Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

Abstract

The electron-donor and unique redox properties of the tetrathiafulvalene (TTF, 1) moiety have led to diverse applications in many areas of chemistry. Monopyrrolotetrathiafulvalenes (MPTTFs, 4) and bispyrrolotetrathiafulvalenes (BPTTFs, 5) are useful structural motifs and have found widespread use in fields such as supramolecular chemistry and molecular electronics. Protocols enabling the synthesis of functionalised MPTTFs and BPTTFs are therefore of broad interest. Herein, we present the synthesis of a range of functionalised MPTTF and BPTTF species. Firstly, the large-scale preparation of the precursor species N-tosyl-(1,3)-dithiolo[4,5-c]pyrrole-2-one (6) is described, as well as the synthesis of the analogue N-tosyl-4,6-dimethyl-(1,3)-dithiolo[4,5-c]pyrrole-2-one (7). Thereafter, we show how 6 and 7 can be used to prepare BPTTFs using homocoupling reactions and functionalised MPTTFs using cross-coupling reactions with a variety of 1,3-dithiole-2-thiones (19). Subsequently, the incorporation of more complex functionality is discussed. We show how the 2-cyanoethyl protecting group can be used to afford MPTTFs functionalised with thioethers, exemplified by a series of ethylene glycol derivatives. Additionally, the merits of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as an alternative to the most common deprotecting agent, CsOH·H2O are discussed. Finally, we show how a copper-mediated Ullman-type reaction can be applied to the N-arylation of MPTTFs and BPTTFs using a variety of aryl halides.

Keywords: Ullman coupling; heterocycles; protecting groups; sulfur chemistry; tetrathiafulvalene.

Figure 1

The sequential, reversible oxidation of TTF (1) to its stable radical cation (2) and dication (3) states.

Figure 2

Structures and possible substitution positions of MPTTFs (4) and BPTTFs (5).

Scheme 1

Large-scale synthesis of 6. Reagents and conditions: a) PhMe, reflux, 19 h, 74%; b) LiBr, NaBH₄, THF, MeOH, −10 °C → rt, 20 h, 77%; c) PBr₃, THF, 0 °C → rt, 20 h, 75%; d) (i) 13, MeCN, DMF, 80 °C, 15 min, (ii) Hg(OAc)₂, CHCl₃, AcOH, rt, 24 h, (iii) DDQ, PhCl, reflux, 4 h, 52% (from 12).

Scheme 2

Preparation of 7. Reagents and conditions: a) TsCl, Et₃N, DMAP, MeCN, rt → reflux, 3.5 h, 82%; b) (i) LiAlH₄, THF, 0 °C, 2.5 h, (ii) AcOH, Et₂O, 0 °C; c) (Im)₂CO, THF, 0 °C, 1 h, 83% (from 17).

Scheme 3

Homo and cross-coupling reactions of 6 or 7 afford BPTTFs and MPTTFs, respectively. Reagents and conditions: a) (EtO)₃P, 120–130 °C, 5–5.5 h, 76–79%; b) (EtO)₃P, 120–135 °C, 1–4 h, 70–87%.

Scheme 4

Deprotection and methylation of cyanoethyl-protected thiol moieties on MPTTFs as reported by Jeppesen et al. [25]. Reagents and conditions: a) (i) 1 equiv CsOH·H₂O, MeOH, THF, rt, 1 h, (ii) MeI, THF, rt, 30 min; b) (i) 1 equiv CsOH·H₂O, MeOH, THF, rt, 1 h, (ii) MeI, THF, rt, 45 min, (iii) 1 equiv CsOH·H₂O, MeOH, THF, rt, 1 h, (iv) MeI, THF, rt, 30 min.

Scheme 5

Deprotection and alkylation of cyanoethyl-protected thiol moieties on MPTTFs using CsOH·H₂O or DBU. Reagents and conditions are detailed in Table 2.

Scheme 6

Deprotection and N-arylation of tosylated MPTTFs. Reagents and conditions: a) NaOMe, THF, MeOH, reflux, 15 min–6 h, 89–95%; b) CuI, K₃PO₄, 29, THF, 80–115 °C (sealed tube), 3–48 h, 25–68%; c) CuI, K₃PO₄, 29, THF, 100–130 °C (microwave), 2–3 h, 51–93%; d) CuI, K₃PO₄, 29, THF, reflux, 3 h, 67%.

Scheme 7

Deprotection and N,N-diarylation of tosylated BPTTFs. Reagents and conditions: a) NaOMe, THF, MeOH, reflux, 30 min–8 h, 95–99%; b) CuI, K₃PO₄, 29, THF or 1,4-dioxane, 98–110 °C (sealed tube), 22–65 h, 24–72%.