The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers one step. No naturally occurring enzymes have been shown catalyze bimolecular reactions. We describe the de novo computational design experimental characterization of catalyzing with high stereoselectivity substrate specificity. X-ray crystallography confirms that structure matches for most active enzymes, binding site substitutions reprogram Designed...

The mechanism of the Pd-catalyzed diamination and carboamination alkenes promoted by N-fluorobenzenesulfonimide (NFBS) was investigated. Stereochemical labeling experiments established that reaction proceeds via overall syn addition two nitrogen groups, whereas is result an anti arene to alkene. intermediate Pd-alkyl complex arising from aminopalladation observed, X-ray crystal structure its 2,2'-bipyridine (bipy) obtained, revealing strong chelation amide protecting group palladium....

This report describes a unique Pd-catalyzed oxidative carboamination of protected aminoalkenes in which inexpensive unactivated nucleophilic arenes are incorporated to give products good yields. A variety amide and carbamate groups tolerated, various five-, six-, seven-membered rings formed Under these conditions, halobenzenes activated at the C-H bond rather than C-X bond, very high regioselectivity for para substitution product is observed all cases. We propose that this takes place via...

A modular approach to the synthesis of a class mixed phosphorus/sulfur ligands was designed identify important ligand structural features for enantioselective palladium-catalyzed allylic subsitutions acyclic and cyclic ayllic esters. After systematic variation substituents at sulfur, phosphorus, backbone, 11k found be optimal in substitution 1,3-diphenylpropenyl acetate with dimethyl malonate or benzylamine high yield excellent enantioselectivity (95−98% ee). similar optimization...

Chiral mixed phosphorus/sulfur ligands 1−3 have been shown to be effective in enantioselective Rh-catalyzed dehydroamino acid hydrogenation and ketone hydrosilylation reactions (eqs 1, 2). After assaying the influence of substituents at sulfur, on ligand backbone, relative stereochemistry within phosphorus, 2c (R = 3,5-dimethylphenyl) 3 were found optimal a variety α-acylaminoacrylates high enantioselectivity (89−97% ee). A similar optimization catalyst for ketones showed that afforded...

A remarkable Pd-catalyzed diamination of unactivated alkenes using N-fluorobenzenesulfonimide (NFBS) as an aminating reagent is described. The reaction occurs in intra/intermolecular fashion, incorporating one nitrogen donor from the substrate and other NFBS, thereby generating cyclic diamine derivatives a single step. products are differentially protected at both nitrogens, allowing for maximal synthetic flexibility. intermediacy Pd(IV) species proposed to be responsible unusual reactivity NFBS.

A mild and facile Pd-catalyzed intramolecular hydroamination of unactivated alkenes is described. This reaction takes place at room temperature tolerant synthetically useful acid-sensitive functional groups. The formation products rather than oxidative amination due to the use a tridentate ligand on Pd which effectively inhibits β-hydride elimination.

Mechanistic studies of the intramolecular hydroamination unactivated aminoalkenes catalyzed by a dicationic [bis(diphenylphosphinomethyl)pyridine]palladium complex highlight important role that protonolysis plays in this reaction. Coordination aminoalkene substrate to activates alkene toward nucleophilic attack form palladium alkyl (6). A stable monocationic (7) was isolated situ deprotonation 6 with mild base, and its structure confirmed X-ray crystallography. Complex 7 reacted rapidly...

We report a highly regioselective metal-free oxidative cyclization of sulfonamides onto tethered, unactivated alkenes using hypervalent iodine and Brønsted acids. Under these conditions the acid counterion is incorporated into cyclized products providing an overall aminotrifluoroacetoxylation alkene. An unusual preference for endo ring closure exhibited in contrast to existing exo selective methods. Multiple sizes can be formed access functionalized pyrrolidines, piperidines, azepanes with...

An enantioselective Pd-catalyzed vicinal diamination of unactivated alkenes using N-fluorobenzenesulfonimide as both an oxidant and a source nitrogen is reported. The use Ph-pybox Ph-quinox ligands afforded differentially protected diamines in good yields with high enantioselectivities. Mechanistic experiments revealed that the enantioselectivity arises from selective formation only one four possible diastereomeric aminopalladation products chiral Pd complex. complex was characterized by...

Monomeric imidozirconocene complexes of the type Cp2(L)ZrNCMe3 (Cp = cyclopentadienyl, L Lewis base) have been shown to activate carbon−hydrogen bonds benzene, but not C−H saturated hydrocarbons. To our knowledge, this singularly important class activation reactions has heretofore observed in imidometallocene systems. The MNR bond formed on heating racemic ethylenebis(tetrahydro)indenyl methyl tert-butyl amide complex, however, cleanly and quantitatively activates a wide range n-alkane,...

A mild and facile Pd-catalyzed intramolecular chloroamination of unactivated alkenes has been described. This reaction takes place at room temperature is tolerant synthetically useful acid-sensitive functional groups. Generally high exo-selectivities are observed in the formation a variety 5- 6-membered rings. system unique its ability to tolerate multidentate ligands on palladium, which opens up possibility controlling absolute sense induction using chiral ligand.

A metal-free oxidative cyclization of ureas onto unactivated alkenes using iodosylbenzene and an acid promoter is described. The products isolated are predominantly bicyclic isoureas resulting from intramolecular oxyamination reaction. type urea substitution have a strong effect on the product formed. variety substrates form isourea with high diastereoselectivity via syn addition including di- trisubstituted alkenes. Hydrolysis gives access to new diastereomerically pure prolinol derivatives.

