Diene Hydroacylation from the Alcohol or Aldehyde Oxidation Level via Ruthenium-Catalyzed C−C Bond-Forming Transfer Hydrogenation: Synthesis of β,γ-Unsaturated Ketones

Abstract

Under the conditions of ruthenium catalyzed transfer hydrogenation, isoprene couples to benzylic and aliphatic alcohols 1a–1g to deliver β,γ-unsaturated ketones 3a–3g in good to excellent isolated yields. Under identical conditions, aldehydes 2a–2g couple to isoprene to provide an identical set of β,γ-unsaturated ketones 3a–3g in good to excellent isolated yields. As demonstrated by the coupling of butadiene, myrcene and 1,2-dimethylbutadiene to representative alcohols 1b, 1c and 1e, diverse acyclic dienes participate in transfer hydrogenative coupling to form β,γ-unsaturated ketones. In all cases, complete branch-regioselectivity is observed and, with the exception of adduct 3j, isomerization to the conjugated enone is not detected. Thus, formal intermolecular diene hydroacylation is achieved from the alcohol or aldehyde oxidation level. In earlier studies employing a related ruthenium catalyst, acyclic dienes were coupled to carbonyl partners from the alcohol or aldehyde oxidation level to furnish branched homoallylic alcohols. Thus, under transfer hydrogenative coupling conditions, all oxidations levels of substrate (alcohol or aldehyde) and product (homoallyl alcohol or β,γ-unsaturated ketone) are accessible.

Ruthenium Hydride-Catalyzed Addition of Aldehydes to Dienes Leading to β,γ-Unsaturated Ketones

“…This result demonstrated that the hydrogen and acyl units that add to the diene do come from different molecules of aldehydes. 13 In summary, we have developed an efficient cross-addition reaction catalyzed by RuHCl(CO)(PPh 3 ) 3 , which provides entry to a wide variety of ,γ-unsaturated ketones starting from the corresponding aldehydes and dienes. The detailed mechanism of this reaction as well as further extension of this chemistry is currently under investigation in this laboratory.…”

Mechanistic study on the regioselectivity of Co-catalyzed hydroacylation of 1,3-dienes

“…Ru-catalyzed hydroacylation of 2a generates C3-selective products [3,4]. The proposed mechanism includes hydrometalation of 1,3-diene, carbonyl addition and beta-H elimination steps.…”

Ruthenium-Catalyzed Transfer Hydrogenation for C–C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs

“…However, the ruthenium catalyst (F 3 CCO 2 )(H)Ru(CO)(PPh 3 ) 2 , which is generated in situ through the acid base reaction of H 2 Ru(CO)(PPh 3 ) 3 and F 3 CCO 2 H, possesses a higher degree of coordinative unsaturation, enabling β-hydride elimination at the stage of the homoallylic ruthenium alkoxide to form the β,γ-unsaturated enones (Scheme 2). 32 Notably, both transformations, diene hydrohydroxyalkylation or hydroacylation, may be conducted from the alcohol or aldehyde (not shown) oxidation level of the reactant. 31,32 Initial studies aimed at directing relative and absolute stereochemistry in alcohol mediated diene hydrohydroxyalkylation relied on the use of 2-trialkylsilyl-butadienes.…”

“…32 Notably, both transformations, diene hydrohydroxyalkylation or hydroacylation, may be conducted from the alcohol or aldehyde (not shown) oxidation level of the reactant. 31,32 Initial studies aimed at directing relative and absolute stereochemistry in alcohol mediated diene hydrohydroxyalkylation relied on the use of 2-trialkylsilyl-butadienes. 33 Hydrometalation of 2-trialkylsilyl-substituted dienes gives rise to crotylmetal species that exist as single geometrical isomers due to allylic strain.…”