Conversion of Primary Alcohols and Butadiene to Branched Ketones via Merged Transfer Hydrogenative Carbonyl Addition–Redox Isomerization Catalyzed by Rhodium

Abstract

The first examples of rhodium-catalyzed carbonyl addition via hydrogen autotransfer are described, as illustrated in tandem butadiene-mediated carbonyl addition−redox isomerizations that directly convert primary alcohols to isobutyl ketones. Related reductive coupling−redox isomerizations of aldehyde reactants mediated by sodium formate also are reported. A doublelabeling crossover experiment reveals that the rhodium alkoxide obtained upon carbonyl addition enacts redox isomerization without dissociation of rhodium at any intervening stage.

Intermolecular Metal-Catalyzed C–C Coupling of Unactivated Alcohols or Aldehydes for Convergent Ketone Construction beyond Premetalated Reagents

“…In a related rhodium-catalyzed reaction, ketone synthesis is achieved using diene pronucleophiles in combination with allylic alcohol proelectrophiles (Scheme 2A). 20 As corroborated by deuterium labeling studies, allyl alcohol dehydrogenation provides a rhodium hydride and an aldehyde. Diene hydrometalation delivers an allylrhodium nucleophile, which upon aldehyde addition delivers a homoallylic alkoxide.…”

“…Abundant, inexpensive cobalt catalysts convert substituted dienes and aromatic aldehydes to β,γ-unsaturated ketones, which are formed with complete levels of ( Z )-alkene stereoselectivity (Scheme A) . Like the preceding ruthenium- and rhodium-catalyzed reactions, − these processes may be viewed as formal diene hydroacylations, thus overcoming a major limitation associated with traditional hydroacylation: the requirement of β-chelating aldehydes to suppress decarbonylation of acylmetal intermediates . Mechanistically, the cobalt-catalyzed reactions occur through diene–aldehyde oxidative coupling to form a π-allyl-containing oxacobaltacycle.…”

Deoxygenative Cross-Coupling of C(aryl)–O and C(amide)═O Electrophiles Enabled by Chromium Catalysis Using Bipyridine Ligand

“…Given that amines are prevalent in many pharmaceuticals, agrochemicals, and bulk chemicals, we considered whether aryl esters could serve as oxo-electrophiles and couple with unsaturated carbonyl oxo-electrophiles of amides, leading to deoxygenative cross-coupling of C–O and CO bonds by hydrogen transfer in forming amines . Transfer hydrogenative couplings, which were pioneered and developed by Krische’s group, have become a powerful tool for molecular construction. − The deoxygenative cross-coupling of C–O/CO electrophiles via the reaction of aryl esters with amides involving hydrogen transfer processes may enable access to diarylmethylated amines, which are a class of intriguing motifs that are prevalent in commercial drugs such as buclizine, hydroxyzine, bifonazole, and SNC-80 (Figure ). Issues associated with this transfer hydrogenative coupling of two oxo-electrophiles include (1) orthogonal deoxygenative coupling of unactivated C–O and unsaturated CO electrophiles; (2) abstraction of hydrogen atoms for forming arylated tertiary hydrocarbons; and (3) impeding the competing homocoupling of C–O bonds and reduction of CO bonds under reductive conditions .…”

Dual Ruthenium-Catalyzed Alkene Isomerization–Hydrogen Auto-Transfer Unlocks Skipped Dienes as Pronucleophiles for Enantioselective Alcohol C–H Allylation

“…In the course of advancing catalytic methods for hydrogen transfer-mediated carbonyl additions, we recently developed novel “chain-walking processes”, in which carbonyl vinylation or allylation mediated by vinyl halides , and butadiene, respectively, is followed by redox isomerization to form saturated ketones (Figure ). , These rhodium-catalyzed processes rely on the reversible dissociation of monodentate phosphine ligands to facilitate generation of coordinatively unsaturated metal centers that engage in β-hydride elimination from the transient allylic or homoallylic rhodium alkoxides . In related ruthenium-catalyzed couplings of primary alcohols and butadiene, the homoallylic alcohol products resist redox isomerization due to “double chelation” of the metal by the product and the bis­(phosphine) ligand, which leads to full occupancy of all coordination sites and suppression of β-hydride elimination (eq , left).…”