Re similarly tested, but poor yields were observed, when ester or carbamate groups had been present in the substrates (Table 2, entries eight and 9). The Lewis acid trimethylsilyl triflate possibly cleaves the benzyloxycarbonyl (Z) group, since the comparable trimethylsilyl iodide (TMSI) is identified to cleave Z guarding groups [17]. Poor yields are obtained within the Lewis acid mediated reaction of nitriles with secondary alcohols like cyclohexanol (Table two, entry 10). No solution at all was obtained, when the tertiary alcohol 1methylcyclohexanol (48) was exposed to these situations (Table 2, entry 11). The Lewis acid promoted Pinner reaction is highly chemoselective; phenols were not acylated by these circumstances and were reisolated with high yields (Table 2, entries 124). In this context we tested 4(2hydroxyethyl)phenol (53) containing an aliphatic as well as a phenolic hydroxy function in the reactionScheme five: Plausible mechanism from the Lewis acidpromoted Pinner reaction.the Br sted acid trifluoromethanesulfonic acid will be to be expected under these reaction situations, but appears to have no influence around the reaction outcome. A comparable reaction with all the addition of a single equivalent of triethylamine led to a practically identical yield (Table 1, entry 9). With the optimized reaction situations we tested a choice of nitriles and alcohols. All reactions needed the application in the nitrile as solvent. Low yields had been observed, when equimolar amounts with the nitrile and the alcohol were employed in methylene chloride as inert solvent. The tested nitriles are acetonitrile, benzyl cyanide, benzonitrile, and acrylonitrile (Table two). Greatest yields were obtained inside the reactions of key alcohols with acetonitrile and benzyl cyanide (Table 2, entries 1). Somewhat reduce yields have been observed with acrylonitrile; nonetheless, reported solutions for the preparation of acrylate 5 bring about related, and in some cases even decrease yields [13,14]. A normal protocol for the synthesis of 9Hfluoren9ylmethyl acrylate starting together with the moisturesensitive acryloyl chloride beneath an inert atmosphere was reported to yield only 33 [15]. TheBeilstein J. Org. Chem. 2013, 9, 1572577.Table two: Variation of nitriles and alcohols.2-Bromo-4-chloro-6-methoxypyridine Order a# R2OH 1 2 3 four 5 six 7 8 9 ten 11 (48) 12 13 14aAlcohol cTMSOTfR1 = Me Item, Yield [ ] 2, 83 7, 80 12, 84 17, 75 22, 90 27, 88 32, 32 (33, 19c) 37, 21 42, 13 46, 15 0 PhOH (49) pNO2C6H4OH (50) 3,4,5Trimethoxyphenol (51) pMeOC6H4CH2OH (52) 0 0 0R1 = BnR1 = PhR1 = VinylFluorenylmethanol (1) Me(CH2)9OH (6) Cl(CH2)6OH (11) Et[O(CH2)2]2OH (16) pNO2C6H4CH2OH (21) pHO2CC6H4CH2OH (26) HO(CH2)6OH (31) EtO2C(CH2)5OH (36) ZNH(CH2)4OH (41) cyHexOH (45)3, 86 eight, 85 13, 90 18, 85 23, 78 28, 87 34, 46 (35, 37c) 38, 16 43, 13 47, 25 0 4, 44 9, 23 14, 27 19, 26 24, 39 29, 31 39, ten 0 5, 52 (67b) ten, 29 (40b) 15, 38 (16b) 20, 23 (19b) 25, 85 30, 64 40, 7 44, 14 (1 equiv), TMSOTf (2 equiv) dissolved within the nitrile (4 mL/mmol alcohol), rt, 65 h.Buy(Bromomethyl)cycloheptane bTMSOTf (two equiv) and nitrobenzene (1 equiv) had been added.PMID:33560469 (4 equiv) was added. Yield in the monoacylated byproducts 33 and 35, respectively, in parentheses.with acetonitrile and benzyl cyanide, respectively (Scheme 6). The respective esters 54 and 55 had been obtained with great yields: no esterification on the phenolic hydroxy group was observed. The reaction of four(2hydroxyethyl)phenol (53) with benzyl cyanide yielded monaspilosin (55), an aromatic ester isolated from the mould fungus Monascus pilosus by Cheng et al. [18]. This compound was rep.
