Thylsubstituted diyne 6d cyclized with 1hexyne 9a to type a 9:1 mixture of regioisomeric isoindolinones 15a and 16a (entry 1). Ethylsubstituted diyne 6e reacted with 1hexyne 11a with lower regioselectivity, giving a two:1 mixture of isoindolinones 15b and 16b (entry 2). Nonetheless, diyne 6e cyclized with 2ethynyltoluene 9l, to give a five:1 mixture of isoindolinones 15c and 16c (entry three). Interestingly, the presence of diastereotopic benzylic protons in the 1H NMR spectrum suggests that isoindolinoneasc.wileyvch.de2013 The Authors. Published by WileyVCH Verlag GmbH Co. KGaA, WeinheimFULL PAPERSTable 4. Cyclizations involving diynes with distinctive alkyne substitutents.[a]Robert W. Foster et al.Entry Diyne six R1 1 two three 4[d] 5[d][a]R2 Me Et Et H HR3 nBu 9a nBu 9a otolyl 9l nBu 9a otolyl 9l3 [mol ] Time [h] Isolated items Yield of (15 16) [ ][b] Ratio of 15:16[c] ten ten 10 3 3 24 24 24 16 16 15a/16a 15b/16b 15c/16c 15d[e] 15e 69 57 73 85 94 9:1 two:1 5:1 20:1 20:6d 6e 6e 6f 6fSiMe3 SiMe3 SiMe3 Me Me[b] [c] [d] [e]Reaction conditions: A answer of six in CPME was added to a stirring solution of 9 and three in CPME over 1 min at room temperature.844501-00-4 Formula Isolated yield. Determined by the analysis of crude 1H NMR spectra. Diyne 6f in CPME was added dropwise over three h to a resolution of 9 and 3 in CPME. Proof of limited homocoupling of 6f was observed in the crude 1H NMR spectrum.15c can be a chiral molecule, presumably resulting from restricted rotation regarding the hindered biaryl unit. The dependence from the cyclotrimerization on an SiMe3 regiodirecting group was also investigated. Diyne 6f having a terminal methyl substituent reacted with 1hexyne 9a below the optimized cyclization circumstances to give isoindolinone 15d in 85 yield (entry 4). Crucially, there was no trace in the regioisomeric isoindolinone 16d by crude 1H NMR. Similarly, diyne 6f cyclized with 2ethynyl toluene 9l to provide isoindolinone 15e in 94 yield, with no proof for the formation of regioisomer 16e (entry five).1367777-12-5 Data Sheet Functional Group Manipulation of Cyclized Merchandise Conversion in the cyclized isoindolinone items into a variety of synthetically interesting motifs was examined.PMID:23539298 Isoindolinone 10a was converted to aryl halides 17 and 18, in 79 and 90 yields, respectively, through an ipso substitution on the silyl group (Scheme three).[22] Therapy of Ntbutylisoindolinone 13a with triflic acid resulted inside a simultaneous deprotection from the lactam and protodesilylation inside 30 min to provide NH isoindolinone 20 in excellent yield.[23] Alternatively, remedy of 13a with iodine monochloride followed by deprotection with triflic acid gave 7iodoisoindolinone 19 in 83 yield. Thus, an NtBu diyne might be applied as an indirect method for the synthesis of NH isoindolinones through this acidmediated deprotection. It was also possible to access a tetrasubstituted monocyclic benzene. Therapy of NH isoindolinoneScheme three. Synthesis of usefully functionalized isoindolinones.Scheme four. Synthesis of a tetrasubstituted benzene ring.19 with ditertbutyl dicarbonate gave NBoc isoindolinone 21, which may be lowered with lithium borohydride to type NBoc protected amino alcohol 22,Adv. Synth. Catal. 2013, 355, 2353 asc.wileyvch.de2013 The Authors. Published by WileyVCH Verlag GmbH Co. KGaA, WeinheimHighly Regioselective Synthesis of Substituted Isoindolinonestogether with cyclic aminol 23, within a combined yield of 78 (Scheme 4). The preparation of monocyclic substituted arenes by way of tethered alkyne cyclotrimerizations has little precedent and such sys.