Chang-Hua Ding

Ag-Catalyzed diastereo- and enantioselective synthesis of beta-substituted tryptophans from sulfonylindoles.

The asymmetric catalytic synthesis of beta-substituted tryptophan derivatives was realized in high diastereo- and enantioselectivity by the reaction of glycine derivatives with sulfonylindoles in the presence of catalyst derived from AgCl and a commercially available chiral monodentate phosphoramidite ligand. The resulting adduct was readily converted to beta-substituted tryptophan in 95% overall yield for two steps, which presented a highly efficient route to chiral beta-substituted tryptophan.

Palladacycle-Catalyzed Reaction of Bicyclic Alkenes with Terminal Ynones: Regiospecific Synthesis of Polysubstituted Furans

A new synthetic strategy to access polysubstituted furans regiospecifically has been developed using simple bicyclic alkenes and terminal ynones as starting materials with palladacycles as unique active catalysts. A rational mechanism has also been proposed. This reaction features mild reaction conditions, easily available starting materials and palladacycle catalysts, a wide substrate scope, and high regiospecificity.

Regio- and Enantioselective Palladium-Catalyzed Allylic Alkylation of Nitromethane with Monosubstituted Allyl Substrates: Synthesis of (R)-Rolipram and (R)-Baclofen

The Pd-catalyzed asymmetric allylic alkylation (AAA) reaction of nitromethane with monosubstituted allyl substrates was realized for the first time to provide corresponding products in high yields with excellent regio- and enantioselectivities. The protocol was applied to the enantioselective synthesis of (R)-baclofen and (R)-rolipram.

Metal-Free Synthesis of Polysubstituted Pyrroles by (Diacetoxyiodo)Benzene-Mediated Cascade Reaction of 3-Alkynyl Amines

Pyrrole has been found extensively as a subunit in pharmacologically active natural and unnatural products. Its derivatives are important building blocks in the syntheses of various heterocyclic compounds. Accordingly, synthetic methods to develop pyrroles have received continuing attention of synthetic chemists since their discovery. Nowadays, a variety of protocols for the construction of pyrroles are available. The classical Hantzsch procedure, Paal–Knorr reaction, various cycloaddition reactions, and aza-Claisen rearrangements, have been widely applied for the syntheses of pyrrole derivatives. Recent developed strategies based upon metal catalysis such as the Buchwald–Hartwig coupling reaction, metal-catalyzed cyclizations, and C H bond amination provide even more synthetic approaches. However, some of them suffer from either multistep synthetic operations, low chemical yield, low regioselectivity, or the use of toxic or expensive metals. An efficient synthetic procedure for the regioselective construction of pyrroles is still to be explored. Recently, we have developed a hypervalent iodine-mediated oxidation of terminal alkynes to afford a-acyloxy ketones by using OAc (Ac= acetyl) as the nucleophile. In this reaction, the key steps involve the formation of the alkynyliodonium salt from terminal alkyne with PhI ACHTUNGTRENNUNG(OAc)2 and the subsequent Michael-type addition of AcOH to the alkynyliodonium salt. Based on the results, we deduced that the amination product of acetylene would be afforded if amines were used as nucleophiles. Herein, we report our preliminary results of the simple and efficient PhI ACHTUNGTRENNUNG(OAc)2-mediated reaction for the regioselective synthesis of polysubstituted pyrroles from alkynyl amines under metal-free conditions. Initially, phenylacetylene was treated with TsNH2, benzylamine, or N-Methyl benzylamine, respectively, in the presence of PhI ACHTUNGTRENNUNG(OAc)2 in AcOH at 70 8C. Unfortunately, only the formation of a-acyloxy ketone, instead of the amination product, was observed. In order to avoid the nucleophilic attack of the OAc anion, we considered that an intramolecular amination of the alkyne could be the solution. To this end, alkynyl amine 1 a was treated with two equivalents of (diacetoxyiodo)benzene in acetic acid at 70 8C for 12 hours under argon. Surprisingly, we did not observe the expected dihydropyrrole, but more appealing 2,3,4-trisubstituted pyrroles 2 a and 3 a were obtained in 34 % and 8 % yields, respectively [Eq. (1)]. The structure of pyrrole 2 a was determined by NOESY experiments. Interestingly, almost the same yield was afforded when the reaction ran under aerobic conditions.

Palladacycle-Catalyzed Methylenecyclopropanation of Bicyclic Alkenes with Propiolates

An efficient way to access functionalized methylenecyclopropanes has been developed by palladacycle-catalyzed cyclopropanation of bicyclic alkenes with propiolates in high yields. The structure of the palladacycle was kept intact in the reaction, shown by (31)P NMR spectrum studies. A rational mechanism has been proposed with a deuterium-labeled experiment. The usefulness of the functionalized methylenecyclopropanes has also been demonstrated.

