Carbonyl Propargylation from the Alcohol or Aldehyde Oxidation Level Employing 1,3‐Enynes as Surrogates to Preformed Allenylmetal Reagents: A Ruthenium‐Catalyzed CC Bond‐Forming Transfer Hydrogenation

Abstract

Over the past half century, numerous protocols for carbonyl propargylation using allenylmetal reagents have been developed.[1] Allenic Grignard reagents were used by Prévost et al.[2a] in carbonyl additions to furnish mixtures of β-acetylenic and α-allenic carbinols, which led to them to coin the term "propargylic transposition." [2a,b] Subsequent studies by Chodkiewicz and co-workers[2c] demonstrated relative stereocontrol in such additions. Shortly thereafter, Lequam and Guillerm[2d] reported that isolable allenic stannanes provide products of carbonyl propargylation upon exposure to chloral. Later, Mukaiyama and Harada[2e] demonstrated that stannanes generated in situ from propargyl iodides and stannous chloride reacted with aldehydes to provide mixtures of β-acetylenic and α-allenic carbinols. Related propargylations employing allenylboron reagents were first reported by Favre and Gaudemar,[2f] and propargylations employing allenylsilicon reagents were first reported by Danheiser and Carini.[2g] Asymmetric variants followed (Scheme 1). Allenylboron reagents chirally modified at the boron center engage in asymmetric propargylation, as was first reported by Yamamoto and coworkers[2h] and Corey et al.[2i] Allenylstannanes chirally modified at the tin center also induce asymmetric carbonyl propargylation, as was first reported by Minowa and Mukaiyama.[2j] Axially chiral allenylstannanes, allenylsilanes, and allenylboron reagents propargylate aldehydes enantiospecifically, as was first described by Marshall et al.,[2k,l] and Hayashi and coworkers,[2m] respectively. Finally, asymmetric aldehyde propargylation using allenylmetal reagents may be catalyzed by chiral Lewis acids or chiral Lewis bases, as was first reported by Keck et al.,[2n] and Denmark and Wynn,[2o] respectively.Here, we report a new approach to carbonyl propargylation based on ruthenium-catalyzed C-C bond-forming transfer hydrogenation. [3][4][5] Specifically, upon exposure of 1,3-enynes 1a-1g to alcohols 2a-2o in the presence of [RuHCl(CO)(PPh 3 ) 3 ]/dppf (dppf =1,1′-bis (diphenylphosphino)ferrocene), hydrogen shuffling between reactants occurs to generate nucleophile-electrophile pairs that regioselectively combine to furnish products of carbonyl

Catalytic Carbonyl Addition through Transfer Hydrogenation: A Departure from Preformed Organometallic Reagents

“…Despite this unfavorable precedent, enyne-alcohol transfer hydrogenative coupling delivers the desired products of carbonyl propargylation as single regioisomers using a catalyst prepared in situ from RuHCl(CO)(PPh 3 ) 3 and DPPF. [38] Iridium complexes also catalyze this process, but ruthenium catalysts were found to be superior.…”

Formation of C–C bonds via ruthenium-catalyzed transfer hydrogenation

“…In contrast, completely atom-economical carbonyl propargylation is achieved upon ruthenium-catalyzed transfer hydrogenation of 1,3-enynes in the presence of benzylic, allylic, and aliphatic alcohols. Here, hydrogen transfer from the primary alcohol to the 1,3-enyne generates aldehyde-allenylruthenium pairs, which combine to form products of carbonyl propargylation directly from the alcohol oxidation level [31] (Scheme 9). Identical propargylation products are achieved through enyne-aldehyde coupling in the presence of isopropyl alcohol as the terminal reductant.…”

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

“…[61][62][63] Initially developed conditions provided products of α-methyl-propargylation as diastereomeric mixtures. 61 Identical products of propargylation are generated upon 2-propanol mediated 1,3-enyne-aldehyde reductive coupling. 62 In subsequent work, it was found that antidiastereoselectivity improves upon use of sterically demanding reactants.…”