- Palladium-Catalyzed Amide N-C Hiyama Cross-Coupling: Synthesis of Ketones
-
N-Acylglutarimides and arylsiloxanes reacted in the presence of Pd(OAc)2/PCy3, Et3N·3HF, and LiOAc to provide the corresponding arylketones in good yields. Aryl-, vinyl-, and alkyl-substituted N-acylglutarimides showed good activity in the coupling reactions of arylsiloxanes. The reaction had a broad substrate scope and showed good functional group tolerance. N-Benzoylsuccinimide and N-protected N-phenylbenzamides showed good activities in coupling reactions with phenylsiloxane. The employment of CuF2 as an activor afforded the decarbonylative products at 160 °C.
- Idris, Muhammad Aliyu,Lee, Sunwoo
-
supporting information
p. 9190 - 9195
(2020/11/18)
-
- N-Acylcarbazoles and N-Acylindoles: Electronically Activated Amides for N-C(O) Cross-Coupling by Nlpto Ar Conjugation Switch
-
The development of new amide precursors for selective, catalytic activation of carbon-nitrogen bonds in amides is a fundamental objective of this emerging reactivity manifold. We report the palladium-catalyzed Suzuki-Miyaura cross-coupling of N-acylcarbazoles and N-acylindoles with arylboronic acids by a highly selective N-C(O) cleavage. The key amide bond ground-state destabilization stems from Nlp to Ar conjugation and enables us for the first time to achieve reactivity similar to that for N-acylsulfonamide and N-acylcarbamate activation in simple anilides.
- Buchspies, Jonathan,Rahman, Md. Mahbubur,Szostak, Roman,Szostak, Michal
-
supporting information
p. 4703 - 4709
(2020/06/17)
-
- Suzuki-Miyaura Cross-Coupling of Amides using Well-Defined, Air-Stable [(PR3)2Pd(II)X2] Precatalysts
-
A versatile method for the Suzuki-Miyaura cross-coupling of amides using highly active, well-defined, and air-stable Pd?phosphine precatalysts is reported. Most notably, the method represents the first example of using practical and operationally-simple Pd(II)?phosphine precatalysts in the emerging amide bond cross-coupling manifold. The reactions are efficient at 0.10 mol% loading, furnishing biaryl ketones with high chemoselectivity for N?C(O) bond cleavage. This versatile method enables for the first time to achieve Pd?phosphine-catalyzed cross-coupling of amides at ppm loading. This C?N cross-coupling can be used to efficiently furnish pharmaceutical intermediates by orthogonal Pd-catalyzed cross-couplings. We fully expect that operationally-simple [(PR3)2Pd(II)X2] precatalysts as effective triggers for N?C(O) cross-coupling will be of broad synthetic and catalytic interest. (Figure presented.).
- Li, Guangchen,Ma, Siyue,Szostak, Michal,Zhou, Tongliang
-
supporting information
(2020/05/26)
-
- 2-Methyltetrahydrofuran (2-MeTHF): A Green Solvent for Pd?NHC-Catalyzed Amide and Ester Suzuki-Miyaura Cross-Coupling by N?C/O?C Cleavage
-
The palladium-NHC-catalyzed (NHC=N-heterocyclic carbene) Suzuki-Miyaura cross-coupling of amides and esters via highly chemoselective N?C(O) and O?C(O) cleavage with aryl boronic acids using green, sustainable and eco-friendly 2-methyltetrahydrofuran (2-MeTHF) is reported. A variety of amides and aryl esters were coupled with aryl boronic acids in high to excellent yields. This method employs commercially-available, air- and moisture-stable Pd(II) ?NHC precatalysts. Crucially, the use of 2-MeTHF leads to the highest TON reported to date in amide N?C(O) bond cross-coupling. This operationally-simple protocol was utilized in the synthesis a bioactive ketone intermediate, emphasizing the potential of 2-MeTHF as a green solvent in unconventional amide bond disconnection. Given the tremendous importance of amide bond cross-coupling strategies and the drive to maintain full sustainability in cross-coupling processes, we expect that the synthetic method will be of broad interest.
