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The calculation presented in Figure 12 is based on the use of 5-10 mol-% of each catalyst (as reported in the literature for typical catalytic processes). The cost associated with additional reagents for these processes has not been considered in calculations presented. That said, the current cost of 2 mol of iPrMgCl is approximately $184 whereas the additional cost associated with use of 5mol-% of (+/-)-BIPHEP is $1,359 (Strem-2008).
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The calculation presented in Figure 12 is based on the use of 5-10 mol-% of each catalyst (as reported in the literature for typical catalytic processes). The cost associated with additional reagents for these processes has not been considered in calculations presented. That said, the current cost of 2 mol of iPrMgCl is approximately $184 whereas the additional cost associated with use of 5mol-% of (+/-)-BIPHEP is $1,359 (Strem-2008).
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126
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74549225400
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4 for a hypothetical reaction run on 1-mol scale would cost approximately $220 Strem 2008
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4 for a hypothetical reaction run on 1-mol scale would cost approximately $220 (Strem 2008).
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127
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74549164529
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4, and no significant precautions need to be taken to exclude trace quantities of air or water from the reaction mixture
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4, and no significant precautions need to be taken to exclude trace quantities of air or water from the reaction mixture.
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Regiochemical control in alkyne functionalization was not achieved as a result of the preorganization envoked. Rather, reactivity of a preformed monocyclic Ta-alkyne complex was achieved with a terminal alkene containing a tethered hydroxy substituent. Also, the position of the hydroxy substituent played a central role in the site-selective reaction of dienes with a preformed Ta-alkyne complex.
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Regiochemical control in alkyne functionalization was not achieved as a result of the preorganization envoked. Rather, reactivity of a preformed monocyclic Ta-alkyne complex was achieved with a terminal alkene containing a tethered hydroxy substituent. Also, the position of the hydroxy substituent played a central role in the site-selective reaction of dienes with a preformed Ta-alkyne complex.
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While the use of substituted alkenes, allenes and alkynes are well known in intramolecular metallacycle-mediated bond construction, barriers associated with reactivity broadly impact the viability of such bond constructions in a bimolecular manifold.
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While the use of substituted alkenes, allenes and alkynes are well known in intramolecular metallacycle-mediated bond construction, barriers associated with reactivity broadly impact the viability of such bond constructions in a bimolecular manifold.
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In the reaction of a Ti-alkyne complex with a carbonyl electrophile, conversion of the metallacyclopropene species to the metallacyclopentene intermediate is coupled to the formation of a strong Ti-O bond. In the related reaction with an alkyne, formation of the metallacyclopentadiene is coupled to the formation of a relatively weak Ti-C bond. For a discussion of the relative position of transition states as a function of the relative exothermicity of the reaction, see: a
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In the reaction of a Ti-alkyne complex with a carbonyl electrophile, conversion of the metallacyclopropene species to the metallacyclopentene intermediate is coupled to the formation of a strong Ti-O bond. In the related reaction with an alkyne, formation of the metallacyclopentadiene is coupled to the formation of a relatively weak Ti-C bond. For a discussion of the relative position of transition states as a function of the relative exothermicity of the reaction, see: a) J. E. Leffier, Science 1953, 117, 340-341;
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M. McLaughlin, M. Takahashi, G. C. Micalizio, Angew. Chem. Int. Ed. 2007, 46, 3912-3914.
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K. Fukuhara, S. Okamoto, F. Sato, Org. Lett. 2003, 5, 2145-2148.
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For an allylic alcohol-alkyne coupling, see:
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For an allylic alcohol-alkyne coupling, see:
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For an allene-imine coupling, see: d) M. McLaughlin, H. L. Shimp, R. Navarro, G. C., Micalizio, Synlett 2008, 735-738.
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For an allylic alcohol-imine coupling, see: f) M. Takahashi, M. McLaughlin, G. C. Micalizio, Angew. Chem. Int. Ed. 2009, 48, 3648-3652.
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For examples of complex Ti-mediated reductive cross-coupling reactions in the synthesis of natural products, see: a) T. K. Macklin, G. C. Micalizio, J. Am. Chem. Soc. 2009, 131, 1392-1393;
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(c) H. A. Reichard, J. C. Rieger, G. C. Micalizio, Angew. Chem. Int. Ed. 2008, 47, 7837-7840.
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