5291-77-0Relevant academic research and scientific papers
Atom Transfer Radical Polymerization-Inspired Room Temperature (sp3)C-N Coupling
Coote, Michelle L.,Fung, Alfred. K. K.,Sherburn, Michael S.,Yu, Li-Juan
, p. 9723 - 9732 (2021/07/20)
A simple nonphotochemical procedure is reported for Cu(I)-catalyzed C-N coupling of aliphatic halides with amines and amides. The process is loosely based on the Goldberg reaction but takes place readily at room temperature. It uses Cu(I)Br, a commonly used and inexpensive atom transfer radical polymerization precatalyst, along with the cheap ligand N,N,N′,N″,N″-pentamethyldiethylenetriamine, to activate the R-X bond of the substrate via inner-sphere electron transfer. The procedure brings about productive C-N bond formation between a range of alkyl halide substrates with heterocyclic aromatic amines and amides. The mechanism of the coupling step, which was elucidated through application of computational methods, proceeds via a unique Cu(I) → Cu(II) → Cu(III) → Cu(I) catalytic cycle, involving (a) inner-sphere electron transfer from Cu(I) to the alkyl halide to generate the alkyl radical; (b) successive coordination of the N-nucleophile and the radical to Cu(II); and finally reductive elimination. In the absence of a nucleophile, debrominative homocoupling of the alkyl halide occurs. Control experiments rule out SN-type mechanisms for C-N bond formation.
Synthesis of Lactams by Reductive Amination of Carbonyl Derivatives with ω-Amino Fatty Acids under Hydrosilylation Conditions
Tongdee, Satawat,Wei, Duo,Wu, Jiajun,Netkaew, Chakkrit,Darcel, Christophe
supporting information, p. 5536 - 5539 (2021/08/07)
An efficient method for the preparation of lactams from ω-amino fatty acids under hydrosilylation is described. A variety of lactams such as pyrrolidinones, piperidinones and 2-azepanones were selectively synthesised in moderate to excellent yields (29 examples, up to 95 % isolated yields) with a good functional group tolerance. Notably, no metallic based catalyst was required to perform this transformation.
Transition-Metal-Free Reductive Functionalization of Tertiary Carboxamides and Lactams for α-Branched Amine Synthesis
Chiba, Shunsuke,Dixon, Darren J.,Fan, Dongyang,Ong, Derek Yiren
supporting information, p. 11903 - 11907 (2020/05/22)
A new method for the synthesis of α-branched amines by reductive functionalization of tertiary carboxamides and lactams is described. The process relies on the efficient and controlled reduction of tertiary amides by a sodium hydride/sodium iodide composite, in situ treatment of the resulting anionic hemiaminal with trimethylsilyl chloride and subsequent coupling with nucleophilic reagents including Grignard reagents and tetrabutylammonium cyanide. The new method exhibits broad functional-group compatibility, operates under transition-metal-free reaction conditions, and is suitable for various synthetic applications on both sub-millimole and on multigram scales.
Solvent-free iron(III) chloride-catalyzed direct amidation of esters
Mkhonazi, Blessing D.,Shandu, Malibongwe,Tshinavhe, Ronewa,Simelane, Sandile B.,Moshapo, Paseka T.
supporting information, (2020/03/17)
Amide functional groups are prominent in a broad range of organic compounds with diverse beneficial applications. In this work, we report the synthesis of these functional groups via an iron(iii) chloride-catalyzed direct amidation of esters. The reactions are conducted under solvent-free conditions and found to be compatible with a range of amine and ester substrates generating the desired amides in short reaction times and good to excellent yields at a catalyst loading of 15 mol%.
Carbonylative C-C bond activation of aminocyclopropanes using a temporary directing group strategy
Wang, Gang-Wei,Sokolova, Olga O.,Young, Tom. A.,Christodoulou, Ektor M. S.,Butts, Craig P.,Bower, John F.
, p. 19006 - 19011 (2020/11/13)
Temporary directing groups (TDGs) underpin a range of C-C bond activation methodologies; however, the use of TDGs for the regiocontrolled activation of cyclopropane C-C bonds is underdeveloped. In this report, we show how an unusual ring contraction process can be harnessed for TDG-based carbonylative C-C bond activations of cyclopropanes. The method involves the transient installation of an isocyanate-derived TDG, rather than relying on carbonyl condensation events as used in previous TDG-enabled C-C bond activations.