Palladium-Catalyzed Regio-, Diastereo-, and Enantioselective Allylation of Nitroalkanes with Monosubstituted Allylic Substrates

Pd-catalyzed asymmetric allylic alkylation of nitroalkanes and monosubstituted allylic substrates was performed to afford products with two adjacent chiral centers and with excellent regio-, diastereo-, and enantioselectivities. The usefulness of the protocol in organic synthesis was demonstrated by transformation of the product to an optically active homoallylamine, a 2,3-disubstituted tetrahydropyridine, and an α,β-disubstituted amino acid derivative.

Recent Developments in Palladium-Catalyzed Asymmetric Intermolecular Heck Reaction

Some important progress has been made in palladium-catalyzed asymmetric intermolecular Heck reaction in re- cent years. The breakthrough was achieved in the use of acyclic olefins, the aryl halide and benzylic electrophiles in asym- metric intermolecular Heck reaction with some newly developed chiral ligands by Jung, Sigman and Zhou groups. Asymmet- ric intermolecular oxidative Heck-type reaction of acyclic α,β-unsaturated carbonyls and boronic acids was realized by Jung group in high enantioselectivity in the presence of chiral NHC-amidate-alkoxide Pd(II) complexes as catalyst. The Heck re- action of acyclic hydroxyl alkenes and allyl alcohol aryldiazonium salts was achieved by Sigman group with a catalyst de- rived from Pd2dba3 and chiral pyridine oxazoline by using a redox-relay strategy, affording β-, γ-, and δ-aryl carbonyl prod- ucts in excellent enantioselectivity. Sigman group also reports a catalytic and enantioselective intermolecular Heck-type reac- tion of trisubstituted-alkenyl alcohols with aryl boronic acids, providing direct access to diverse molecular building blocks containing an enantiomerically enriched quaternary carbon center. The first examples of asymmetric Mizoroki-Heck reaction using benzyl electrophiles was reported by Zhou group with their newly developed phosphoramidite as the optimal chiral ligand. With this strategy, a key intermediate in asymmetric synthesis of (+)-anisomycin was quickly afforded when p-methoxybenzyl trifluoroacetate was adopted as starting material. Zhou group also realized the first Heck reaction of aryl bromides and chlorides with various cyclic olefins in high enantioselectivities with (R)-Xyl-SDP(O) as the ligand. The use of alcoholic solvents and alkylammonium salts were essential to creating cationic aryl-Pd species for enantioselective olefin insertion. Zhou group has also realized desymmetrization of substituted cyclic olefins successfully via asymmetric Heck reac- tion and found that the use of bisphosphine mono oxide as ligand was important. The Heck reaction of substituted cyclopen- tenes gives almost exclusively trans isomers and establishes two stereocenters in high ee. Under the effect of some newly developed chiral ligands, fused carbo- and heterocycles are synthesized in high ee via asymmetric domino cyclizations. The method is applied to a short synthesis of chiral diamine en route to (-)-martinellic acid. Keywords palladium-catalysis; asymmetric catalysis; Heck reaction; intermolecular reaction

Highly Diastereo‐ and Enantioselective Palladium‐Catalyzed [3+2] Cycloaddition of Vinyl Aziridines and α,β‐Unsaturated Ketones

An asymmetric [3 + 2] cycloaddition reaction of vinyl epoxides with α,β-unsaturated ketones, the single activated electron-deficient alkenes, has been achieved under Pd-catalysis in excellent diastereo- and enantioselectivity. The utilities of the protocol are demonstrated by transformation of the products into other useful chiral molecules. Density functional theory calculations rationalize the stereocontrol of the reaction.

Desymmetrization of Bicyclo[3.n.1]-3-one Derivatives by Palladium-Catalyzed Asymmetric Allylic Alkylation

Desymmetrization of carbon nucleophiles by palladium-catalyzed asymmetric allylic alkylation has been realized for the first time. Products with three chiral centers were obtained in good yield and with high diastereo- and enantioselectivity. The method offers an efficient access to optically active tropane derivatives.

Palladium-Catalyzed Asymmetric Allylic Alkylation of Alkyl-Substituted Allyl Reagents with Acyclic Amides

A wide range of alkyl-substituted allyl reagents, as well as nonstabilized carbon nucleophiles, was successfully used for the first time in the palladium-catalyzed asymmetric allylic alkylation reaction, affording the corresponding allylic alkylated products in high yields with high enantioselectivities. The usefulness of the protocol has been demonstrated by the enantioselective synthesis of an important chiral building block and enantiomer of Dubiusamine A.