Polymer-supported chiral phosphinooxathiane ligands for palladium-catalyzed asymmetric allylations

Novel polymer-supported chiral ligands of PS–DES, PS–Et, and TentaGel supporting Pd-phosphinooxathianes were prepared and found to provide high levels of enantioselectivity (up to 99% ee) in palladium-catalyzed asymmetric allylic alkylations and aminations.     

Copper + nickel-in-charcoal (Cu-Ni/C): a bimetallic, heterogeneous catalyst for cross-couplings

A new heterogeneous catalyst composed of copper and nickel oxide particles supported within charcoal has been developed. It catalyzes cross-couplings that traditionally use palladium, nickel, or copper, including Suzuki-Miyaura reactions, Buchwald-Hartwig aminations, vinylalane alkylations, etherifications of aryl halides, aryl halide reductions, asymmetric conjugate reductions of activated olefins, and azide-alkyne "click" reactions.     

Solid‐Phase Synthesis of a 1‐Thio‐β‐d‐GlcNAc Carbohydrate Mimetic Library

The solid phase synthesis of N‐acetyl‐2‐deoxy‐1‐thio‐β‐d‐glucopyranoside derivatives by reacting an immobilized sugar thiol with Michael acceptors and α‐chloroketones, followed by ketone reductions, reductive aminations, acylations and alkylations was developed to yield a library of 1088 compounds. Such carbohydrate mimetic libraries are synthesized efficiently on the solid phase without the need for protection of the sugar hydroxyl groups. The library was designed for the identification of potential inhibitors of β‐d‐GlcNAc binding proteins.     

Synthesis of aldehyde-linked nucleotides and DNA and their bioconjugations with lysine and peptides through reductive amination

5-(5-Formylthienyl)-, 5-(4-formylphenyl)- and 5-(2-fluoro-5-formylphenyl)cytosine 2'-deoxyribonucleoside mono- (dC(R)MP) and triphosphates (dC(R)TP) were prepared by aqueous Suzuki-Miyaura cross-coupling of 5-iodocytosine nucleotides with the corresponding formylarylboronic acids. The dC(R)TPs were excellent substrates for DNA polymerases and were incorporated into DNA by primer extension or PCR. Reductive aminations of the model dC(R)MPs with lysine or lysine-containing tripeptide were studied and optimized. In aqueous phosphate buffer (pH?6.7) the yields of the reductive aminations with tripeptide?III were up to 25?%. Bioconjugation of an aldehyde-containing DNA with a lysine-containing tripeptide was achieved through reductive amination in yields of up to 90?% in aqueous phosphate buffer.     

Highly enantioselective syntheses of heterocycles via intramolecular Ir-catalyzed allylic amination and etherification

[reaction: see text] Enantioselective Ir-catalyzed intramolecular allylic aminations and etherifications are described. Up to 97% ee was achieved using catalysts prepared by in situ activation of mixtures of phosphorus amidites and [Ir(COD)Cl]2. Sequential aminations of bis-allylic carbonates, involving an inter- followed by an intramolecular reaction, gave trans-N-benzyl-2,5-divinylpyrrolidine and trans-N-benzyl-2,6-divinylpiperidine with > or = 99% ee. New phosphorus amidites as well as improved conditions for intermolecular aminations are reported.     

Synthesis of Aldehyde‐Linked Nucleotides and DNA and Their Bioconjugations with Lysine and Peptides through Reductive Amination

5‐(5‐Formylthienyl)‐, 5‐(4‐formylphenyl)‐ and 5‐(2‐fluoro‐5‐formylphenyl)cytosine 2′‐deoxyribonucleoside mono‐ ( dC^RMP ) and triphosphates ( dC^RTP ) were prepared by aqueous Suzuki–Miyaura cross‐coupling of 5‐iodocytosine nucleotides with the corresponding formylarylboronic acids. The dC^RTP s were excellent substrates for DNA polymerases and were incorporated into DNA by primer extension or PCR. Reductive aminations of the model dC^RMP s with lysine or lysine‐containing tripeptide were studied and optimized. In aqueous phosphate buffer (pH 6.7) the yields of the reductive aminations with tripeptide III were up to 25 %. Bioconjugation of an aldehyde‐containing DNA with a lysine‐containing tripeptide was achieved through reductive amination in yields of up to 90 % in aqueous phosphate buffer.     

