Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

Abstract

SummaryThe synthesis of N-arylated pyrroles and indoles is documented, as well as their functionalization by deprotonative metallation using the base in situ prepared from LiTMP and ZnCl2·TMEDA (1/3 equiv). With N-phenylpyrrole and -indole, the reactions were carried out in hexane containing TMEDA which regioselectively afforded the 2-iodo derivatives after subsequent iodolysis. With pyrroles and indoles bearing N-substituents such as 2-thienyl, 3-pyridyl, 4-methoxyphenyl and 4-bromophenyl, the reactions all took place on the substituent, at the position either adjacent to the heteroatom (S, N) or ortho to the heteroatom-containing substituent (OMe, Br). The CH acidities of the substrates were determined in THF solution using the DFT B3LYP method in order to rationalize the experimental results.

Contrasting Synergistic Heterobimetallic (Na–Mg) and Homometallic (Na or Mg) Bases in Metallation Reactions of Dialkylphenylphosphines and Dialkylanilines: Lateral versus Ring Selectivities

“…Molecular structure of [(TMEDA)Na(TMP)(CH 2 PCH 3 Ph)Mg(TMP)] 2 with thermalellipsoids at 40 %p robability.H ydrogen atomsh ave been omitted for clarity.Selected bond lengths( )a nd angles (8): Mg(1)ÀN(1), 2.069(5); Mg(1)ÀN(2), 2.001(5); Mg(1)ÀC(1), 2.182(6);Na(1)ÀN(1), 2.463(5); Na(1)ÀN(3), 2.528(6); Na(1)ÀN(4), 2.495(5);Na(1)ÀP(1), 2.919(2);P (1)ÀC(1), 1.777(6); P(1)ÀC(2), 1.823 (8);N(1)-Na(1)-P(1), 95.24 (12); Na(1)-N(1)-Mg(1), 103.5(2);N (1)-Mg(1)-C(1), 108.8(2); Mg(1)-C(1)-P(1), 118.4(3); C(1)-P(1)-Na(1), 88.40 (19). (16); Mg(1)ÀN(2), 1.9989 (17);N a(1)ÀC(3), 3.036(2);Na(1)ÀC(4), 2.648(2);N a(1)ÀN(3), 2.4779(18);Na(1)ÀN(4), 2.5401(18); Na(1)ÀN(5),2 .5291 (18);N(2)-Mg(1)-C(3), 120.48 (8); N(2)-Mg(1)-N(3), 134.32 (7); N(3)-Mg(1)-C(3), 105.16 (7); Na(1)-N(3)-Mg(1), 89.35 (6). (3); Na(1)ÀN(2), 2.457(3); Na(1)ÀN(4), 2.569(3); Na(1)ÀC(2), 3.038(4);Na(1)ÀC(3), 2.684(4); N(1)-Mg(1)-N(3), 133.51 (13);N(1)-Mg(1)-C(3), 119.21 (14);C(3)-Mg(1)-N(3), 107.11 (13);N a(1)-N(3)Mg(1), 87.25 (11).…”

“…[14,15] These metallating agents usually consist of a mixeda lkyl or amido lithiums peciesw ith either ad ivalent metals alt or ad ialkyl/amido metallic species. Of particular relevance to this work are the bimetallicb ases formed by the cocomplexation of an alkali metal amide (most commonly NaTMP) and ad ialkyl subordinate metal partner, typically zinc, [12,[16][17][18] magnesium [14,15,19,20] aluminium [21,22] or manganese. [23][24][25] Early examples of the effectiveness of these bases include the magnesiation (CÀHt oC ÀMg) of benzene [26] and the selective meta-magnesiation of toluene, [27] both achieved utilising the sodium magnesiate base [(TMEDA)Na(nBu)-(TMP)Mg(TMP)].…”

Characterising Supramolecular Architectures in Crystals Featuring I⋯Br Halogen Bonding: Persistence of X⋯X’ Secondary-Bonding in Their Congeners

“…The next structural motif also involves two molecules but these are connected over a centre of inversion via two I• • • Br contacts. This motif is adopted in the crystals of 4 [44], 5 [45], 6 [46], 7 [47] and 8 [48]. In each of 4 and 6, two independent molecules comprise the asymmetric unit, but only one self-associates across an inversion centre; in 6, the second independent molecule associates into a dimer via Br• • • Br halogen bonding contacts (Table S1).…”

In Situ ‘Trans-Metal Trapping’: An Efficient Way to Extend the Scope of Aromatic Deprotometalation

“…As a consequence, N-(3-pyridyl)pyrrole and -indole are, for example, deprotolithiated next to the pyridine nitrogen before interception by Zn(TMP) 2 (Scheme 14). 44 Whereas LiTMP is rarely employed to deprotometalate benzenes, LiTMP-Zn(TMP) 2 (1:1) can be used for both aromatic heterocycles benefiting from relatively acidic hydro- Ferrocenes bearing electrophilic functional groups such as carboxamides, nitrile and esters can undergo a similar treatment at room temperature to provide, after subsequent trapping, either the 2-iodo derivatives or the Negishitype coupling products. From bromoferrocene, the recorded result evidenced a competitive halogen 'dance' 15 at this temperature (Table 10).…”