Stereoselective Synthesis of Chiral β-Fluoro α-Amino Acids via Pd(II)-Catalyzed Fluorination of Unactivated Methylene C(sp³)–H Bonds: Scope and Mechanistic Studies

Journal of the American Chemical Society, Год журнала: 2015, Номер 137(25), С. 8219 - 8226

Опубликована: Июнь 12, 2015

The synthesis of fluorinated complex molecules via direct C(sp(3))-H fluorination is attractive yet remains challenging. Here we describe the Pd(II)-catalyzed unactivated methylene bonds by an inner-sphere mechanism. This method allows site- and diastereoselective β-methylene α-amino acid derivatives. A range substrates containing both aliphatic benzylic were compatible with this protocol, leading to array β-fluorinated acids. Stoichiometric isolated palladacycle intermediate takes place rapidly under very mild reaction conditions (room temperature, 5-10 min). Data from preliminary mechanistic studies are consistent C-F reductive elimination a high-valent intermediate.

Язык: Английский

---

A remarkable solvent effect of fluorinated alcohols on transition metal catalysed C–H functionalizations

Organic Chemistry Frontiers, Год журнала: 2016, Номер 3(3), С. 394 - 400

Опубликована: Янв. 1, 2016

Fluorinated solvents like 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) and trifluoroethanol (TFE) have recently emerged as a remarkable synthetic hint allowing challenging C–H activation reactions.

Язык: Английский

---

Reusable directing groups [8-aminoquinoline, picolinamide, sulfoximine] in C(sp3)–H bond activation: present and future

Tetrahedron, Год журнала: 2015, Номер 71(26-27), С. 4450 - 4459

Опубликована: Апрель 21, 2015

Язык: Английский

---

Site‐Selective δ‐C(sp³)−H Alkylation of Amino Acids and Peptides with Maleimides via a Six‐Membered Palladacycle

Angewandte Chemie International Edition, Год журнала: 2018, Номер 57(20), С. 5858 - 5862

Опубликована: Март 26, 2018

The site-selective functionalization of unactivated C(sp3 )-H bonds remains one the greatest challenges in organic synthesis. Herein, we report on δ-C(sp3 alkylation amino acids and peptides with maleimides via a kinetically less favored six-membered palladacycle presence more accessible γ-C(sp3 bonds. Experimental studies revealed that C-H bond cleavage occurs reversibly preferentially at γ-methyl over δ-methyl while subsequent proceeds exclusively is generated by δ-C-H activation. selectivity can be explained Curtin-Hammett principle. exceptional compatibility this various oligopeptides renders procedure valuable for late-stage peptide modifications. Notably, process also first palladium(II)-catalyzed Michael-type reaction through

Язык: Английский

---

Site-Selective Alkenylation of δ-C(sp³)–H Bonds with Alkynes via a Six-Membered Palladacycle

Journal of the American Chemical Society, Год журнала: 2016, Номер 138(34), С. 10750 - 10753

Опубликована: Авг. 16, 2016

Most chelation-assisted aliphatic C-H activation proceeds through a kinetically favored five-membered cyclometalated intermediate. Here, we report the first site-selective alkenylation of δ-C(sp(3))-H in presence more accessible γ-C(sp(3))-H bonds via less six-membered palladacycle. A wide range functional groups are tolerated, and unique protocol can be applied to synthesis chiral piperidines. Moreover, mechanistic insights have been conducted elucidate origin unusual site-selectivity.

Язык: Английский

---