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Volumn 133, Issue 20, 2011, Pages 7859-7871

Highly selective methods for synthesis of internal (α-) vinylboronates through efficient NHC-Cu-catalyzed hydroboration of terminal alkynes. Utility in chemical synthesis and mechanistic basis for selectivity

Author keywords

[No Author keywords available]

Indexed keywords

CATALYST LOADINGS; CATALYTIC REACTIONS; CHEMICAL SYNTHESIS; CU COMPLEXES; ELECTRON-WITHDRAWING SUBSTITUENTS; HYDROBORATION; IMIDAZOLINIUM SALTS; MECHANISTIC STUDIES; N-HETEROCYCLIC CARBENES; NHC LIGANDS; PROPARGYL ALCOHOL; SILYL ETHERS; SITE SELECTIVE; TERMINAL ALKYNE;

EID: 79957681266     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja2007643     Document Type: Article
Times cited : (273)

References (87)
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    • Alkyl-substituted α-vinylboronates can be accessed through hydroborations that require stoichiometric amounts of a Cu complex (1.1 equiv of CuCl, KOAc, and LiCl or a phosphine), and only in up to 91% selectivity (typically 9-71%). See
    • Alkyl-substituted α-vinylboronates can be accessed through hydroborations that require stoichiometric amounts of a Cu complex (1.1 equiv of CuCl, KOAc, and LiCl or a phosphine), and only in up to 91% selectivity (typically 9-71%). See: Takahashi, K.; Ishiyama, T.; Miyaura, N. J. Organomet. Chem. 2001, 625, 47-53
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    • 1H NMR spectrum of the product mixture prior to purification attempts
    • 1H NMR spectrum of the product mixture prior to purification attempts.
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    • It may be suggested that propargyl alcohol and amine are first converted to the corresponding boronate ester or amide, and it is such entities that undergo Cu-catalyzed net hydroboration. However, such a scenario would require the consumption of an equivalent of bis(pinacolato)diboron (1), likely through reaction of NHC-Cu-OMe with 1 to generate NHC-Cu-B(pin), which subsequently reacts with an alcohol or amine to deliver the aforementioned derivatives. Since only 1 equiv of 1 is used in all reactions and ≥83% conversion is observed, such a pathway can occur, at best, to only a minor extent
    • It may be suggested that propargyl alcohol and amine are first converted to the corresponding boronate ester or amide, and it is such entities that undergo Cu-catalyzed net hydroboration. However, such a scenario would require the consumption of an equivalent of bis(pinacolato)diboron (1), likely through reaction of NHC-Cu-OMe with 1 to generate NHC-Cu-B(pin), which subsequently reacts with an alcohol or amine to deliver the aforementioned derivatives. Since only 1 equiv of 1 is used in all reactions and ≥83% conversion is observed, such a pathway can occur, at best, to only a minor extent.
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    • For an example of vinyl halide conversion to a vinyllithium followed by (pinacolato)-isopropoxyboron utilized in the course of a natural product total synthesis, see
    • For an example of vinyl halide conversion to a vinyllithium followed by (pinacolato)-isopropoxyboron utilized in the course of a natural product total synthesis, see: Murelli, R. P.; Cheung, A. K.; Snapper, M. L. J. Org. Chem. 2007, 72, 1545-1552
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    • Reaction with p -methoxyphenylacetylene under identical conditions gives rise to 58% conversion and 62:38 α:β selectivity (pure α-vinylboronate is isolated in 33% yield after silica gel chromatography)
    • Reaction with p -methoxyphenylacetylene under identical conditions gives rise to 58% conversion and 62:38 α:β selectivity (pure α-vinylboronate is isolated in 33% yield after silica gel chromatography).
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    • See the Supporting Information for details
    • See the Supporting Information for details.
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    • For a method for synthesis of cyclic vinylboronates through the use of β-borylallylsilanes, prepared by Pd-catalyzed B-Si additions to allenes, see: Suginome, M.; Ohmori, Y.; Ito, Y. J. Am. Chem. Soc. 2001, 123, 4601-4602 For synthesis of cyclic vinylboronates through Pd-catalyzed C-H borylation, see: Olsson, V. J.; Szabó, K. J. Angew. Chem., Int. Ed. 2007, 46, 6891-6893
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    • Cyclic vinylboronates have also been prepared through Ni-catalyzed borylation processes that involve C-O activation:;;;; Chem.-Eur. J. 2011, 17, 786-791