A heterotrimetallic Pd-Sm-Pd complex for asymmetric Friedel-Crafts alkylations of pyrroles with nitroalkenes

Catalytic asymmetric Friedel-Crafts alkylations of pyrroles and nitroalkenes were carried out by using a novel heterotrimetallic Pd-Sm-Pd catalyst based on a simple chiral ligand 1, to give the adducts with high yields and up to 93% ee.     

Development of new asymmetric two-center catalysts in phase-transfer reactions

A new asymmetric two-center phase-transfer catalyst was designed and a catalyst library containing more than 40 new two-center catalysts was constructed. The catalysts were applied in phase-transfer alkylations and Michael additions to afford the corresponding products in up to 93% ee and 82% ee, respectively.     

Highly regioselective asymmetric copper-catalyzed allylic alkylation with dialkylzincs using monodentate chiral spiro phosphoramidite and phosphite ligands

The copper complexes of chiral spiro phosphoramidite and phosphite ligands were found to be effective catalysts in the asymmetric allylic alkylations of cinnamyl halides with dialkylzincs. The allylic alkylation products were obtained in high regioselectivities (S_N2′/S_N2 up to 98:2) and enantiomeric excesses of up to 74% for S_N2′ products.     

Synthesis of two new chiral fluorous bis(oxazolines) and their applications as ligands in catalytic asymmetric reactions

Two new chiral fluorous bis(oxazolines) with a fluorous content of 56.9% and 59.3%, respectively, have been prepared starting from (S)-serine and (S)-tyrosine. Applications of these compounds as fluorous box ligands in asymmetric alkylations gave ees up to 92%, and in allylic oxidations ees up to 50%. Recycling and reuse of the ligands in asymmetric alkylation and of the catalytic system in allylic oxidation gave the same enantioselectivities.     

Palladium-catalyzed amination of aryl and heteroaryl tosylates at room temperature

Mild palladium-catalyzed aminations of aryl tosylates and the first aminations of heteroaryl tosylates are described. In the presence of the combination of L2Pd(0) (L = P(o-tol)3) and the hindered Josiphos ligand CyPF-t-Bu, a variety of primary alkylamines and arylamines react with both aryl and heteroaryl tosylates at room temperature to form the corresponding secondary arylamines in high yields with complete selectivity for the monoarylamine. These reactions at room temperature occur in many cases with catalyst loadings of 0.1 mol % and 0.01 mol % in one case, constituting the most efficient aminations of aryl tosylates by nearly 2 orders of magnitude. This catalyst is made practical by the development of a convenient method to synthesize the L2Pd(0) precursor. This complex is stable to air as a solid. In contrast to conventional relative rates for reactions of aryl sulfonates, the reactions of aryl tosylates are faster than parallel reactions of aryl triflates, and the reactions of aryl tosylates are faster than parallel or competitive reactions of aryl chlorides.     

Novel C2-symmetric bisoxazolines with a chiral trans-(2R,3R)-diphenylcyclopropane backbone: preparation and application in several enantioselective catalytic reactions

Various chiral bisoxazoline ligands with a chiral trans-(2R,3R)-diphenylcyclopropane backbone have been efficiently synthesized (five examples). These chiral ligands were tested and compared in palladium(0)-catalysed enantioselective allylic alkylations (up to 97% ee), copper(I)-catalysed enantioselective cyclopropanations (up to 89% ee) and aziridinations (up to 90% ee). We observed that the presence of a stereogenic centre on the oxazoline moiety is mandatory in order to obtain acceptable enantioselectivities.     

Design,Synthesis, and Application of Chiral C2‐Symmetric Spiroketal‐Containing Ligands in Transition‐Metal Catalysis

We present an expedient and economical route to a new spiroketal‐based C₂‐symmetric chiral scaffold, termed SPIROL. Based on this spirocyclic scaffold, several chiral ligands were generated. These ligands were successfully employed in an array of stereoselective transformations, including in iridium‐catalyzed hydroarylations (up to 95 % ee), palladium‐catalyzed allylic alkylations (up to 97 % ee), intermolecular palladium‐catalyzed Heck couplings (up to 94 % ee), and rhodium‐catalyzed dehydroalanine hydrogenation (up to 93 % ee).     

