Pyrroles reductive elimination

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

An analogous cyclization to eventually form five-membered rings has also been observed for l-metalla-l,3,5-hexatrienes with an additional heteroatom within the chain, such as in the complexes 157. These are obtained by Michael additions of imines to alkynylcarbene complexes in good to excellent yields (reaction type F in Scheme 4), and their configurations were determined to be Z (>91%) in all cases. Upon warming in THF solution, complexes 157 underwent cyclization with reductive elimination to furnish 2Ff-pyrroles 158 in up to 97% yield (Scheme 34). With two cyclopropyl substituents at the terminus in... 

The regioselectivity observed in these reactions can be correlated with the resonance structure shown in Fig. 2. The reaction with electron-rich or electron-poor alkynes leads to intermediates which are the expected on the basis of polarity matching. In Fig. 2 is represented the reaction with an ynone leading to a metalacycle intermediate (formal [4C+2S] cycloadduct) which produces the final products after a reductive elimination and subsequent isomerisation. Also, these reactions can proceed under photochemical conditions. Thus, Campos, Rodriguez et al. reported the cycloaddition reactions of iminocarbene complexes and alkynes [57,58], alkenes [57] and heteroatom-containing double bonds to give 2Ff-pyrrole, 1-pyrroline and triazoline derivatives, respectively [59]. 

One-electron oxidation of the Fe(IIl) complexes Fe(Por)R can either give an observable Fe(lV) complex, [Fe(Por)R]", or can induce migration of the R group to a pyrrole nitrogen, essentially an intramolecular reductive elimination process. 

The Pd-catalyzed amination of / -rm-butylphenyl bromide with pyrrole in the presence of Pd(OAc)2, dppf and one equivalent of NaOr-Bu led to the Af-arylation product 88. A simplified version of the mechanism commences with the oxidative addition of p-te/t-butylphenyl bromide to Pd(0), giving rise to the palladium complex 89. Ligand exchange with pyrrole followed by deprotonation by the base (NaOr-Bu) results in amido complex 90. Reductive elimination of 90 then gives the amination product 88 with concomitant regeneration of Pd(0) catalyst. If the amine had a (3-hydride in amido complex 90, a (3-hydride elimination would be a competing pathway, although reductive elimination is faster than P-hydride elimination in most cases. 

A one-pot synthesis of pyrroles (90) from 1,2,5-selenadiazoles (88) with 1,3-diketones in the presence of zinc powder and acetic acid was reported. Initial reductive elimination of selenium gave a diamine (89), then one amino group was condensed with a 1,3-diketone followed by intramolecular cyclization to afford a pyrrole (90). [94JCS(P1)2201]... 

Conditions first described by Fagnou were used to affect the C-H to C-H bond cyclization, which proceeded in 47% yield. Mechanistically the direct coupling reaction is thought to proceed via intramolecular nucleophilic attack of the pyrrole moiety onto the Pd(II) centre. It was postulated that the electron rich DavePhos ligand facilitates both oxidative addition and forms a more reactive cationic Pd(II) species by dissociation of the halide. Following a deprotonation step, reductive elimination of Pd(0) then resulted in formation of the biaryl bond, completing the core framework. Application of this direct palladium-catalyzed biaryl coupling facilitates a very efficient and concise synthesis of rhazinilam as a racemate. 

Pyrroles almost exclusively add to acetylenes as Ai-centered nucleophiles however, when the acetylene is activated by a strong electron-withdrawing substituent, pyrrole can add to the triple bond as a C-centered nucleophile. " In their gold-catalyzed alkynylation of pyrrole with silyl-protected alkynyl benziodoxolone hypervalent iodine reagent 6, members of the Waser laboratory only saw C-alkynylated products (Scheme 10.2). Using this method, 1/f-pyrrole (1) could be C2-funtionalized to afford 7 in 62% yield, whereas Ai-TIPS pyrrole (8) was selectively transformed into C3-product 9 in 79% yield. In both cases, auration of the heterocycle led to an organogold(III) intermediate that reductively eliminated to afford the alkynylated products. 

Steric hindrance was not problematic for three- and seven-substituted pyrroles. The reaction is postulated to occur via Rh coordination to the nitrogen atom of the 2-pyrimidyl group, followed by cyclometalation to render a five-membered rhodacycle. The pentavalent arylsilicate activated by AgF then transfers the aryl group to the Rh-catalyst. Reductive elimination affords the desired arylated product, and either AgF or Cu(OAc)2 reoxidizes Rtf... 

In 2009, Miura et al. reported an elegant assembly of pyrroles 38 from alkynes and A-sulfonyl-1,2,3-triazoles 36 (Scheme 12.16) [18,19]. The reaction proceeded at 100 °C in the presence of a nickel catalyst and aluminum co-catalyst to afford substituted pyrroles 38. It is worth mentioning that the starting material 36 can be produced readily by the copper-catalyzed azide-alkyne Huisgen cycloaddition. The reaction is thought to be initiated by tautomerization of the triazole to an a-iminodiazo compound, which reacts with Ni(0) to give a nickel carbenoid and then the azanickelacycle 37. Subsequent alkyne insertion to the azanickelacycle and reductive elimination lead to the formation of 38. 

The coupling of alkynes and iminocarbene complexes (e.g., 4, Scheme 17.2) affords pyrrole ring systems (e.g., 6) in a formal [3-1-2]-cycloaddition process [2,3]. The pyrroles obtained are analogous to those obtained from nitrile ylide cycloadditions. A mechanism was proposed involving a net metalla-[4- -2] cycloaddition to afford azametallacycle 7 followed by reductive elimination and alkene isomerization. The regiochemistry arises through a nonconcerted addition to the triple bond via... 

The palladium-catalyzed reductive cyclization of endiynal-derived imines 72 with formic acid reported by Oh et al. can be considered to be a pyrrole formation through formal 5-exo cyclization between C=N and alkyne moieties (Scheme 19.15) [24]. They proposed a mechanism in which the intermediate 73 is formed by reductive carbopalladation of the internal alkyne by in situ-generated HPdOCOH. The intermediate 73 can then be converted to pyrrole 71 by nucleophilic attack of the imine nitrogen to the palladium nucleus accompanying hydride transfer, followed by reductive elimination. This reaction can be used for furan synthesis without using the amine component (see Scheme 19.34). 

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