Diels-Alder reactions alkynes

Diethylacetylene reacted with 4-phenyloxazole 55 in an autoclave for 3 days at 250°C to afford a 70% yield of 3,4-diethylfuran 124 (Fig. 3.35). This furan was then converted into the interesting tetraoxaporphyrin 125 in two steps. The novel diimidazole copper ligand 127 is formed in 84% yield by the cycloaddition of 4-phenyloxazole with the acetylenic diimidazole 126 at 185°C for 18 h (Fig. 3.36). An application of the oxazole-alkyne Diels-Alder reaction in natural product synthesis is exemplified by the construction of the maleic anhydride portion of the... 

Jacobi has used intramolecular oxazole-alkyne Diels-Alder reactions, elegantly and with great success, to prepare a number of natural products containing fruan, lactone, and butenolide rings. These syntheses and the methodology based on the oxazole Diels-Alder reaction, termed bis-heteroannulation, have been reviewed in detaU. ... 

Padwa and co-workers reported an approach to the pyrrolophenanthridone alkaloids (e.g., hippadine) that uses an intramolecular oxazole-alkyne Diels-Alder reaction. Thus the 2-acetamidooxazole model system 217 was thermolyzed at 200°C to produce the tricyclic furan 218 in 93% yield (Fig. 3.63). 

TABLE 3.2 INTERMOLECULAR OXAZOLE-ALKYNE DIELS-ALDER REACTIONS, 445... 

Diels-Alder reaction is the 1,4-addition of an alkene or alkyne (dienophile) across a conjugated diene. An example is the addition of pro-penal to buta-l,3-diene to give A -tetrahy-... 

The novel intramolecular reaction of the alkenyl bromide with the terminal alkyne in 328, followed by intramolecular Diels-Alder reaction, afforded the highly strained dynemicin A structure 329 in one stepf237]. 

The primary and secondary products of photolysis of common diazirines are collected in Table 4. According to the table secondary reactions include not only isomerization of alkenes and hydrogen elimination to alkynes, but also a retro-Diels-Alder reaction of vibrationally excited cyclohexene, as well as obvious radical reactions in the case of excited propene. 

Alkynes substituted with one or two trifluoromethyl groups are also highly reactive dienophiles [9] Indeed, hexafluoro-2-butyne is used increasingly as a definitive acetylenic dienophile in "difficult Diels-Alder reactions. It was used, for example, to prepare novel inside-outside bicycloalkanes via its reaction with cir,trnns -l,3-undecadiene [74] (equation 67) and to do a tandem Diels-Alder reaction with a l,l-bis(pyrrole)methane [75] (equation 68) Indeed, its reactions with pyrrole derivatives and furan have been used in the syntheses of 3,4-bis(tri-fluoromethyl)pyrrole [76, 77] (equation 69) and ],4-bis(trifluoromethyl)benzene-2,3-oxide [78] (equation 70), respectively. 

The 2n component 2, the so-called dipolarophile (analogously to the dieno-phile of the Diels-Alder reaction) can be an alkene or alkyne or a heteroatom derivative thereof. Generally those substrates will be reactive as dipolarophiles, that also are good dienophiles. 

The selectivity for two-alkyne annulation can be increased by involving an intramolecular tethering of the carbene complex to both alkynes. This was accomplished by the synthesis of aryl-diynecarbene complexes 115 and 116 from the triynylcarbene complexes 113 and 114, respectively, and Danishefsky s diene in a Diels-Alder reaction [70a]. The diene adds chemoselectively to the triple bond next to the electrophilic carbene carbon. The thermally induced two-alkyne annulation of the complexes 115 and 116 was performed in benzene and yielded the steroid ring systems 117 and 118 (Scheme 51). This tandem Diels-Alder/two-alkyne annulation, which could also be applied in a one-pot procedure, offers new strategies for steroid synthesis in the class O—>ABCD. 

A cross-coupling reactions of terminal alkynes with terminal alkenes 32 supported on Merrifield-resin (Scheme 4.5) in the presence of Grubs ruthenium initiator [Cl2(PCy3)2Ru = CHPh] provided efficient access to supported 1,3-dienes 33 which were transformed into octahydrobenzazepinones 34 via MeAlCl2 catalyzed Diels-Alder reaction [27]. 

