Enantioselective Reductive Coupling of 1,3-Enynes to Glyoxalates Mediated by Hydrogen:  Asymmetric Synthesis of β,γ-Unsaturated α-Hydroxy Esters

Abstract

Catalytic hydrogenation of 1,3-enynes 1a-8a in the presence of ethyl glyoxalate at ambient pressure and temperature using a rhodium catalyst modified by (R)-(3,5-tBu-4-MeOPh)-MeO-BIPHEP results in highly regio- and enantioselective reductive coupling to furnish the corresponding alpha-hydroxy esters 1b-8b. As demonstrated by the elaboration of alpha-hydroxy ester 1b, the terminal and internal olefin moieties embodied by the diene side chain are subject to selective manipulation, one over the other.

Unlocking Hydrogenation for C–C Bond Formation: A Brief Overview of Enantioselective Methods

“…20 Conjugated enynes and diynes also participate in reductive couplings to ( N -sulfinyl)iminoacetates under the conditions of rhodium catalyzed hydrogenation. 21 Using an appropriately substituted N -sulfinyl substituent, 22 the corresponding β, γ-unsaturated α-amino acid esters are generated as single diastereomers.…”

Catalytic Asymmetric Synthesis of Allylic Alcohols and Derivatives and their Applications in Organic Synthesis

“…More atom economic processes have been developed by Krische and co-workers by performing the reductive coupling under hydrogenation conditions, thereby avoiding the use of metal-based reducing agents and minimizing the formation of waste products. [191] Atom-economic rhodium-catalyzed asymmetric reductive coupling reactions of 1,3-diynes, [192,193] 1,3enynes, [194][195][196] and acetylene [197] with various carbonyl compounds (aldehydes, glyoxal, ethyl glyoxylate, a-ketoesters) have been successfully developed, thereby affording structurally diverse allylic alcohols, which can be further elaborated, for example, by epoxidation, hydrogenation, and cross-metathesis (Table 4, Figure 8). Intramolecular reductive coupling of acetylenic aldehydes has also been developed under hydrogenation conditions to give cyclic allylic alcohols in excellent enantiomeric excess.…”

(R)- and (S)-2,2′-Bis(diphenylphosphino)-6,6′-dimethoxy-1,1′-biphenyl

“…114 Brønsted acids have a profound effect on both isolated yield and enantioselectivities and are believed to prevent a four-centered transition state for σ-bond metathesis. It is noteworthy that the counterion on rhodium had no effect on yields or selectivities.…”