Ni-Catalyzed Direct Carboxylation of Benzyl Halides with CO₂

A novel Ni-catalyzed carboxylation of benzyl halides with CO₂ has been developed. The described carboxylation reaction proceeds under mild conditions (atmospheric CO₂ pressure) at room temperature. Unlike other routes for similar means, our method does not require well-defined and sensitive organometallic reagents and thus is a user-friendly and operationally simple protocol for assembling phenylacetic acids

Ni-Catalyzed Direct Carboxylation of Benzyl Halides with CO₂

A novel Ni-catalyzed carboxylation of benzyl halides with CO₂ has been developed. The described carboxylation reaction proceeds under mild conditions (atmospheric CO₂ pressure) at room temperature. Unlike other routes for similar means, our method does not require well-defined and sensitive organometallic reagents and thus is a user-friendly and operationally simple protocol for assembling phenylacetic acids

Ni-Catalyzed Carboxylation of C(sp²)– and C(sp³)–O Bonds with CO₂

In recent years a significant progress has been made for the carboxylation of aryl and benzyl halides with CO₂, becoming convenient alternatives to the use of stoichiometric amounts of well-defined metal species. Still, however, most of these processes require the use of pyrophoric and air-sensitive reagents and the current methods are mostly restricted to organic halides. Therefore, the discovery of a mild, operationally simple alternate carboxylation that occurs with a wide substrate scope employing readily available coupling partners will be highly desirable. Herein, we report a new protocol that deals with the development of a synergistic activation of CO₂ and a rather challenging activation of inert C­(sp²)–O and C­(sp³)–O bonds derived from simple and cheap alcohols, a previously unrecognized opportunity in this field. This unprecedented carboxylation event is characterized by its simplicity, mild reaction conditions, remarkable selectivity pattern and an excellent chemoselectivity profile using air-, moisture-insensitive and easy-to-handle nickel precatalysts. Our results render our method a powerful alternative, practicality and novelty aside, to commonly used organic halides as counterparts in carboxylation protocols. Furthermore, this study shows, for the first time, that traceless directing groups allow for the reductive coupling of substrates without extended π-systems, a typical requisite in many C–O bond-cleavage reactions. Taking into consideration the limited knowledge in catalytic carboxylative reductive events, and the prospective impact of providing a new tool for accessing valuable carboxylic acids, we believe this work opens up new vistas and allows new tactics in reductive coupling events

Asymmetric Intermolecular Cobalt-Catalyzed Pauson–Khand Reaction Using a P‑Stereogenic Bis-phosphane

The asymmetric intermolecular and catalytic Pauson–Khand reaction has remained an elusive goal since Khand and Pauson discovered this transformation. Using a novel family of P-stereogenic phosphanes, we developed the first catalytic system with useful levels of enantioselection for the reaction of norbornadiene and trimethylsilylacetylene. The results demonstrate that Co–bisphosphane systems are sufficiently reactive and that they lead to high selectivity in the intermolecular process

Asymmetric Intermolecular Cobalt-Catalyzed Pauson–Khand Reaction Using a P‑Stereogenic Bis-phosphane

The asymmetric intermolecular and catalytic Pauson–Khand reaction has remained an elusive goal since Khand and Pauson discovered this transformation. Using a novel family of P-stereogenic phosphanes, we developed the first catalytic system with useful levels of enantioselection for the reaction of norbornadiene and trimethylsilylacetylene. The results demonstrate that Co–bisphosphane systems are sufficiently reactive and that they lead to high selectivity in the intermolecular process

Asymmetric Intermolecular Cobalt-Catalyzed Pauson–Khand Reaction Using a P‑Stereogenic Bis-phosphane

The asymmetric intermolecular and catalytic Pauson–Khand reaction has remained an elusive goal since Khand and Pauson discovered this transformation. Using a novel family of P-stereogenic phosphanes, we developed the first catalytic system with useful levels of enantioselection for the reaction of norbornadiene and trimethylsilylacetylene. The results demonstrate that Co–bisphosphane systems are sufficiently reactive and that they lead to high selectivity in the intermolecular process

TMP–Magnesium and TMP–Zinc Bases for the Regioselective Metalation of the Cinnoline Scaffold

A regioselective functionalization of cinnolines in positions 3 and 8 using metalations has been developed. This involves either the use of a frustrated Lewis pair consisting of BF₃·Et₂O and TMP₂Mg·2LiCl or the in situ generated base TMP₂Zn·2MgCl₂·2LiCl. Successive metalations allow the preparation of 3,8-disubstituted cinnolines. Various functionalizations by acylation, allylation, and cross-coupling reactions with aryl halides or alkenyl iodides were carried out successfully

Transition-Metal-Free Cross-Coupling of Aryl and <i>N</i>‑Heteroaryl Cyanides with Benzylic Zinc Reagents

Functionalized 4-benzylated pyridines can be efficiently prepared by a transition-metal-free cross-coupling between various benzylic zinc chlorides and substituted 4-cyanopyridines in THF/DMPU under microwave irradiation (40 °C, 0.5–1.5 h). Selective benzylations on polycyano-aromatics have also been achieved under these mild conditions. We also report a novel oxidative nucleophilic substitution of a hydrogen on 1,3-dicyanobenzene using benzylic zinc reagents

Stereodivergent S_N2@P Reactions of Borane Oxazaphospholidines: Experimental and Theoretical Studies

The stereodivergent ring-opening of 2-phenyl oxazaphospholidines with alkyl lithium reagents is reported. N-H oxazaphospholidines derived from both (+)-<i>cis</i>-1-amino-2-indanol and (−)-norephedrine provide inversion products in a highly stereoselective process. In contrast, N-Me oxazaphospholidines yield ring-opening products with retention of configuration at the P center, as previously reported by Jugé and co-workers. As a result, from a single amino alcohol auxiliary, both enantiomers of key P-stereogenic intermediates could be synthesized. Theoretical studies of ring-opening with model oxazaphospholidines at the DFT level have elucidated the streochemical course of this process. N-H substrates react in a single step via preferential backside S_N2@P substitution with inversion at phosphorus. N-methylated substrates react preferentially via a two-step frontside S_N2@P, yielding a ring-opened product in which the nucleophilic methyl binds to P with retention of configuration. DFT calculations have shown that the BH₃ unit is a potent directing group to which the methyl lithium reagent coordinates via Li in all the reactions studied

Stereodivergent S_N2@P Reactions of Borane Oxazaphospholidines: Experimental and Theoretical Studies

The stereodivergent ring-opening of 2-phenyl oxazaphospholidines with alkyl lithium reagents is reported. N-H oxazaphospholidines derived from both (+)-<i>cis</i>-1-amino-2-indanol and (−)-norephedrine provide inversion products in a highly stereoselective process. In contrast, N-Me oxazaphospholidines yield ring-opening products with retention of configuration at the P center, as previously reported by Jugé and co-workers. As a result, from a single amino alcohol auxiliary, both enantiomers of key P-stereogenic intermediates could be synthesized. Theoretical studies of ring-opening with model oxazaphospholidines at the DFT level have elucidated the streochemical course of this process. N-H substrates react in a single step via preferential backside S_N2@P substitution with inversion at phosphorus. N-methylated substrates react preferentially via a two-step frontside S_N2@P, yielding a ring-opened product in which the nucleophilic methyl binds to P with retention of configuration. DFT calculations have shown that the BH₃ unit is a potent directing group to which the methyl lithium reagent coordinates via Li in all the reactions studied