No abstract

Stereospecific substitutions of optically pure 1-(pyridinyl)ethyl methanesulfonates with various amines are described. The reaction of (R)- or (S)-1-(2-pyridinyl)ethyl methanesulfonate with primary amines, including amino acid esters, gives N-substituted (S)- or (R)-1-(2-pyridinyl)ethylamines (4) with inversion of the configuration. Secondary cyclic amines are also reacted with (R)-2 to give the corresponding substituted amines (5) in excellent yields. Optically pure and meso triamine ligands having two pyridine rings, (S,S)-4f and meso-4f, (S,S)-9e, (S,R)-9e, and (S,S)-9f, have been prepared in stereochemically pure form by this method. Not only the substitution reaction of optically active 2 but also that of 1-(4-pyridinyl)ethyl and 1-(3-pyridinyl)ethyl methanesulfonates 11 and 14 take place stereospecifcally with inversion of the chiral center.

Hafnium trifluoromethanesulfonate [Hf(OTf) 4 ]-and scandium trifluoromethanesulfonate [Sc(OTf) 3 ]-catalyzed conjugated addition of 3-position of indoles to several enones proceeded in acetonitrile as solvent. Especially, Hf(OTf) 4 exhibited high catalytic activity and gave the conjugate addition product in good yield.Indoles are the key components of many drugs and some biologically active compounds, and the development of new forming methods leading to indole derivatives has attracted much attention in organic synthesis. 1 Especially, 3-substituted indoles exhibit several biological activities, and are versatile intermediates for the synthesis of several indole derivatives. 2 Based on these reasons, there are several addition reactions of indoles to enones, 3 and recently the Lewis acid-catalyzed conjugate addition of the 3-position of indoles to enones had been reported by several groups. The reaction using a Lewis acid requires careful control to prevent side reactions such as the dimerization or polymerization of indoles. For example, Bi(NO) 3 , 4 Bi(OTf) 3 , 5 InBr 3 , 6 InCl 3 7 and Yb(OTf) 3 8 have been reported as useful Lewis acid catalysts for this reaction. However, the reaction usually demands over a 10 mol% catalyst and requires several hours. Also, Kobayashi and co-worker reported Sc(DS) 3 (DS = dodecyl sulfate) catalyzed the conjugate addition of indoles to a,b-enones in water, however, they also reported Sc(OTf) 3 exhibited a low catalytic activity in water. 9 Herein, we report that the Sc(OTf) 3 10 catalyzed the indole addition to enones in MeCN solvent, and furthermore, Hf(OTf) 4 11 exhibited a high catalytic activity even at a lower catalyst loading for this reaction.We examined the reaction of indole (1a) and methyl vinyl ketone (2a) using some Lewis acid catalysts in MeCN (Scheme 1, Table 1). The reaction with 10 mol% Sc(OTf) 3 proceeded smoothly and gave 90% of the conjugate addition product (entry 1). The reaction rate was faster than other reported catalysts, and the amount of Sc(OTf) 3 was reduced to 5 mol% without decreasing the yield (entry 2). On the other hand, Hf(OTf) 4 showed a really high reactivity for this reaction. The reaction using the 10 mol% catalyst was complete only in ten minutes. The reaction with Sc(DS) 3 also finished in ten minutes, although the reaction yield was lower than that with Hf(OTf) 4 (entries 3 and 4). Thus, Hf(OTf) 4 was a very effective catalyst for this conjugate addition of indoles to enones, and the reaction with 1 mol% of Hf(OTf) 4 proceeded efficiently to give the product in 90% yield (entry 5).The results of the 5-substituted indoles (1b and 1c) and 1-methyl indole (1d) addition to several enones catalyzed by Hf(OTf) 4 compared to Sc(OTf) 3 are summarized in Table 2. In all cases, the reation with Hf(OTf) 4 was faster than the reaction with Sc(OTf) 3 . The reaction of the 5-substituted indoles to methyl vinyl ketone (2a) smoothly proceeded with Sc(OTf) 3 (entries 1 and 3), and the same reactions were catalyzed by Hf(OTf) 4 in a much shorter Scheme ...