    • Selander, N.; Willy, B.; Szabó, K. J. Angew. Chem., Int. Ed. 2010, 49, 4051-4053 Cyclic vinylboronates have also been prepared through Ni-catalyzed borylation processes that involve C-O activation: Huang, K.; Yu, D.-G.; Zheng, S.-F.; Wu, Z.-H.; Shi, Z.-J. Chem.-Eur. J. 2011, 17, 786-791
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    • For an early report regarding the synthesis of cyclic vinylboronates through catalytic RCM of dienes, see:; J. Am. Chem. Soc. 1998, 120, 7995-7996
    • Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168-8179 For an early report regarding the synthesis of cyclic vinylboronates through catalytic RCM of dienes, see: Renaud, J.; Ouellet, S. G. J. Am. Chem. Soc. 1998, 120, 7995-7996
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    • Ref 1e
    • Ref 1e.
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    • Reference 15b. For a review on C-B bond formation, including vinylboronates, through catalytic C-H activation
    • Reference 15b. For a review on C-B bond formation, including vinylboronates, through catalytic C-H activation, see
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    • For hydroborations of terminal alkynes with (pinacolato)boron hydride and catalyzed by NHC-Rh complexes, see:;;;;; Tetrahedron 2008, 64, 6853-6862
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    • Reference 8
    • Reference 8.
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    • For NHC-Cu-catalyzed pinacolatoboron conjugate additions to α,β-unsaturated carbonyls, see
    • For NHC-Cu-catalyzed pinacolatoboron conjugate additions to α,β-unsaturated carbonyls, see: O'Brien, J. M.; Lee, K.-S.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132, 10630-10633
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    • See ref 28a. The NHC-Cu-catalyzed reactions of the corresponding trisubstituted allylic carbonates that bear an electron-rich aryl substituent, however, result in the formation of benzylic C-B bonds
    • See ref 28a. The NHC-Cu-catalyzed reactions of the corresponding trisubstituted allylic carbonates that bear an electron-rich aryl substituent, however, result in the formation of benzylic C-B bonds; see
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    • ref 29.
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    • 2 (with MeOH present) with alkyl,aryl-substituted internal alkynes afford β -boryl products; high efficiency is observed with methyl-substituted substrates
    • 2 (with MeOH present) with alkyl,aryl-substituted internal alkynes afford β -boryl products; high efficiency is observed with methyl-substituted substrates. See: Kim, H. R.; Jung, I. G.; Yoo, K.; Jang, K.; Lee, E. S.; Yun, J.; Son, S. U. Chem. Commun. 2010, 46, 758-760
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    • It may be argued that Cu-B addition might be reversible but the NHC-Cu-boronate remains coordinated to the same alkyne substrate. Although evidence to address such a possibility is not yet available, the fact that the presence of a large excess of a second, and nearly identical, alkyne (e.g., 23 in Scheme 6) does not lead to significant cross-over, suggests otherwise
    • It may be argued that Cu-B addition might be reversible but the NHC-Cu-boronate remains coordinated to the same alkyne substrate. Although evidence to address such a possibility is not yet available, the fact that the presence of a large excess of a second, and nearly identical, alkyne (e.g., 23 in Scheme 6) does not lead to significant cross-over, suggests otherwise.
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    • D values of 2.7 and 3.6 have been measured for reactions of terminal alkyne 2 (cf. Table 1 and entry 1, Table 2) and 5-chloro-1-pentyne (Scheme 6) performed in the presence of NHC-Cu complex 10 (see Table 1). See the Supporting Information for details
    • D values of 2.7 and 3.6 have been measured for reactions of terminal alkyne 2 (cf. Table 1 and entry 1, Table 2) and 5-chloro-1-pentyne (Scheme 6) performed in the presence of NHC-Cu complex 10 (see Table 1). See the Supporting Information for details.
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    • For a review of the Tolman electronic parameter (TEP) for phosphine ligands, see: The TEP values for NHC ligands were obtained from: Organometallics 2008, 27, 202-210
