174311-02-5Relevant articles and documents
Enantioselective Synthesis of α-Allyl Amino Esters via Hydrogen-Bond-Donor Catalysis
Bendelsmith, Andrew J.,Kim, Seohyun Chris,Wasa, Masayuki,Roche, Stéphane P.,Jacobsen, Eric N.
supporting information, p. 11414 - 11419 (2019/08/20)
We report a chiral-squaramide-catalyzed enantio- and diastereoselective synthesis of α-allyl amino esters. The optimized protocol provides access to N-carbamoyl-protected amino esters via nucleophilic allylation of readily accessible α-chloro glycinates. A variety of useful α-allyl amino esters were prepared, including crotylated products bearing vicinal stereocenters that are inaccessible through enolate alkylation, with high enantioselectivity (up to 97% ee) and diastereoselectivity (>10:1). The reactions display first-order kinetic dependence on both the α-chloro glycinate and the nucleophile, consistent with rate-limiting C-C bond formation. Computational analysis of the uncatalyzed reaction predicts an energetically inaccessible iminium intermediate, and a lower energy concerted SN2 mechanism.
Enantioselective intramolecular C-H amination of aliphatic azides by dual ruthenium and phosphine catalysis
Qin, Jie,Zhou, Zijun,Cui, Tianjiao,Hemming, Marcel,Meggers, Eric
, p. 3202 - 3207 (2019/03/21)
The catalytic enantioselective intramolecular C(sp3)-H amination of aliphatic azides represents an efficient method for constructing chiral saturated cyclic amines which constitute a prominent structural motif in bioactive compounds. We report a dual catalytic system involving a chiral-at-metal bis(pyridyl-NHC) ruthenium complex and tris(4-fluorophenyl)phosphine (both 1 mol%), which facilitates the cyclization of aliphatic azides to chiral α-aryl pyrrolidines with enantioselectivities of up to 99% ee, including a pyrrolidine which can be converted to the anti-tumor alkaloid (R)-(+)-crispine. Mechanistically, the phosphine activates the organic azide to form an intermediate iminophosphorane and transfers the nitrene unit to the ruthenium providing an imido ruthenium intermediate which engages in the highly stereocontrolled C-H amination. This dual catalysis combines ruthenium catalysis with the Staudinger reaction and provides a novel strategy for catalyzing enantioselective C-H aminations of unactivated aliphatic azides.
Enantioselective Radical Cyclization for Construction of 5-Membered Ring Structures by Metalloradical C-H Alkylation
Wang, Yong,Wen, Xin,Cui, Xin,Zhang, X. Peter
, p. 4792 - 4796 (2018/04/17)
Radical cyclization represents a powerful strategy for construction of ring structures. Traditional radical cyclization, which is based on radical addition as the key step, necessitates the use of unsaturated substrates. Guided by the concept of metalloradical catalysis, a different mode of radical cyclization that can employ saturated C-H substrates is demonstrated through the development of a Co(II)-based system for catalytic activation of aliphatic diazo compounds for enantioselective radical alkylation of various C(sp3)-H bonds. It allows for efficient construction of chiral pyrrolidines and other valuable 5-membered cyclic compounds. This alternative strategy of radical cyclization provides a new retrosynthetic paradigm to prepare five-membered cyclic molecules from readily available open-chain aldehydes through the union of C-H and C=O elements for C-C bond formation.
Cobalt-Porphyrin-Catalysed Intramolecular Ring-Closing C?H Amination of Aliphatic Azides: A Nitrene-Radical Approach to Saturated Heterocycles
Kuijpers, Petrus F.,Tiekink, Martijn J.,Breukelaar, Willem B.,Broere, Dani?l L. J.,van Leest, Nicolaas P.,van der Vlugt, Jarl Ivar,Reek, Joost N. H.,de Bruin, Bas
supporting information, p. 7945 - 7952 (2017/06/19)
Cobalt-porphyrin-catalysed intramolecular ring-closing C?H bond amination enables direct synthesis of various N-heterocycles from aliphatic azides. Pyrrolidines, oxazolidines, imidazolidines, isoindolines and tetrahydroisoquinoline can be obtained in good to excellent yields in a single reaction step with an air- and moisture-stable catalyst. Kinetic studies of the reaction in combination with DFT calculations reveal a metallo-radical-type mechanism involving rate-limiting azide activation to form the key cobalt(III)-nitrene radical intermediate. A subsequent low barrier intramolecular hydrogen-atom transfer from a benzylic C?H bond to the nitrene-radical intermediate followed by a radical rebound step leads to formation of the desired N-heterocyclic ring products. Kinetic isotope competition experiments are in agreement with a radical-type C?H bond-activation step (intramolecular KIE=7), which occurs after the rate-limiting azide activation step. The use of di-tert-butyldicarbonate (Boc2O) significantly enhances the reaction rate by preventing competitive binding of the formed amine product. Under these conditions, the reaction shows clean first-order kinetics in both the [catalyst] and the [azide substrate], and is zero-order in [Boc2O]. Modest enantioselectivities (29–46 % ee in the temperature range of 100–80 °C) could be achieved in the ring closure of (4-azidobutyl)benzene using a new chiral cobalt-porphyrin catalyst equipped with four (1S)-(?)-camphanic-ester groups.