- Lei, Peng,Ling, Yun,An, Jie,Nolan, Steven P.,Szostak, Michal
-
supporting information
p. 5654 - 5660
(2019/11/16)
-
- Pd-Catalyzed Suzuki–Miyaura Cross-Coupling of Arylboronic Acids and α-Iminonitriles through C–CN Bond Activation
-
A Pd-catalyzed Suzuki–Miyaura cross-coupling reaction between arylboronic acids and α-iminonitriles has been developed. The reaction proceeds through selective activation of the C–CN bond, tolerates a wide range of substituents, and delivers the versatile ketone products in moderate to excellent yields.
- Liu, Kui,Tao, Shou-Wei,Qian, Chun,Zhu, Yong-Ming
-
supporting information
p. 4769 - 4775
(2018/09/06)
-
- Pd-PEPPSI: Water-Assisted Suzuki?Miyaura Cross-Coupling of Aryl Esters at Room Temperature using a Practical Palladium-NHC (NHC=N-Heterocyclic Carbene) Precatalyst
-
A Pd-PEPPSI-catalyzed (Pd=Palladium, PEPPSI=pyridine-enhanced precatalyst preparation stabilization and initiation) Suzuki-Miyaura cross-coupling of aryl esters via selective C?O cleavage at room temperature is reported. The developed catalyst system displays broad substrate scope with respect to both components under practical ambient reaction conditions using readily-available, cheap, modular, air- and moisture-stable Pd-NHC precatalyst (NHC=N-heterocyclic carbene). The use of water proved crucial for achieving high reactivity in this coupling. The catalyst system represents the mildest conditions for the Suzuki?Miyaura cross-coupling of aryl esters reported to date. The protocol also allowed for achieving TON >1,000 (TON=turnover number) in the Suzuki?Miyaura ester coupling for the first time. (Figure presented.).
- Li, Guangchen,Shi, Shicheng,Lei, Peng,Szostak, Michal
-
supporting information
p. 1538 - 1543
(2018/03/01)
-
- General Method for the Suzuki-Miyaura Cross-Coupling of Primary Amide-Derived Electrophiles Enabled by [Pd(NHC)(cin)Cl] at Room Temperature
-
A general, highly selective method for the room temperature Suzuki-Miyaura cross-coupling of commonly encountered primary benzamides is reported. A combination of site-selective N,N-di-Boc-activation (tert-butoxycarbonyl activation) of the amide nitrogen with practical air- and moisture-stable, well-defined, and highly reactive [Pd(NHC)(cin)Cl] (NHC = N-heterocyclic carbene; cin = cinnamyl) provides a highly effective route to biaryl ketones from primary amides in high yields. For the first time, a TON of >1000 has been achieved in amide acyl cross-coupling.
- Lei, Peng,Meng, Guangrong,Ling, Yun,An, Jie,Nolan, Steven P.,Szostak, Michal
-
p. 6510 - 6513
(2017/12/26)
-
- Reactions catalyzed by a binuclear copper complex: Selective oxidation of alkenes to carbonyls with O2
-
Terminal alkenes were selectively cleaved into ketones and aldehydes catalyzed by a binuclear copper catalyst bearing a simple salicylate ligand with O2 as the oxidant. The reaction was carried out under an atmosphere of O2 (balloon) with 0.5 mol% of catalyst and could be performed on a gram scale, providing a convenient and practical method for the cleavage of terminal alkenes into carbonyl compounds.
- Liu, Yuxia,Xue, Dong,Li, Chaoqun,Xiao, Jianliang,Wang, Chao
-
p. 5510 - 5514
(2017/12/08)
-
- N-Methylamino Pyrimidyl Amides (MAPA): Highly Reactive, Electronically-Activated Amides in Catalytic N-C(O) Cleavage
-
Despite recent progress in catalytic cross-coupling technologies, the direct activation of N-alkyl-N-aryl amides has been a challenging transformation. Here, we report the first Suzuki cross-coupling of N-methylamino pyrimidyl amides (MAPA) enabled by the controlled nN → πAr conjugation and the resulting remodeling of the partial double bond character of the amide bond. The new mode of amide activation is suitable for generating acyl-metal intermediates from unactivated primary and secondary amides.
