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Volumn 129, Issue 11, 2007, Pages 3408-3419

Mild and selective hydrozirconation of amides to aldehydes using Cp 2Zr(H)Cl: Scope and mechanistic insight

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOSELECTIVITY; WEINREB'S AMIDES;

EID: 33947409881     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja066362+     Document Type: Article
Times cited : (197)

References (104)
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    • The commercially available reagent is stable for several months if the bottle is purged with argon following each use, the cap wrapped with parafilm, and stored in a desiccator at room temperature. The reagent should exist as a white powder, and discoloration to an off-white or pinkish hue is usually indicative of impure reagent. Lipshutz has noted that the reagent can last ca. 3 months with careful handling; see ref 5. After this time, the reagent loses its efficiency even in the absence of appearance changes. We have noticed a similar trend. In addition to its commercial availability, Cp2Zr(H)Cl may also be synthesized from the dichloride in high purity following the procedure of Buchwald et al, see: Buchwald, S. L, LaMaire, S. J, Nielsen, R. B, Watson, B. T, King, S. M. Tetrahedron Lett. 1987, 28, 3895-3898
    • 2Zr(H)Cl may also be synthesized from the dichloride in high purity following the procedure of Buchwald et al. (see: Buchwald, S. L.; LaMaire, S. J.; Nielsen, R. B.; Watson, B. T.; King, S. M. Tetrahedron Lett. 1987, 28, 3895-3898.
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    • 1H NMR following the procedure of Schwartz et al. (Gell, K. I.; Posin, B.; Schwartz, J.; Williams, G. M. J. Am. Chem. Soc. 1982, 104, 1846-1855)
    • 1H NMR following the procedure of Schwartz et al. (Gell, K. I.; Posin, B.; Schwartz, J.; Williams, G. M. J. Am. Chem. Soc. 1982, 104, 1846-1855)
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    • and Buchwald et al. (see Org. Synth. reference above).
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    • 2Zr(H)Cl (0.29 mmol) is suspended in THF (3 mL) under argon at room temperature in a flame-dried round bottom flask. To this suspension is added the substrate (0.24 mmol) in THF (2 mL) also at room temperature. The mixture is stirred until the reaction turns clear usually within 15-30 min. Workup by the addition of silica gel (ca. 3 g) and removal of the solvent in vacuo, followed by elution through a short path silica gel column, affords the aldehyde.
    • 2Zr(H)Cl (0.29 mmol) is suspended in THF (3 mL) under argon at room temperature in a flame-dried round bottom flask. To this suspension is added the substrate (0.24 mmol) in THF (2 mL) also at room temperature. The mixture is stirred until the reaction turns clear usually within 15-30 min. Workup by the addition of silica gel (ca. 3 g) and removal of the solvent in vacuo, followed by elution through a short path silica gel column, affords the aldehyde.
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    • This information was published while this manuscript was under review: McGilvra, J. D.; Unni, A. K.; Modi, K.; Rawal, V. H. Angew. Chem., Int. Ed. 2006, 118, 6276-6279.
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    • For a recent example of iminium ion trapping with cyanide, see
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    • The authors report the flash chromatography purification of various α-aminonitriles: Heydari, A.; Fatemi, P.; Alizadeh, A.-A. Tetrahedron Lett. 1998, 39, 3049-3050.
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    • The authors report the -NCHO- proton at 5.64 ppm for an indole-derived cyclic N,O-acetal: Austin, J. F.; Kim, S.-G.; Sinz, C. J.; Xiao, W.-J.; MacMillan, D. W. C. Prof. Natl. Acad. Sci. U.S.A. 2004, 101, 5482-5487.
    • The authors report the -NCHO- proton at 5.64 ppm for an indole-derived cyclic N,O-acetal: Austin, J. F.; Kim, S.-G.; Sinz, C. J.; Xiao, W.-J.; MacMillan, D. W. C. Prof. Natl. Acad. Sci. U.S.A. 2004, 101, 5482-5487.
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    • 11C spectra are available in the Supporting Information of: Suginome, M.; Uehlin, L.; Murakami, M. J. Am. Chem. Soc. 2004, 126, 13196-13197.
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    • The crystal structure for compound 80 can be found in the Supporting Information. It was first reported in: Clarke, J. F.; Drew, M. G. B. Acta Crystallogr. 1974, B30, 2267-2269.
    • The crystal structure for compound 80 can be found in the Supporting Information. It was first reported in: Clarke, J. F.; Drew, M. G. B. Acta Crystallogr. 1974, B30, 2267-2269.
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    • 1H NMR) along with 30% of p-methoxybenzyl alcohol. This shows that 81 is a viable substrate for hydrozirconation. The formation of the alcohol is most likely due to instability of the intermediate to the reagent as the nitrogen lone pair should be less available for coordination to zirconium.
    • 1H NMR) along with 30% of p-methoxybenzyl alcohol. This shows that 81 is a viable substrate for hydrozirconation. The formation of the alcohol is most likely due to instability of the intermediate to the reagent as the nitrogen lone pair should be less available for coordination to zirconium.
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    • This observation could also be due to H-Cl exchange between the reagent and solvent
    • This observation could also be due to H-Cl exchange between the reagent and solvent.
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    • The addition of pyridine to 1 before the addition of substrate results in a deep red color that changes upon the addition of substrate in pyridine.
    • The addition of pyridine to 1 before the addition of substrate results in a deep red color that changes upon the addition of substrate in pyridine.
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    • The crude proton spectrum clearly shows the imine product with excess p-anisidine. See the Supporting Information.
    • The crude proton spectrum clearly shows the imine product with excess p-anisidine. See the Supporting Information.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.