Formate-Mediated Cross-Electrophile Reductive Coupling of Aryl Iodides and Bromopyridines.

Two catalytic systems for the formate-mediated cross-electrophile reductive coupling of 4-iodoansiole with 6-bromopyridines are described. Using homogenous rhodium or heterogeneous palladium catalysts, the product of reductive biaryl cross-coupling could be formed in moderate yield with excellent levels of chemoselectivity.

Vinyl Triflate-Aldehyde Reductive Coupling-Redox Isomerization Mediated by Formate: Rhodium-Catalyzed Ketone Synthesis in the Absence of Stoichiometric Metals.

Direct conversion of aldehydes to ketones is achieved via rhodium-catalyzed vinyl triflate-aldehyde reductive coupling-redox isomerization mediated by potassium formate. This method circumvents premetalated C-nucleophiles and discrete redox manipulations typically required to form ketones from aldehydes.

Conversion of Aldehydes to Branched or Linear Ketones via Regiodivergent Rhodium-Catalyzed Vinyl Bromide Reductive Coupling-Redox Isomerization Mediated by Formate.

A regiodivergent catalytic method for direct conversion of aldehydes to branched or linear alkyl ketones is described. Rhodium complexes modified by P tBu2Me catalyze formate-mediated aldehyde-vinyl bromide reductive coupling-redox isomerization to form branched ketones. Use of the less strongly coordinating ligand, PPh3, promotes vinyl- to allylrhodium isomerization en route to linear ketones. This method bypasses the 3-step sequence often used to convert aldehydes to ketones involving the addition of pre-metalated reagents to Weinreb or morpholine amides.

Rhodium-Catalyzed Aldehyde Arylation via Formate-Mediated Transfer Hydrogenation: Beyond Metallic Reductants in Grignard/Nozaki-Hiyami-Kishi-Type Addition.

The first intermolecular carbonyl arylations via transfer hydrogenative reductive coupling are described. Using rhodium catalysts modified by tBu2PMe, sodium formate-mediated reductive coupling of aryl iodides with aldehydes occurs in a chemoselective fashion in the presence of protic functional groups and lower halides. This work expands the emerging paradigm of transfer hydrogenative coupling as an alternative to pre-formed carbanions or metallic reductants in C═X addition.

The In Situ Enzymatic Screening (ISES) Approach to Reaction Discovery and Catalyst Identification.

The importance of discovering new chemical transformations and/or optimizing catalytic combinations has led to a flurry of activity in reaction screening. The in situ enzymatic screening (ISES) approach described here utilizes biological tools (enzymes/cofactors) to advance chemistry. The protocol interfaces an organic reaction layer with an adjacent aqueous layer containing reporting enzymes that act upon the organic reaction product, giving rise to a spectroscopic signal. ISES allows the experimentalist to rapidly glean information on the relative rates of a set of parallel organic/organometallic reactions under investigation, without the need to quench the reactions or draw aliquots. In certain cases, the real-time enzymatic readout also provides information on sense and magnitude of enantioselectivity and substrate specificity. This article contains protocols for single-well (relative rate) and double-well (relative rate/enantiomeric excess) ISES, in addition to a colorimetric ISES protocol and a miniaturized double-well procedure. © 2017 by John Wiley & Sons, Inc.

Mini-ISES identifies promising carbafructopyranose-based salens for asymmetric catalysis: Tuning ligand shape via the anomeric effect.

This study introduces new methods of screening for and tuning chiral space and in so doing identifies a promising set of chiral ligands for asymmetric synthesis. The carbafructopyranosyl-1,2-diamine(s) and salens constructed therefrom are particularly compelling. It is shown that by removing the native anomeric effect in this ligand family, one can tune chiral ligand shape and improve chiral bias. This concept is demonstrated by a combination of (i) x-ray crystallographic structure determination, (ii) assessment of catalytic performance, and (iii) consideration of the anomeric effect and its underlying dipolar basis. The title ligands were identified by a new mini version of the in situ enzymatic screening (ISES) procedure through which catalyst-ligand combinations are screened in parallel, and information on relative rate and enantioselectivity is obtained in real time, without the need to quench reactions or draw aliquots. Mini-ISES brings the technique into the nanomole regime (200 to 350 nmol catalyst/20 µml organic volume) commensurate with emerging trends in reaction development/process chemistry. The best-performing ß-d-carbafructopyranosyl-1,2-diamine-derived salen ligand discovered here outperforms the best known organometallic and enzymatic catalysts for the hydrolytic kinetic resolution of 3-phenylpropylene oxide, one of several substrates examined for which the ligand is "matched." This ligand scaffold defines a new swath of chiral space, and anomeric effect tunability defines a new concept in shaping that chiral space. Both this ligand set and the anomeric shape-tuning concept are expected to find broad application, given the value of chiral 1,2-diamines and salens constructed from these in asymmetric catalysis.