63587-57-5

Upstream product

• 98-59-9 p-toluenesulfonyl chloride 
• 109-05-7 2-Methylpiperidin 
• 81097-32-7 N-hex-5-enyl(4-methylphenyl)sulfonamide 
• 4703-22-4 N-tosylpiperidine 

Downstream Products

• 626232-71-1 6-methyl-1-(toluene-4-sulfonyl)piperidin-2-one 
• 626232-75-5 6-(1-ethoxybuta-1,3-dienyl)-2-methyl-1-(toluene-4-sulfonyl)-1,2,3,4-tetrahydropyridine 
• 626232-73-3 trifluoromethanesulfonic acid 6-methyl-1-(toluene-4-sulfonyl)-1,4,5,6-tetrahydropyridin-2-yl ester 
• 124920-12-3 2-ethyl-1-(toluene-4-sulfonyl)-pyrrolidine 
• 91411-10-8 1-<(4-Methylphenyl)sulfonyl>-2-methoxy-6-methylpiperidine 

Relevant academic research and scientific papers

Exploring Electrochemical C(sp3)-H Oxidation for the Late-Stage Methylation of Complex Molecules

The magic methyl effect, a dramatic boost in the potency of biologically active compounds from the incorporation of a single methyl group, provides a simple yet powerful strategy employed by medicinal chemists in the drug discovery process. Despite significant advances, methodologies that enable the selective C(sp3)-H methylation of structurally complex medicinal agents remain very limited. In this work, we disclose a modular, efficient, and selective strategy for the α-methylation of protected amines (i.e., amides, carbamates, and sulfonamides) by means of electrochemical oxidation. Mechanistic analysis guided our development of an improved electrochemical protocol on the basis of the classic Shono oxidation reaction, which features broad reaction scope, high functional group compatibility, and operational simplicity. Importantly, this reaction system is amenable to the late-stage functionalization of complex targets containing basic nitrogen groups that are prevalent in medicinally active agents. When combined with organozinc-mediated C-C bond formation, our protocol enabled the direct methylation of a myriad of amine derivatives including those that have previously been explored for the magic methyl effect. This synthesis strategy thus circumvents multistep de novo synthesis that is currently necessary to access such compounds and has the potential to accelerate drug discovery efforts.

Bis(trifluoromethanesulfonimide) (BSI): Acidity and application to hydrofunctionalization as a Br?nsted acid catalyst

A binaphthyl derivative, bearing bis(trifluoromethanesulfonimide) (BSI) moiety, was developed as a novel Br?nsted acid. Computational prediction of the pKa value of BSI indicated its classification as a strong Br?nsted acid. BSI catalyzed the h

Stereoinversion of Unactivated Alcohols by Tethered Sulfonamides

The direct, catalytic substitution of unactivated alcohols remains an undeveloped area of organic synthesis. Moreover, catalytic activation of this difficult electrophile with predictable stereo-outcomes presents an even more formidable challenge. Described herein is a simple iron-based catalyst system which provides the mild, direct conversion of secondary and tertiary alcohols to sulfonamides. Starting from enantioenriched alcohols, the intramolecular variant proceeds with stereoinversion to produce enantioenriched 2- and 2,2-subsituted pyrrolidines and indolines, without prior derivatization of the alcohol or solvolytic conditions.

Calcium(II)-Catalyzed Intra- and Intermolecular Hydroamidation of Unactivated Alkenes in Hexafluoroisopropanol

A combination of a calcium(II) triflimide salt and hexafluoroisopropanol (HFIP) was found to be a highly efficient promoter system for the intra- and intermolecular hydroamidation of unactivated alkenes. Unlike other methods, a vast array of functional groups is tolerated at the nitrogen and alkene moieties. The reaction produces the corresponding nitrogen-containing compounds in excellent yields and good diastereoselectivities. The use of HFIP as solvent proved crucial for the proper carrying out of this transformation. Its role, as well as that of calcium and its NTf2 ligand, was rationalized by DFT computations. These calculations show how the [(NTf2)Ca(HFIP)n]+ complex can activate the amide via a basic site of the NTf2 ligand and the alkene with one acidic HFIP proton. The acidity of HFIP is exacerbated by the coordination to the calcium center, the more so as n increases.