- Meng, Guangrong,Lalancette, Roger,Szostak, Roman,Szostak, Michal
-
supporting information
p. 4656 - 4659
(2017/09/12)
-
- Suzuki-Miyaura cross-coupling of amides and esters at room temperature: Correlation with barriers to rotation around C-N and C-O bonds
-
The Suzuki-Miyaura cross-coupling has been widely recognized as one of the most important methods for the construction of C-C bonds. However, in contrast to traditional aryl halide or pseudohalide electrophiles, coupling reactions with unactivated C-N and C-O electrophiles have proven significantly more challenging. Here we report the first general palladium-catalyzed Suzuki-Miyaura cross-coupling of both common amides and aryl esters through the selective cleavage of the C-N and C-O bonds under exceedingly mild conditions. Notably, for the first time we demonstrate selective C(acyl)-N and C(acyl)-O cleavage/cross-coupling under the same reaction conditions. The reaction uses a commercially available, bench-stable and operationally-convenient (η3-1-t-Bu-indenyl)Pd(IPr)(Cl) precatalyst. Furthermore, we demonstrate that the reactivity of generic amides and aryl esters can be correlated with barriers to isomerization around the C(acyl)-X (X = N, O) bond, thus providing a blueprint for the development of a broad range of novel coupling reactions of ester and amide electrophiles by the selective activation of C-O and C-N bonds.
- Lei, Peng,Meng, Guangrong,Shi, Shicheng,Ling, Yun,An, Jie,Szostak, Roman,Szostak, Michal
-
p. 6525 - 6530
(2017/08/29)
-
- Pd-PEPPSI: A General Pd-NHC Precatalyst for Suzuki-Miyaura Cross-Coupling of Esters by C-O Cleavage
-
The Suzuki-Miyaura cross-coupling of aryl esters by selective C-O bond cleavage represents a powerful methodology in organic synthesis. Here, we report that versatile, easily prepared, well-defined Pd-PEPPSI type precatalysts serve as highly reactive catalysts for the direct Suzuki-Miyaura cross-coupling of esters. Sterically and electronically diverse aryl esters couple with arylboronic acids in good to excellent yields using a single, operationally simple protocol. Kinetic studies demonstrate that the cross-coupling of aryl esters proceeds with rates similar to the cross-coupling of amides. This study strongly supports the use of well-defined Pd(II)-NHC precatalysts bearing pyridine throw-away ligands for the selective C(acyl) cleavage of bench-stable carboxylic acid derivatives. Considering the modular scaffold of Pd-NHC precatalysts, we envision that the method will be of general interest for the development of new catalysts for C-O cleavage reactions.
- Shi, Shicheng,Lei, Peng,Szostak, Michal
-
p. 3784 - 3789
(2017/10/13)
-
- Pd-PEPPSI: Pd-NHC Precatalyst for Suzuki-Miyaura Cross-Coupling Reactions of Amides
-
Pd-PEPPSI-IPr serves as a highly reactive precatalyst in the direct Suzuki-Miyaura cross-coupling of amides. An array of amides can be cross-coupled with a range of arylboronic acids in very good yields using a single, operationally simple protocol. The studies described represent the first use of versatile PEPPSI type of Pd-NHC complexes as catalysts for the cross-coupling of amides by N-C bond activation. The method is user-friendly, since it employs a commercially available, air- and moisture-stable Pd-PEPPSI-IPr complex. Pd-PEPPSI-IPr provides a significant improvement over all current Pd/phosphane catalysts for amide N-C bond activation. Mechanistic studies provide insight into the reaction rates of Pd-NHC-catalyzed cross-coupling of different amides, with Pd-PEPPSI-IPr being particularly effective for the cross-coupling of N-Boc carbamates under the developed conditions.
