Dihydropyrrole

Pyrrole is known to slowly undergo hydrogenation to 2,5-dihydropyrrole, which is then easily hydrogenated to pyrrolidine. 

Work out the energy of both hydrogenations (data for 2,5-dihydropyrrole and pyrrolidine are available the energy of H2 is given at right). Are both reactions equally exothermic If not, why not Why is the first hydrogenation step slower than the second step ... 

Scheme 11.33. Aminocyclopropanation of N-protected 2,5-dihydropyrroles 126 and debenzylation of the exo-6-amino-3-azabicyclo[3.1. OJhexane 129 [105b, 113].

With regard to the Pd-catalyzed arylation of dihydropyrroles presented in Section 2.5, it is noteworthy that the readily available 2,5-dihydropyrroles 197 can be smoothly isomerized to 2,3-dihydropyrroles 198 under the influence of Pd [144],... 

Ring-closing metathesis of diene 318 with a Grubbs second-generation catalyst gave 2,5-dihydropyrrole 319 (Equation 56). The absolute stereochemistry was assigned based on single crystal X-ray diffraction analysis... 

Products from reactions with diacylamines or nosylamines can be very easily deprotected to give primary aUylamines. These were used as nucleophiles in allyhc substitutions to give secondary amines, which were transformed into unsymmetri-cally 2,5-disubstituted 2,5-dihydropyrroles (Scheme 9.28) [28aj. Thus, the allylic... 

Scheme 9.28 2,5-Disubstituted 2,5-dihydropyrroles via allylic substitution in combination with ring-closing metathesis.

A series of symmetrical and unsymmetrical photochromic 3,4-dihe-taryl-2,5-dihydropyrroles 147-150 containing the furan, thiophene, oxa-zole, or indole rings were synthesized as described above in 60-80% yields starting from p-anisidine (05JOC5001). 

Scheme 6.86 Typical 2-aryl-2,5-dihydropyrrole derivatives prepared with the asymmetric [3 + 2] cycloaddition between buta-2,3-dienoic acid ethyl ester and various DPP-protected (hetero)aromatic imines catalyzed by phosphinothiourea 75.

However, treatment of the precursor 74, where there is no substitution at C(4) (i.e., R = Me) led to a single [3+2] cycloadduct 75 with methyl acrylate. The unstable oxazolines 75, are considered to open spontaneously to their valence bond, 1,3-dipole tautomers 76, which are trapped in situ by the dipolarophile. Use of DMAD led to the formation of the expected 2,5-dihydropyrrole (77), but difficulties in isolation required DDQ aromatization to pyrrole 78 (Scheme 3.19). 

The enantioselective introduction of aromatic substituents into the 3-position of the heterocycles is also possible, starting from 2,5-dihydroaromatics. In a representative example A-protcctcd 2,5-dihydropyrrole was coupled with er-naphthyl tiflate in the presence of the chiral palladium-BINAP catalyst to give the 3-naphthyl-2,3-dihydropyrole derivative in moderate yield and enantioselectivity (6.55.),85... 

Tetrachloro-l-methylpyrrole is fluorinated92 with potassium tetrafluorocobalt-ate(III) at 180°C to give a mixture (ca. 60% yield) of 3,4-dichloro-2,2,5,5-tetrafluoro-l-methyl-2,5-dihydropyrrole (1) and 3,4-dichloro-2,2,5,5-tetrafluoro-l-(fluoromethyl)-2,5-dihydropyr-role (2). 

Dihydropyrroles have recently become readily available by ring-closing metathesis. For this purpose, N-acylated or N-sulfonylated bis(allyl)amines are treated with catalytic amounts of a ruthenium carbene complex, whereupon cyclization to the dihydropyrrole occurs (Entries 6 and 7, Table 15.3 [30,31]). Catalysis by carbene complexes is most efficient in aprotic, non-nucleophilic solvents, and can also be conducted on hydrophobic supports such as cross-linked polystyrene. Free amines or other soft nucleophiles might, however, compete with the alkene for electrophilic attack by the catalyst, and should therefore be avoided. 

Alkylidene-3-arylamino-2,5-dihydropyrrol-2-ones 721 can rearrange under acidic conditions to form the intermediate 1,3,5-triketoacid equivalent 722, which cyclizes to afford 5,6-fused 2-carbamoylpyran-4-ones (Scheme 178) <2004SL2779>. 

Reaction of 1-methyl- and 1-benzyl-2,5-dihydropyrrole, (160) and (161) respectively, with either 4-nitro- or 4-cyanophenylazide led to the triazolines (162a-c) in moderate yields. These compounds were subsequently treated with methyl iodide to yield the quaternary ammonium iodides (66a-c) <80JHC267>. 

Most of the important general methods for forming 1H-1,2,3-triazole derivatives involve the thermal 1,3-dipolar cycloaddition of hydrazoic acid or organic azides to suitable dipolarophiles (69CRV345,74AHC(16)33). For example, the cycloaddition of aryl azides to l-alkyl-2,5-dihydropyrroles gives pyrrolo[3,4-rf][l,2,3]triazoIes (equation 34) (80JHC267). 

Catalytic reduction of pyrroles gives successively 2,5-dihydropyrroles then pyrrolidines. Tetrahydrofurans are formed by the catalytic reduction of furans with Raney nickel and hydrogen ring-cleavage products may also be formed, e.g., 212 213 Me(CH2)2CH(OH)CH2OH + Me(CH2)4OH. 

Dihydropyrroles, e.g., 214, are formed on the reduction of pyrroles and simple alkylpyrroles with zinc and acid. These are derived from the corresponding -protonated species. 

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