Iridium-Catalyzed Asymmetric Cascade Allylation/Retro-Claisen Reaction

Abstract

An enantiomerically enriched 3-hydroxymethyl pentenal unit is one of the key structural cores in plenty of natural products and drug candidates with significant biological activities. However, very few synthetic methodologies for the facile construction of the related skeletons have been reported to date. Herein, an elegant iridium-catalyzed asymmetric cascade allylation/retro-Claisen reaction of readily available β-diketones with VEC was successfully developed, and a wide range of functionalized chiral 3-hydroxymethyl pentenal derivatives could be prepared in good yields with excellent enantioselectivities. Various 1,3-diketones and functionalized ketones containing different electron-withdrawing groups on the β-position were well tolerated as outstanding partners with high reactivity and excellent regio-/chemo-/enantioselectivity. The synthetic utility of product chiral 3-hydroxymethyl pentenal derivatives was well shown through gram-scale transformation, hydrogenation, cyclopropanation, hydroboration, and olefin metathesis. Moreover, this elegant protocol demonstrated synthetic applications in the concise synthesis of synthetically useful chiral building block (S)-Taniguchi lactone and the formal synthesis of natural product cytisine. A rational reaction pathway was proposed based on the experimental results and control experiments.

Acyl transfer-enabled catalytic asymmetric Michael addition of α-hydroxy-1-indanones to nitroolefins

“…For example, Mondal, Song et al developed the asymmetric cascade Michael/acyl transfer reactions of α-nitroketones and 1,3-diketones using bifunctional organocatalysts [3][4][5][6][7][8][9][10][11] . Rodriguez and Luo reported the secondary or primary amine-catalyzed acyl transfer reactions [12][13][14][15][16] . Very recently, Yi et al have established an elegant iridium-catalyzed asymmetric cascade allylation/acyl transfer reaction for the synthesis of enantiomerically enriched 3-hydroxymethyl pentenal units [17] .…”

Asymmetric Retro-Claisen Reaction Catalyzed by Chiral Aza-Bisoxazoline–Zn(II) Complex: Enantioselective Synthesis of α-Arylated Ketones

“…Although both α-unsubstituted (Scheme a, R 1 = H) and α-monosubstituted (Scheme a, R 1 ≠ H) β-diketones are well studied in retro-Claisen reactions, neither of them is suitable for asymmetric retro-Claisen reaction since no chiral center would be created on the α-position of ketones after C–C bond cleavage. In this case, α,α-disubstituted β-diketones are required for the formation of a tertiary carbanion, which could be used to construct a tertiary carbon stereocenter after enantioselective protonation.…”

Ir-Catalyzed Asymmetric Cascade Allylation/Spiroketalization Reaction for Stereoselective Synthesis of Oxazoline-Spiroketals

“…5-Methyleneoxazolines are widely utilized as useful reagents/intermediates in a variety of chemical reactions . In particular, You and co-workers achieved an iridium-catalyzed asymmetric allylic aromatization reaction by using allylic alcohols as π-allyl-iridium precursor , and 5-methyleneoxazolines as a nucleophilic reagent (Scheme b). Inspired by this elegant report, we hypothesized that 2-aryl-5-methyleneoxazolines bearing 4,4-disubstitution could avoid the aromatization reaction and act as stable exocyclic vinyl ethers engaging the allylation/spiroketalization reaction with 2-(1-hydroxyallyl)­phenol to synthesize the unique oxazoline-spiroketals (Scheme c).…”