    • For a review of the Tolman electronic parameter (TEP) for phosphine ligands, see: Tolman, C. A. Chem. Rev. 1977, 77, 313-348 The TEP values for NHC ligands were obtained from: Kelly, R. A., III; Clavier, H.; Giudice, S.; Scott, N. M.; Stevens, E. D.; Bordner, J.; Samardjiev, I.; Hoff, C. D.; Cavallo, L.; Nolan, S. P. Organometallics 2008, 27, 202-210
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    • It is unclear, however, whether the presence of an electron-withdrawing group within the alkyne substrate results in an increase in reaction rate
    • It is unclear, however, whether the presence of an electron-withdrawing group within the alkyne substrate results in an increase in reaction rate.
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    • For a general discussion of secondary orbital interactions and their significance in predicting selectivity, see
    • For a general discussion of secondary orbital interactions and their significance in predicting selectivity, see: Ginsburg, D. Tetrahedron 1983, 39, 2095-2135
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    • The local softness parameters were calculated from Hirshfeld population analyses (HPA) of the optimized structures of aryl alkynes as described in the Supporting Information, following a finite difference approximation. For quantitative descriptions of softness, see
    • The local softness parameters were calculated from Hirshfeld population analyses (HPA) of the optimized structures of aryl alkynes as described in the Supporting Information, following a finite difference approximation. For quantitative descriptions of softness, see: Yang, W.; Parr, R. G. Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 6723-6726
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    • An alternative reaction manifold might be suggested that involves the intermediacy of Cu(I) hydrides and accounts for the observed site selectivities. The presence of MeOH in the mixture would thus cause the formation of reduction byproducts (i.e., net hydrogenation). In none of the reactions reported herein, however, were such byproducts observed, leading us to put forward the modes of Cu-B addition illustrated in Scheme 7. For an example of a Cu-catalyzed hydroboration reaction for which the intermediacy of Cu-H has been proposed, see:;;;, For a Cu-H-catalyzed 1,2-addition/transmetalation process involving acetylenic esters, affording alkenylboronates, see:;; Angew. Chem., Int. Ed. 2008, 47, 10183-10186
    • An alternative reaction manifold might be suggested that involves the intermediacy of Cu(I) hydrides and accounts for the observed site selectivities. The presence of MeOH in the mixture would thus cause the formation of reduction byproducts (i.e., net hydrogenation). In none of the reactions reported herein, however, were such byproducts observed, leading us to put forward the modes of Cu-B addition illustrated in Scheme 7. For an example of a Cu-catalyzed hydroboration reaction for which the intermediacy of Cu-H has been proposed, see: Noh, D.; Chea, H.; Ju, J.; Yun, J. Angew. Chem., Int. Ed. 2009, 48, 6062-6064 For a Cu-H-catalyzed 1,2-addition/transmetalation process involving acetylenic esters, affording alkenylboronates, see: Lipshutz, B. H.; Boskovic, Z. V.; Aue, D. H. Angew. Chem., Int. Ed. 2008, 47, 10183-10186
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    • For studies indicating the metallacyclopropene character of Cu-alkyne complexes, see
    • For studies indicating the metallacyclopropene character of Cu-alkyne complexes, see: Nakamura, E.; Mori, S.; Nakamura, M.; Morokuma, K. J. Am. Chem. Soc. 1997, 119, 4887-4899
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    • Catalytic hydroborations can be performed with nearly similar efficiency and selectivity in tetrahydrofuran or toluene
    • Catalytic hydroborations can be performed with nearly similar efficiency and selectivity in tetrahydrofuran or toluene.
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    • Attempts to examine transformations of allylic esters, such as an acetate or a tosylate, were thwarted by substrate instability or generation of complex product mixtures
    • Attempts to examine transformations of allylic esters, such as an acetate or a tosylate, were thwarted by substrate instability or generation of complex product mixtures.
