Copper‐catalyzed one‐pot synthesis of propargylamines via C?H activation in PEG

An efficient and convenient three‐component A³ coupling reaction of aldehyde, amine and alkyne via C? H activation with CuI alone as the catalyst in PEG is developed, providing a wide range of propargylamines with yields ranging from moderate to excellent. Additionally, the catalyst system was recovered and reused several times without evident loss in activity. Copyright © 2010 John Wiley & Sons, Ltd.     

Pd(II)/Brønsted acid catalyzed enantioselective allylic C-H activation for the synthesis of spirocyclic rings

A Pd(II)/Br?nsted acid catalyzed migratory ring expansion for the synthesis of indene derivatives possessing a stereogenic spirocyclic carbon center was developed. This transformation is believed to mechanistically proceed via enantioselective allylic C-H activation with concomitant semipinacol ring expansion to the nascent π-allylpalladium species. Enantioselectivities as high as 98% ee were attainable.     

Facile synthesis of azaarene-substituted 3-hydroxy-2-oxindoles via Brønsted acid catalyzed sp3 C-H functionalization

Br?nsted acid catalyzed functionalization of sp(3) C-H bonds in 2-methyl azaarenes has been achieved in the reaction with isatins. This method provides facile synthesis of biologically important azaarene-substituted 3-hydroxy-2-oxindoles in one step in moderate to good yields.     

A facile enantioselective synthesis of (+)-rolipram via C-H insertion process

Rolipram, (±)-4-(3-cyclopentyloxyl-4-methoxylphenyl)-2-pyrrolidinone,is known as a potent and selective inhibitor of phosphodiesterase type IV(PDE IV)1.In fact, although both enantiomers are active, the levorotatory isomer, for which several synthesis has been recently reported2, has proved to be the most active one. Hashimoto and Jung have repored rolipram,s synthesis via intramolecular C-H insertion reaction of α-methoxylcarbonyl-α-diazoacetamide and α-phenylsulfonyl-α-diazoacetamid…     

Green synthesis of quinolines via A3-coupling by using graphene oxide-supported Brønsted acidic ionic liquid

Research on Chemical Intermediates - Graphene oxide-supported Bronsted acidic ionic liquid ([GrBenzImi]SO3H) has been prepared by covalent grafting of benzimidazole unit in the matrix of graphene...     

A gram-scale synthesis of multi-substituted arenes via palladium catalyzed C–H halogenation

(6-Amino-2-chloro-3-fluorophenyl)methanol is prepared through both traditional methods and palladium catalyzed iterative C–H halogenation reactions.In comparison to traditional approach,the C–H functionalization strategy demonstrated a few advantages including milder reaction conditions higher yields,better selectivity and practicality,and high chemical diversity.     

A convenient method for the synthesis of fluorinated α-cyanoacetates via phase-transfer catalysis

A simple and convenient method for the synthesis of fluorinated α-cyanoacetate derivatives has been developed by using electrophilic fluorination of allyl and benzyl substituted α-cyanoacetates with N-fluorobenzensulfonimide (NFSI) as electrophilic fluorinating agent via phase transfer catalysis. The reaction is transition metal free and carried out in aqueous and mild reaction conditions in the presence of readily available tetra-N-butylammonium iodide (TBAI) as phase-transfer catalyst.     

A concise synthesis of (±)-pregabalin via intramolecular C-H insertion of N-cumyl á-diazoacetamide

Pregabalin 1 (3-aminomethyl-5-methyl hexanoic acid) is a potent anticonvulsant related to the inhibitory neurotransmitter γ-aminobutyric acid (GABA).1 In preclinical trials of anticonvulsant activity, pregabalin is three to ten times more potent than gabapentin. Therefore, pregabalin can be used for the potential treatment of several central nervous system (CNS) disorders including epilepsy, neuropathic pain, anxiety and social phobia. Many synthetic routes have been developed to prepare p…     

Cp*Co(III) catalyzed annulation of N-Cbz hydrazones for the redox-neutral synthesis of isoquinolines via C–H/N–N bond activation

Abstract

A new cascade oxidative cyclization reaction of N-Cbz hydrazones with internal alkynes has been explored for the preparation of isoquinoline derivatives using Cp*Co^III-catalyst through C–H and N–N bond functionalization. N-Cbz hydrazones are rarely explored as directing group for redox-neutral [4?+?2] cyclization reaction through the cyclometallation and this catalyst system does not require any external oxidizing agent, as well as, silver or antimony salt. The current efficient approach has been utilized for the synthesis of different isoquinoline derivatives with good regioselectivity and yields.     

NR transfer reactivity of azo-compound I of P450. How does the nitrogen substituent tune the reactivity of the species toward C-H and C=C activation?

