A Diastereoselective Formal Synthesis of Berkelic Acid

Wenderski, Todd A.; Marsini, Maurice A.; Pettus, Thomas R. R.

doi:10.1021/ol102652t

Cited by 50 publications

(22 citation statements)

References 21 publications

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“…The natural product’s complexity required some modifications to our original method. With the benzylic ethereal stereocenter in mind, we designed o -QM precursor 36 , which contained a tethered acetate leaving group [12]. Deprotonation of the phenol with t -BuMgCl resulted in an elimination to generate an o -QM that underwent a [4 + 2] cycloaddition with exocyclic enol ether 37 to afford the respective spiroketals in a 3:1 ratio favoring the endo kinetic isomer.…”

Section: Resultsmentioning

confidence: 99%

New strategies for natural products containing chroman spiroketals

Green

Burnett

Pettus

2012

Pure and Applied Chemistry

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Two cycloaddition strategies are described that lead to various chroman spiroketals from assorted exocyclic enol ethers. Unlike conventional thermodynamic ketalization strategies, the stereochemical outcome for this approach is determined by a kinetic cycloaddition reaction. Thus, the stereochemical outcome reflects the olefin geometry of the starting materials along with the orientation of the associated transition state. However, the initial kinetic product can also be equilibrated by acid catalysis and reconstituted into a thermodynamic stereochemical arrangement. Thus, these strategies uniquely enable synthetic access to either the thermodynamic or kinetic conformation of the spiroketal stereocenter itself. Applications of these strategies in the syntheses of berkelic acid, β-rubromycin, and paecilospirone are presented along with the use of a chroman spiroketal for the construction of heliespirones A and C.

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Section: Resultsmentioning

confidence: 99%

New strategies for natural products containing chroman spiroketals

Green

Burnett

Pettus

2012

Pure and Applied Chemistry

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“…The corresponding δ-lactone 100 appeared fluxional enough to undergo the desired reaction with enol ether 65′ affording the carboxylic acid 101 in 60% yield (Scheme 7 III). 48 The phenolic acetate of an unsubstituted salicylalcohol 102 underwent cycloaddition with excess dihydrofuran to give tricycle 103 in good yield (Scheme 7 IV). 49 The OBoc δ-lactone 104 also underwent addition of organocerium and subsequent cycloaddition with enol ether 67′ to produce the ketone 105 , thereby demonstrating formation of the C–C bond at an entirely new site (Scheme 7 V).…”

Section: Benzopyrans and Chroman Ketals From O -Qmmentioning

confidence: 99%

The Domestication of ortho-Quinone Methides

et al. 2014

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ConspectusAn ortho-quinone methide (o-QM) is a highly reactive chemical motif harnessed by nature for a variety of purposes. Given its extraordinary reactivity and biological importance, it is surprising how few applications within organic synthesis exist. We speculate that their widespread use has been slowed by the complications that surround the preparation of their precursors, the harsh generation methods, and the omission of this stratagem from computer databases due to its ephemeral nature.About a decade ago, we discovered a mild anionic triggering procedure to generate transitory o-QMs at low temperature from readily available salicylaldehydes, particularly OBoc derivatives. This novel reaction cascade included both the o-QM formation and the subsequent consumption reaction. The overall transformation was initiated by the addition of the organometallic reagent, usually a Grignard reagent, which resulted in the formation of a benzyloxy alkoxide. Boc migration from the neighboring phenol produced a magnesium phenoxide that we supposed underwent β-elimination of the transferred Boc residue to form an o-QM for immediate further reactions. Moreover, the cascade proved controllable through careful manipulation of metallic and temperature levers so that it could be paused, stopped, or restarted at various intermediates and stages. This new level of domestication enabled us to deploy o-QMs for the first time in a range of applications including diastereocontrolled reactions.This sequence ultimately could be performed in either multipot or single pot processes. The subsequent reaction of the fleeting o-QM intermediates included the 1,4-conjugate additions that led to unbranched or branched ortho-alkyl substituted phenols and Diels–Alder reactions that provided 4-unsubstituted or 4-substituted benzopyrans and chroman ketals. The latter cycloadducts were obtained for the first time with outstanding diastereocontrol. In addition, the steric effects of the newly created stereocenters in subsequent reactions of chroman ketals and acetals were studied and proved predictable. Through the use of a chiral auxiliary, Diels–Alder products were deployed in numerous enantioselective reactions including several complex natural products syntheses. In this Account, we summarize our efforts, which we hope have contributed to the synthetic renaissance for this venerable species.

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“…cal activity of several of these compounds and is regarded as the privileged pharmacophore. [6] Despite the progress achieved in recent years, [7,8] preparation of diversely functionalized aromatic spiroketals remains a challenge. In contrast, the construction of their aliphatic counterparts has been extensively explored.…”

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confidence: 99%

Copper(I)‐Catalyzed Hydroalkoxylation/Hydrogen‐Bonding‐Induced Asymmetric Hetero‐Diels–Alder Cycloaddition Cascade: An Approach to Aromatic Spiroketals

Xue

Huang³

et al. 2012

Chemistry An Asian Journal

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One thing leads to another: Bis(benzannelated) 5,6‐spiroketal skeletons can be constructed by an efficient cascade process involving an unprecedented CuI‐catalyzed intramolecular alkyne hydroalkoxylation and an asymmetric hetero‐Diels–Alder cycloaddition. The method yields a series of diversely functionalized spiroketals from two readily available open‐chained starting materials in good yields and excellent diastereoselectivities.

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A Diastereoselective Formal Synthesis of Berkelic Acid

Cited by 50 publications

References 21 publications

New strategies for natural products containing chroman spiroketals

New strategies for natural products containing chroman spiroketals

The Domestication of ortho-Quinone Methides

Copper(I)‐Catalyzed Hydroalkoxylation/Hydrogen‐Bonding‐Induced Asymmetric Hetero‐Diels–Alder Cycloaddition Cascade: An Approach to Aromatic Spiroketals

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