An N-nitrilium cation. The former ought to be far more nucleophilic than an alcohol and also the latter must be an effective electrophile (Scheme 5). Reaction of silyl ether and nitrilium cation results in a cationic N,O-bis(trimethylsilyl)imino ester, which can be hydrolyzed to a carboxylic ester. Formation ofBeilstein J. Org. Chem. 2013, 9, 1572577.Table 1: Collection of optimization experiments.# 1 2 three 4 five six 7 8aYieldsLewis acid (equiv) Hf(OTf)four (two.0) Hf(OTf)4 (0.two) Hf(OTf)four (0.two) AlBr3 (2.0) AlBr3 (2.0) AlBr3 (2.0), Hf(OTf)four (0.1) TMSOTf (two.0) TMSCl (2.0) TMSOTf (2.0)Circumstances MeCN, rt, 48 h MeCN, rt, 65 h MeCN/H2O ten:1, rt, 65 h MeCN, rt, 65 h MeCN, 50 , 90 h MeCN, rt, 65 h MeCN, rt, 65 h MeCN, rt, 65 h MeCN, Et3Nb, rt, 65 hYield (s. m.)a [ ] 72 (15) 25 (69) 3 (81) 50 (39) 65 (20) 64 (24) 83 (9) 33 (59) 80 (ten)of recovered beginning material (s. m.) provided in parentheses. bEt3N (1 equiv) was added.herein reported Lewis acid promoted Pinner reaction furnished 52 of this substrate, where a less-sensitive substrate could possibly be applied with no the necessity of an inert atmosphere.Melittin supplier The comparatively low yields within the reactions with benzonitrile are most most likely triggered by the reduce electrophilicity from the benzonitrilium ion. The good charge is considerably stabilized by the +M effect with the system. The high yields observed in the reactions of para-nitrobenzyl alcohol (21) and specifically in its reaction with acrylonitrile brought us towards the speculation that the nitro group includes a special valuable effect on this reaction, possibly as radical scavenger. It turned out that the addition of nitrobenzene [16] within the reactions with acrylonitrile led to elevated yields in some cases. Other radical scavengers like hydroquinone had a equivalent effect. Reaction of hexane-1,6-diol (31) gives moderate yields with the diacylated products, exactly where substantial amounts from the monoesters were isolated (Table 2, entry 7). Alcohols with further functional groups were similarly tested, but poor yields had been observed, when ester or carbamate groups have been present inside the substrates (Table 2, entries 8 and 9). The Lewis acid trimethylsilyl triflate possibly cleaves the benzyloxycarbonyl (Z) group, since the comparable trimethylsilyl iodide (TMSI) is recognized to cleave Z defending groups [17]. Poor yields are obtained in the Lewis acid mediated reaction of nitriles with secondary alcohols such as cyclohexanol (Table two, entry 10).Afatinib dimaleate site No item at all was obtained, when the tertiary alcohol 1-methylcyclohexanol (48) was exposed to these circumstances (Table 2, entry 11).PMID:23912708 The Lewis acid promoted Pinner reaction is highly chemoselective; phenols had been not acylated by these conditions and have been re-isolated with high yields (Table 2, entries 124). Within this context we tested 4-(2-hydroxyethyl)phenol (53) containing an aliphatic and also a phenolic hydroxy function within the reactionScheme 5: Plausible mechanism of the Lewis acid-promoted Pinner reaction.the Br sted acid trifluoromethanesulfonic acid is to be expected under these reaction circumstances, but appears to have no influence around the reaction outcome. A related reaction with the addition of one equivalent of triethylamine led to a virtually identical yield (Table 1, entry 9). Using the optimized reaction circumstances we tested a collection of nitriles and alcohols. All reactions required the application on the nitrile as solvent. Low yields have been observed, when equimolar amounts with the nitrile and the alcohol have been utilized in methylene chloride as inert solvent. Th.