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    • 10 metal complexes [Cu(I), Ag(I), and Au(I)] from linearity, see:;;, These investigations indicate that the barrier to distortion in Cu(I) complexes, much of which is due to the bending in L-Cu-L′ systems, is diminished with the more strongly donating ligands. For examples of distortion from linearity in an NHC-metal-ligand bond and related discussions, see:;;;;;; Chem.-Eur. J. 2010, 16, 14354-14364 For examples of structural distortion as a result of trans-influence, see:;; Acta Chem. Scand. 1996, 50, 1069-1073
    • 10 metal complexes [Cu(I), Ag(I), and Au(I)] from linearity, see: Carvajal, M. A.; Novoa, J. J.; Alvarez, S. J. Am. Chem. Soc. 2004, 126, 1465-1477 These investigations indicate that the barrier to distortion in Cu(I) complexes, much of which is due to the bending in L-Cu-L′ systems, is diminished with the more strongly donating ligands. For examples of distortion from linearity in an NHC-metal-ligand bond and related discussions, see: Poater, A.; Ragone, F.; Correa, A.; Szadkowska, A.; Barbasiewicz, M.; Grela, K.; Cavallo, L. Chem.-Eur. J. 2010, 16, 14354-14364 For examples of structural distortion as a result of trans-influence, see: Lövqvist, K. C.; Wendt, O. F.; Leipoldt, J. G. Acta Chem. Scand. 1996, 50, 1069-1073
    • (2004) J. Am. Chem. Soc. , vol.126 , pp. 1465-1477
    • Carvajal, M.A.1    Novoa, J.J.2    Alvarez, S.3    Poater, A.4    Ragone, F.5    Correa, A.6    Szadkowska, A.7    Barbasiewicz, M.8    Grela, K.9    Cavallo, L.10    Lövqvist, K.C.11    Wendt, O.F.12    Leipoldt, J.G.13
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    • The near-linear nature of an NHC-Cu-B(pin) is supported by a previously reported X-ray structure (C-Cu-B = 168°); see ref 31a. For X-ray structures on a linear NHC-Ag-Cl complex
    • The near-linear nature of an NHC-Cu-B(pin) is supported by a previously reported X-ray structure (C-Cu-B = 168°); see ref 31a. For X-ray structures on a linear NHC-Ag-Cl complex, see
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    • For X-ray structure data regarding a planar bent Cu(I) complex, see:; Proc. Nat. Acad. Sci. U.S.A. 2008, 105, 2779-2782
    • Lee, K.-S.; Hoveyda, A. H. J. Org. Chem. 2009, 74, 4455-4462 For X-ray structure data regarding a planar bent Cu(I) complex, see: Shapiro, N. D.; Toste, F. D. Proc. Nat. Acad. Sci. U.S.A. 2008, 105, 2779-2782
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    • The (pinacolato)boron ligand can impose a strong trans influence as well, as illustrated in a number of previous reports
    • The (pinacolato)boron ligand can impose a strong trans influence as well, as illustrated in a number of previous reports. See: Zhu, J.; Lin, Z.; Marder, T. B. Inorg. Chem. 2005, 44, 9384-9390
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    • The B-based ligand, however, is a constant structural feature in all the systems under investigation; it is the variation in the electronic and steric attributes caused by the change in the identity of the NHC ligand that gives rise to the observed differences in site selectivity. Accordingly, our discussions are focused on the impact caused by the latter component of the catalyst structure
    • Dang, L.; Lin, Z.; Marder, T. B. Chem. Commun. 2009, 3987-3995. The B-based ligand, however, is a constant structural feature in all the systems under investigation; it is the variation in the electronic and steric attributes caused by the change in the identity of the NHC ligand that gives rise to the observed differences in site selectivity. Accordingly, our discussions are focused on the impact caused by the latter component of the catalyst structure
    • (2009) Chem. Commun. , pp. 3987-3995
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    • 79957727698 scopus 로고    scopus 로고
    • The basis for β-selective reactions promoted by chiral sulfonate-based bidentate NHC-Cu complexes (cf. 5 in Scheme 2) will be the subject of a separate investigation and report. Such bidentate carbenes, in contrast to the monodentate systems examined here, give rise to NHC-based cuprates (vs NHC-Cu) complexes, and their substrate association and reactivity are therefore governed by different steric and electronic requirements
    • The basis for β-selective reactions promoted by chiral sulfonate-based bidentate NHC-Cu complexes (cf. 5 in Scheme 2) will be the subject of a separate investigation and report. Such bidentate carbenes, in contrast to the monodentate systems examined here, give rise to NHC-based cuprates (vs NHC-Cu) complexes, and their substrate association and reactivity are therefore governed by different steric and electronic requirements.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.