Pyrroles acetylene derivs

Not only acetylene derivatives do undergo palladium catalysed intarmolecular carbon-nitrogen bond formation with amines. The similar reaction of olefins in a Wacker-type process also leads to ring closure. (0-Aminopentenes bearing a suitable leaving group in the 4-position were converted to pyrroles in a cyclization-isomerisation-elimination sequence (3.65.),82... 

The palladium catalysed annulation of / -iodoamines and acetylene derivatives has been widely used in the construction of pyrroles and indole derivatives. The strategy, first reported by Larock, is efficient in converting both cyclic and open chain 2-iodo-allylamine derivatives to 3-alkylidene-... 

Acetylenecarboxylic esters, reactions with nitrogen-containing heterocycles, 23, 263 Acetylenic derivatives of pyrazoles, synthesis and properties of, 82, 1 Acetylenic esters, synthesis of heterocycles through nucleophilic additions to, 19,297 Acid-catalyzed polymerization of pyrroles and indoles, 2, 287... 

Synthesis and properties of fluoropyrroles and their analogues 12S2115. Synthesis of pyrroles from acetylene derivatives 13MI21. 

Pyrrole from a/iAj dir -4-hydroxyimidazolium hydroxide ring and acetylene derivs. O 3,4-Dihydro-2 f-pyrrolo 2,l- l,3 thiazines... 

Benzyne trapping agents s. 19, 910 Benzotropolone-l, 2 -quinones from o-quinones via l, 2 -dihydroxybenzotropolones s. 18, 914 Pyrroles by 1,3-dipolar addition from acetylene derivatives... 

The photocycloaddition of 2tf-azirines to electron-deficient olefins produces d -pyrrolines as primary photoproducts. Some of the dipolarophiles used include acrylic esters, acrylonitriles, fumaric and maleic esters, methyl allenecarboxylate, norbornene, and l,2-dicyanocyclobutene. Similarly, styrenes and vinylpyridines undergo smooth photocycloaddition to 2H-azirines. Addition of acetylene derivatives to the transient nitrile ylide gives 2H-pyrroles (18, 20) which rearrange to pyrroles (19) if the C-2 atom is monosubstituted. 3-Phenyl-2/f-azirines have been found to cycloadd to vinylphosphonium salts and to vinyl sulfones. The initial adducts (22 and 24) undergo ready loss of the phosphorous or sulfur substituent to give 2H-pyrroles (23 and 25). ... 

Phenyl-4,4-bis(trifluoromethyl)-5,5,5 - trimethoxy - 4,5-dihydr 0-1,3,5-oxazaphos-ph(V)ol heated 10 hrs. at 125-135° with dimethyl acetylenecarboxylate in anhydrous xylene -> 2,2-bis(trifluoromethyl)-3,4-bis(methoxycarbonyl)-5-phenyl-2H-pyrrole. Y 70%. F. e., also zl -pyrrolines from ethylene derivs., s. K. Burger and J. Fehn, Ang. Ch. 83, 761 (1971) with unsym. ethylene or acetylene derivs. s. ibid. 83, 762. 

Pyrroles hy 1,3-dipolar addition from acetylene derivatives... 

Mycalidae Mycale Cyclic peroxides, macrolides, diterpenes (isocopalane), brominated acetogenines en Cns, acetylenic derivatives, pyrrole derivatives... 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

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. 

These reactions are related to the formation of pyrroles and quinolines from aminocarbonyl compounds and acetylenes (582,583) and may be contrasted with the formation of pyran derivatives by electrophilic attack on an enamine, followed by addition of an oxygen function to the imonium carbon (584-590). 

In a related reaction, heating ketones in the presence of TlClsOTf leads to 1,3,5-trisubstituted arenes. " Nitriles react with 2 mol of acetylene, in the presence of a cobalt catalyst, to give 2-substituted pyridines. " Triketones fix nitrogen gas in the presence of TiCU and lithium metal to form bicyclic pyrrole derivatives. " ... 

The formation of 2H-pyrroles (21) and a pyrrole derivative (22) from the reaction of 3-phenyl-2//-azirines and acetylenic esters in the presence of molybdenum hexacarbonyl is intriguing mechanistically (Schemes 24, 25).53 Carbon-nitrogen bond cleavage must occur perhaps via a molybdenum complex (cf. 23 in Scheme 26) but intermediate organometallic species have not yet been isolated.53 Despite the relatively poor yields of 2H-pyrrole products, the process is synthetically valuable since the equivalent uncatalyzed photochemical process produces isomeric 2H-pyrroles from a primary reaction of azirine C—C cleavage54 (Scheme 24). 

Hendrickson and co-workers have used the reaction of a-amino-ketones with acetylenic esters for synthesizing pyrrole derivatives. Thus, in the reaction of a-aminopropiophenone with DMAD, an intermediate enamine adduct (56) is formed, which ultimately gives rise to the pyrrole 57 in presence of methanolic HCl [Eq. (16)]. Pandit and Huisman have shown the generality of this scheme in the synthesis of polycyclic pyrrole derivatives. 

Pyrroles and fiirans were prepared by the intramolecular carbon-carbon bond formation between pendant acetylene and nitrile or carbonyl functions. The process, running in acetic acid, starts by the fraw-acetoxypalladation of the acetylene moiety, which initiates a series of further transformations. The nature of the ring formed is determined by heteroatom bridging the two reactive units. The propargylamine derivative in 3.88., for example gave a pyrrole ring.112... 

Furane derivatives, like pyrroles, couple effectively with acetylenes. In case both the a-, and / -position are available for the reaction, like in the case of 4,5-dibromo-furfural in 6.45., the cross-coupling takes place preferentially in the former position65 The observed selectivity is in line with other palladium catalyzed transformations of dihalofuranes, such as their Stifle coupling.66... 

Huisgen s group488 have described a new synthesis of pyrroles (26) from oxazol-5-ones (azlactones) (25) with DMAD and MP. The pyrrole derivatives formed in situ from 2,4-dimethyl- and 4-benzyl-2-methyloxazolone with DMAD underwent nucleophilic addition to a second mole of the acetylenic ester to give the Michael adducts 27 and 28... 

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