Highly Stereoselective Construction of β,β-Diaryl-α-Branched Ketones by the Chiral Primary Amine-Catalyzed Asymmetric Retro-Claisen Reaction

Han, Yanling; Zhang, Long; Luo, Sanzhong

doi:10.1021/acs.orglett.2c00435

Cited by 8 publications

(9 citation statements)

References 39 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[ 46 ] The reactions feature a sequence of stereoselective C—C formation, C—C cleavage, and a highly stereospecific enamine protonation. [ 47‐48 ]…”

Section: Bi/multi‐function Strategy: Development and Application Of C...mentioning

confidence: 99%

See 1 more Smart Citation

Bio‐inspired Small Molecular Catalysis

2022

Self Cite

View full text Add to dashboard Cite

Comprehensive Summary Nature is an inspiring resource for chemists to exploit uncharted chemical spaces. Enzymes in nature are characteristic of high efficiency and exquisite stereocontrol under rather mild conditions. Not surprisingly, chemists have a long history in developing new catalysts by learning from and imitating the natural enzymes. This review summarizes our long‐standing efforts in developing bio‐inspired small molecular catalysis. These were categorized according to the employed strategies: 1) bi‐/multi‐functional strategy for the bio‐inspired chiral primary amine catalyst; 2) cofactor strategy for bio‐inspired ortho‐quinone catalyst; 3) intermediate strategy for chiral latent carbocation catalysis based on natural carbocation process. Each section includes brief introduction of the biological origin, design of catalyst, development of methodology as well as the underlying mechanistic insights. What is the most favorite and original chemistry developed in your research group? I hope it's always the next one. How do you get into this specific field? Could you please share some experiences with our readers? Nature provides many astonishing catalytic machineries for building up molecular complexity and harnessing energy in the most efficient ways. Nature's recipe for catalysis serves as a starting point to develop new catalyst for synthetic and energy chemistry. I was trained as a synthetic chemist in a physical organic group in Nankai and ICCAS, and spent part of my graduate studies doing enzymatic synthesis of oligosaccharide and its related biological applications in Ohio State University. This gave me a mixed view on organocatalysis, then under its golden stage of renaissance, not only for its synthetic potentials as a new catalytic concept, but also with an eye on its biological origin and possible impact beyond synthesis. I also benefit a lot from the physical organic chemistry training which helps to shape my research path in width and depth, in a way I never imagined and expected at the beginning of my career. How do you supervise your students? Try to inspire beyond instruct. I learned and am still learning. “因材施教” is easy to say than to do. In reality, I become bossy the way I dislike and have to instruct heavily. What is the most important personality for scientific research? Curiosity, broad reading and sufficient “free time” for daydreaming. In order to have enough time to waste, you have to work really hard at first. Who influences you mostly in your life? My Ph.D. supervisor, Prof. Jin‐Pei Cheng who teaches me a rational and quantitative view for chemistry and inspires me all the time to pursue a rational approach in research.

show abstract

“…[ 46 ] The reactions feature a sequence of stereoselective C—C formation, C—C cleavage, and a highly stereospecific enamine protonation. [ 47‐48 ]…”

Section: Bi/multi‐function Strategy: Development and Application Of C...mentioning

confidence: 99%

“…In addition, asymmetric retro‐Claisen reactions have also been achieved in the enamine‐quinone methide coupling processes. [ 46‐48 ]…”

Section: Bi/multi‐function Strategy: Development and Application Of C...mentioning

confidence: 99%

Bio‐inspired Small Molecular Catalysis

2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…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] .…”

Section: Introductionmentioning

confidence: 99%

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

Xu¹,

Li²,

Chang³

et al. 2023

Chem Synth

View full text Add to dashboard Cite

We report herein an enantioselective acyl transfer protocol via electrophile activation. The reaction cascade sequence encompasses dinuclear zinc-catalyzed asymmetric Michael addition, intramolecular cyclization, and retro-Claisen reaction, which leads to a step- and atom-economic approach to a variety of protected cyclic tertiary α-hydroxyketones in good yields with excellent enantioselectivities (24 examples, 56%-82% yield, 1.5-13 dr and 79%-96% ee). Besides, the large-scale synthesis and further transformation of the products demonstrate the effectiveness of this method for organic synthesis.

show abstract

“…The asymmetric catalytic cascade reaction generally emerged as a valuable and powerful tool to construct complex chiral molecules with functional diversity, which always features high synthetic efficiency, excellent selective control, and greatly subtractive operation numbers/steps. − Therefore, it could potentially work as an efficient protocol to resolve these challenging problems. Vinylethylene carbonate (VEC) has been intensively employed as an important precursor for the generation of dipoles in cycloaddition reactions, , which also could work as important reaction partners to introduce homoallylic alcohol manifolds. − Driven by the widespread occurrence of the key 3-hydroxymethyl pentenal skeletons, as illustrated in Scheme b, we designed a conceptually new cascade synthetic strategy based on the combination of our recent studies on Ir-catalyzed enantioselective allylation of readily available VEC , and the subsequent intramolecular retro-Claisen reaction. − The protocol has its good points of simplicity, convergence, and high atom economy with carbon dioxide as the sole byproduct. According to the retrosynthetic analysis, the initial Ir-catalyzed asymmetric allylation − of β-diketones with VEC could lead to the crucial intermediate 2,4-dione bearing hydroxymethyl group I in an enantiopure form, which then undergoes a retro-Claisen reaction, leading to the expected key functionalized chiral 3-hydroxymethyl pentenal units.…”

Section: Introductionmentioning

confidence: 99%

Iridium-Catalyzed Asymmetric Cascade Allylation/Retro-Claisen Reaction

Lü

Chang

et al. 2022

J. Am. Chem. Soc.

View full text Add to dashboard Cite

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.

show abstract

Highly Stereoselective Construction of β,β-Diaryl-α-Branched Ketones by the Chiral Primary Amine-Catalyzed Asymmetric Retro-Claisen Reaction

Cited by 8 publications

References 39 publications

Bio‐inspired Small Molecular Catalysis

Bio‐inspired Small Molecular Catalysis

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

Iridium-Catalyzed Asymmetric Cascade Allylation/Retro-Claisen Reaction

Contact Info

Product

Resources

About