Concise Synthesis of (±)-Clopidogrel via Carboxylation of Benzylamine with CO₂

<div><p></p><p>A concise and efficient synthesis of (±)-clopidogrel, an antithrombotic agent, is achieved by inserting CO₂ at the benzylic position as the key reaction without using any toxic transition metals. The overall yield of the synthetic process is 38% and the salient features include operationally simple process chemistry and fewer steps.</p></div

Organocatalytic Sequential α-Amination/Corey–Chaykovsky Reaction of Aldehydes: A High Yield Synthesis of 4-Hydroxypyrazolidine Derivatives

A tandem reaction of <i>in situ</i> generated α-amino aldehydes with dimethyloxosulfonium methylide under Corey–Chaykovsky reaction conditions proceeds efficiently to give 4-hydroxypyrazolidine derivatives in high yields with excellent enantio- and diastereoselectivities. This organocatalytic sequential method provides for the efficient synthesis of <i>anti-</i>1,2-aminoalcohols, structural subunits present in several bioactive molecules as well

Rh-Catalyzed Synthesis of Coumarin Derivatives from Phenolic Acetates and Acrylates <i>via</i> C–H Bond Activation

An efficient annulation strategy involving the reaction of phenolic acetates with acrylates in the presence of [Rh₂(OAc)₄] as catalyst and formic acid as reducing agent, leading to the high yield synthesis of coumarin derivatives, has been developed. The addition of NaOAc as a base increased the yield of the products. The reaction is quite successful for both electron-rich as well as electron-deficient phenolic acetates, affording coumarins with excellent regioselectivity, and proceeds <i>via</i> C–H bond activation proven by deuterium incorporation studies

Concise Enantioselective Synthesis of Naturally Active (<i>S</i>)-3-Hydroxypiperidine

<div><p></p><p>A short and efficient enantioselective synthesis of natural product (<i>S</i>)-3-hydroxypiperidine has been achieved starting from commercially available raw materials employing two catalytic routes: (i) cocatalyzed hydrolytic kinetic resolution (HKR) of racemic methyl-3-(oxiran-2-yl)propanoate; (ii) proline-catalyzed α-aminooxylation followed by Horner–Wardsworth–Emmons olefination in high enantiomeric purity (97% ee) and high overall yield (38%).</p></div

I₂‑Catalyzed Regioselective Oxo- and Hydroxy-acyloxylation of Alkenes and Enol Ethers: A Facile Access to α‑Acyloxyketones, Esters, and Diol Derivatives

I₂-catalyzed oxo-acyloxylation of alkenes and enol ethers with carboxylic acids providing for the high yield synthesis of α-acyloxyketones and esters is described. This unprecedented regioselective oxidative process employs TBHP and Et₃N in stoichiometric amounts under metal-free conditions in DMSO as solvent. Additionally, I₂-catalysis allows the direct hydroxy-acyloxylation of alkenes with the sequential addition of BH₃·SMe₂ leading to monoprotected diol derivatives in excellent yields

Regioselective Oxo-Amination of Alkenes and Enol Ethers with <i>N</i>‑Bromosuccinimide–Dimethyl Sulfoxide Combination: A Facile Synthesis of α‑Amino-Ketones and Esters

An unprecedented conversion of alkenes and enol ethers to the corresponding α-imido carbonyl compounds with excellent regioselectivity and yields has been developed. This oxo-amination process employs readily available <i>N</i>-bromosuccinimide (NBS) and secondary amines as N-sources and dimethyl sulfoxide (DMSO) as the oxidant and also leads to the production of amino alcohols in a single step on reduction, thus broadening the scope of this operationally simple reaction. For the first time, the formation of reactive Me₂S⁺–O–Br species generated by the interaction of NBS with DMSO has been proven

Proline-Catalyzed Sequential <i>syn</i>-Mannich and [4 + 1]-Annulation Cascade Reactions To Form Densely Functionalized Pyrrolidines

A highly efficient one-pot [4 + 1]-annulation process for the asymmetric synthesis of densely functionalized pyrrolidine derivatives is described. The in situ generated <i>syn</i>-Mannich adduct obtained via proline catalysis acts as a four-atom component, and Corey’s sulfur ylide or ethyl bromoacetate acts as a one-atom carbon source to construct pyrrolidine units in a highly enantio- and diastereoselective manner

CuCN-Mediated Cascade Cyclization of 4‑(2-Bromophenyl)-2-butenoates: A High-Yield Synthesis of Substituted Naphthalene Amino Esters

A new method of CuCN-mediated one-pot cyclization of 4-(2-bromophenyl)-2-butenoates leading to efficient synthesis of substituted naphthalene amino esters including phenanthrene aromatic structural units is described. Deuterium labeling studies establish that this one-pot cascade cyclization proceeds through isomerization of olefin, intramolecular C–C bond cyclization, and aromatization as the key intermediates, all occurring in a single step

CuCN-Mediated Cascade Cyclization of 4‑(2-Bromophenyl)-2-butenoates: A High-Yield Synthesis of Substituted Naphthalene Amino Esters

A new method of CuCN-mediated one-pot cyclization of 4-(2-bromophenyl)-2-butenoates leading to efficient synthesis of substituted naphthalene amino esters including phenanthrene aromatic structural units is described. Deuterium labeling studies establish that this one-pot cascade cyclization proceeds through isomerization of olefin, intramolecular C–C bond cyclization, and aromatization as the key intermediates, all occurring in a single step