Optimising Stereoselectivity in Intramolecular Diels-Alder Reactions of Pentadienyl Acrylates: Synthetic and Computational Investigations into the “Steric Directing Group” Approach

Cayzer, Tory N.; Wong, Leon S.‐M.; Turner, Peter; Paddon‐Row, Michael N.; Sherburn, Michael S.

doi:10.1002/1521-3765(20020201)8:3<739::aid-chem739>3.0.co;2-1

Cited by 38 publications

(34 citation statements)

References 74 publications

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“…The stationary points were verified as transition‐state structures by observing that the vibrational mode of the single imaginary frequency corresponded to concerted bond formation along the reaction coordinate. Unscaled ZPVE‐corrected electronic energies were used in place of free energies, as these parameters had been shown to give acceptable results for regioisomeric IMDA cycloadditions 7c. Although the calculated Boltzmann populations at 180 °C accurately predicted the major and minor diastereomers, there appeared to be some deviation with respect to the ratios of 15 / 17 and 18 / 20 (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of (±) Wine Lactone and Its Analogues by a Diels–Alder Approach

2009

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A novel route to (Ϯ)-wine lactone (1) by a cis-selective kinetically controlled intramolecular Diels-Alder (IMDA) cycloaddition of the linear triene 2 is reported. The triene precursor was synthesised by TBAF-catalysed coupling of an acyl fluoride with an silyl enol ether. Four butadienyl but-3-enoates were prepared and cyclised under mild conditions to give a series of wine lactone analogues. The diastereoselectivity of the IMDA cycloadditions was determined by NMR spectroscopy and GC-MS, whereby the formation of the natural

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Section: Resultsmentioning

confidence: 99%

Synthesis of (±) Wine Lactone and Its Analogues by a Diels–Alder Approach

2009

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“…As will be discussed later in more detail a very recent joint synthetic computational investigation into the optimization of the stereoselectivity in the IMDA reaction of pentadienyl acrylates has corroborated this expectation. 35 Subsequent isomerization of the trans-fused lactone (b) to the more stable cis-configuration should afford the desired stereochemistry (a) as present in derivatives 14a and 15a. A further strategic choice allowing for the convergent synthesis of both 14 and 15, which only differ in the connecting unit, consists of the incorporation of a vinylic halogen atom (i.e., R = Br), whose replacement using one of the several existing cross-coupling reactions, should allow for the completion of the carbon framework of the molecule possessing the genuine D-ring as in 14 and 15.…”

Section: Methodsmentioning

confidence: 99%

“…Lastly, the cycloaddition of a C-3 bromine substituted pentadienyl acrylate, described by Paddon−Row and Sherburn (iv) leads to the corresponding stereoisomers a and b, with again a clear preference for the anti,exo-adduct b. 35 Interestingly in the previous studies elaborate DFT calculations have corroborated the experimental results. Since the cycloadditions were shown to proceed under kinetic control, the relative energies of the different transition states were calculated.…”

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confidence: 99%

Synthesis and binding affinity studies of muscarinic receptor antagonists related to dehydrohimbacine

Gao¹,

Cauwenberge²,

Hosten³

et al. 2003

Arkivoc

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The intramolecular Diels−Alder reaction of bromo-substituted nonatrienoate 24 leads to a mixture of the anti-adducts 25a and 25b, in which the trans-fused lactone 25b, the result of an expected exo-addition, predominates (6.2:1 stereoselectivity). Further introduction of a 2,6-transdisubstituted piperidine ring (26 and 27) via palladium catalyzed cross-coupling reactions (Stille and Sonogashira) affords intermediates that are easily transformed into dehydrohimbacine derivatives 14a, 14b, 15a, and 15b. Binding affinity studies for the muscarine receptors M 1 , M 2 , M 3 , and M 4 show that 15a possesses a 18-fold selectivity for the M 2 relative to the M 1 receptor, but with concomittant loss in affinity compared to the naturally occurring (+)-himbacine (1), a recognized muscarinic receptor antagonist.

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“…156 The key precursor, disubstituted [3]dendralene 176, was prepared in six steps from ethyl glycolate using Ramirez olefination and cross-coupling chemistry. 157 An initial intermolecular DA reaction with the dienophile methyl acrylate generated a cycloadduct which underwent in situ lactonization to gen-erate bicycle 177. A second DA reaction, with substituted benzoquinone dienophile 178, generated tetracycle 179, completing the formation of the carbon framework of triptolide.…”

Section: Double Diels-alder Sequencesmentioning

confidence: 99%

The Diels–Alder Reaction in Steroid Synthesis

Mackay

Sherburn

2014

Synthesis

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This review explores the myriad ways in which the Diels-Alder reaction has been employed in the construction of the tetracyclic steroid nucleus. A systematic analysis of possible approaches highlights both the synthetic versatility of this ubiquitous reaction and also opportunities for new routes to fused tetracarbocyclic steroid frameworks. 1.1 Introduction 1.2 Classification of the Approaches 2.1 Installation of a Non-Skeletal Ring 2.2 Construction of the A-Ring 2.3 Construction of the BRing 2.4 Construction of the C-Ring 2.5 Double Diels-Alder Sequences 3 Conclusions and Future Prospects

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Optimising Stereoselectivity in Intramolecular Diels-Alder Reactions of Pentadienyl Acrylates: Synthetic and Computational Investigations into the “Steric Directing Group” Approach

Cited by 38 publications

References 74 publications

Synthesis of (±) Wine Lactone and Its Analogues by a Diels–Alder Approach

Synthesis of (±) Wine Lactone and Its Analogues by a Diels–Alder Approach

Synthesis and binding affinity studies of muscarinic receptor antagonists related to dehydrohimbacine

The Diels–Alder Reaction in Steroid Synthesis

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