We studied electronic structures and reactivity patterns of azo-compound I species (RN-Cpd I) by comparison to O-Cpd I of, e.g., cytochrome P450. The study shows that the RN-Cpd I species are capable of C=C aziridination and C-H amidation, in a two-state mechanism similar to that of O-Cpd I. However, unlike O-Cpd I, here the nitrogen substituent (R) exerts a major impact on structure and reactivity. Thus, it is demonstrated that Fe=NR bonds of RN-Cpd I will generally be substantially longer than Fe=O bonds; electron-withdrawing R groups will generate a very long Fe=N bond, whereas electron-releasing R groups should have the opposite effect and hence a shorter Fe=N bond. The R substituent controls also the reactivity of RN-Cpd I toward C=C and C-H bonds by exerting steric and electronic effects. Our analysis shows that an electron-releasing substituent will lower the barriers for both bond activation reactions, since the electronic factor makes the reactions highly exothermic, while an electron-withdrawing one should raise both barriers. The steric bulk of the substituent is predicted to inhibit more strongly the aziridination reactions. It is predicted that electron-releasing substituents with small bulk will create powerful aziridination reagents, whereas electron-withdrawing substituents like MeSO(2) will prefer C-H bond activation with preference that increases with steric bulk. Finally, the study predicts (i) that the reactions of RN-Cpd I will be less stereospecific than those of O-Cpd I and (ii) that aziridination will be more stereoselective than amidation.     

A new method for the synthesis of β-halonitroalkanes

Summary A new method is elaborated for the synthesis of -chloronitroalkanes; it consists in the reaction of phosphorus pentachloride with acetals obtained by the addition of primary -nitro alcohols to vinyl alkyl ethers.     

A new strategy for the stereoselective synthesis of 2,3-dideoxy-3-fluoro-D-ribofuranose derivatives

The important intermediate for syntheses of various anti-HIV nucleoside analogues, methyl 2,3-dideoxy-3-fluoro-6-O-(p-methylbenzoyl)-a-D-ribofuranoside, was synthesized starting from 2-deoxy-D-ribose in 5 steps with an overall yield of 24%. This strategy can be also used for synthesizing other analogues with various substitutions at 3-C position.     

Manganese-catalyzed bicyclic annulations of imines and α,β-unsaturated esters via C-H activation

A manganese-catalyzed bicyclic annulation of imines with α,β-unsaturated esters via C–H activation is described, which provides an expedient access to fused β-lactams in one-step operation with high efficiency and good functional group tolerance. Of note, both ketimines and aldimines are amenable to this transformation. Mechanistic studies have identified a five-membered azamanganacycle as the key reaction intermediate.     

I2–DMSO catalyzed synthesis of 1,2,2-triarylethanones via dual C–H activation of aryl methyl ketones

An I₂–DMSO promoted domino protocol was developed for the synthesis of 1,2,2-triarylethanones from readily available aromatic methyl ketones and methoxybenzenes. The 1,2,2-triarylethanones are important precursors for the synthesis of Tamoxifen and Droloxifene. The use of mild reaction conditions, high yield, and single step synthesis are the advantages of the present protocol.     

A facile synthesis of ω-substituted conjugated polyenones via arsonium salt and its application towards the synthesis of navenone A

In the presence of K₂CO₃, a variety of aldehydes condensed with the arsonium bromide 8 at 0–3°C to give exclusively ω-substituted polyenones 1 in good yields, and the synthesis of navenone A was achieved by this procedure.     

Polyphosphorous acid catalyzed cyclization in the synthesis of cryptolepine derivatives

11-Oxo-10,11-dihydroxy-5H-indolo[3,2,b]quinoline 7-carboxylic acid was obtained specifically by polyphosphorous acid catalyzed cyclization with optimal reaction conditions.Biological assays showed that it potentially inhibits the proteasomal chymotrypsin-like activity in vitro and suppresses breast cancer cell growth.     

A simple protocol for the synthesis of α-substituted phosphonates

An efficient, easy-to-handle, and mild substitution reaction approach has been developed for the synthesis of phosphonate derivatives, which are very important in the field of industrial, agricultural, and medicinal chemistry. A large number of nucleophiles, including arylamines, alkylamines, heteroarylamines, primary amines and secondary amines, sulfides, and carbides were attempted to react with α-tosyloxyphosphonate 1. The reaction proceeded under catalyst-free and neat conditions and the corresponding phosphonates 2 were afforded in good yields.     

A new strategy for the synthesis of chiral β-alkynyl esters via sequential palladium and copper catalysis

A new strategy for the synthesis of chiral β-alkynyl esters which relies on sequential Pd and Cu catalysis is reported. Terminal alkynes bearing aryl, alkyl, and silyl groups can be employed without prior activation yielding a wide range of important chiral building blocks. The reaction sequence utilizes a robust Pd(II)-catalyzed hydroalkynylation of ynoates with terminal alkynes providing geometrically pure ynenoates which are readily reduced by CuH. In contrast to previous reports, where additions to ynenoates proceed with marginal preference for the 1,6-pathway, this conjugate reduction occurs with high 1,4-selectivity yielding β-alkynyl esters with excellent levels of enantioselectivity. Importantly, the method tolerates a wide range of functionality, including allylic carbonates and carbamates, and thus allows for rapid elaboration of the β-alkynyl esters into a variety of chiral, substituted heterocycles.