Osmium-Promoted Dipolar Cycloadditions with Pyrroles: An Efficient, Stereoselective Synthesis of 7-Azanorbornanes

Abstract

A series of 7-azabicyclo[2.2.l]hept-5-ene complexes are prepared from [0s(NH3)5(q2-L)l2+ (L = pyrrole, 1-methylpyrrole, 2,5-dimethylpyrrole, 1,2,5-trimethylpyrrole, or 1-(trimethylsily1)pyrrole) and various dipolarophiles (e.g., acrylonitrile, methyl acrylate, a-methylene-y-butyrolactone, dimethyl maleate, dimethyl fumarate, N-phenyl maleimide, cyclopentene-1,2-dicarboxylic acid anhydride, and (E>-and (a-methyl 3-(3'-pyridyl)acrylate). The cycloaddition is promoted by coordination of the pyrrole with [Os(NH&]*+ across C3 and C4, transforming the uncoordinated portion of the pyrrole nucleus into an azomethine ylide capable of undergoing 1,3-dipolar cycloadditions.The metal serves not only to activate the pyrrole ring but also to stabilize the resulting 7-azabicyclo[2.2.l]heptene ligands. A number of organic 7-azabicyclo[2.2. llheptanes, including analogs of the alkaloid epibatidine, have been synthesized by this methodology. For the cases examined, the cycloaddition favors ex0 stereochemistry of the electronwithdrawing substituent when the pyrrole nitrogen is unsubstituted. Crystal structures have been determined for the complexes obtained from the reactions of pyrrole with N-phenylmaleimide @a), 2,5dimethylpyrrole with dimethyl maleate (13a), and 2,5-dimethylpyrrole with a-methylene-y-butyrolactone (22a).

Metal-Assisted Cycloaddition Reactions in Organotransition Metal Chemistry

“…Scheme 19) from substituted pyrroles and olefins superficially looks like a Diels-Alder reaction, however, as has been shown in section II.C.1, it is in fact a 1,3-dipolar [3+2] cycloaddition. 356,357 Investigations on the influence of coordinated metal fragments on the reactivity of "remote", uncoordinated 1,3-diene moieties in cycloaddition reactions have been performed by several groups. Vogel, Roulet, et al [595][596][597][598][599] have prepared extensive series of stereochemically well-defined mono-and bis-metalcoordinated complexes of (poly)cyclic polyenes with exocyclic s-cis-butadiene groups, such as 371-373.…”

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…Thus for instance, the reactions of certain 1-alkylpyrroles with nitrileimines have been demonstrated to give pyrrolo-fused pyrazoles [512,513], whereas intramolecular cyclization of nitrile oxide functionalities onto pyrroles involved unstable pyrrolofused isoxazole adducts that underwent ring opening of the isoxazole ring [514]. It has also been established that a series of osmium pyrrole complexes, for example 320 [Os (II)¼[Os(NH 3 ) 5 ](OTf) 2 ], participate as dipoles in cycloadditions with alkenes, for instance providing the endo-adduct 321 in good yield along with minor amounts of the exo-isomer (Scheme 4.96) [515,516].…”

Diels–Alder reactions of five-membered heterocycles containing one heteroatom

“…It is reported that cycloaddition reactions of pyrroles with alkenes are limited by the inherent thermodynamic instability of the cycloadducts wherein cycloreversion or retro-Mannich reactions (followed by rearomatization) are predominant. 15–17 When we treated pyrrole 14 with maleimide 3 , in toluene at 60 °C as shown in Scheme 5, we observed no cycloadducts from these reactants. However, we did obtain a small amount of adduct that arose from maleimide 3 and a furan-containing contaminant that was present in our commercial sample of 14 , which we determined to have an empirical formula of C 19 H 19 NO 3 from mass spectral analysis.…”

“…However, as previously mentioned, cycloadducts of pyrroles with dienophiles are inherently thermodynamically unstable. 15–17 Osmium complexation of pyrroles has allowed the production of cycloadducts with maleimides and other dienophiles; however, decomplexation is not straightforward and stable cycloadducts can only be isolated after reduction of the resulting dihydropyrrole. 15 The greater aromatic character of pyrroles, as compared with furans or thiophenes, limits their reactivity towards cycloaddition reactions.…”

“…15 The greater aromatic character of pyrroles, as compared with furans or thiophenes, limits their reactivity towards cycloaddition reactions. 15 …”