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Volumn 349, Issue 14-15, 2007, Pages 2286-2300

Applicability aspects of transition metal-catalyzed aromatic amination protocols in medicinal chemistry

Author keywords

Amination; Copper; Cross coupling; Homogeneous catalysis; Medicinal chemistry; Palladium

Indexed keywords


EID: 36048965181     PISSN: 16154150     EISSN: 15213897     Source Type: Journal    
DOI: 10.1002/adsc.200700133     Document Type: Article
Times cited : (76)

References (67)
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    • These demands are in clear contrast to those for industrial scale-up, examples of which using Pd-catalyzed amination reactions have been published most recently: elaborate fine-tuning of reaction conditions has to be performed to optimize yields, reduce side reactions, facilitate workup or decrease hazardous potential due to exothermic conversions and to decrease amount of catalyst to get dirt-cheap and thus economically attractive processes; see S. L. Buchwald, C. Mauger, G. Mignani, U. Scholz, Adv. Synth. Catal. 2006, 348, 23-39.
    • These demands are in clear contrast to those for industrial scale-up, examples of which using Pd-catalyzed amination reactions have been published most recently: elaborate fine-tuning of reaction conditions has to be performed to optimize yields, reduce side reactions, facilitate workup or decrease hazardous potential due to exothermic conversions and to decrease amount of catalyst to get dirt-cheap and thus economically attractive processes; see S. L. Buchwald, C. Mauger, G. Mignani, U. Scholz, Adv. Synth. Catal. 2006, 348, 23-39.
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    • Several applications of catalyzed aromatic aminations in industrial research have been reported in the recent past, these, however, rather focused on the introduction of a defined amine into a special target molecule, including a detailed ligand screen and condition optimization, and did not aim at the generation of diverse libraries around one structural core unit. For a review on such applications with a focus on practical issues of the methodology, see B. Schlummer, U. Scholz, Adv. Synth. Catal. 2004, 346, 1599-1626
    • Several applications of catalyzed aromatic aminations in industrial research have been reported in the recent past, these - however - rather focused on the introduction of a defined amine into a special target molecule, including a detailed ligand screen and condition optimization, and did not aim at the generation of diverse libraries around one structural core unit. For a review on such applications with a focus on practical issues of the methodology, see B. Schlummer, U. Scholz, Adv. Synth. Catal. 2004, 346, 1599-1626.
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    • In ref.[14, a competition experiment is presented in which 4-bromotoluene was aminated with morpholine in the presence of 4-chlorotoluene to proceed in favor of the aryl bromide in a 97:3 ratio
    • 14], a competition experiment is presented in which 4-bromotoluene was aminated with morpholine in the presence of 4-chlorotoluene to proceed in favor of the aryl bromide in a 97:3 ratio.
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    • For a test reaction using for example, benzylamine and 4-bromobenzonitrile using conditions A and B1, similar conversions were observed using either BINAP or DPPF (quantitative), but only traces of product formation were observed applying method C1.
    • For a test reaction using for example, benzylamine and 4-bromobenzonitrile using conditions A and B1, similar conversions were observed using either BINAP or DPPF (quantitative), but only traces of product formation were observed applying method C1.
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    • Lancaster catalogue 2004/2005, sodium tert-pentoxide (OrderCode X15112) vs. sodium feri-butoxide (OrderCode X15051).
    • Lancaster catalogue 2004/2005, sodium tert-pentoxide (OrderCode X15112) vs. sodium feri-butoxide (OrderCode X15051).
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    • Complete chemoselectivity for amination of the bromine site over chlorine site in 1,3-bromochlorobenzene under these conditions at room temperature has been reported: X. Z. Yan, J. Pawlas, T. Goodson III, J. F. Hartwig, J. Am. Chem. Soc. 2005, 127, 9105-9116.
    • Complete chemoselectivity for amination of the bromine site over chlorine site in 1,3-bromochlorobenzene under these conditions at room temperature has been reported: X. Z. Yan, J. Pawlas, T. Goodson III, J. F. Hartwig, J. Am. Chem. Soc. 2005, 127, 9105-9116.
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    • In the original protocol ref.[17, NaOPh was prepared as an anhydrous base in contrast to a trihydrate as commercially available used within this work
    • [17]), NaOPh was prepared as an anhydrous base in contrast to a trihydrate as commercially available used within this work.
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    • For other Xantphos applications in couplings of bromoarenes and amides, carbamates, oxazolidinones and ureas, see: a) B. H. Yang, S. L. Buchwald, Org. Lett. 1999, 7, 35-37;
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    • 2-Xantphos derivative has been utilized.
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    • For a succesful amination of an aryl chloride with indole using the sterically more congested representative of the monodentate biphenyl-phosphine ligands 3c, see ref.[6
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    • A DPPF based protocol did not qualify as an alternative, as it was only established for aminations of sterically unhindered aryl bromides (that is, no ortho substitution): G. Mann, J. F. Hartwig, M. S. Driver, C. Fernandez-Rivas, J. Am. Chem. Soc. 1998, 120, 827-828.
    • A DPPF based protocol did not qualify as an alternative, as it was only established for aminations of sterically unhindered aryl bromides (that is, no ortho substitution): G. Mann, J. F. Hartwig, M. S. Driver, C. Fernandez-Rivas, J. Am. Chem. Soc. 1998, 120, 827-828.
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    • A further possibility for such a conversion might be a copper catalyzed reaction, even though only established for iodoarenes in combination with similar amine substrates; see ref.[7
    • A further possibility for such a conversion might be a copper catalyzed reaction, even though only established for iodoarenes in combination with similar amine substrates; see ref.[7]
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    • Similar side product formation was described in, e.g, refs, 13,16
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    • Only small quantities of starting 4-chloroquinazoli'ne were detected by LC-MS to have lost the acetyl group.
    • Only small quantities of starting 4-chloroquinazoli'ne were detected by LC-MS to have lost the acetyl group.
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    • Recently, similar conversions were published to be accomplished successfully using bulky electron-rich biaryl pjlosphine ligands: M. D. Charles, P. Schultz, S. L. Buchwald, Org. Lett. 2005, 7, 3965-3968.
    • Recently, similar conversions were published to be accomplished successfully using bulky electron-rich biaryl pjlosphine ligands: M. D. Charles, P. Schultz, S. L. Buchwald, Org. Lett. 2005, 7, 3965-3968.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.