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For examples of ECA reactions that involve alkylmetal reagents and afford quaternary carbon stereogenic centers, see: a
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For examples of ECA reactions that involve alkylmetal reagents and afford quaternary carbon stereogenic centers, see: (a) Wu, J.; Mampreian, D. M.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127, 4584.
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(h) May, T. L.; Brown, M. K.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2008, 47, 7358.
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18
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21244439594
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For catalytic ECA of vinylzirconiums and silanes, respectively, which afford tertiary C-C bonds, see: a
-
For catalytic ECA of vinylzirconiums and silanes, respectively, which afford tertiary C-C bonds, see: (a) Nicolaou, K. C.; Tang, W.; Dagneau, P.; Faraoni, R. Angew. Chem., Int. Ed. 2005, 44, 3874.
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35948938877
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(b) Shintani, R.; Ichikawa, Y.; Hayashi, T.; Chen, J.; Nakao, Y.; Hiyama, T. Org. Lett. 2007, 9, 4643. For related processes with vinylboronic acids, see ref 1c.
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20
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36749091836
-
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For three examples of ECA reactions of vinylaluminum reagents to β-methylcyclohexenone affording products in 75:25-91:9 er, see: a
-
For three examples of ECA reactions of vinylaluminum reagents to β-methylcyclohexenone affording products in 75:25-91:9 er, see: (a) Vuagnoux-d'Augustin, M.; Alexakis, A. Chem.-Eur. J. 2007, 13, 9647.
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(b) Hawner, C.; Li, K.; Cirriez, V.; Alexakis, A. Angew. Chem., Int. Ed. 2008, 47, 8211.
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For an expanded disclosure largely with the same substrate, see
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(c) Palais, L.; Alexakis, A. Chem.-Eur. J. 2009, 15, 10473. For an expanded disclosure largely with the same substrate, see:
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(d) Müller, D.; Hawner, C.; Tissot, M.; Palais, L.; Alexakis, A. Synlett. 2010, 1694.
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24
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73349084972
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Such chiral complexes have been utilized in enantioselective allylic substitutions with vinylaluminum reagents. See
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Such chiral complexes have been utilized in enantioselective allylic substitutions with vinylaluminum reagents. See: Akiyama, K.; Gao, F.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2010, 49, 419.
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For example, see: a
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For example, see: (a) Hara, S.; Dojo, H.; Takinami, S.; Suzuki, A. Tetrahedron Lett. 1983, 24, 731.
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53849104288
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For previous applications of catalytic ECA reactions affording quaternary carbon stereogenic centers to natural product synthesis, see: a
-
For previous applications of catalytic ECA reactions (affording quaternary carbon stereogenic centers) to natural product synthesis, see: (a) Peese, K. M.; Gin, D. Y. Chem.-Eur. J. 2008, 14, 1654.
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Van Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127, 6877.
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35
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79851505363
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For determination of the absolute stereochemistry of the ECA products, see the Supporting Information
-
For determination of the absolute stereochemistry of the ECA products, see the Supporting Information.
-
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36
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Brown, M. K.; May, T. L.; Baxter, C. A.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2007, 46, 1097.
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79851498305
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i-Bu addition product 8 is generated through an NHC-Cu-catalyzed process in 89:11 er. See ref 2h
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The i-Bu addition product (8) is generated through an NHC-Cu-catalyzed process in 89:11 er. See ref 2h.
-
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38
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68849103295
-
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opposite sense of absolute stereochemistry observed with sulfonate-containing Cu complexes derived from 2 and 3a-c entries 2-5, Table 1, vs those obtained through phenoxy-based 1 entry 1 or monodentate 4 entry 6, might be due to their unique stereochemical characteristics. Structural studies indicate that, unlike the bridging aryloxide in 1 or monodentate carbenes such as those obtained via 4 and 5, the sulfonate in such chiral Cu complexes is oriented syn to the neighboring Ph group of the NHC backbone. See
-
The opposite sense of absolute stereochemistry observed with sulfonate-containing Cu complexes derived from 2 and 3a-c (entries 2-5, Table 1), vs those obtained through phenoxy-based 1 (entry 1) or monodentate 4 (entry 6), might be due to their unique stereochemical characteristics. Structural studies indicate that, unlike the bridging aryloxide in 1 or monodentate carbenes such as those obtained via 4 and 5, the sulfonate in such chiral Cu complexes is oriented syn to the neighboring Ph group of the NHC backbone. See: Lee, Y.; Li, B.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 11625.
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0034725069
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For brief discussions regarding the relative difficulty of cyclopentenones as ECA substrates, see: a
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For brief discussions regarding the relative difficulty of cyclopentenones as ECA substrates, see: (a) Escher, I. H.; Pfaltz, A. Tetrahedron 2000, 56, 2879.
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For cross-coupling reactions with sterically hindered vinyl iodides, see: (a) Just, Z. W.; Larock, R. C. J. Org. Chem. 2008, 73, 2662.
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79851499318
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Preliminary studies indicate that, under the same conditions, NHC-Cu-catalyzed addition of nonsilyl-containing β-vinylaluminum reagents proceeds with equal efficiency but lower enantioselectivity e.g., 19 in 65:35 er and with the same sense of absolute stereochemistry. Investigations regarding identification of catalysts and conditions that promote such processes with high efficiency and enantioselectivity are in progress and will be reported in due course
-
Preliminary studies indicate that, under the same conditions, NHC-Cu-catalyzed addition of nonsilyl-containing β-vinylaluminum reagents proceeds with equal efficiency but lower enantioselectivity (e.g., 19 in 65:35 er) and with the same sense of absolute stereochemistry. Investigations regarding identification of catalysts and conditions that promote such processes with high efficiency and enantioselectivity are in progress and will be reported in due course.
-
-
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50
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0029741112
-
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Rccardiphenol B has previously been synthesized by a 12-step sequence through utilization of a chiral auxiliary-based process. See: a, For preparation ofanalogues in the racemic form, see
-
Rccardiphenol B has previously been synthesized by a 12-step sequence through utilization of a chiral auxiliary-based process. See: (a) Tori, M.; Hamaguchi, T.; Sagawa, K.; Sono, M.; Asakawa, Y. J. Org. Chem. 1996, 61, 5362. For preparation ofanalogues in the racemic form, see:
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79851501556
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Treatment of the Li-enolate derived from 22 with the appropriately substituted benzyl bromide leads to <2% of the desired alkylation product. In contrast, when benzyl bromide is used, the desired product is obtained in 74% yield >20:1 dr. The above findings suggest that subtle structural alterations of the electrophile can inhibit reaction of the sterically congested enolate. The stereochemical identity of the alkylation product >98% dr is projected on the basis of steric factors and has not been rigorously determined
-
Treatment of the Li-enolate derived from 22 with the appropriately substituted benzyl bromide leads to <2% of the desired alkylation product. In contrast, when benzyl bromide is used, the desired product is obtained in 74% yield (>20:1 dr). The above findings suggest that subtle structural alterations of the electrophile can inhibit reaction of the sterically congested enolate. The stereochemical identity of the alkylation product (>98% dr) is projected on the basis of steric factors and has not been rigorously determined.
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