- Lei, Peng,Meng, Guangrong,Ling, Yun,An, Jie,Szostak, Michal
-
p. 6638 - 6646
(2017/07/15)
-
- General Method for the Suzuki-Miyaura Cross-Coupling of Amides Using Commercially Available, Air- and Moisture-Stable Palladium/NHC (NHC = N-Heterocyclic Carbene) Complexes
-
The direct Suzuki-Miyaura cross-coupling of amides catalyzed by Pd-NHC complexes is reported. Using a single protocol, commercially available, air- and moisture-stable (NHC)Pd(R-allyl)Cl complexes can effect Suzuki-Miyaura cross-coupling of a wide range of amides with arylboronic acids in very good yields. The studies described herein represent the use of versatile Pd-NHC complexes as catalysts for transition-metal-catalyzed cross-coupling of amides by N-C bond activation. The Pd-NHC catalysts provide a significant improvement over all current Pd-PR3 systems employed for the amide N-C bond activation. Mechanistic studies provide strong support for the development of a unified reactivity scale of the amide bond for the generation of acyl-metal intermediates.
- Lei, Peng,Meng, Guangrong,Szostak, Michal
-
p. 1960 - 1965
(2017/08/14)
-
- Suzuki-Miyaura Cross-Coupling of N-Acylpyrroles and Pyrazoles: Planar, Electronically Activated Amides in Catalytic N-C Cleavage
-
The formation of C-C bonds from amides by catalytic activation of the amide bond has been thus far possible by steric distortion. Herein, we report the first example of a general Pd-catalyzed Suzuki-Miyaura cross-coupling of planar amides enabled by the combination of (i) electronic-activation of the amide nitrogen in N-acylpyrroles and pyrazoles and (ii) the use of a versatile Pd-NHC catalysis platform. The origin and selectivity of forming acylmetals, including the role of twist, are discussed.
- Meng, Guangrong,Szostak, Roman,Szostak, Michal
-
p. 3596 - 3599
(2017/07/15)
-
- Efficient Synthesis of Diaryl Ketones by Nickel-Catalyzed Negishi Cross-Coupling of Amides by Carbon–Nitrogen Bond Cleavage at Room Temperature Accelerated by a Solvent Effect
-
The first Negishi cross-coupling of amides for the synthesis of versatile diaryl ketones by selective C?N bond activation under exceedingly mild conditions is reported. The cross-coupling was accomplished with bench-stable, inexpensive precatalyst [Ni(PPh3)2Cl2] that shows high functional-group tolerance and enables the synthesis of highly functionalized diaryl ketone motifs. The coupling occurred with excellent chemoselectivity favoring the ketone (cf. biaryl) products. Notably, this process represents the mildest conditions for amide N?C bond activation accomplished to date (room temperature, 10 min). Considering the versatile role of polyfunctional biaryl ketone linchpins in modern organic synthesis, availability, and excellent functional-group tolerance of organozinc reagents, this strategy provides a new platform for amide N?C bond/organozinc cross-coupling under mild conditions.
- Shi, Shicheng,Szostak, Michal
-
p. 10420 - 10424
(2016/07/21)
-
- Synthesis of structurally diverse diarylketones through the diarylmethyl sp3 C-H oxidation
-
Under open-flask conditions, an efficient method to assemble a series of diversely functionalized diarylketones in the presence of commercially available NBS has been developed. Yields of up to 99% have been achieved employing diarylmethanes as starting material. Based on 18O-labeled experiment, the addition of stoichiometric water eventually leads to excellent yields in all carbonylation cases.
- He, Chao,Zhang, Xiaohui,Huang, Ruofeng,Pan, Jing,Li, Jiaqiang,Ling, Xuege,Xiong, Yan,Zhu, Xiangming
-
p. 4458 - 4462
(2014/08/05)
-
- Steric and electronic effects influencing β-aryl elimination in the Pd-catalyzed carbon-carbon single bond activation of triarylmethanols
-
An analysis of the palladium-catalyzed activation of carbon-carbon single bonds within triarylmethanols has led to a greater understanding of factors influencing the β-aryl elimination process responsible for C-C bond cleavage. A series of competition reactions were utilized to determine that β-aryl elimination of aryl substituents containing ortho-substitution proceeds with significant preference to unsubstituted phenyl rings. Further experiments indicate that substrates containing either strongly donating or withdrawing substituents are cleaved from triarylmethanols more readily than relatively neutral species.
- Bour, James R.,Green, Jacob C.,Winton, Valerie J.,Johnson, Jeffrey B.
-
p. 1665 - 1669
(2013/03/28)
-
