75400-50-9Relevant articles and documents
Direct Synthesis of Ketones from Methyl Esters by Nickel-Catalyzed Suzuki–Miyaura Coupling
Daneshfar, Omid,Hong, Xin,Houk, Kendall N.,Newman, Stephen G.,Xie, Pei-Pei,Zheng, Yan-Long
supporting information, p. 13476 - 13483 (2021/05/10)
The direct conversion of alkyl esters to ketones has been hindered by the sluggish reactivity of the starting materials and the susceptibility of the product towards subsequent nucleophilic attack. We have now achieved a cross-coupling approach to this transformation using nickel, a bulky N-heterocyclic carbene ligand, and alkyl organoboron coupling partners. 65 alkyl ketones bearing diverse functional groups and heterocyclic scaffolds have been synthesized with this method. Catalyst-controlled chemoselectivity is observed for C(acyl)?O bond activation of multi-functional substrates bearing other bonds prone to cleavage by Ni, including aryl ether, aryl fluoride, and N-Ph amide functional groups. Density functional theory calculations provide mechanistic support for a Ni0/NiII catalytic cycle and demonstrate how stabilizing non-covalent interactions between the bulky catalyst and substrate are critical for the reaction's success.
Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors
Li, Hao,Sibley, Christopher D.,Kharel, Yugesh,Huang, Tao,Brown, Anne M.,Wonilowicz, Laura G.,Bevan, David R.,Lynch, Kevin R.,Santos, Webster L.
, (2021/01/07)
The sphingosine 1-phosphate (S1P) signaling pathway is an attractive target for pharmacological manipulation due to its involvement in cancer progression and immune cell chemotaxis. The synthesis of S1P is catalyzed by the action of sphingosine kinase 1 or 2 (SphK1 or SphK2) on sphingosine and ATP. While potent and selective inhibitors of SphK1 or SphK2 have been reported, development of potent dual SphK1/SphK2 inhibitors are still needed. Towards this end, we report the structure–activity relationship profiling of 2-(hydroxymethyl)pyrrolidine-based inhibitors with 22d being the most potent dual SphK1/SphK2 inhibitor (SphK1 Ki = 0.679 μM, SphK2 Ki = 0.951 μM) reported in this series. 22d inhibited the growth of engineered Saccharomyces cerevisiae and decreased S1P levels in histiocytic lymphoma myeloid cell line (U937 cells), demonstrating inhibition of SphK1 and 2 in vitro. Molecular modeling studies of 22d docked inside the Sph binding pocket of both SphK1 and SphK2 indicate essential hydrogen bond between the 2-(hydroxymethyl)pyrrolidine head to interact with aspartic acid and serine residues near the ATP binding pocket, which provide the basis for dual inhibition. In addition, the dodecyl tail adopts a “J-shape” conformation found in crystal structure of sphingosine bound to SphK1. Collectively, these studies provide insight into the intermolecular interactions in the SphK1 and 2 active sites to achieve maximal dual inhibitory activity.
Gold-Catalyzed Asymmetric Thioallylation of Propiolates via Charge-Induced Thio-Claisen Rearrangement
Kim, Hanbyul,Jang, Jiwon,Shin, Seunghoon
supporting information, p. 20788 - 20795 (2020/11/27)
A gold(I)-catalyzed enantioselective thioallylation of propiolates with allyl sulfides is described. The key mechanistic element is a sulfonium-induced Claisen rearrangement which helps minimize the allyl dissociation and render higher enantioselectivity. This protocol features remarkable scope of the allyl moiety, allowing enantiocontrolled synthesis of all-carbon quaternary centers, and exhibits exceptional functional group compatibility with many Lewis bases and π-bonds. This intermolecular variant of Claisen rearrangement forges both C-S and C-C bonds concomitantly, providing efficient access to interesting optically active organosulfur compounds which can be transformed further through the vinyl sulfide as a functional handle. The rate of the reaction was zeroth order with respect to allyl sulfides, which suggested a reversible inhibition, providing a resting state for the catalyst. The Hammett plot displayed a correlation with σp values, suggesting a turnover-limiting sigmatropic rearrangement where decreased electron-density on sulfur accelerated the rearrangement.
Vinylogous acyl triflates as an entry point to α,β-disubstituted cyclic enones via Suzuki-Miyaura cross-coupling
Kim, Daria E.,Zhu, Yingchuan,Newhouse, Timothy R.
supporting information, p. 1796 - 1799 (2019/02/20)
An alternative protocol for the B-alkyl Suzuki-Miyaura reaction to produce cyclic α,β-disubstituted enones is reported. The use of β-triflyl enones as coupling partners in lieu of their halogenated analogs provides enhanced substrate stability to light and chromatography without adversely affecting reactivity. This protocol allows efficient access to the synthetically challenging α,β-disubstituted enone motif under mild conditions.
