Titanium‐promoted Intramolecular Photoenolization/Diels–Alder Reaction to Construct Polycyclic Terpenoids: Formal Synthesis of Mycoleptodiscin A

Xue, Dongsheng; Xu, Mengmeng; Zheng, Chaoying; Yang, Baochao; Hou, Min; He, Haibing; Gao, Shuanhu

doi:10.1002/cjoc.201800555

Cited by 25 publications

(11 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…76a The first total synthesis of mycoleptodiscin A was published in 2015, 76b while later, in 2019, Xue et al reported a formal synthesis of the natural product by starting from (+)-sclareolide and utilizing a Ti(IV)-promoted photoenolization with subsequent intramolecular cyclization as the key step (Scheme 54). 77…”

Section: Formal Synthesis Of Mycoleptodiscin Amentioning

confidence: 99%

Recent Applications of the Diels–Alder Reaction in the Synthesis of Natural Products (2017–2020)

et al. 2021

View full text Add to dashboard Cite

The Diels-Alder reaction has long established its high rank in the toolbox of any natural product chemist. The tremendous toleration of building blocks of various complexity and derivatization degree, as well as the enablement of furnishing six-membered rings with well-defined stereochemistry represents its main features and advantages. In recent years, many total syntheses of natural products relied at some point on the use of a [4+2]-cycloaddition step. Among classic approaches, several modifications of the Diels-Alder reaction, such as hetero-Diels-Alder reactions, dehydro-Diels-Alder reactions or domino-Diels-Alder reactions have been employed to extend the scope in the synthesis of natural products. Our review covers the application of the Diels-Alder reaction in natural product syntheses from 2017 to 2020, as well as selected methodologies which were inspired by, or could be used to access natural products.

show abstract

Section: Formal Synthesis Of Mycoleptodiscin Amentioning

confidence: 99%

Recent Applications of the Diels–Alder Reaction in the Synthesis of Natural Products (2017–2020)

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Recently, the Gao group reported the use of a Lewis acid to facilitate the Diels–Alder phase of the process, permitting the first catalytic enantioselective processes. This methodology has been applied at an early stage in the total syntheses of oncocalyxone B, mycloeptodiscin A, , (+)-xestoquinone, and (+)-adociaquinones A/B . The robust nature of the PEDA sequence has also permitted application outside of target-based synthesis such as photoligation, photoremovable protecting groups, and photoactivated fragrances …”

Section: Introductionmentioning

confidence: 99%

Tuning Photoenolization-Driven Cycloadditions Using Theory and Spectroscopy

et al. 2022

View full text Add to dashboard Cite

The first broad spectrum investigation into the photoenolization/Diels-Alder (PEDA) sequence was carried out using M06-2X/6-31+G(d,p) in conjunction with SMD solvation and supported by experimental UV−vis spectroscopy. A test set of 20 prodienes was chosen to examine the role of the H atom acceptor group (substituted and unsubstituted carbonyl, thiocarbonyl, and imine), the H atom donor group, and bystander ring substituents. As reaction partners for the photogenerated dienes, a diverse test set of 20 dienophiles was examined, comprising electron rich, electron poor, neutral, strain activated, hydrocarbon, and heteroatom-containing molecules including CO 2 and CO. A key finding of this work is the demonstration that the PEDA sequence of carbonyl based prodienes is tolerant of most substitution patterns. Another is that thiocarbonyl derivatives should behave analogously to the carbonyls but are likely to do so much more slowly, due to an inefficient intersystem crossing, an endothermic 1,5-hydrogen atom transfer (HAT) step, and a [1,5] sigmatropic H shift to regenerate the starting material that outcompetes the [4 + 2]cycloaddition. In contrast, the T 1 state of the ortho-alkyl imines displays the incorrect orbital symmetry for 1,5-HAT and is correspondingly accompanied by higher barriers, even in the excited state. However, provided these barriers can be overcome, the remaining steps in the PEDA sequence are predicted to be facile. The Diels−Alder reaction is predicted to be of much broader scope than reported synthetic literature: while electron poor dienophiles are expected to be the most reactive partners, ethylene and electron rich alkenes should react at a synthetically useful rate. CO is predicted to undergo a facile (4 + 1)cheletropic addition instead of the normal [4 + 2]cycloaddition pathway. This unique photoenolization/cheletropic addition (PECA) sequence could provide metal-free access to benzannelated cyclopentanones.

show abstract

“…Our synthesis commenced with the key asymmetric photoenolization/Diels–Alder (APEDA) reaction between fragments 15 and 16 , which could be efficiently prepared in decagram scale (see details in the Supporting Information). Recently, we found that a Lewis acid plays a key role in the PEDA reaction, which helps to activate the inert dienophiles and control the diastereoselectivity. − However, catalytic asymmetric PEDA reaction using sterically hindered multiple substituted olefins as dienophiles has been elusive. , We speculated that a bifunctional catalyst might meet the challenges of asymmetric UV-light initiated cycloaddition. A combination of Lewis acid [Ti(O i -Pr) 4 ] and a chiral ligand was designed to control the enantioselectivity and suppress the background reaction.…”

mentioning

confidence: 99%

“…to 95%. We envisioned that a chiral dinuclear species Ti-TADDOLate 17 was formed as a bifunctional catalyst, and the cycloaddition occurred through an endo direction in the chiral environments. − , This is the first application of the APEDA reaction in total synthesis to construct the vicinal quaternary stereocenters, which is a synthetic challenge in organic synthesis.…”

mentioning

confidence: 99%

Asymmetric Total Synthesis and Biosynthetic Implications of Perovskones, Hydrangenone, and Hydrangenone B

et al. 2021

Self Cite

View full text Add to dashboard Cite

Perovskones and hydrangenones are a family of structurally complex triterpenoids that were mainly isolated from the genus Salvia medicinal plants. These isoprenoids exhibit a broad range of biological activities, such as antitumor and antiplasmodial activities. Here, we report the collective total synthesis of perovskone, perovskones C, D, F, hydrangenone, and hydrangenone B. The key strategies in this work include the following: (1) an asymmetric photoenolization/Diels–Alder reaction was developed to construct a tricyclic ring bearing three contiguous quaternary centers, which was used to build the core icetexane skeleton; (2) a bioinspired Diels–Alder reaction of perovskatone D with trans-α-ocimene was applied to stereospecifically generate perovskones; (3) late-stage oxidations and ring forming steps were developed to synthesize perovskones and hydrangenones. Our synthetic work suggests that (1) perovskatone D may serve as the precursor of the biosynthesis of perovskones and (2) the formation of hydrangenone and hydrangenone B, containing a five-membered D ring, may involve an oxidative ring cleavage and ring regeneration process.

show abstract

Titanium‐promoted Intramolecular Photoenolization/Diels–Alder Reaction to Construct Polycyclic Terpenoids: Formal Synthesis of Mycoleptodiscin A

Cited by 25 publications

References 72 publications

Recent Applications of the Diels–Alder Reaction in the Synthesis of Natural Products (2017–2020)

Recent Applications of the Diels–Alder Reaction in the Synthesis of Natural Products (2017–2020)

Tuning Photoenolization-Driven Cycloadditions Using Theory and Spectroscopy

Asymmetric Total Synthesis and Biosynthetic Implications of Perovskones, Hydrangenone, and Hydrangenone B

Contact Info

Product

Resources

About