Atersoluble substrates. Following the optimization study the situations described in entry 11 have been taken because the “optimized” cyACHTUNGREclization circumstances as they needed a decreased excess of monoyne and minimized the formation of dimer 11. Crucially this protocol did not require the CPME solvent to be either degassed or dried. This, with each other together with the environmental advantages of CPME, makes this reaction a very practical process for the synthesis of isoindolinones. Dimer 11 may be readily separated in the preferred product by flash column chromatography, and the optimized situations described in entry 11 gave the target isoindolinone 10a in 81 isolated yield (Table 2, entry 1). This reaction was also scaled up to a 500mg scale and isoindolinone 10a was isolated in 66 yield (428 mg item).Monoyne Scope The cyclization of 6a was then examined having a variety of monoynes employing the optimized circumstances described above to decide how robust the reaction was to get a range of various substrates. Diyne 6a cyclized with a wide array of monynes 9 as detailed in Table 2. Crucially, no evidence for the formation of regioisomeric isoindolinones was observed in any of the cyclization reactions. Alkyl monoynes 9a cyclized efficiently with 6a to offer the corresponding isoindolinones 10a in excellent isolated yield (entries 1, 6683 ). Tiny formation from the undesired dimer 11 was observed, except in the reaction of tertbutylacetylene 9b, presumably because of higher steric crowding regarding the monoalkyne. Carbamate 9f cyclized with 6a to offer 10f in reasonable yield and with modest levels of homocoupling (entry 6).Buy1373253-24-7 Ether 9g and acetal 9h each underwent cyclotrimerization with 6a, but with the formation of considerable quantities of dimer 11. Propargylic alcohol 9i and methoxyacetylene 9j each failed to cyclize with diyne 6a, with only starting material being recovered in each cases.Perfluorohexyloctane uses As well as aliphatic monoynes, diyne 6a cyclized effectively using a broad selection of aromatic monoynes. Electronrich (entries 12, 13, 17 and 18), electronpoor (entry 16) and sterically hindered substrates (entries 12 and 14) could all be tolerated and productsasc.wileyvch.de2013 The Authors. Published by WileyVCH Verlag GmbH Co. KGaA, WeinheimFULL PAPERSTable 2. Reaction of diyne 6a having a choice of monoynes 9.[a]Robert W. Foster et al.Entry 1 two three four five six 7 eight 9 ten 11 12 13 14 15 16 17 18 19 20Alkyne3 [mol ] three three 3 three three five 3 three three 3 4 three 4 three 3 3 five 10 3 20Time [h] 16 16 16 16 16 24 16 24 16 16 24 16 24 16 24 24 24 24 16 24Product 10 10a 10b 10c 10d 10e 10f 10g 10h 10k 10l 10m 10n 10o 10p 10q 10r 10t 10uYield of 10 [ ][b] 81 66 81 81 83 63 56 43 0 0 83 93 83 80 83 79 79 79 0 50Ratio 10:11[c] 9:1 2:1 9:1 six:1 eight:1 2:1 three:2 four:5 6:1 ten:1 6:1 8:1 five:1 five:1 six:1 7:1 two:1 [a]10v3:[b] [c]Reaction conditions: A resolution of 6a in CPME was added dropwise to a stirring solution of 9 and three in CPME more than three h at area temperature.PMID:33459059 Isolated yield. Determined by the evaluation of crude 1H NMR spectra.had been isolated in fantastic yields (793 ) with low levels of diyne homocoupling. For most of these examples longer reaction instances (as much as 24 h), and in some caseshigher catalyst loadings, were necessary to drive the reaction to completion. On the other hand the reactions with orthosubstituted arylacetylenes 9l and 9n reachedAdv. Synth. Catal. 2013, 355, 2353 asc.wileyvch.de2013 The Authors. Published by WileyVCH Verlag GmbH Co. KGaA, WeinheimHighly Regioselective Synthesis of Substituted Isoindolinones Table 3. Cyclizations invol.