Palladium-Catalyzed Construction of Quaternary Stereocenters by Enantioselective Arylation of γ-Lactams with Aryl Chlorides and Bromides
Jette, Carina I.,Geibel, Irina,Bachman, Shoshana,Hayashi, Masaki,Sakurai, Shunya,Shimizu, Hideki,Morgan, Jeremy B.,Stoltz, Brian M.
supporting information, p. 4297 - 4301 (2019/02/27)
Herein, we report the first Pd-catalyzed enantioselective arylation of α-substituted γ-lactams. Two sets of conditions were developed for this transformation, allowing for the use of either aryl chlorides or bromides as electrophiles. Utilizing a highly electron-rich dialkylphosphine ligand we have been able to construct α-quaternary centers in good yields (up to 91 % yield) and high enantioselectivities (up to 97 % ee).
Transition-Metal-Free Deconstructive Lactamization of Piperidines
Romero-Iba?ez, Julio,Cruz-Gregorio, Silvano,Sandoval-Lira, Jacinto,Hernández-Pérez, Julio M.,Quintero, Leticia,Sartillo-Piscil, Fernando
supporting information, p. 8867 - 8871 (2019/05/28)
One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp3)–C(sp3) bonds, which requires using transition or precious metal catalysts. We present here an alternative: the deconstructive lactamization of piperidines without using transition metal catalysts. To this end, we use 3-alkoxyamino-2-piperidones, which were prepared from piperidines through a dual C(sp3)–H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that this unprecedented lactamization occurs in a tandem manner involving an oxidative deamination of 3-alkoxyamino-2-piperidones to 3-keto-2-piperidones, followed by a regioselective Baeyer–Villiger oxidation to give N-carboxyanhydride intermediates, which finally undergo a spontaneous and concerted decarboxylative intramolecular translactamization.
Schmidt Reaction of ω-Azido Valeryl Chlorides Followed by Intermolecular Trapping of the Rearrangement Ions: Synthesis of Assoanine and Related Pyrrolophenanthridine Alkaloids
DIng, Shao-Lei,Ji, Yang,Su, Yan,Li, Rui,Gu, Peiming
, p. 2012 - 2021 (2019/02/14)
The Schmidt reaction of ω-azido valeryl chlorides in the presence of an additional nucleophile was explored. The arenes, alcohols, and amines were demonstrated as the intermolecular trapping reagents for isocyanate ion and N-acyliminium ion from the Schmidt rearrangement, affording the corresponding products with moderate to excellent yields. Two 2-oxoindoles from the reaction were successfully converted into four natural alkaloids, namely, assoanine, anhydrolycorine, oxoassoanine, and anhydrolycorinone.
Ruthenium-catalyzed synthesis of: N -substituted lactams by acceptorless dehydrogenative coupling of diols with primary amines
Zheng, Yanling,Nie, Xufeng,Long, Yang,Ji, Li,Fu, Haiyan,Zheng, Xueli,Chen, Hua,Li, Ruixiang
supporting information, p. 12384 - 12387 (2019/10/19)
Herein, we report the first example of synthesis of N-substituted lactams via an acceptorless dehydrogenative coupling of diols with primary amines in one step, which was enabled by combining Ru3(CO)12 with a hybrid N-heterocyclic carbene-phosphine-phosphine ligand as the catalyst.
C-Alkylation of N-alkylamides with styrenes in air and scale-up using a microwave flow reactor
Barham, Joshua P.,Tamaoki, Souma,Egami, Hiromichi,Ohneda, Noriyuki,Okamoto, Tadashi,Odajima, Hiromichi,Hamashima, Yoshitaka
supporting information, p. 7568 - 7573 (2018/11/02)
C-Alkylation of N-alkylamides with styrenes is reported, proceeding in ambient air/moisture to give arylbutanamides and pharmaceutically-relevant scaffolds in excellent mass balance. Various amide and styrene derivatives were tolerated, rapidly affording molecular complexity in a single step; thus highlighting the future utility of this transformation in the synthetic chemistry toolbox. Reaction scalability (up to 65 g h-1 product) was demonstrated using a Microwave Flow reactor, as the first example of a C-alkylation reaction using styrenes in continuous flow.