Synthetic efforts toward the Lycopodium alkaloids inspires a hydrogen iodide mediated method for the hydroamination and hydroetherification of olefins

Progress toward the total syntheses of a diverse set of fawcettimine-type Lycopodium alkaloids via a "Heathcock-type" 6-5-9 tricycle is disclosed. This route features an intermolecular Diels-Alder cycloaddition to rapidly furnish the 6-5-fused bicycle and a highly chemoselective directed hydrogenation to build the azonane fragment. While conducting these synthetic studies, trimethylsilyl iodide was found to effect a hydroamination reaction to furnish the tetracyclic core of serratine and related natural products. This observation has been expanded into a general method for the room temperature hydroamination of unactivated olefins with tosylamides utilizing catalytic "anhydrous" HI (generated in situ from trimethylsilyl iodide and water). The presence of the iodide anion is critical to the success of this Bronsted acid catalyzed protocol, possibly due to its function as a weakly coordinating anion. These conditions also effect the analogous hydroetherification reaction of alcohols with unactivated olefins.

On the understanding of BF3·Et2O-promoted intra- and intermolecular amination and oxygenation of unfunctionalized olefins

BF3·Et2O was found to be effective for both intra- and intermolecular amination and oxygenation of unfunctionalized olefins. In the presence of 3 equiv. of BF3·Et2O, intramolecular hydroamination of N-(pent-4-enyl)-p-toluenesulfonamides, N-(hex-5-enyl)-p-toluenesulfonamides, intermolecular hydroamination between sulfonamides and cyclohexene, norbornene or styrene, lactonization of pent-4-enoic acid or hex-5-enoic acid compounds and esterification of cyclohexene with different carboxylic acids all proceeded readily, leading to the corresponding amination or oxygenation products in up to 99% isolated yields. Preliminary NMR experiments and DFT calculations suggested that the intramolecular hydroamination reactions proceeded via a sulfonimidic acid intermediate (N=S-OH), and formation of the corresponding Bronsted acid HF or HBF4 was less likely.

Heptadecafluorooctanesulfonic acid (C8F17SO3H) catalyzed intramolecular hydroamination of olefinic sulfonamides in fluorous biphase system (FBS)

A practical, efficient, and environmentally benign intramolecular hydroamination of olefinic sulfonamides was carried out in fluorous biphase system (FBS) using commercially available heptadecafluorooctanesulfonic acid (C8F17SO3

New Synthetic Approach to Cyclopenta-Fused Heterocycles Based upon a Mild Nazarov Reaction

The Pd-catalyzed coupling reaction of lactam or lactone-derived vinyl triflates and phosphates with α-alkoxydienylboronates gives conjugated alkoxytrienes in which one of the double bonds is embedded in a heterocyclic moiety. If subjected to mild acidic hydrolysis, these compounds undergo a 4π electrocyclization process (Nazarov reaction) which furnishes cyclopenta-fused O- and N-heterocycles in good yields. The scope of the work has been that of closely examining the role and effect of both the heteroatom and the heterocycle ring size on the outcome of the electrocyclization, as well as the torquoselectivity of this process. The presence of the heteroatom was essential in stabilizing the oxyallyl cation intermediate, thus allowing the reaction to occur. The ring size was also a basic parameter in the cyclization step: five-membered azacycles required more drastic conditions to give 5-5 fused systems and did so only after an initial hydrolysis to the corresponding divinyl ketones. As for the torquoselectivity, with both 2-methyl and 4-methyl substituted lactam derivatives steric interactions seem to have a role in forcing the conrotatory process to take place in one sense only: allowing the synthesis of diastereomerically pure compounds to be realized. Because different patterns of substitution on the heterocycle are compatible with the reaction conditions, the methodology developed could be very useful for the synthesis of natural products and biologically active compounds containing cyclopenta-fused O- and N-heterocycle moieties.

2-(Penta-1,3-dienyl)oxazolidines: Synthesis of hydroxylated piperidines by a stereoselective Diels-Alder reaction

Hexa-2,4-dienal condensed with (-)-ephedrine to give predominantly the oxazolidine 4, which underwent a stereoselective Diels-Alder reaction with benzyl nitrosoformate to give the cycloadducts 9 and 10 in a ca 5:2 ratio. Further transformations of 9 to give the optically active mono- and tri-hydroxypiperidine derivatives 11 and 15 have also been performed.