Asymmetric Formal [3 + 2] Cycloaddition Reaction of Succinaldehyde via Diarylprolinol-mediated Domino Aldol–Acetalization Reaction for the Construction of Tetrahydrofuran

Hayashi, Yujiro; Nishino, Kentaro; Sato, Iwao

doi:10.1246/cl.130544

Cited by 14 publications

(7 citation statements)

References 20 publications

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Section: Asymmetric Cross‐aldol Reactionsmentioning

confidence: 99%

“…Interestingly, the Hayashi's group reported the aldol reaction of succinaldehyde with activated aldehydes, organocatalyzed by prolinol 1 b, to accomplish the enantioselective synthesis of tetrahydrofurans (Scheme 4). [15] Specifically, in the formal [3 + 2] cycloaddition reaction, succinaldehyde acted as a three-carbon unit in a domino sequence, involving the aldol reaction, followed by intramolecular acetal cyclization. The product treated with HC(OMe) 3 in the presence of p-toluene- sulfonic acid (p-TsOH) in MeOH, afforded the major α-methoxy cis-isomer of tetrahydrofuran dimethyl acetals in modest yields, but with excellent enantioselectivity in all cases.…”

Section: Asymmetric Cross-aldol Reactionsmentioning

confidence: 99%

See 1 more Smart Citation

Diaryl Prolinols in Stereoselective Catalysis and Synthesis: An Update

2019

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Discovered more than one decade ago, α,α‐diaryl prolinols, most of them commercially available compounds, demonstrated to be distinctive organocatalysts in asymmetric synthesis. Their application successfully spanned across different carbon‐carbon or carbon‐heteroatom bond forming reactions and cascade processes, exploiting covalent and noncovalent activation of the reagents. In this minireview, the advances from 2013 up to the end of 2018 in α,α‐diaryl prolinols promoted stereoselective catalysis and synthesis of biologically active compounds, are illustrated.

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Section: Asymmetric Cross‐aldol Reactionsmentioning

confidence: 99%

Section: Asymmetric Cross-aldol Reactionsmentioning

confidence: 99%

Diaryl Prolinols in Stereoselective Catalysis and Synthesis: An Update

2019

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“…Our group has an interest in the synthesis of PGs and reported several syntheses. , On the basis of our asymmetric Michael reaction of aldehydes and nitroalkenes (eq ), we developed a domino Michael/Henry reaction of succinaldehyde ( 36 ) and nitroalkene 35 , a formal [3 + 2] cycloaddition reaction, for the construction of cis -cyclopentene skeleton 39 that proceeded with excellent enantioselectivity (eq ). Using this reaction, we accomplished a three-pot synthesis of prostaglandin E 1 (PGE 1 ) methyl ester (Scheme ). …”

Section: Prostaglandin E1 Methyl Estermentioning

confidence: 99%

Time and Pot Economy in Total Synthesis

Hayashi

2021

Acc. Chem. Res.

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Conspectus We would all like to make or obtain the materials or products we want as soon as possible. This is human nature. This is true also for chemists in the synthesis of organic molecules. All chemists would like to make their target molecules as soon as possible, particularly when their interest is in the physical or biological properties of those molecules. As demonstrated by today’s COVID-19 (SARS-CoV-2) pandemic, rapid synthesis is also crucial to enable chemists to deliver effective therapeutic agents to the community. Several concepts are currently well-accepted as important for achieving this: atom economy, step economy, and redox economy. Considering the importance of synthesizing organic molecules rapidly, I recently proposed adding the concept of time economy. In a multisep synthesis, each step has to be completed within a short period of time to make the desired molecule rapidly. The development of rapid reactions is important but also insufficient. After each step, frequent and repetitive workup operations such as quenching the reaction, extraction, separation of water and organic phases, drying the organic phase, filtration, evaporation, and purification may be required, and the time necessary for these processing operations must be taken into account. Indeed, some of the most time-consuming operations in most syntheses are the purification stages. On the other hand, one-pot reactions are processes in which several sequential reactions are conducted in a single reaction vessel, which avoids the need to purify intermediates. One-pot reactions are a useful way to shorten the total synthesis time, and the approach generally leads to an increase in the yield and a reduction in the amount of chemical waste formed. Thus, I also propose the importance of pot economy. On the basis of these concepts of time and pot economy, we have accomplished efficient syntheses of several natural products and medicines. The key to the success of these syntheses is the use of diphenylprolinol silyl ether as an effective catalyst in a one-pot reaction, in which it does not disturb the subsequent reactions. Our strategy is (1) to construct the chiral key skeletons and/or key components of natural products and medicines directly using organocatalyst-mediated one-pot reactions and (2) to conduct the subsequent transformations to the final molecules in a small number of pots utilizing the internal quench method. By means of this strategy, PGE1 methyl ester, estradiol methyl ether, and clinprost were synthesized in three, five, and seven pots, respectively. Furthermore, (−)-oseltamivir, ABT-341, baclofen, and Corey lactone were synthesized in a single reaction vessel. Further optimization of the reactions in terms of time economy allowed (−)-oseltamivir and Corey lactone to be synthesized within 60 and 152 min, respectively. These syntheses will be highlighted as case studies. Although the organocatalyst is a key compound in this Account, pot- and time-economical syntheses can be expanded to organometallic chemistry and, ind...

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“…20 Very recently, Hayashi and co-workers have also reported a domino approach for the asymmetric synthesis of tetrahydrofurans 36 through formal [3 + 2] cycloaddition of succinaldehyde 6 with other aromatic/activated aldehydes 35 (Scheme 7). 21 The overall process proceeds through diarylprolinol 3 catalyzed direct aldol reaction of succinaldehyde 6 with various aldehydes 35, followed by an intramolecular acetal-cyclization with good yields and high selectivities (up to 99% ee).…”

Section: Succinaldehydementioning

confidence: 99%

Linear dialdehydes as promising substrates for aminocatalyzed transformations

et al. 2015

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Organocatalytic domino reactions involving amine activation of carbonyl compounds have become the latest chemical technology towards the design and development of useful synthetic methods. In this direction, linear dialdehydes such as succinaldehyde, glutaraldehyde, and other homologous compounds have attracted considerable attention as suitable substrates for amine catalyzed transformations. Due to their unique structural features, dialdehydes can easily engage in recreation of cascade/tandem transformations for the synthesis of valuable natural products and drug molecules. In this review article we discuss the current scenario and potential applications of linear dialdehydes as adequate synthetic substrates for amine catalyzed transformations to access biologically important complex scaffolds.

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Asymmetric Formal [3 + 2] Cycloaddition Reaction of Succinaldehyde via Diarylprolinol-mediated Domino Aldol–Acetalization Reaction for the Construction of Tetrahydrofuran

Cited by 14 publications

References 20 publications

Diaryl Prolinols in Stereoselective Catalysis and Synthesis: An Update

Diaryl Prolinols in Stereoselective Catalysis and Synthesis: An Update

Time and Pot Economy in Total Synthesis

Linear dialdehydes as promising substrates for aminocatalyzed transformations

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