Thierry León

Ni-Catalyzed Direct Carboxylation of Benzyl Halides with CO2

A novel Ni-catalyzed carboxylation of benzyl halides with CO(2) has been developed. The described carboxylation reaction proceeds under mild conditions (atmospheric CO(2) 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(sp(2))-O and C(sp(3))-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.

Primary and Secondary Aminophosphines as Novel P-Stereogenic Building Blocks for Ligand Synthesis†

Chiral phosphine ligands are central to asymmetric metal catalysis. The effect of the majority of these ligands arises from the chirality of their backbones; however, P-stereogenic (P*) ligands have garnered renewed interest. After the decisive work of Knowles and co-workers with PAMP and DIPAMP ligands, several efficient syntheses of all-carbon P* compounds have been reported. In contrast, P* compounds that contain heteroatoms directly linked to the phosphorus center are scarce, and have found little application in catalysis. This class of substances includes secondary phosphine oxides, which exist in equilibrium with their trivalent phosphinite form. P* aminophosphines, which are the corresponding nitrogen analogues, are even more rare, as free primary aminophosphines tend to dimerize with the evolution of ammonia. However, Kolodiazhnyi et al. have reported that borane aminophosphines of type I are stable and that they can be obtained in diastereomerically pure form using 2-phenylethylamine as a chiral amine (Scheme 1). Nonetheless, type I compounds do not have any reported applications in asymmetric catalysis, nor has their hydrogenolysis been described. We envisioned that reductive cleavage of the arylethyl fragment should provide boraneprotected primary aminophosphines of type II, which would be amenable to further transformations and become useful P* building blocks in catalysis. Herein, we report the synthesis of enantiopure P-chiral primary and secondary aminophosphines (II) and diphosphinoamines (III). We began by investigating the hydrogenolysis of the known compound 1a, which contains a tert-butyl(phenyl)phosphinamine moiety (Scheme 2), under various

Stereoselective Synthesis of P-Stereogenic Aminophosphines: Ring Opening of Bulky Oxazaphospholidines

A highly diastereoselective and efficient synthesis of P-stereogenic bulky alkyl and aryl aminophosphines that relies on ring opening of tert-butyl-oxazaphospholidine 2 is described. Ring opening with several organometallic reagents takes place with inversion of configuration at the phosphorus center as it has been demonstrated by X-ray analysis of two ring-opened intermediates. The unprecedented reactivity observed is attributed to the presence of a free NH functionality that facilitates the attack of the organometallic reagent in an S(N)2@P-type process.

P‐Stereogenic Secondary Iminophosphorane Ligands and Their Rhodium(I) Complexes: Taking Advantage of NH/PH Tautomerism

Have a good SIP: P-stereogenic secondary iminophosphorane (SIP) ligands with a sulfonyl group attached to nitrogen have been prepared. In the presence of rhodium, the tautomeric equilibrium is shifted from the favored PH tautomer towards the P(III) tautomer, thereby allowing coordination of the SIP ligand through the P and O atoms. The resulting Rh complexes are effective in the [2+2+2] cycloaddition of enediynes with terminal alkynes.

Stereodivergent SN2@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 (+)-cis-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(N)2@P substitution with inversion at phosphorus. N-methylated substrates react preferentially via a two-step frontside S(N)2@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.

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.