In a further cluster of experiments, we investigated the aryne phosphate reaction using phosphomonoesters as starting materials (scheme 3, A). These transformations lead to phosphodiester products. 5,5,5-Trifluoropentylphosphate (38) was chosen as standard substrate in the aryne scope delineation (scheme 3, A+B), as the CF3-moiety can be used as an analytical handle for NMR-detection of products. 38 was reacted with 2.5 equivalents of o-silylaryltriflates and TBAF following the procedure described above. Only little overreaction to phosphate triesters was generally observed (<10%) and these triesters usually decomposed during chromatographic purification. Under the applied conditions, 38 was successfully transformed into arylalkyldiester 40 in 51% yield. Dimethylphenyldiesters 41 and 42 were isolated in 67% and 60% yield, respectively. The reaction tolerates donor-and acceptor-substituted arynes delivering e.g. dimethoxyphenyland trifluoromethylphenyl diesters 43 and 44 yields of 57% and 50%. In the case of unsymmetric 44, the para-product was preferred in a ratio of 85:15. Sesamol-derived diester 45 was isolated in 61% yield. An alkynylated aryne precursor (SI-23) was developed and successfully applied generating 46 in 64% yield and a para:meta ratio of 84:16. Such clickable phosphordiester can be further functionalized by copper catalysed Huisgen-type cycloadditions. Br-and Cl-substituted diesters (47, 48) were synthesized in comparable yields of 57%, while the Br-substituent induced a higher regioselectivity. Furthermore, naphtyldiester 49 was isolated in 43% yield and indolyl-diester 50 was generated in a yield of 38% with a C5 positional preference of 85:15. Finally the pyryne was transformed to diester 51 in 58% yield and with a C2-preference of 78:22. Subsequently, the phosphate scope was investigated using several organophosphates under the conditions described above (scheme 3, C+D). Diphenylphosphate 52 was synthesized in 55% yield. Similarly, pentylphenylphosphate 53 was isolated in 56% yield and alkynylated derivative 55 was obtained in 48%. Notably, the reaction extends to phosphonates as demonstrated by the O-arylation of phenylphosphonate in 46% yield (54). In addition, terpenoide phosphates were successfully arylated leading to isoprenol derivative 56 in 39% yield and the challenging geraniol-based allylphosphate 57 in 27% yield. The chemoselectivity regarding hydroxy-and phosphate-groups -both O-nucleophiles -was studied using bifunctional 6hydroxy-hexylphosphate as a model substrate. Under the described reaction conditions, the phosphate group could however not be arylated selectively to give 58. Hydroxyarylation occurred to a comparable extent, leading to a modest yield of 15%. This also explains that a highly selective phosphate arylation of unprotected nucleotides like adenosine monophosphate could not be achieved. In contrast, nucleotide analogue d4T-monophosphate was arylated successfully, generating 59 in 41% yield. Furthermore, also organodiphosphates were arylated, as demonstrated by d4Tdiphosphate arylation to derivative 60 in 33% yield. Finally, diphenylpyrophosphate (61) was isolated in 47% yield. While overall good results were obtained in our cluster II studies, an obvious reduction in yields was observed as compared to cluster I. We now understand this limitation, as many reactions shown in scheme 3 also generated distinct byproducts, which can be explained mechanistically as outlined in scheme 4: In addition to pathway 1 leading to the desired products, byproduct formation according to pathway 2 was observed on the order of 25%. In this case, the TBAF-solvent tetrahydrofuran (THF, 64) intercepts the aryne (2) under formation of cyclic oxonium-ion 65. Subsequently, the corresponding phosphate 62 attacks 65 in an SN2-process leading to isolable byproduct 66. The noninnocence of THF towards arynes was already reported in 1970 and is sometimes exploited synthetically in multicomponent approaches. Suppression of pathway 2, by changing TBAF-solvent from THF to MeCN (scheme 4, B), should therefore increase the yields significantly. We demonstrate this with pentylphosphate (67), where solvent exchange led to the substantially improved yield of 72% as compared to 56% when the medium contained THF. Therefore, it should be possible to increase the yields of the reactions summarized in scheme 3 at the expense of an additional solvent exchange procedure. Of note, the THF-derived byproducts were not observed for cluster I reactions (scheme 2), as in these cases Pi and PPi were applied in excess accompanied by reduced TBAF-equivalents.