Asymmetric lithiation trapping of N -boc heterocycles at temperatures above -78°C
Gelardi, Giacomo,Barker, Graeme,O'Brien, Peter,Blakemore, David C.
supporting information, p. 5424 - 5427 (2013/11/19)
The asymmetric lithiation trapping of N-Boc heterocycles using s-BuLi/chiral diamines at temperatures up to -20°C is reported. Depending on the N-Boc heterocycle, lithiation is accomplished using s-BuLi and (-)-sparteine or the (+)-sparteine surrogate in the temperature range -50 to -20°C for short reaction times (2-20 min). Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered functionalized N-Boc heterocycles in 47-95% yield and 77:23-93:7 er. With N-Boc pyrrolidine, trapped products can be generated in ～90:10 er even at -20°C.
Synthetic applications and inversion dynamics of configurationally stable 2-lithio-2-arylpyrrolidines and -piperidines
Beng, Timothy K.,Woo, Jin Sun,Gawley, Robert E.
supporting information, p. 14764 - 14771 (2012/11/07)
In diethyl ether, N-Boc-2-lithio-2-arylpiperidines have been found to be configurationally stable at -80 °C, whereas N-Boc-2-lithio-2- arylpyrrolidines are configurationally stable at -60 °C. Several tertiary benzylic carbanions derived from enantioenriched 2-aryl heterocycles have been successfully alkylated or acylated with little to no loss of enantiopurity. The scope of the reactions has been explored. The enantiomerization dynamics of N-Boc-2-lithio-2-phenylpyrrolidine and N-Boc-2-lithio-2-phenylpiperidine have been studied in the presence of different solvents and achiral ligands.
Highly effective asymmetric hydrogenation of cyclic N -alkyl imines with chiral cationic Ru-MsDPEN catalysts
Chen, Fei,Ding, Ziyuan,Qin, Jie,Wang, Tianli,He, Yanmei,Fan, Qing-Hua
supporting information; experimental part, p. 4348 - 4351 (2011/10/13)
A range of cyclic N-alkyl imines were efficiently hydrogenated by using a chiral cationic Ru(η6-cymene)(MsDPEN)(BArF) complex (MsDPEN = N-(methanesulfonyl)-1,2-diphenylethylenediamine) in high yields and up to 98% ee. A one-pot synthesis of chiral 2-phenylpyrrolidine via reductive amination was also developed.
Development of an asymmetric trimethylenemethane cycloaddition reaction: Application in the enantioselective synthesis of highly substituted carbocycles
Trost, Barry M.,Silverman, Steven M.,Stambuli, James P.
, p. 19483 - 19497 (2012/01/06)
A protocol for the enantioselective [3+2] cycloaddition of trimethylenemethane (TMM) with electron-deficient olefins has been developed. The synthesis of novel phosphoramidite ligands was critical in this effort, and the preparation and reactivity of these ligands is detailed. The evolution of the ligand design, commencing with acyclic amine-derived phosphoramidites and leading to cyclic pyrrolidine and azetidine structures, is discussed. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of alkene acceptors, providing the desired methylenecyclopentanes with high levels of enantioselectivity. The donor scope was also explored, and substituted systems were tolerated, including one bearing a nitrile moiety. These donors were reactive with unsaturated acylpyrroles, giving the product cyclopentane rings bearing three stereocenters in high enantioselectivity and complete diastereoselectivity.
Enantioselective, palladium-catalyzed α-arylation of N-Boc pyrrolidine: In situ react IR spectroscopic monitoring, scope, and synthetic applications
Barker, Graeme,McGrath, Julia L.,Klapars, Artis,Stead, Darren,Zhou, George,Campos, Kevin R.,O'Brien, Peter
, p. 5936 - 5953 (2011/10/09)
A comprehensive study of the enantioselective Pd-catalyzed α-arylation of N-Boc pyrrolidine has been carried out. The protocol involves deprotonation of N-Boc pyrrolidine using s-BuLi/(-)-sparteine in TBME or Et2O at -78 °C, transmetalation with ZnCl2 and Negishi coupling using Pd(OAc)2, t-Bu3P-HBF4 and the aryl bromide. This paper reports several new features including in situ React IR spectroscopic monitoring of the process; use of (-)-sparteine and the (+)-sparteine surrogate to access products with opposite configuration; development of a catalytic asymmetric lithiation-Negishi coupling reaction; extension to a wide range of heteroaromatic bromides; total synthesis of (R)-crispine A, (S)-nicotine and (S)-SIB-1508Y via short synthetic routes; and examples of α-vinylation of N-Boc pyrrolidine using vinyl bromides exemplified by the total synthesis of naturally occurring (+)-maackiamine (thus establishing its configuration as (R)). In this way, the full scope and limitations of the methodology are delineated.
A new sparteine surrogate for asymmetric deprotonation of N-Boc pyrrolidine
Stead, Darren,O'Brien, Peter,Sanderson, Adam
supporting information; experimental part, p. 1409 - 1412 (2009/04/12)
(Chemical Equation Presented) The s-BuLi complex of a cyclohexane-derived diamine is as efficient as s-BuLi/(-)-sparteine for the asymmetric deprotonation of N-Boc pyrrolidine. This is the first example of high enantioselectivity using a non-sparteine-like diamine in such reactions. The ( S, S)-diamine is a useful (+)-sparteine surrogate and was utilized in short syntheses of (-)-indolizidine 167B and an intermediate for the synthesis of the CCK antagonist (+)-RP 66803.
