Highly Diastereoselective Synthesis of a Novel Functionalized Benzocyclotrimer

The high yielding synthesis of a novel benzocyclotrimer is herein presented. The syn-diastereomer is obtained as major product, presumably in virtue of the presence of oxa-bridge of the bicylic components. The three oxa-bridges can be used for further functionalization, as well as the six bromine atoms of the three aromatic rings, as demonstrated in the aromatization of the a mixture of anti-6 and syn-6 (3:7) leading to trinaphthylene 7.


Introduction
Benzocyclotrimers 1 are rigid molecules characterized by one or two cavities, which have been successfully employed in supramolecular chemistry. 2amongst these, benzocyclotrimers bearing aromatic rings are characterized by large stiff cavities.The cavities are particularly deep and suitable for supramolecular applications in the case of the more symmetrical syn-diastereomer, which is generally obtained in lower amounts.In this report we describe the highly diastereoselective synthesis of the benzocyclotrimer syn-6, displaying one rigid and functionalized hemi-cavity in the bottom of the structure, concomitantly with three relatively reactive oxa-bridges (Figure 1).The reactivity of these moieties can be conveniently used for further functionalization of the less valuable diastereomer anti-6, which furnished the more symmetrical trinaphtylene 7 (Figure 1).
The starting material for the synthesis of the benzocyclotrimers syn-6 and anti-6 is vic-bromostannane 5, which obtained from commercially available 1,2,4,5-tetrabromobenzene 1.The key reagent 5 for the cyclotrimerization is obtained either by lithium-de-protonation of halide 3 with lithium diisopropylamide (LDA), or by lithium-de-bromination of the dibromide 4 with n-butyl lithium, followed in both cases by trans-metalation with trimethyltin chloride, furnishing the desired stannane 5 in 96% yields in both cases.The high chemo-selectivity of the lithium-de-bromination observed in the second approach is surprisingly high: indeed, the bromine atoms of the aromatic ring resulted completely unaffected by the metalating agent.
In order to accomplish the cyclotrimerization, the vic-bromostannane 5 is treated with copper(I) 2thiophenecarboxylate (CuTC) in dry NMP at low temperature.The two isomeric benzocyclotrimers are obtained in a highly favourable 7:3 syn to anti ratio and in a very good isolated yield (92%).
The cyclotrimers syn-6 and anti-6 are a potential source of polyaromatic rings.When syn-6 and anti-6 is treated with titanium(III), generated in situ from TiCl 4 , lithium aluminumhydride (LAH) and triethylamine (TEA) in refluxing THF, a quantitative yield of trinaphthylene 7 is obtained.

Conclusions
In conclusion, a straightforward and high yielding synthesis of a new benzocyclotrimer was studied.The cyclotrimerization reaction afforded the two possible diastereomers syn to anti in a very favourable 7:3 ratio.The more valuable syn-diastereomer will be considered for supramolecular applications.In the other hand, anti and syn diastereomers can be conveniently employed for the preparation of polyaromatic structures.