To avoid problems with the separation of regiomers, dimethyl acetylene dicarboxylate (DMAD) was chosen as a dienophile. The intermolecular Diels-Alder reactions were performed in refluxing dichlorobenzene (bp 132 °C), while the intramolecular reaction of alkyne tethered pyrazinone required a solvent with a higher boiling point (bromobenzene, bp 156 °C). In the case of 3-methoxy or 3-phenyl pyrazinones a mixture of pyridinones and pyridines was obtained, while for the alkyne tethered analogue only the di-hydrofuropyridinone was isolated as the single reaction product. 

For the microwave-assisted experiments, both solvents were replaced by 1,2-dichlorobenzene, as it couples very effectively with microwaves (loss-tangent (tan 5) at 20 °C 1,2-dichlorobenzene 0.280 as compared to 0.101 for chlorobenzene). Diels-Alder reactions of 3-methoxy or 3-phenyl pyrazinones with DMAD were performed at a pre-selected maximum temperature of 200 °C, whereas the intramolecular reaction of alkyne tethered pyrazinone required a higher temperature (220 °C). The yields obtained under microwave irradiation are comparable with those obtained under conventional conditions, while for the dihydrofuropyridinone the yield was improved from... 

Diels-Alder reactions of cyclopentadienones with alkynes... 

The Diels-Alder reaction is an organic chemical reaction (specifically, a cycloaddition) between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can also proceed if the alkene is replaced by an alkyne moiety or even if some of the atoms... 

The tricyclic compound 20-C, a potential intermediate for alkaloid synthesis, has been prepared by an intramolecular Diels-Alder reaction of the ketone obtained by deprotection and oxidation of 20-B. Compound 20-B was prepared from 20-A using alkyne-ethene metathesis chemistry. Show the mechanistic steps involved in conversion of 20-A to 20-B. 

A combination of a metathesis and a Diels-Alder reaction was published by North and coworkers [263]. However, this is not a true domino reaction, as the dienophile (e. g., maleic anhydride) was added after the in situ formation of the his-butadiene 6/3-89 from the fois-alkyne 6/3-88 and ethylene. The final product is the fois-cycloadduct 6/3-90, which was obtained in 34% yield. Using styrene as an un-symmetrical alkene instead of ethylene, the mono-cycloadduct 6/3-91 was formed as a mixture of double-bond isomers, in 38% yield (Scheme 6/3.26). 

The forerunner in the Co-catalyzed [2+2+2] cycloaddition domino processes was that identified by Vollhardt and colleagues [273], with their excellent synthesis of steroids. Reaction of 6/4-1 with [CpCo(CO)2] gave compound 6/4-3 with an aromatic ring B via the intermediate 6/4-2. In this process, trimerization of the three alkyne moieties first takes place, and this is followed by an electrocyclic ring opening of the formed cyclobutene to give o-quinodimethane. This then undergoes a Diels-Alder reaction to provide the steroid 6/4-3 (Scheme 6/4.1). 

It is not quite clear which step takes place first - the Co-catalyzed [2+2+1] cycloaddition of the outer alkyne moiety, or the Diels-Alder reaction of the diene with the inner alkyne to form a 1,4-cyclohexadiene, which then undergoes a Pauson-Khand reaction with the remaining alkyne. Recently, it has been shown that a domino reaction can also be performed using 1 mol of a 1,7-diphenyl-1,6-diyne 6/4-20 and a 1,3-diene 6/4-21 in the presence of Co/C at 150 °C under 30 atm CO, to give the polycyclic compounds 6/4-22 as sole product (Scheme 6/4.7) [282]. 

As described previously, the Co-mediated carbonylahve Co-cydization of an alkyne and an alkene, is a very powerful procedure in the preparation of cyclopen-tenones [268], However, depending on the reaction conditions it also allows the preparation of 1,3-dienes, which may be intercepted by a Diels-Alder reaction, as described by Carretero and coworkers [285]. As expected, reaction of 6/4-28 with Co2(CO)8 in refluxing acetonitrile led exclusively to the diastereomeric cyclopen-tenones 6/4-29 and 6/4-30 as a 59 41 mixture. However, using trimethylamine-N-... 

Figure 17.3 Maleimide-modified glass slides (1) can be derivatized using two chemoselective ligation reactions to create biotin modifications. In the first step, alkyne-PEG4-cyclopentadiene linkers (2) are added to the maleimide groups using a Diels-Alder reaction. In the second reaction, an azido-PEG4-biotin compound (3) is reacted with the terminal alkyne on the slide using click chemistry to result in another cycloaddition product, a triazole ring.

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