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If two coupling reactions could occur on a single methyl group of CrTol (333), then it seemed 3 possible that multiple methyl groups such in tricarbonylchromium complexes of p-xylene 888 and 8 mesitylene 999 could be activated as well. Referring back to Scheme 1-12, the triarylmethane 9 complex’s tertiary benzylic center is thermodynamically more acidic than the di- or mono- arylmethane center, so we were concerned that persistent deprotonation of the tertiary center and disfavored formation of a di-anion would hamper further reactivity of the other aryl methyl group (Scheme 1-14 below).

Scheme 1-14: Reaction at multiple benzylic positions on a single arene: Would the presence of a persistent triarylmethane anion prevent the less acidic tolyl proton from reacting?

The p-xylene complex 8888 was reacted with the bulky (doubly ortho-substituted) aryl bromide 1,3,5- triisopropylbenzene, which was expected to only undergo coupling once per benzylic position, disfavoring further deprotonation and reaction. The reaction was sluggish due to the large size of the aryl bromide, but an encouraging mixture of single-coupled intermediate 10101010 and desired double-coupled product 111111 was observed. Full conversion was obtained using more forcing 11 conditions (≥5 equiv. base and >10 mol% catalyst loading with heating at 55 °C for 24 hours), and 111111 was isolated in 73% yield (Scheme 1-14). 11

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Scheme 1-15: Single coupling on each methyl of (η6_{-p-xylene)Cr(CO)3 (8888) with the extremely bulky} arene 1,3,5-triisopropylbromobenzene.

Moving on to a less sterically bulky aryl bromide in which deprotonatable triarylmethane centers could be generated and remain deprotonated in solution meant that an even larger excess of LiHMDS was expected to be necessary to form the tetraarylated product 121212 (Scheme 1-16). In 12 this case, nearly 10 equivalents of LiHMDS was required for full conversion (70% yield), also suggesting the possibility of polyanions such as 131313----Li13LiLi2Li22 forming reversibly during the reaction.2 50,a The 70% isolated yield obtained here reflects a per-coupling yield of 91%.

Scheme 1-16: Tetra-arylated complex 121212 is formed in good yield from 812 888, though large excess of base and 10 mol % catalyst loading is needed for full conversion.

We also examined arylation of the mesitylene complex CrMesCrMesCrMesCrMes (9999) with both bulky 1,3,5- triisopropylbromobenzene and electron-rich 4-bromoanisole or slightly electron-poor 4- bromofluorobenzene. Coupling at 2 of the 3 methyl groups of the mesitylene did not pose much difficulty. Diarylation with 1,3,5-triisopropylbenzene led to product 14141414 in up to 55% yield, and tetraarylation with 4-bromofluorobenzenee provided 15151515 in up to 64% yield (Scheme 1-17).

a _{The tricarbonylchromium group has been known to stabilize di- and tri-anions directly on the arene ring,}

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However, achieving full conversion to the C3-symmetric products tri-arylated 161616 from 1,3,5-16 triisopropylbenzene (up to 33% yield) or hexa-arylated 17171717 from 4-bromoanisole (43% yield, or >86% yield per coupling event) proved to be more difficult. This is not surprising, considering the massive crowding at the central arene due to the multiple aryl groups and the tricarbonylchromium group, which forces all benzylic aryl groups upward (see the x-ray crystal structure of 17171717a _{below, Figure 1-12). In reactions of CrMesCrMesCrMes (9CrMes 999) with 1,3,5-triisopropylbenzene or} 4-bromofluorobenzene, LDA was also examined as an alternative base to LiHMDS due to its greater basicity, in hopes that the tri- and hexa-arylated products could be isolated. However, the less substituted di- and tetra-coupled products 141414 and 1514 151515b _{were generated as the major product} instead of the fully substituted C3-symmetric products. Since equilibrium of deprotonation of the benzylic position is considered to lie far to the right for the much stronger LDA (pKa of iPr₂NH vs HMDS-H is 36 and 26, respectively, in THF solvent. See Table 1-1 on p. 10), this may support the idea that the Cr(CO)3 group can stabilize more than one anion on the benzlic position (see Scheme 1-16 above). It is also possible that the lithiated species that is assumed to be oligomeric in solution does not transmetallate as readily with the diisopropylamine when there is excessive crowding.

Scheme 1-17: Reactions using (η6_{-mesitylene)Cr(CO)3 9999 showed that coupling products 14141414 or 151515 15} formed relatively easily at 2 of 3 methyl groups, though complete coupling to form the C3-symmetric products 161616 and 1716 1717was difficult due to sterics. 17 a_{LDA was used as base instead.}

a _{The crystal structure for 17171717 can also be accessed through the Cambridge Crystallographic Data Centre}

(use the reference ID number: CCDC 775771).

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Figure 1-12: X-ray crystal structure (side and top views) of the pinwheel-like 17171717 illustrates the sterically crowded nature of the complex. Thermal ellipsoids are at 50% probability. CO ligands are unusually distorted, see full details on page 264.

Next we examined reaction with ortho-substituted xylene complex CroXyl (18181818, Scheme 1-18). Single arylation of each benzylic methyl could be achieved with a 2,6-di-substituted bromobenzene (this time using 2-bromo-1,3-dimethylbenzene) to give 19191919 in 85% yield. Using less the sterically demainding aryl bromide N,N-dimethy-4-bromoaniline and 3 equiv. of LiHMDS and running the reaction for 20 h provided the racemic planar chiral complex 20202020, in which the two couplings happened at a single methyl, in 64% isolated yield; a symmetrical coupling product analogous to 19191919 was not observed. By simply increasing the amount of LiHMDS to 5 equiv. and increasing the run time of the reaction to 24 h, the tri-arylated product 21212121 was isolated as the major product (48% yield). Despite attempting reaction of CroXyl (181818) with large amounts of 18 excess base, formation of tetracoupled product 22222222 was not observed; as can ben seen in Scheme 1-19, both formation and transmetallation with 21212121----LiLiLiLi would be extremely unfavorable due to sterics.

Scheme 1-18: Coupling of (η6_{-o-xylene)Cr(CO)3 18181818 with various aryl bromides leads to symmetrical di-} coupled 191919, planar chiral di-coupled 2019 202020, and tri-coupled 21212121 products.

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Scheme 1-19: In the coupling reaction of 18181818 with 4-NMe2-C6H4-Br, the reaction stops at 3 coupling events due to sterics which prevent deprotonation and further reaction at the second benzylic site.

As seen in the activation and coupling at multiple C–H bonds of toluene, xylene, and mesitylene, the reactions presented here have a distinct advantage over other cross-coupling methods. Tricarbonylchromium allows us to perform up to 6 coupling reactions per equivalent of tricarbonylchromium to form highly symmetric complexes. We can also synthesize unusual planar-chiral complexes that lack central chirality centers. Further functionalization of Ar–F bonds47 _{or deprotection and then functionalization of Ar–OMe bonds could potentially establish} these polyarylated methanes as useful dendrimer cores.