Enantio- and Diastereoselective Synthesis of <i>N</i>‑Acetyl Dihydrotetrafibricin Methyl Ester

A highly diastereoselective synthesis of <i>N</i>-acetyl dihydrotetrafibricin methyl ester (<b>34</b>) is described. The synthesis features three enantioselective double allylboration reactions and an intramolecular hydrosilylation/Fleming–Tamao oxidation sequence to establish seven of the hydroxy-bearing stereocenters of <b>34</b>. Especially noteworthy is the fragment-assembly double allyboration reaction of <b>2</b> and <b>7</b> using reagent <b>3</b>, which provides the advanced intermediate <b>6</b> with >20:1 diastereoselectivity

(Diisopinocampheyl)borane-Mediated Reductive Aldol Reactions of Acrylate Esters: Enantioselective Synthesis of <i>Anti</i>-Aldols

The (diisopinocampheyl)borane promoted reductive aldol reaction of acrylate esters <b>4</b> is described. Isomerization of the kinetically formed <i>Z</i>(O)<i>-</i>enolborinate <b>5</b><i><b>Z</b></i> to the thermodynamic <i>E</i>(O)-enolborinate <b>5</b><i><b>E</b></i> via 1,3-boratropic shifts, followed by treatment with representative achiral aldehydes, leads to <i>anti</i>-α-methyl-β-hydroxy esters <b>9</b> or <b>10</b> with excellent diastereo- (up to ≥20:1 dr) and enantioselectivity (up to 87% ee). The results of double asymmetric reactions of <b>5</b><i><b>E</b></i> with several chiral aldehydes are also presented

(Diisopinocampheyl)borane-Mediated Reductive Aldol Reactions of Acrylate Esters: Enantioselective Synthesis of <i>Anti</i>-Aldols

The (diisopinocampheyl)borane promoted reductive aldol reaction of acrylate esters <b>4</b> is described. Isomerization of the kinetically formed <i>Z</i>(O)<i>-</i>enolborinate <b>5</b><i><b>Z</b></i> to the thermodynamic <i>E</i>(O)-enolborinate <b>5</b><i><b>E</b></i> via 1,3-boratropic shifts, followed by treatment with representative achiral aldehydes, leads to <i>anti</i>-α-methyl-β-hydroxy esters <b>9</b> or <b>10</b> with excellent diastereo- (up to ≥20:1 dr) and enantioselectivity (up to 87% ee). The results of double asymmetric reactions of <b>5</b><i><b>E</b></i> with several chiral aldehydes are also presented

Synthesis of Chiral Azabicycles from Pyroglutaminols

The stereocontrolled synthesis of a range of substituted bicyclic morpholine and piperazine derivatives is reported from substituted pyroglutaminols via an intramolecular S_N2 cyclization as the key step. This enantiospecific approach toward chiral bicyclic morpholines and piperazines offers new opportunities to access these challenging ring systems, which are becoming increasingly common motifs in drug discovery

Synthesis of Chiral Azabicycles from Pyroglutaminols

The stereocontrolled synthesis of a range of substituted bicyclic morpholine and piperazine derivatives is reported from substituted pyroglutaminols via an intramolecular S_N2 cyclization as the key step. This enantiospecific approach toward chiral bicyclic morpholines and piperazines offers new opportunities to access these challenging ring systems, which are becoming increasingly common motifs in drug discovery

Synthesis of Chiral Azabicycles from Pyroglutaminols

The stereocontrolled synthesis of a range of substituted bicyclic morpholine and piperazine derivatives is reported from substituted pyroglutaminols via an intramolecular S_N2 cyclization as the key step. This enantiospecific approach toward chiral bicyclic morpholines and piperazines offers new opportunities to access these challenging ring systems, which are becoming increasingly common motifs in drug discovery

Synthesis of Chiral Azabicycles from Pyroglutaminols

The stereocontrolled synthesis of a range of substituted bicyclic morpholine and piperazine derivatives is reported from substituted pyroglutaminols via an intramolecular S_N2 cyclization as the key step. This enantiospecific approach toward chiral bicyclic morpholines and piperazines offers new opportunities to access these challenging ring systems, which are becoming increasingly common motifs in drug discovery

Visible-Light-Driven Photocatalytic Initiation of Radical Thiol–Ene Reactions Using Bismuth Oxide

A nontoxic and inexpensive photocatalytic initiation of anti-Markovnikov hydrothiolation of olefins using visible light is reported. This method is characterized by low catalyst loading, thereby enabling a mild and selective method for radical initiation in thiol–ene reactions between a wide scope of olefins and thiols

Access to Highly Substituted 7‑Azaindoles from 2‑Fluoropyridines via 7‑Azaindoline Intermediates

A versatile synthesis of 7-azaindoles from substituted 2-fluoropyridines is described. C3-metalation and 1,4-addition to nitroolefins provide substituted 2-fluoro-3-(2-nitroethyl)­pyridines. A facile oxidative Nef reaction/reductive amination/intramolecular S_NAr sequence furnishes 7-azaindolines. Finally, optional regioselective electrophilic C5-substitution (e.g., bromination or nitration) and subsequent in situ oxidation delivers highly functionalized 7-azaindoles in high overall efficiency

Sulfones: A New Functional Group for Modular Radical Cross-Coupling

<div>Cross-coupling chemistry comprises the vast majority of reactions employed in the synthesis of medicines, agrochemicals, and other functional materials. The interest in single-electron-induced coupling chemistry stems from the unique ability of these methods to facilitate the formation of challenging C(sp2)–C(sp3) linkages. This work introduces a new functional group, PT sulfones, for radical cross-coupling, enabling the simplified modular assembly of complex structures in an ordered, practical fashion. The scope of this method is extensively explored, and its strategic application is exemplified through the streamlined preparation of medicinally-oriented fluorine-containing scaffolds that previously required multiple steps, toxic reagents, and non-modular retrosynthetic blueprints. This work has also resulted in the development of five reagents for the rapid assembly of a vast set of structures, many of which contain challenging fluorination patterns. <br></div><div><br></div