Synthesis and crystallographic characterization of chiral bis-oxazoline-amides. Fine-tunable ligands for Pd-catalyzed asymmetric alkylations

New chiral chelating C2 bis-oxazoline-amide ligands (1) exhibiting a highly flexible molecular structure have been prepared in high yield through a versatile synthetic pathway. Combined crystallographic, variable temperature (VT)-NMR, IR, and ESI-MS studies have been carried out to investigate the nature of the 1-Pd complexes that are effective tools in controlling the stereochemical outcome of Pd-catalyzed allylic alkylations (ee up to 98%).     

Asymmetric alkylation of diphenylmethane derivatives using (−)-sparteine

Alkylation of 2-oxygenated diphenylmethane derivatives using sec-butyllithium and (−)-sparteine gave enantiomeric excesses of up to 60% with allyl bromide but alkylations with methyl electrophiles were poorly selective. When compounds with a free hydroxy in the 2-position were alkylated the selectivity was reversed.     

Design,Synthesis, and Application of Chiral C2‐Symmetric Spiroketal‐Containing Ligands in Transition‐Metal Catalysis

We present an expedient and economical route to a new spiroketal‐based C₂‐symmetric chiral scaffold, termed SPIROL. Based on this spirocyclic scaffold, several chiral ligands were generated. These ligands were successfully employed in an array of stereoselective transformations, including in iridium‐catalyzed hydroarylations (up to 95 % ee), palladium‐catalyzed allylic alkylations (up to 97 % ee), intermolecular palladium‐catalyzed Heck couplings (up to 94 % ee), and rhodium‐catalyzed dehydroalanine hydrogenation (up to 93 % ee).     

Complementing Pyridine‐2,6‐bis(oxazoline) with Cyclometalated N‐Heterocyclic Carbene for Asymmetric Ruthenium Catalysis

A strategy for expanding the utility of chiral pyridine‐2,6‐bis(oxazoline) (pybox) ligands for asymmetric transition metal catalysis is introduced by adding a bidentate ligand to modulate the electronic properties and asymmetric induction. Specifically, a ruthenium(II) pybox fragment is combined with a cyclometalated N‐heterocyclic carbene (NHC) ligand to generate catalysts for enantioselective transition metal nitrenoid chemistry, including ring contraction to chiral 2H‐azirines (up to 97 % ee with 2000 TON) and enantioselective C(sp³)?H aminations (up to 97 % ee with 50 TON).     

Asymmetric alkylation of diarylmethane derivatives

Deprotonation-alkylation of prochiral diarylmethane substrates using sec-BuLi and (−)-sparteine has been carried out in excellent yields and up to 94% ee. A variety of enantioselective alkylations, silylations and stannylations have been performed on four different diarylmethanes. Surrogates for (+)-sparteine have also been applied in this study including a novel surrogate.     

Iodine(III)-mediated intermolecular allylic amination under metal-free conditions

A new approach to direct intermolecular allylic amination has been developed using metal-free conditions at room temperature. The reaction employs a hypervalent iodine(III) reagent as an oxidant and bistosylimide as a nitrogen source. A series of different allylic aminations are presented with up to a 99% yield. Mechanistic studies including isotope labeling and Hammett correlation suggest that depending on the substrate structure two different mechanisms can be operating.     

Synthesis of Indenes via Graphene Oxide Mediated Manipulation of Morita-Baylis-Hillman Alcohols

A new metal-free synthetic approach to functionalized indenes is documented. The use of commercially available graphene oxide (GO) allowed the direct access to indenyl cores (yield up to 80 %) via intramolecular Friedel-Crafts-type allylic alkylations with readily available Morita-Baylis-Hillman alcohols. Combined experimental and spectroscopic investigations contributed to shed light on the reaction mechanism dealing with a nanostructured carbon material-based C−C bond forming reaction.