Diastereo-and enantioselective pinacol coupling reactions of chiral α-ketoamides mediated by samarium diiodide afforded extremely high diastereoselectivities. Enantiopure (S,S)-or (R,R)-2,3-dialkyltartaric acid and derivatives can be synthesized. Diels-Alder cyclo-additions of S-indoline chiral acrylamides with cyclopentadiene in the presence of Lewis acids proceed with high diastereofacial selectivity, giving either endo-R or endo-S products depending on Lewis acid and the structures of chiral dienophiles.
Stereo differentiated asymmetric syntheses have been achieved by S-indoline derivations. Diels-Alder cycloadditions of S-indoline chiral acrylamides with cyclopentadiene proceed with high diastereofacial selectivity, giving either endo-R or endo-S products depending on Lewis acid and the structures of chiral dienophiles. Diastereo-and enantioselective pinacol coupling reactions of chiral α-ketoamides mediated by samarium diiodide afforded extremely high diastereoselectivities. Enantiopure (S,S)-or (R,R)-2,3-dialkyltartaric acid and derivatives can be synthesized for the first time depending on the structure of α-ketoamides.Lewis acid-catalyzed addition of dienes to chiral acrylamides is a useful reaction because it provides one of the most effective methods for creating new chiral centers during the formation of six-membered rings [1]. Lewis acids have been used for chelate formation in Diels-Alder cyclizations to obtain high diastereofacial selectivities [1][2][3][4][5]. In general, the S-form of the chiral dienophile (auxiliary) exclusively affords the endo-R adduct over the endo-S one, and the R form exclusively gives the S adduct over the endo-R one. Issues associated with this absolute stereochemical control depending upon Lewis acids and the structures of dienophiles provide an important challenge in the area of practical Diels-Alder reaction designs.In the hope of obtaining the opposite configuration of the endo adduct and understanding the mechanism, three different dienophiles 1, 2, and 3 were prepared and reacted with dienes in the presence of various Lewis acids. Here we describe the intriguing results obtained during development of Lewis acid-dependent stereocontrol toward both endo-R and endo-S configuration with high diastereofacial selectivity. In order to generalize the results, the requisite dienophiles 1-3 were synthesized from (S)-indoline-2-carboxylic acid [6]. They were purified, and their optical purities (>99.8% ee) were determined by high-performance liquid chromatography (HPLC) (Daicel chiral OD column, 5:95). The preliminary studies involved reaction of 1-3 with 4 and 5, as shown in Scheme 1.Extremely high levels of asymmetric induction can be achieved in Diels-Alder cycloadditions of 1 or 3 with 4; in contrast to other general disnophiles, 1 containing a carboxylate moiety reacts with 4 to give differently configures adducts depending on the Lewis acids employed; in the presence of TiCl 4 , Ti(OPr i ) 4 , or SnCl 4 , 6a was obtained as the major diastereomer (6a:6b = endo-R:endo-S = >99:1; entries 4-6 in Table 1), but with AlEt 2 Cl, ZnCl 3 , or BF 3 ·Et 2 O the opposite configuration of 6b was obtained (6a:6b = 1: >99; entries 1-3 in Table 1). In the case of 2, the same trend of 7b was observed, but in a less diastereoselective manner than for 1 (entries 16 and 17). In particular, 3 containing a diphenylsubstituted tertiary alcohol moiety affords exceptionally high diastereofacial selectivities (8a:8b = >99:1, yield = >90%; entries 7-15) regardless of the natures of the Lewi...
Diels-Alder cycloadditions of S-indoline chiral acrylamides with cyclopentadiene in the presence of Lewis acids proceed with high diastereofacial selectivity, giving either endo-R or endo-S products depending on Lewis acid and the structures of chiral dienophiles. Diastereo-and enantioselective pinacol coupling reactions of chiral α-ketoamides mediated by samarium diiodide afforded extremely high diastereoselectivities. Enantiopure (S,S)-or (R,R)-2,3-dialkyltartaric acid and derivatives can be synthesized. Furthermore, it was demonstrated that α,β-unsaturated amides coupled with SmI 2 to dimerized products containing two chiral carbons which were first obtained as the adjacent chiral carbons.Lewis acid-catalyzed addition of dienes to chiral acrylamides is a useful reaction because it provides one of the most effective methods for creating new chiral centers during the formation of six-membered rings [1]. Lewis acids have been used for chelate formation in Diels-Alder cyclizations to obtain high diastereofacial selectivities [1][2][3][4][5]. In general, the S-form of the chiral dienophile (auxiliary) exclusively affords the endo-R adduct over the endo-S one, and the R-form exclusively gives the S adduct over the endo-R one.In the hope of obtaining the opposite configuration of the endo adduct and understanding the mechanism, three different dienophiles 1, 2, and 3 were prepared and reacted with dienes in the presence of various Lewis acids. Here, we describe the intriguing results obtained during development of Lewis acid-dependent stereocontrol toward both endo-R and endo-S configuration with high diastereofacial selectivity. In order to generalize the results, the requisite dienophiles 1-3 were synthesized from (S)-indoline-2-carboxylic acid [6]. They were purified, and their optical purities (>99.8% ee) were determined by high-performance liquid chromatography (HPLC) (Daicel chiral OD column, 5:95). The preliminary studies involved reaction of 1-3 with 4 and 5, as shown in Scheme 1.Extremely high levels of asymmetric induction can be achieved in Diels-Alder cycloadditions of 1 or 3 with 4; in contrast to other general dienophiles, 1 containing a carboxylate moiety reacts with 4 to give differently configures adducts depending on the Lewis acids employed; in the presence of TiCl 4 , Ti(OPr i ) 4 , or SnCl 4 , 6a was obtained as the major diastereomer (6a:6b = endo-R:endo-S = >99:1), but with AlEt 2 Cl, ZnCl 3 , or BF 3 ·Et 2 O, the opposite configuration of 6b was obtained (6a:6b = 1:>99). In the case of 2, the same trend of 7b was observed, but in a less diastereoselective manner than for 1. In particular, 3 containing a diphenyl-substituted tertiary alcohol moiety affords exceptionally high diastereofacial selectivities (8a:8b = >99:1, yield = >90%) regardless of the natures of the Lewis acid. The endo configurations were readily ascertained by iodolactonization of 6a-8a with I 2 in DMF [5b]. The ratio of endo-R and endo-S was determined by HPLC with the crude 6a-8a and 6b-8b without purification. The absolute...
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