Switchable Selectivity in the Pd-Catalyzed Alkylative Cross-Coupling of Esters
Masson-Makdissi, Jeanne,Vandavasi, Jaya Kishore,Newman, Stephen G.
supporting information, p. 4094 - 4098 (2018/07/15)
The Pd-catalyzed cross-coupling of phenyl esters and alkyl boranes is disclosed. Two reaction modes are rendered accessible in a selective fashion by interchange of the catalyst. With a Pd-NHC system, alkyl ketones can be prepared in good yields via a Suzuki-Miyaura reaction proceeding by activation of the C(acyl)-O bond. Use of a Pd-dcype catalyst enables alkylated arenes to be synthesized by a modified pathway with extrusion of CO. Applications of this divergent coupling strategy and the origin of the switchable selectivity are discussed.
Asymmetric Synthesis of Dihydropyranones via Gold(I)-Catalyzed Intermolecular [4+2] Annulation of Propiolates and Alkenes
Choi, Su Yeon,Kim, Hanbyul,Shin, Seunghoon
supporting information, p. 13130 - 13134 (2018/09/21)
Intermolecular asymmetric gold catalysis involving alkyne activation presents a significant challenge due to its distinct mechanistic mode from other metals. Herein, we report a highly enantioselective synthesis of α,β-unsaturated δ-lactones from [4+2] annulation of propiolates and alkenes in upto 95 percent ee. Notably, for the desired chiral recognition, the choice of 1,1,2,2-tetrachloroethane as solvent was found to be crucial. Furthermore, an anionic surfactant (sodium dodecyl sulfate) improved the product selectivity in the divergence of the cyclopropyl gold carbene intermediate.
Copper-Catalyzed Addition of Alkylboranes to Iminoacetates: Access to α-Alkyl Branched α-Amino Acids
Xiao, Xinsheng,Zhang, Wei,Lu, Xiaoxia,Deng, Yuanfu,Jiang, Huangfeng,Zeng, Wei
, p. 2497 - 2509 (2016/08/16)
A copper(I)-catalyzed addition of alkylborane reagents to α-iminoacetates has been developed to assemble both acyclic and cyclic α-branched α-amino carboxylic acid derivatives in good yields. A wide variety of unactivated alkenes are well tolerated in this transformation. (Figure presented.).
The copper-catalysed Suzuki-Miyaura coupling of alkylboron reagents: disproportionation of anionic (alkyl)(alkoxy)borates to anionic dialkylborates prior to transmetalation
Basnet, Prakash,Thapa, Surendra,Dickie, Diane A.,Giri, Ramesh
supporting information, p. 11072 - 11075 (2016/09/19)
We report the first example of CuI-catalysed coupling of alkylboron reagents with aryl and heteroaryl iodides that affords products in good to excellent yields. Preliminary mechanistic studies with alkylborates indicate that the anionic (alkoxy)(alkyl)borates, generated from alkyllithium and alkoxyboron reagents, undergo disproportionation to anionic dialkylborates and that both anionic alkylborates are active for transmetalation to a CuI-catalyst. Results from a radical clock experiment and the Hammett plot imply that the reaction likely proceeds via a non-radical pathway.
Catalytic, enantioselective, intramolecular carbosulfenylation of olefins. preparative and stereochemical aspects
Denmark, Scott E.,Jaunet, Alex
supporting information, p. 140 - 171 (2014/01/17)
The first catalytic, enantioselective, intramolecular carbosulfenylation of isolated alkenes with aromatic nucleophiles is described. The combination of N-phenylsulfenylphthalimide, a chiral selenophosphoramide derived from BINAM, and ethanesulfonic acid as a cocatalytic Bronsted acid induced an efficient and selective cyclofunctionalization of various alkenes (aliphatic and aromatic) tethered to a 3,4-methylenedioxyphenyl ring. Under these conditions, 6-phenylthio-5,6,7,8-tetrahydronaphthalenes are formed diastereospecifically in good yields (50-92%) and high enantioselectivities (71:29-97:3 er). E-Alkenes reacted much more rapidly and with much higher selectivity than Z-alkenes, whereas electron-rich alkenes reacted more rapidly but with comparable selectivity to electron-neutral alkenes and electron-deficient alkenes. The Bronsted acid played a critical role in effecting reproducible enantioselectivity. A model for the origin of enantioselectivity and the dependence of rate and selectivity on alkene structure is proposed along with a rationale for the site selectivity in reactions with monoactivated arene nucleophiles.
A tandem elimination-cyclization-suzuki approach: Efficient one-pot synthesis of functionalized (Z)-3-(arylmethylene)isoindolin-1-ones
Sun, Caiyun,Xu, Bin
supporting information; experimental part, p. 7361 - 7364 (2009/05/07)
(Chemical Equation Presented) A novel and efficient one-pot regioselective elimination-cyclization-Suzuki approach was developed to afford (Z)-3-arylmethyleneisoindolin-1-ones in good to excellent yields from easily accessible o-gem-dihalovinylbenzamides and organoboron reagents.