The Morita–Baylis–Hillman reaction forms a carbon–carbon bond between the α-carbon of conjugated carbonyl compound and carbon electrophile. mechanism involves Michael addition nucleophile catalyst at β-carbon, followed by formation with electrophile disassociation to release product. We used Rosetta design 48 proteins containing active sites predicted carry out this mechanism, which two show catalytic activity mass spectrometry (MS). Substrate labeling measured MS site-directed mutagenesis...

A mild palladium-catalyzed cross-coupling of unsubstituted and 2-alkyl-substituted aziridines with arylboronic acid nucleophiles is presented. The reaction highly regioselective compatible diverse functionality. catalytic amount base, a sterically demanding triarylphosphine ligand, phenol additive are critical to the success reaction. Coupling deuterium-labeled substrate established that ring opening aziridine occurs inversion stereochemistry.

An efficient one-pot synthesis of branched poly(3-alkylthiophene)s (b-P3ATs) is achieved via a dehydrohalogenative polycondensation reaction. The structures the b-P3ATs are assigned based on 1H NMR spectra by comparing them to model dendritic polymer and oligo(3-hexylthiophene-2,4-diyl). palladium-catalyzed 2-bromo-3-alkylthiophenes was found provide P3AT with tunable degree branching (DB = 0–0.42) high molecular weights. Viscosity measurements different indicate that they display more...

The selective replacement of C–H bonds in complex molecules, especially natural products like terpenoids, is a highly efficient way to introduce new functionality and/or couple fragments. Here, we report the development metal-free allylic amination alkenes that allows introduction wide range nitrogen at position with unique regioselectivity and no transposition. This reaction employs catalytic amounts selenium form phosphine selenides or selenoureas. Simple sulfonamides sulfamates can be...

A highly diastereoselective intramolecular hydroamination is the key step in a modular synthesis of 2,6-disubstituted piperazines. The requisite substrates were prepared excellent yields by nucleophilic displacement cyclic sulfamidates derived from amino acids. variety alkyl and aryl substituents at 2-position tolerated. stereochemistry piperazines was determined to be trans X-ray crystallography, which also showed preferred conformation piperazine twist-boat due A1,3 strain.

Post-polymerization modification (PPM) via direct C-H functionalization is a powerful synthetic strategy to convert polymer feed-stocks into value-added products. We found that metal-free, Se-catalyzed allylic amination provided an efficient method for PPM of polynorbornenes (PNBs) produced ring-opening metathesis polymerization. Inherent the mechanism amination, on PNBs preserved alkene functional groups along backbone, while also avoiding transposition double bonds. Amination using series...

A Pd-catalyzed alkoxyamination of protected aminoalkenes promoted by N-fluorobenzenesulfonimide is described. This mild transformation allows the direct formation ethers from carbon-carbon double bonds. An unusual switch exo to endo selectivity in polar solvents was discovered, allowing selective either regioisomer careful choice reaction conditions.

Accumulation of end-of-life plastics presents ongoing environmental concerns. One strategy to solve this grand challenge is invent new techniques that modify post-consumer waste and impart functionality. While promising approaches for the chemical upcycling commodity polyolefins polyaromatics exist, analogous repurpose unsaturated polymers (e.g., polybutadiene) are scarce. In work, we propose a method upcycle polybutadiene, one most widely used commercial rubbers, via mild, metal-free...

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTChiral Mixed Phosphorus/Sulfur Ligands for Palladium-Catalyzed Allylic Alkylations and AminationsDavid A. Evans, Kevin R. Campos, Jason S. Tedrow, Forrest E. Michael, Michel GagnéView Author Information Department of Chemistry Chemical Biology, Harvard University, Cambridge, Massachusetts 02138 Cite this: J. Org. Chem. 1999, 64, 9, 2994–2995Publication Date (Web):April 2, 1999Publication History Received25 February 1999Published online2 April...

Dicationic (bpy)Pt(II) complexes were found to catalyze the intramolecular hydrohydrazination of alkenes. Reaction optimization revealed Pt(bpy)Cl2 (10 mol %) and AgOTf (20 in DMF-d7 be an effective catalyst system for conversion substituted hydrazides five- six-membered N-amino lactams (N-amino = N-acetamido at 120 °C, N-phthalimido 80 −OTf trifluoromethanesulfonate). Of four possible regioisomeric products, only product 5-exo cyclization proximal nitrogen is formed, without reaction distal...

A pincer for high selectivity: mild palladium-catalyzed hydroamination of protected amino-1,3-dienes is possible. This highly regioselective reaction employs a tridentate PNP ligand and leads to cyclic homoallylic amines in yields. Substrates with wide array amine protecting groups diene substitution patterns were cyclized form five- six-membered heterocycles. PG=protecting group. As service our authors readers, this journal provides supporting information supplied by the authors. Such...

Herein we report an intermolecular propargylic C-H amination of alkynes. This reaction is operationally convenient and requires no transition metal catalysts or additives. Terminal, silyl, internal alkynes bearing a wide range functional groups can be aminated in high yields. The regioselectivity for unsymmetrical strongly influenced by substitution pattern (tertiary > secondary primary) relatively remote heteroatomic substituents. We demonstrate that α-stereocenters occurs with retention...