Enantioselective Decarboxylative α-Alkynylation of β-Ketocarbonyls via a Catalytic α-Imino Radical Intermediate

Abstract

A distinctive aminocatalysis via α-imino radical is reported on the basis of SET oxidation of a secondary enamine. The combination of chiral primary amine catalysis and visible-light photoredox catalysis enables the enantioselective decarboxylative coupling of propiolic acid and β-ketocarbonyls to afford alkynylation adducts with high enantioselectivity. Mechanism studies indicate the reaction proceeds via an α-imino radical addition.

Alkynylation of radicals: spotlight on the “Third Way” to transfer triple bonds

“…In 2017, Zhang and Luo reported the asymmetric alkynylation of activated carbonyl compounds using dual organophotoredox catalysis with hypervalent iodine reagents in combination with a chiral amine catalyst (Scheme 39). 100 Condensation of chiral amine catalyst 30 with a β-keto ester forms first an enamine, which upon oxidation and deprotonation can delivered a chiral α-iminyl radical II . Simultaneously, in situ formation of highly reactive carboxylate hypervalent iodine reagents I from ynoic acids and hydroxybenziodoxolone 18 is important: radical alkynylation may be assisted by H-bonding, thus delivering the alkynes with high enantiomeric excess, albeit in low to medium yields.…”

Catalytic enantioselective C(sp3)–H functionalization involving radical intermediates

“…The amine catalyst is finely tuned so that only the si face of this radical cation is exposed for potential reaction with a SOMO nucleophile, e.g., allylsilane 37 , thus providing a high level of enantiocontrol. In addition to enantioselective allylation, a panel of other transformations 38 such as vinylation 39 , arylation 40 , alkynylation 41 , and alkylation 42,43 reactions have been also established. Besides, the SOMO activation strategy has been extended to the γ-alkylation of enal via a dienamine intermediate formed by condensation with proline-derived catalyst 5.…”

Recent Synthetic Applications of the Hypervalent Iodine(III) Reagents in Visible-Light-Induced Photoredox Catalysis

“…Zhang, Luo, and coworker achieved enantioselective decarboxylative coupling of propiolic acid and β-ketocarbonyls by combination of chiral primary amine catalysis and visible-light photoredox catalysis ( Figure 10C ) (Wang et al, 2017 ). Various of alkynylation adducts were synthesized with excellent enantioselectivities under mild conditions.…”