Mechanistic Insights into the ReIO₂(PPh₃)₂-Promoted Reductive Coupling of Alcohols

Abstract

A mechanistic investigation of the reductive coupling of benzylic and allylic alcohols by triphenylphosphine catalyzed by ReIO2(PPh3)2 (1) is disclosed utilizing (1) stoichiometric reaction studies of 1 with alcohols, with PPh3 and with OPPh3; (2) rate law determination of the reaction of benzhydrol with PPh3 catalyzed by 1; (3) substrate structure-dependent reactivity/selectivity studies; and (4) DFT computational analysis of various potential reaction pathways in the benzyl alcohol/PPh3 reaction. In situ NMR monitoring of reactions of 1 with PPh3 and various alcohols demonstrate (a) facile, reversible PPh3 dissociation from 1; (b) association of various alcohols to form Re-alcohol/alkoxide complexes, (Ph3P)­IReO2(ROH) and (Ph3P)­IReO­(OH)­(OR); and (c) thermal conversion of these alcohol­(ate)-rhenium complexes to Ph2CH–CHPh2 and OPPh3 at >50 °C. Under pseudo-first-order conditions, the initial rate kinetics of reductive coupling of Ph2CHOH/PPh3 catalyzed by 1 shows (a) a reaction rate that is first-order each in ROH, catalyst and first-order (or higher) in PPh3 and (b) the reaction is inhibited by OPPh3. Alcohol structure effects show (a) relative reactivity of sec-, tert-benzylic = allylic > prim-benzylic/allylic ≫ sec-, prim-alkyl and (b) low regioselectivity of the dimers from unsymmetrical allylic alcohols. A DFT computational study of the reaction of benzyl alcohol/PPh3 with 1 reveals a preferred pathway involving: (a) formation of rhenium–alcohol and −alkoxide intermediates, (Ph3P)­IReO2(ROH) and (Ph3P)­IReO­(OH)­(OR); (b) reduction of the latter by PPh3 to form (OPPh3)­(Ph3P)­IRe­(OH)­(OBn) (E); (c) association of a second BnOH with E to give (Ph3P)­IRe­(OBn)2 (K); (d) facile dissociation of a benzyl radical from K by C–O homolysis; and (e) a second rhenium–O–Bn homolysis from (PPh3)­IRe­(H2O)­(OBn) (O), giving bibenzyl via benzyl radical recombination and regenerating (PPh3)­ReIO2.

Oxo-Rhenium-Catalyzed Radical Addition of Benzylic Alcohols to Olefins

“…Supported by our recent experimental and computational studies of the reductive coupling of alcohols catalyzed by I , we suggest the operation of the catalytic pathway for the radical additions outlined in Scheme . Beginning with alcohol association with I , the O-transfer reduction of the Re­(V)-alkoxide II by PPh 3 (or piperidine or BnOH) would produce Re­(III)-alcoholate III .…”

“…Homolytic C–O bond scission of III would give the Re­(IV)-oxyl species IV and benzyl radical. Our recent studies of the reductive coupling of benzylic (and allylic) alcohols by the same reductant/catalyst combination, PPh 3 / I , support the intermediacy of C-free radicals from: (1) the product distribution-dimeric hydrocarbons (R–R) and/or the reduced hydrocarbon (R–H); (2) the selectivity, unsymmetrical allylic alcohols giving regioisomeric mixtures; (3) DFT-B3LYP computations that indicate a very low Re­(III,IV)­O–R bond dissociation energy (20–25 kcal/mol); and (4) the observed addition products and selectivity in the current study, that is, the ready additions to EWG–alkenes, consistent with the nucleophilic character of benzyl radicals (and inconsistent with electrophilic intermediates, e.g., carbocations). The C-radical can then be trapped by olefin to give the adduct radical, which can either disproportionate (when alkene = diphenylethylene) or H-abstract from the Re-OH species IV (for other alkenes) to give the reduced product and regenerate I .…”

“…At 1.0 M concentration of the reactants, the combined yield of 3A / 3B increased to 48% at 70% conversion (see the Supporting Information, Table S1). Gas chromatography–mass spectrometry (GC–MS) analysis of the reaction mixtures revealed the coproduction of other benzyl alcohol derived byproducts, including toluene, benzaldehyde, benzyl iodide (from precatalyst), and bibenzyl, products observed in the reductive coupling reactions (in the absence of alkene). , Further optimization studies evaluated the effects of reactant ratios on the reaction efficiency (Table ). The adduct yields were modestly improved by employing an excess of either the alkene (entry 1 vs 2) or the alcohol (entry 2 vs 3).…”

Deoxygenative Transition-Metal-Promoted Reductive Coupling and Cross-Coupling of Alcohols and Epoxides

“…An experimental and computational study of the Recatalyzed reductive coupling was carried out, leading to the suggestion of a preferred reaction pathway. 28 The key findings of experimental and DFT computations are: (1) rhenium-alcohol and -alkoxide adducts can be detected by NMR spectroscopic analysis under ambient conditions; (2) phosphines reduce these adducts, likely to Re III -benzyloxide species; (3) facile cleavage of the latter intermediate occurs homolytically to benzyl-and rhenium(IV)-oxyl-centered radicals, with activation energies of only 20-25 kcal/mol (cf. ca.…”

“…In light of our recent experimental and computational studies on the reductive coupling of alcohols catalyzed by ReIO 2 (PPh 3 ) 2 , 27,28 we proposed the operation of a catalytic pathway for the additions via carbon free-radicals (Scheme 29). Initially, the alcohol likely associates with the Re-catalyst; O-transfer reduction of the Re V -alkoxide by PPh 3 (or piperidine or BnOH) produces the reduced Re III -alcoholate.…”