by an added dipolarophile, detected spectroscopically, or in some cases isolated74. FVP of 131 (R = SiMe3) at 440°C, for example, gives the nitrile imine which can be isolated as a solid at liquid nitrogen temperature and trapped by cycloaddition to methyl propiolate or bis(trimethylsilyl) fumarate75. In contrast to this behaviour, the lH-tetrazoles 133, readily formed from cycloaddition of HN3 to nitriles, act as a useful source of carbenes by loss of N2 to give first 134 and then 135. This method... 

The l,3- dipolar cycloaddition of alkynes to anhydro-5-hydroxyoxazolium hydroxides leads to pyrroles (equation 66). Electron-withdrawing substituents in the alkyne are activating and DMAD reacts 48 times faster with compound (235) than does methyl propiolate, which in turn is 7000 times more reactive than oct-l-yne. The reaction has many ramifications and it is frequently used to trap unisolable munchnones with or without substituents on the nitrogen atom by an in situ reaction in which the betaine is generated in the presence of the dipolarophile (equation 67). It has become an important method for constructi ng the pyrrole ring of fused heterocyclic systems, as in the example of equation (68). 

Prior to 1973, nitrones were believed to add to monosubstituted dipolarophiles in a unidirectional fashion, giving 5-substituted adducts exclusively (Fig. 7). An exception to this behavior was reported by Huisgen a mixture of 4- and S-substituted isoxazolines form in the reaction of methyl propiolate with C-phenyl-N-methylni-trone19, as shown in Fig. 7. 

Padwa and coworkers found that a-cyanoaminosilane 12a is a convenient synthon for azomethine ylide 15 which is extensively used in heterocyclic synthesis [7]. AgP has been adopted to generate the ylide 15 from 12a for the preparation of pyrrolidine derivative 14 (Sch. 4). Various dipolarophiles including A-phenylmaleimide (13) can be used for the cycloaddition. When iV-[(trimethylsilyl)methyl]-substituted indole 16 is reacted with AgP in the presence of maleimide 13, pyrrolo[l,2-a]indole 17 is formed in good yield, retaining the CN group [8]. A silver-bonded carbonium ion is assumed to be a reactive intermediate. Reaction of a cyano-substituted azomethine ylide, derived from (silylmethylamino)malononitrile 12b and AgP, with methyl propiolate (18) provides 3-carbomethoxy-A-benzylpyrrole (19) [9]. Epibatidine, a novel alkaloid, was successfully synthesized by employing the [3 + 2] cycloaddition of azomethine ylide with electron-deficient alkenes as a key step [10]. 

Hi) both orientations followed in the addition of the same dipolarophile, as for styrene and phenylacetylene in (o), for methyl propiolate in (c), and for phenylacetylene and methyl propiolate in ( 2) (see footnotes). 

Gowravaram and Gallop adapted the rhodium-catalyzed generation of isomunchnones from diazo imides to the solid-phase synthesis of furans, following a 1,3-dipolar cycloaddition reaction with alkynes. A variety of furans 492 were prepared in this fashion (Fig. 4.150). With unsymmetrical electron-deficient alkynes (e.g., methyl propiolate), the anticipated regiochemistry is observed, e.g., HOMO-dipole LUMO-dipolarophile, as seen previously. 

The regiospedfic [3+2] 1,3-dipolar cycloaddition of 2-amino-1,3-thiazolium-4-olates (2-aminothioisomunchnones) to methyl propiolate to form pyridone derivatives has been investigated. In this study a dipolarophile, 13, was tethered to 1-amino-1-deoxy-D-glucitol pentaacetate and formed pyridone 14 upon 1,3-dipolar cycloaddition to but-2-yndioic acid dimethyl ester. ... 

Potts et al. (333) condensed dipolarophiles (DMA, dibenzoylacetylene, ethyl propiolate) with ylides (81) obtained by quaternization of 4-methyl-thiazole with an a-bromoketone or ester and subsequent deprotonation. In fact the 1 1 molar adduct obtained (82) rearranged to a pyr-rolothiazine (83). One example of this reaction is described Scheme 49. 

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